Autonomic/CV Drugs — MCQs

Question 1: Which antithyroid drug is safer during the first trimester of pregnancy?

• A. Radioactive iodine
• B. Carbimazole
• C. Propylthiouracil (Correct Answer)
• D. Methimazole
• E. Propranolol

Explanation: ***Propylthiouracil*** - **Propylthiouracil (PTU)** is the preferred drug for treating hyperthyroidism in the **first trimester of pregnancy** due to a lower risk of teratogenic effects compared to methimazole or carbimazole. - While PTU carries a risk of hepatic toxicity, it is generally favored during early pregnancy to avoid the established teratogenic risks of other thionamides. *Radioactive iodine* - **Radioactive iodine (RAI)** is absolutely contraindicated in pregnancy as it crosses the placenta and can cause permanent **fetal hypothyroidism** or **agenesis of the fetal thyroid gland**. - Its use can lead to the destruction of the fetal thyroid, which is unacceptable given the availability of safer alternatives. *Carbimazole* - **Carbimazole** is converted to methimazole in the body and is associated with a higher risk of **fetal embryopathy** during the first trimester, including aplasia cutis, choanal atresia, and esophageal atresia. - It should generally be avoided in the first trimester if possible, switching to PTU instead. *Methimazole* - **Methimazole** is structurally similar to carbimazole and also carries a significant risk of **teratogenic effects** such as **aplasia cutis**, omphalocele, and choanal atresia when used in the first trimester. - It is often reserved for the second and third trimesters if a thionamide is required, or for patients who cannot tolerate PTU, but ideally avoided in early pregnancy. *Propranolol* - **Propranolol** is a beta-blocker used for symptomatic management of hyperthyroidism (controlling tachycardia, tremor, anxiety) but is not an antithyroid drug and does not treat the underlying hyperthyroidism. - While generally safe in pregnancy, it only provides adjunctive therapy and cannot replace definitive antithyroid treatment.

Question 2: A patient on SSRI sertraline was also prescribed amitriptyline and subsequently developed serotonin toxicity. What is the likely treatment for serotonin toxicity?

• A. Flumazenil
• B. Cyproheptadine (Correct Answer)
• C. L-Carnitine
• D. Leucovorin
• E. Naloxone

Explanation: ***Cyproheptadine*** - **Cyproheptadine** is a serotonin antagonist that can help reverse the effects of excessive serotonin in the central nervous system. - It works by blocking **serotonin 5-HT2A receptors**, which are implicated in the pathophysiology of serotonin toxicity. *Flumazenil* - **Flumazenil** is a benzodiazepine receptor antagonist used to reverse the effects of benzodiazepine overdose. - It has no role in the treatment of **serotonin toxicity**, as it does not affect serotonin pathways. *L-Carnitine* - **L-Carnitine** is a mitochondrial co-factor used in fatty acid metabolism, sometimes supplemented for certain metabolic disorders or muscle pain. - It does not have any direct action on **serotonin receptors** or the serotonin system, making it ineffective for serotonin toxicity. *Leucovorin* - **Leucovorin** (folinic acid) is used to counteract the effects of methotrexate toxicity or to enhance the effects of fluorouracil in chemotherapy. - It is not involved in modulating **neurotransmitter levels** or reversing the symptoms of serotonin toxicity. *Naloxone* - **Naloxone** is an opioid receptor antagonist used to reverse opioid overdose. - It has no effect on **serotonin receptors** or serotonergic pathways, making it ineffective for treating serotonin toxicity.

Question 3: Which of the following drugs is used in opioid maintenance therapy?

• A. Naltrexone
• B. Clonidine
• C. Buprenorphine (Correct Answer)
• D. Disulfiram
• E. Naloxone

Explanation: ***Buprenorphine*** - **Buprenorphine** is a **partial opioid agonist** used in opioid maintenance therapy to reduce cravings and withdrawal symptoms without producing the full euphoric effects of other opioids. - It is often combined with **naloxone** (as Suboxone) to prevent misuse by injection, as naloxone is only active if injected. - Buprenorphine has a **ceiling effect** for respiratory depression, making it safer than full agonists like methadone. *Naltrexone* - **Naltrexone** is an **opioid antagonist** that blocks opioid receptors, preventing the euphoric effects of opioids and reducing cravings. - While used in opioid use disorder treatment, it is primarily for relapse prevention and not typically for the active maintenance phase where agonist effects are desired. *Clonidine* - **Clonidine** is an **alpha-2 adrenergic agonist** primarily used to manage the **autonomic symptoms of opioid withdrawal**, such as anxiety, sweating, and rapid heart rate. - It does not directly act on opioid receptors and is not a primary agent for long-term opioid maintenance therapy. *Disulfiram* - **Disulfiram** is a drug used in the treatment of **alcohol use disorder**, not opioid use disorder. - It works by inhibiting acetaldehyde dehydrogenase, leading to an unpleasant reaction when alcohol is consumed. *Naloxone* - **Naloxone** is an **opioid antagonist** used for **emergency reversal of opioid overdose**, not for maintenance therapy. - It rapidly displaces opioids from receptors and reverses respiratory depression. - While combined with buprenorphine in Suboxone to prevent misuse, naloxone itself is not used for maintenance therapy.

Question 4: Which of the following growth hormone analogues is not used for the treatment of GH deficiency but is used in the treatment of HIV associated lipodystrophy?

• A. Tesamorelin (Correct Answer)
• B. Sermorelin
• C. Somatropin
• D. Pegvisomant
• E. Mecasermin

Explanation: ***Tesamorelin*** - **Tesamorelin** is a **growth hormone-releasing hormone (GHRH) analogue** approved specifically for the treatment of **HIV-associated lipodystrophy**. - It works by stimulating the natural production and release of endogenous growth hormone, which helps reduce **visceral adipose tissue** observed in this condition. - **Key distinction:** NOT used for GH deficiency, but specifically for lipodystrophy. *Sermorelin* - **Sermorelin** is also a **GHRH analogue**, but it is primarily used to diagnose and treat **growth hormone deficiency** in children. - It is not approved for lipodystrophy and works by stimulating the pituitary to secrete growth hormone. *Somatropin* - **Somatropin** is the recombinant form of **human growth hormone (GH)** itself, used to treat **growth hormone deficiency** in both children and adults. - While it can affect body composition, its primary indication is not HIV-associated lipodystrophy. *Mecasermin* - **Mecasermin** is recombinant **insulin-like growth factor-1 (IGF-1)** used to treat severe primary IGF-1 deficiency. - It is used for growth failure in children with GH gene deletion or GH receptor defects, not for HIV-associated lipodystrophy. *Pegvisomant* - **Pegvisomant** is a **growth hormone receptor antagonist** used to treat **acromegaly**, a condition caused by excessive growth hormone. - It works by blocking the action of growth hormone at its receptor, directly opposing the therapeutic goal for lipodystrophy.

Question 5: Caffeine is a widely used stimulant that promotes wakefulness. Which of the following mechanisms is responsible for this effect?

• A. Adenosine antagonism (Correct Answer)
• B. Increased discharge of norepinephrine from the locus ceruleus
• C. Release of histamine
• D. Inhibition of phosphodiesterase
• E. Dopamine reuptake inhibition

Explanation: ***Adenosine antagonism*** - Caffeine acts as a **competitive antagonist** at **adenosine receptors** (primarily A1 and A2A) in the brain. - **Adenosine** is an inhibitory neurotransmitter that promotes drowsiness and reduces neuronal activity; by blocking its receptors, caffeine prevents this sedation and promotes wakefulness. - This is the **primary mechanism** responsible for caffeine's stimulant effects at typical dietary doses. *Increased discharge of norepinephrine from the locus ceruleus* - While increased **norepinephrine** can promote wakefulness, it is not the primary direct mechanism by which caffeine exerts its stimulant effects. - Caffeine may indirectly affect norepinephrine release as a downstream consequence of adenosine receptor blockade, but this is a secondary effect. *Release of histamine* - **Histamine** is indeed a neurotransmitter involved in wakefulness and arousal, but caffeine does not primarily promote wakefulness by directly causing histamine release. - Some antihistamines cause drowsiness by blocking central histamine receptors, but caffeine's mechanism is distinct from the histaminergic system. *Inhibition of phosphodiesterase* - Caffeine does inhibit **phosphodiesterase (PDE)** enzymes, leading to increased intracellular **cAMP** levels. - However, PDE inhibition occurs at significantly **higher concentrations** than those required for adenosine receptor antagonism, making it a less important mechanism for caffeine's typical stimulant effects at common dietary doses (1-3 cups of coffee). *Dopamine reuptake inhibition* - While some CNS stimulants (e.g., **methylphenidate**, **cocaine**) work primarily through dopamine reuptake inhibition, this is **not** caffeine's primary mechanism. - Caffeine may have minor indirect effects on dopamine neurotransmission through its adenosine receptor antagonism, but direct dopamine reuptake inhibition is not a significant mechanism of action.

Question 6: Which of the following is commonly used for maintenance therapy in opioid abuse?

• A. Clonidine
• B. Buprenorphine (Correct Answer)
• C. Butorphanol
• D. Naloxone
• E. Methadone

Explanation: ***Buprenorphine*** - **Buprenorphine** is a **partial opioid agonist** commonly used for the maintenance treatment of **opioid use disorder** due to its ability to reduce cravings and prevent withdrawal symptoms. - It has a "ceiling effect," meaning that its opioid effects level off at higher doses, which contributes to its **safety profile** and lower risk of overdose compared to full agonists. - Preferred over methadone in many settings due to its **superior safety profile**, lower abuse potential, and ability to be prescribed in office-based settings. *Clonidine* - **Clonidine** is an **alpha-2 adrenergic agonist** primarily used to manage **autonomic symptoms** of opioid withdrawal (e.g., sweating, hypertension), but it does not address cravings or provide opioid effects. - It is not considered a primary maintenance therapy for opioid use disorder. *Butorphanol* - **Butorphanol** is a **mixed opioid agonist-antagonist** often used for pain relief, but its partial agonist activity and potential for withdrawal in opioid-dependent individuals make it unsuitable for maintenance therapy in opioid abuse. - It can precipitate **opioid withdrawal** in patients who are opioid-dependent. *Naloxone* - **Naloxone** is an **opioid antagonist** used to rapidly reverse the effects of opioid overdose by blocking opioid receptors. - While critical in overdose situations, it is not used for maintenance therapy as it would induce immediate and severe opioid withdrawal symptoms. *Methadone* - **Methadone** is a **full opioid agonist** that is also used for maintenance therapy in opioid use disorder, particularly in specialized opioid treatment programs. - However, it requires **daily supervised dosing** in most jurisdictions, has a higher risk of overdose, respiratory depression, and QT prolongation, making buprenorphine often the **preferred first-line agent** for maintenance therapy.

Question 7: A patient presents with symptoms of tachycardia, tachypnea, hypertension, and hypocalcemia after consuming an unknown substance. The patient also has high anion gap metabolic acidosis. Which of the following substances was most likely consumed?

• A. Iron
• B. Methanol
• C. Ethylene glycol (Correct Answer)
• D. Digoxin
• E. Isopropanol

Explanation: ***Ethylene glycol*** - Ethylene glycol poisoning is characterized by **tachycardia**, **tachypnea**, **hypertension**, **hypocalcemia**, and a **high anion gap metabolic acidosis** due to the accumulation of toxic metabolites like oxalic and glycolic acids. - The formation of **calcium oxalate crystals** in the kidneys contributes to hypocalcemia and acute kidney injury, a hallmark of severe ethylene glycol toxicity. *Iron* - Iron overdose typically presents with **gastrointestinal symptoms** (vomiting, diarrhea, abdominal pain), shock, and metabolic acidosis, but not specifically with hypocalcemia or the characteristic crystal formation seen with ethylene glycol. - While it can cause metabolic acidosis, the absence of **hypocalcemia** and specific renal effects pointing to oxalate crystals differentiates it from ethylene glycol. *Methanol* - Methanol poisoning causes a **high anion gap metabolic acidosis**, visual disturbances (e.g., "snowstorm" vision), and central nervous system depression. - It does not typically lead to **hypocalcemia** or the kidney damage associated with calcium oxalate crystal formation. *Isopropanol* - Isopropanol (rubbing alcohol) poisoning causes **CNS depression**, **hypotension**, and an **osmolar gap** without significant anion gap metabolic acidosis. - It does not cause **hypocalcemia** or the high anion gap metabolic acidosis characteristic of ethylene glycol toxicity. *Digoxin* - Digoxin toxicity primarily affects the **cardiac system**, causing bradycardia, arrhythmias (e.g., ventricular fibrillation, heart block), and **gastrointestinal symptoms**. - It does not cause a high anion gap metabolic acidosis, hypocalcemia, or the other systemic sympathetic effects described in the scenario.

Question 8: A 45-year-old male with a history of chronic alcohol use is admitted to the hospital. He presents with anxiety, tremors, and agitation after his last drink 24 hours ago. Which of the following medications is most appropriate for controlling alcohol withdrawal symptoms?

• A. Lorazepam (Correct Answer)
• B. Fomepizole
• C. Disulfiram
• D. Buspirone
• E. Naltrexone

Explanation: ***Lorazepam*** - **Lorazepam**, a **benzodiazepine**, is the first-line treatment for alcohol withdrawal symptoms due to its ability to enhance **GABAergic activity**, which is deficient during withdrawal. - Its **intermediate half-life** and **lack of active metabolites** make it suitable for patients with liver impairment, common in chronic alcohol users. *Fomepizole* - **Fomepizole** is an antidote used to treat poisoning from **methanol** or **ethylene glycol**, not alcohol withdrawal. - It works by inhibiting **alcohol dehydrogenase**, an enzyme involved in the metabolism of these toxic alcohols. *Disulfiram* - **Disulfiram** is an **aldehyde dehydrogenase inhibitor** used to deter alcohol consumption in recovering alcoholics by causing unpleasant reactions if alcohol is consumed. - It is **not used to treat acute alcohol withdrawal symptoms** and can be dangerous if given during withdrawal due to potential interactions. *Buspirone* - **Buspirone** is an **anxiolytic** that acts as a **serotonin receptor agonist** and is used for generalized anxiety disorder. - It is **ineffective for acute alcohol withdrawal** due to its slow onset of action and lack of anticonvulsant properties. *Naltrexone* - **Naltrexone** is an **opioid receptor antagonist** used for relapse prevention and reducing alcohol craving in patients with alcohol use disorder. - It is **not effective for acute alcohol withdrawal symptoms** and does not prevent seizures or delirium tremens, which are life-threatening complications of withdrawal.

Question 9: A patient being treated for hypertriglyceridemia developed flushing, gout, hyperglycemia, and raised liver enzymes. Which drug is the most likely cause?

• A. Atorvastatin
• B. Fenofibrate
• C. Nicotinic acid (Correct Answer)
• D. Ezetimibe
• E. Gemfibrozil

Explanation: ***Nicotinic acid*** - **Nicotinic acid (Niacin)** is known to cause **flushing** due to prostaglandin release. - It also commonly leads to **hyperglycemia**, **hyperuricemia** (which can precipitate gout), and **elevated liver enzymes** as side effects. *Atorvastatin* - While atorvastatin can cause **elevated liver enzymes** and, less commonly, **myopathy**, it does not typically cause flushing, gout, or hyperglycemia. - Its primary role is to lower **LDL cholesterol**, with a lesser effect on triglycerides. *Fenofibrate* - **Fenofibrate** is used to treat hypertriglyceridemia and can rarely cause **elevated liver enzymes** and **gallstones**. - It is not associated with significant flushing, hyperglycemia, or gout. *Gemfibrozil* - **Gemfibrozil** is another fibrate used for hypertriglyceridemia treatment. - While it can cause **elevated liver enzymes** and **myopathy** (especially when combined with statins), it does not cause the characteristic flushing or hyperglycemia seen with nicotinic acid. *Ezetimibe* - **Ezetimibe** primarily inhibits cholesterol absorption and is generally well-tolerated. - Common side effects are mild and include abdominal pain and diarrhea, with no association to flushing, gout, or hyperglycemia.

Question 10: Lidocaine is used in a loading dose for the treatment of arrhythmias. The loading dose of this drug depends upon which of the following factors?

• A. Clearance
• B. Volume of distribution (Correct Answer)
• C. Half-life
• D. Bioavailability
• E. Elimination rate constant

Explanation: ***Volume of distribution*** - The **loading dose** of a drug is primarily determined by its **volume of distribution (Vd)** and the **target plasma concentration**. - A larger **Vd** means the drug distributes widely into tissues, requiring a larger loading dose to achieve the desired concentration in the central compartment. *Clearance* - **Clearance** dictates the **maintenance dose** needed to sustain a steady-state concentration once the loading dose has been administered. - It reflects the rate at which the drug is eliminated from the body, not how much is initially needed to fill the distribution volume. *Half-life* - **Half-life** determines the **time required to reach steady-state** and the **dosing interval** for maintaining therapeutic concentrations. - While related to clearance and Vd, it does not directly determine the magnitude of the initial loading dose itself. *Bioavailability* - **Bioavailability** is the fraction of administered drug that reaches the systemic circulation in an unchanged form. - It influences the oral dose required to achieve a certain plasma concentration, but the concept of loading dose is typically considered for the intravenous route where bioavailability is 100%. *Elimination rate constant* - The **elimination rate constant (ke)** describes the rate of drug elimination and is related to clearance and volume of distribution (ke = Cl/Vd). - Like clearance, it determines the **maintenance dose** and dosing frequency, not the initial loading dose required to achieve therapeutic levels.

Question 11: A patient with a history of binge alcohol intake presented to the emergency department with convulsions, altered sensorium, and a plasma glucose level of $45 \mathrm{mg} / \mathrm{dL}$. Which of the following treatments is needed?

• A. Thiamine
• B. $25 \% $ Dextrose
• C. Thiamine followed by Dextrose (Correct Answer)
• D. Fomepizole
• E. Glucagon

Explanation: ***Thiamine followed by Dextrose*** - In patients with **alcoholism** and suspected **hypoglycemia**, thiamine should always be administered before or concurrently with dextrose to prevent **Wernicke encephalopathy**. - Dextrose alone can precipitate or worsen Wernicke encephalopathy in **thiamine-deficient** individuals by increasing carbohydrate metabolism, thereby depleting residual thiamine. *Thiamine* - While **thiamine** is crucial for patients with chronic alcohol intake, administering it alone will not immediately resolve the **hypoglycemia** and associated neurological symptoms like convulsions and altered sensorium. - Thiamine is essential to prevent complications like **Wernicke-Korsakoff syndrome**, but the immediate life-threatening issue is the low blood glucose. *25% Dextrose* - Administering **dextrose** alone to an **alcohol-dependent** patient is risky because it can precipitate or worsen **Wernicke's encephalopathy** by increasing glucose metabolism without adequate thiamine. - While dextrose will correct the **hypoglycemia**, its administration without prior thiamine is contraindicated in this patient population. *Glucagon* - **Glucagon** works by mobilizing hepatic glycogen stores to raise blood glucose levels. - In patients with **chronic alcohol intake**, hepatic glycogen stores are often **depleted**, making glucagon ineffective. - Additionally, glucagon has a **slower onset** compared to intravenous dextrose, making it unsuitable for this emergency situation with convulsions and altered sensorium. *Fomepizole* - **Fomepizole** is an antidote used in cases of **methanol** or **ethylene glycol poisoning** to inhibit alcohol dehydrogenase. - It is not indicated for treating **alcohol withdrawal**, **hypoglycemia**, or related complications in patients with binge alcohol intake.

Question 12: What is a potential consequence of administering indomethacin beyond 36 weeks of gestation?

• A. Teratogenic
• B. No effect
• C. Premature closure of the patent ductus arteriosus (PDA) (Correct Answer)
• D. Still birth
• E. Oligohydramnios

Explanation: ***Premature closure of the patent ductus arteriosus (PDA)*** - **Indomethacin**, a non-steroidal anti-inflammatory drug (NSAID), inhibits **prostaglandin synthesis**, which is crucial for maintaining PDA patency in utero. - **Premature closure of the PDA** beyond 36 weeks of gestation can lead to **pulmonary hypertension** and **fetal heart failure**, as blood flow through the fetal circulation would be significantly altered. - This is the **most serious cardiovascular complication** of indomethacin use in late pregnancy. *Teratogenic* - While some medications can be teratogenic (cause birth defects), **indomethacin** is not generally considered to have a significant teratogenic risk when used in the third trimester. - The primary concern with NSAID use in late pregnancy is related to their effects on fetal circulation and renal function, not structural anomalies. *No effect* - This statement is incorrect because **indomethacin** has well-documented and significant effects on fetal circulation, particularly on the **ductus arteriosus**, especially in the third trimester. - Its mechanism of action profoundly impacts the maintenance of the fetal circulatory shunts. *Still birth* - While **indomethacin** use in late pregnancy can lead to serious fetal complications such as **pulmonary hypertension** and **renal dysfunction**, leading to **fetal compromise**, it does not directly or exclusively cause stillbirth. - The specific and most direct consequence on the cardiovascular system is the premature closure of the PDA. *Oligohydramnios* - While **oligohydramnios** (decreased amniotic fluid) can occur with prolonged NSAID use due to **decreased fetal urine output** from renal effects, this is not the primary concern beyond 36 weeks. - The more immediate and serious risk is **premature PDA closure** with its cardiovascular consequences.

Question 13: A 50-year-old patient with renal insufficiency was recently operated on for pyelolithotomy. Which drug is the most appropriate choice for post-operative analgesia?

• A. Diclofenac sodium
• B. Naproxen
• C. Indomethacin
• D. Acetaminophen (Correct Answer)
• E. Ketorolac

Explanation: ***Acetaminophen*** - **Acetaminophen** is primarily metabolized in the liver, with minimal renal excretion, making it a safer option for patients with **renal insufficiency**. - It provides effective **analgesia** without the adverse renal effects associated with NSAIDs. *Diclofenac sodium* - **Diclofenac** is a non-steroidal anti-inflammatory drug (**NSAID**) that can impair renal function, especially in patients with pre-existing **renal insufficiency**, by inhibiting prostaglandin synthesis. - Its use can lead to further **kidney damage** or exacerbate existing renal impairment. *Naproxen* - **Naproxen** is an **NSAID** that carries a significant risk of causing acute kidney injury in patients with **compromised renal function**. - It reduces renal blood flow and glomerular filtration rate, making it unsuitable for this patient. *Indomethacin* - **Indomethacin** is a potent **NSAID** known for its adverse renal effects, including acute renal failure. - It should be avoided in patients with **renal insufficiency** due to its potential to further decline kidney function. *Ketorolac* - **Ketorolac** is a potent **NSAID** commonly used for post-operative pain but is **contraindicated** in patients with renal insufficiency. - It has significant nephrotoxic potential and can cause acute renal failure, especially in patients with pre-existing kidney disease.

Question 14: Which of the following is false about pheochromocytoma?

• A. Surgery is the treatment of choice
• B. VMA (vanillylmandelic acid) is a diagnostic test
• C. Propranolol is the preferred drug for hypertension control (Correct Answer)
• D. Catecholamines are a diagnostic test
• E. Most pheochromocytomas are benign

Explanation: ***Propranolol is the preferred drug for hypertension control*** - Propranolol, a **beta-blocker**, is generally contraindicated as monotherapy in pheochromocytoma because blocking beta-receptors unopposed can lead to a **hypertensive crisis** due to unopposed alpha-adrenergic vasoconstriction. - **Alpha-blockers** (e.g., phenoxybenzamine) are the first-line agents for hypertension control, followed by beta-blockers once adequate alpha-blockade is established. *Surgery is the treatment of choice* - **Surgical resection** of the tumor is indeed the definitive treatment for pheochromocytoma once the patient has been appropriately prepared with alpha-blockade. - This approach aims to remove the source of excessive catecholamine production and resolve the associated symptoms. *VMA (vanillylmandelic acid) is a diagnostic test* - **VMA** is a metabolic breakdown product of catecholamines, and its measurement in a **24-hour urine collection** is a long-standing method for diagnosing pheochromocytoma. - Elevated VMA levels indicate overproduction of catecholamines, which is characteristic of the tumor. *Catecholamines are a diagnostic test* - Measuring **plasma free metanephrines** and **24-hour urinary fractionated metanephrines** (which are methylated metabolites of catecholamines) are highly sensitive and specific diagnostic tests for pheochromocytoma. - Elevated levels confirm the excessive secretion of these hormones by the tumor. *Most pheochromocytomas are benign* - Approximately **90% of pheochromocytomas are benign**, with only about 10% being malignant. - The **"rule of 10s"** is a helpful mnemonic: 10% bilateral, 10% extra-adrenal, 10% malignant, 10% familial, and 10% occur in children.

Question 15: Which of the following drugs is used for the long term management of obesity

• A. Fenfluramine
• B. Sibutramine
• C. Liraglutide (Correct Answer)
• D. Metformin
• E. Orlistat

Explanation: ***Liraglutide*** - **Liraglutide** is a **GLP-1 receptor agonist** approved for **long-term weight management** in adults with obesity or overweight with comorbidities. - It works by **delaying gastric emptying**, increasing satiety, and reducing appetite, leading to sustained weight loss. *Fenfluramine* - **Fenfluramine** was an **anorectic drug** that was withdrawn from the market due to its association with **pulmonary hypertension** and **cardiac valvulopathy**. - It is **not used** for the long-term management of obesity due to severe cardiovascular side effects. *Sibutramine* - **Sibutramine** is a **serotonin-norepinephrine reuptake inhibitor** previously used for weight loss, but it was withdrawn due to increased risk of **cardiovascular events** such as heart attack and stroke. - It is **not recommended** for long-term obesity management due to its significant cardiovascular risks. *Orlistat* - **Orlistat** is a **pancreatic lipase inhibitor** that is approved for long-term obesity management but works by **reducing fat absorption** in the gastrointestinal tract. - While approved for long-term use, it is **less preferred** than GLP-1 agonists due to gastrointestinal side effects (steatorrhea, fecal incontinence) and lower efficacy in weight reduction compared to newer agents like liraglutide. *Metformin* - **Metformin** is primarily an **antidiabetic drug** used for type 2 diabetes and sometimes for polycystic ovary syndrome (PCOS). - While it may cause modest weight loss as a side effect, it is **not approved or indicated** as a primary drug for the long-term management of obesity in individuals without diabetes.

Question 16: Topiramate is used in

• A. 1st Line Treatment of ADHD
• B. Treatment of Acute Migraine
• C. Management of Seizures in Lennox-Gastaut Syndrome (Correct Answer)
• D. Treatment of Dementia
• E. Treatment of Bipolar Disorder

Explanation: ***Management of Seizures in Lennox-Gastaut Syndrome*** - Topiramate is an **antiepileptic drug** approved for the treatment of **partial-onset seizures**, tonic-clonic seizures, and seizures associated with **Lennox-Gastaut syndrome**. - Its multiple mechanisms of action, including blocking **voltage-gated sodium channels**, enhancing **GABAergic activity**, and antagonizing **AMPA/kainate glutamate receptors**, make it effective in managing complex seizure disorders. - This is a **primary FDA-approved indication** for topiramate. *1st Line Treatment of ADHD* - First-line treatments for ADHD typically involve **stimulants** like methylphenidate or amphetamines, or non-stimulants such as atomoxetine. - While topiramate can have cognitive side effects like "brain fog," it is **not considered a primary treatment** for ADHD. *Treatment of Acute Migraine* - Topiramate is used for **migraine prophylaxis (prevention)**, not for the acute treatment of a migraine attack. - Acute migraine treatments include triptans, NSAIDs, and CGRP inhibitors. - The key distinction is **prophylaxis vs. acute treatment**. *Treatment of Dementia* - There is **no evidence** that topiramate is effective in treating dementia or improving cognitive function in patients with dementia. - Current treatments for dementia often involve cholinesterase inhibitors or NMDA receptor antagonists. *Treatment of Bipolar Disorder* - While topiramate has been studied in bipolar disorder, it is **not FDA-approved** for this indication. - Standard mood stabilizers include lithium, valproate, carbamazepine, and atypical antipsychotics. - Topiramate lacks sufficient evidence for efficacy in bipolar disorder management.

Question 17: A 19-year-old woman with a history of poorly controlled asthma presents to her pulmonologist for a follow-up visit. She was recently hospitalized for an asthma exacerbation. It is her third hospitalization in the past five years. She currently takes inhaled salmeterol and medium-dose inhaled budesonide. Her past medical history is also notable for psoriasis. She does not smoke and does not drink alcohol. Her temperature is 98.6°F (37°C), blood pressure is 110/65 mmHg, pulse is 75/min, and respirations are 20/min. Physical examination reveals bilateral wheezes that are loudest at the bases. The patient’s physician decides to start the patient on zileuton. Which of the following is the most immediate downstream effect of initiating zileuton?

• A. Decreased signaling via the leukotriene receptor
• B. Decreased signaling via the muscarinic receptor
• C. Decreased mast cell degranulation
• D. Decreased production of leukotrienes (Correct Answer)
• E. Decreased IgE-mediated pro-inflammatory activity

Explanation: ***Decreased production of leukotrienes*** - **Zileuton** is a **5-lipoxygenase inhibitor**. This enzyme is crucial for the synthesis of **leukotrienes** from arachidonic acid. - By inhibiting 5-lipoxygenase, zileuton directly reduces the overall production of all types of leukotrienes, including LTB4, LTC4, LTD4, and LTE4. *Decreased signaling via the leukotriene receptor* - This describes the mechanism of action for **leukotriene receptor antagonists** (LTRAs) like montelukast and zafirlukast, which block leukotriene receptors. - While zileuton ultimately reduces leukotriene effects, its direct and immediate action is on leukotriene synthesis, not receptor blockade. *Decreased signaling via the muscarinic receptor* - This is the mechanism of action for **anticholinergic bronchodilators** (e.g., ipratropium, tiotropium), which block the action of acetylcholine at muscarinic receptors. - Zileuton does not act on the muscarinic receptor system. *Decreased mast cell degranulation* - This is the primary action of **mast cell stabilizers** like cromolyn and nedocromil, which prevent the release of inflammatory mediators from mast cells. - While leukotrienes are involved in inflammation, zileuton's direct action is not on preventing mast cell degranulation itself but rather on blocking a pathway downstream from initial triggers. *Decreased IgE-mediated pro-inflammatory activity* - This describes the mechanism of action for **omalizumab**, a monoclonal antibody that targets IgE, preventing its binding to mast cells and basophils. - Zileuton acts on the leukotriene synthesis pathway, independent of IgE-mediated processes.

Question 18: A 60-year-old man presents to the emergency department for fatigue and feeling off for the past week. He has not had any sick contacts and states that he can’t think of any potential preceding symptoms or occurrence to explain his presentation. The patient has a past medical history of diabetes, hypertension, and congestive heart failure with preserved ejection fraction. His temperature is 98°F (36.7°C), blood pressure is 125/65 mmHg, pulse is 90/min, respirations are 14/min, and oxygen saturation is 100% on room air. Laboratory values are obtained and shown below. Hemoglobin: 12 g/dL Hematocrit: 36% Leukocyte count: 6,500/mm^3 with normal differential Platelet count: 197,000/mm^3 Serum: Na+: 147 mEq/L Cl-: 105 mEq/L K+: 4.1 mEq/L HCO3-: 26 mEq/L BUN: 21 mg/dL Glucose: 100 mg/dL Creatinine: 1.1 mg/dL Ca2+: 10.1 mg/dL AST: 12 U/L ALT: 10 U/L Urine: Appearance: clear Specific gravity: 1.003 The patient is admitted to the floor, a water deprivation test is performed, and his urine studies are repeated yet unchanged. Which of the following is the best next step in management?

• A. Administer desmopressin (Correct Answer)
• B. Administer hypotonic fluids
• C. Perform a head CT
• D. Administer demeclocycline
• E. Obtain a serum renin:aldosterone ratio

Explanation: ***Administer desmopressin*** - The patient's presentation with **fatigue**, **hypernatremia**, **dilute urine** (specific gravity 1.003), and unchanged urine studies after a **water deprivation test** is characteristic of **central diabetes insipidus**. - **Desmopressin (dDAVP)** is a synthetic analog of **ADH** and is the primary treatment for central diabetes insipidus, as it will **replace the missing ADH** and allow the kidneys to concentrate urine. *Administer hypotonic fluids* - Administering hypotonic fluids would be indicated for **hypernatremia** due to **dehydration**, but the underlying issue here is the **inability to retain water** due to **ADH deficiency**, not solely insufficient fluid intake. - While necessary to correct the hypernatremia, without addressing the underlying ADH deficiency, the patient would continue to excrete large volumes of dilute urine, leading to persistent hypernatremia or requiring continuous, large volumes of hypotonic fluids. *Perform a head CT* - A head CT could be considered later to investigate the **cause of central diabetes insipidus** (e.g., tumor, trauma, inflammation), but the immediate priority is to **treat the ADH deficiency** to prevent severe dehydration and neurological complications from hypernatremia. - While diagnosing the underlying cause is important, it is not the best *next step in management* for the acute symptoms and electrolyte imbalance. *Administer demeclocycline* - **Demeclocycline** is a drug used to treat the **syndrome of inappropriate antidiuretic hormone (SIADH)**, which is characterized by **hyponatremia** and **concentrated urine** due to excessive ADH. - This patient presents with **hypernatremia** and **dilute urine**, which is the exact opposite of SIADH, making demeclocycline an inappropriate treatment. *Obtain a serum renin:aldosterone ratio* - A serum **renin:aldosterone ratio** is used to evaluate for primary **hyperaldosteronism** (Conn's syndrome), which is characterized by **hypertension**, **hypokalemia**, and **metabolic alkalosis**. - This patient has **hypernatremia** and a normal potassium level, with no clear indication of hyperaldosteronism.

Question 19: A 25-year-old female with a history of childhood asthma presents to clinic complaining of a three month history of frequent, loose stools. She currently has three to four bowel movements per day, and she believes that these episodes have been getting worse and are associated with mild abdominal pain. She also endorses seeing red blood on the toilet tissue. On further questioning, she also endorses occasional palpitations over the past few months. She denies fevers, chills, headache, blurry vision, cough, shortness of breath, wheezing, nausea, or vomiting. She describes her mood as slightly irritable and she has been sleeping poorly. A review of her medical chart reveals a six pound weight loss since her visit six months ago, but she says her appetite has been normal. The patient denies any recent illness or travel. She is a non-smoker. Her only current medication is an oral contraceptive pill. Her temperature is 37°C (98.6°F), pulse is 104/min, blood pressure is 95/65 mmHg, respirations are 16/min, and oxygen saturation is 99% on room air. On physical exam, the physician notes that her thyroid gland appears symmetrically enlarged but is non-tender to palpation. Upon auscultation there is an audible thyroid bruit. Her cranial nerve is normal and ocular exam reveals exophthalmos. Her abdomen is soft and non-tender to palpation. Deep tendon reflexes are 3+ throughout. Lab results are as follows: Serum: Na+: 140 mEq/L K+: 4.1 mEq/L Cl-: 104 mEq/L HCO3-: 26 mEq/L BUN: 18 mg/dL Creatinine 0.9 mg/dL Hemoglobin: 14.0 g/dL Leukocyte count: 7,400/mm^3 Platelet count 450,000/mm^3 TSH & Free T4: pending A pregnancy test is negative. The patient is started on propranolol for symptomatic relief. What is the most likely best next step in management for this patient?

• A. Thyroid scintigraphy with I-123
• B. Surgical thyroidectomy
• C. IV hydrocortisone
• D. Adalimumab
• E. Methimazole (Correct Answer)

Explanation: ***Methimazole*** - The patient's symptoms (tachycardia, weight loss despite normal appetite, irritability, insomnia, diarrhea, exophthalmos, goiter with bruit, hyperreflexia) are classic for **hyperthyroidism**, most likely **Graves' disease**. - **Methimazole** is an antithyroid drug that inhibits thyroid hormone synthesis and is a primary treatment for hyperthyroidism. *Thyroid scintigraphy with I-123* - While thyroid scintigraphy is useful for differentiating causes of hyperthyroidism, it is typically performed **after initial laboratory confirmation** of hyperthyroidism (TSH and T4 levels) to guide long-term treatment. - Given the strong clinical picture, immediate treatment to control symptoms (propranolol) and reduce hormone synthesis (methimazole) is a more pressing next step. *Surgical thyroidectomy* - **Thyroidectomy** is a definitive treatment for hyperthyroidism but is usually reserved for cases that fail medical therapy, have very large goiters, or suspicion of malignancy. - It also requires the patient to be **euthyroid** before surgery to minimize operative risks. *IV hydrocortisone* - **IV hydrocortisone** is used for the treatment of **thyroid storm**, a severe, life-threatening manifestation of hyperthyroidism, or in cases of adrenal crisis. - While the patient is symptomatic, her vital signs and lack of severe multi-organ dysfunction do not suggest thyroid storm. *Adalimumab* - **Adalimumab** is a TNF-alpha inhibitor used to treat autoimmune conditions like inflammatory bowel disease (Crohn's disease, ulcerative colitis), rheumatoid arthritis, or psoriasis. - Although the patient has GI symptoms, **inflammatory bowel disease** is less likely given the constellation of other symptoms pointing to hyperthyroidism, and adalimumab is not a treatment for thyroid disease.

Question 20: A 12-year-old boy is brought to the emergency department by his mother because of progressive shortness of breath, difficulty speaking, and diffuse, colicky abdominal pain for the past 3 hours. Yesterday he underwent a tooth extraction. His father and a paternal uncle have a history of repeated hospitalizations for upper airway and orofacial swelling. The patient takes no medications. His blood pressure is 112/62 mm Hg. Examination shows edematous swelling of the lips, tongue, arms, and legs; there is no rash. Administration of a drug targeting which of the following mechanisms of action is most appropriate for this patient?

• A. Antagonist at bradykinin receptor (Correct Answer)
• B. Antagonist at histamine receptor
• C. Agonist at glucocorticoid receptor
• D. Agonist at androgen receptor
• E. Inhibitor of angiotensin-converting enzyme

Explanation: ***Antagonist at bradykinin receptor*** - The patient's symptoms (laryngeal edema, abdominal pain, diffuse limb swelling without rash), family history (recurrent angioedema), and recent dental procedure (a known trigger) are highly suggestive of **hereditary angioedema (HAE)**. - HAE is caused by a deficiency or dysfunction of **C1 esterase inhibitor**, leading to uncontrolled activation of the **kallikrein-kinin system** and excessive production of **bradykinin**, which mediates the edema. Treatment involves targeting bradykinin directly (e.g., icatibant, a bradykinin B2 receptor antagonist) or replacing C1 esterase inhibitor. *Antagonist at histamine receptor* - **Antihistamines** are effective for histamine-mediated angioedema, which typically presents with **urticaria (hives)** and pruritus. - The absence of a rash and lack of pruritus in this patient, along with the specific triggers and family history, make histamine-mediated angioedema (e.g., allergic angioedema) unlikely. *Agonist at glucocorticoid receptor* - **Glucocorticoids** (corticosteroids) are effective in treating inflammatory conditions and allergic reactions, often used for histamine-mediated angioedema. - They are **ineffective** in acute attacks of hereditary angioedema because bradykinin-mediated pathways do not primarily involve inflammation responsive to corticosteroids. *Agonist at androgen receptor* - **Androgens** (e.g., danazol, stanozolol) are used for the **long-term prophylaxis** of hereditary angioedema by increasing C1 esterase inhibitor production. - They are **not appropriate for acute treatment** due to their slow onset of action and are contraindicated in prepubertal children due to side effects. *Inhibitor of angiotensin-converting enzyme* - **ACE inhibitors** can cause acquired angioedema by **inhibiting bradykinin degradation**, leading to its accumulation. - However, the patient is currently on no medications, making **ACE inhibitor-induced angioedema unlikely**, and stopping the ACE inhibitor (if he were on one) would be crucial, but an acute specific treatment targeting bradykinin is still needed.

Question 21: A 23-year-old primigravid woman at 8 weeks' gestation is brought to the emergency department by her husband because of increasing confusion and high-grade fever over the past 16 hours. Three days ago, she was prescribed metoclopramide by her physician for the treatment of nausea and vomiting. She has a history of depression. Current medications include fluoxetine. She is confused and not oriented to time, place, or person. Her temperature is 39.8°C (103.6°F), pulse is 112/min, and blood pressure is 168/96 mm Hg. Examination shows profuse diaphoresis and flushed skin. Muscle rigidity is present. Her deep tendon reflexes are decreased bilaterally. Mental status examination shows psychomotor agitation. Laboratory studies show: Hemoglobin 12.2 g/dL Leukocyte count 17,500/mm3 Serum Creatinine 1.4 mg/dL Total bilirubin 0.7 mg/dL Alkaline phosphatase 45 U/L AST 122 U/L ALT 138 U/L Creatine kinase 1070 U/L Which of the following drugs is most likely to also cause the condition that is responsible for this patient’s current symptoms?

• A. Haloperidol (Correct Answer)
• B. Amitriptyline
• C. Atropine
• D. Dextroamphetamine
• E. Succinylcholine

Explanation: ***Haloperidol*** - The patient has **neuroleptic malignant syndrome (NMS)**, caused by metoclopramide (a dopamine D2 receptor antagonist). Key diagnostic features include **muscle rigidity, hyperthermia, autonomic instability, altered mental status, elevated creatine kinase (1070 U/L), and decreased deep tendon reflexes**. - **Haloperidol** is a first-generation antipsychotic and potent **dopamine D2 receptor antagonist** that is a classic cause of NMS. It would cause the **exact same condition** as metoclopramide. - NMS results from **dopamine D2 receptor blockade** in the basal ganglia and hypothalamus, leading to the characteristic syndrome of rigidity, hyperthermia, and autonomic dysfunction. *Amitriptyline* - Amitriptyline is a **tricyclic antidepressant (TCA)** that inhibits reuptake of serotonin and norepinephrine. When combined with SSRIs like fluoxetine, it could potentially contribute to **serotonin syndrome**, not NMS. - **Serotonin syndrome** presents differently with **hyperreflexia, clonus, mydriasis**, and more prominent GI symptoms—features NOT seen in this patient who has **decreased reflexes** (characteristic of NMS, not serotonin syndrome). - TCA toxicity typically presents with **anticholinergic effects** (dry mouth, urinary retention, blurred vision) and **cardiac conduction abnormalities** (QRS widening, QT prolongation). *Atropine* - Atropine is an **antimuscarinic anticholinergic agent** that does not cause NMS or interact significantly with dopaminergic pathways. - Atropine toxicity presents as **anticholinergic syndrome**: dry skin (anhidrosis), hyperthermia, delirium, mydriasis, and urinary retention—remembered as "hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter." - This patient has **profuse diaphoresis** (sweating), which rules out anticholinergic toxicity and is consistent with NMS. *Dextroamphetamine* - Dextroamphetamine is a **sympathomimetic stimulant** that increases release of dopamine, norepinephrine, and serotonin, causing a **hyperadrenergic state**. - While it can cause hyperthermia, tachycardia, and hypertension, it does not typically cause the **severe muscle rigidity** and **marked CK elevation** seen in NMS. - High doses of amphetamines with SSRIs could theoretically contribute to serotonin syndrome, but this would present with hyperreflexia and clonus, not the decreased reflexes seen here. *Succinylcholine* - Succinylcholine is a **depolarizing neuromuscular blocker** used for rapid sequence intubation. It does not affect dopaminergic or serotonergic pathways and does not cause NMS. - Its major complication is **malignant hyperthermia (MH)** in genetically susceptible individuals (RYR1 or CACNA1S mutations), triggered by volatile anesthetics or succinylcholine itself. - MH presents with hyperthermia, rigidity, tachycardia, and elevated CK, but occurs in the **perioperative setting** with specific genetic predisposition, not from drug interactions with antidepressants.

Question 22: Which of the following compounds is most responsible for the maintenance of appropriate coronary blood flow?

• A. VEGF
• B. Epinephrine
• C. Nitric oxide (Correct Answer)
• D. Histamine
• E. Norepinephrine

Explanation: ***Nitric oxide*** - **Nitric oxide (NO)** is a potent **vasodilator** produced by endothelial cells, crucial for relaxing vascular smooth muscle and increasing blood flow. - In the coronary circulation, NO helps to match oxygen supply with myocardial demand by regulating **coronary artery tone**. *VEGF* - **Vascular Endothelial Growth Factor (VEGF)** is primarily involved in **angiogenesis** (formation of new blood vessels) and blood vessel permeability, not immediate regulation of blood flow. - While important for long-term vascular health and collateral circulation, it does not directly mediate acute changes in **coronary blood flow**. *Epinephrine* - **Epinephrine** (adrenaline) primarily causes **vasoconstriction** in many vascular beds via alpha-1 adrenergic receptors, although it can cause vasodilation in skeletal muscle via beta-2 receptors. - Its overall effect on coronary arteries is complex and can include **increased heart rate and contractility**, which increases myocardial oxygen demand, rather than directly maintaining appropriate coronary blood flow through vasodilation. *Histamine* - **Histamine** is a mediator of allergic reactions and inflammation, causing **vasodilation** and increased vascular permeability. - While it can cause vasodilation, its primary physiological role is not the routine maintenance of **coronary blood flow** under normal conditions. *Norepinephrine* - **Norepinephrine** primarily stimulates **alpha-1 adrenergic receptors**, leading to **vasoconstriction** in most vascular beds, including systemic arteries. - This effect generally reduces blood flow to organs, making it unsuitable for maintaining appropriate and adaptive **coronary blood flow**.

Question 23: A 55-year-old female with a history of poorly controlled hyperlipidemia and obesity presents to her primary care physician for a follow-up visit. She reports that she feels well and has no complaints. She currently takes atorvastatin. Her temperature is 99°F (37.2°C), blood pressure is 135/80 mmHg, pulse is 80/min, and respirations are 16/min. Her BMI is 31 kg/m2. Her total cholesterol is 290 mg/dl, triglycerides are 120 mg/dl, and LDL cholesterol is 215 mg/dl. Her physician considers starting her on a medication that forces the liver to consume cholesterol to make more bile salts. Which of the following adverse effects is this patient at highest risk of developing following initiation of the medication?

• A. Pruritus
• B. Acanthosis nigricans
• C. Facial flushing
• D. Gallstones (Correct Answer)
• E. Fat malabsorption

Explanation: ***Gallstones*** - The physician plans to start a bile acid sequestrant (e.g., cholestyramine, colestipol, colesevelam), which forces the liver to consume cholesterol to make more bile salts, thus reducing LDL. - An increase in bile acid synthesis and secretion can alter the **cholesterol-to-bile acid ratio** in bile, leading to increased cholesterol saturation and the formation of **cholesterol gallstones**. *Pruritis* - While pruritus can be associated with cholestasis (impaired bile flow), it is not a direct or highly common adverse effect of **bile acid sequestrants** themselves. - Pruritus in hyperlipidemia often relates to severe hypertriglyceridemia not addressed by this class of drug, or in primary biliary cholangitis. *Acanthosis nigricans* - **Acanthosis nigricans** is a skin condition characterized by hyperpigmented, velvety plaques, often indicative of **insulin resistance** or malignancy. - While the patient has obesity, a risk factor for insulin resistance, this condition is not directly caused by or exacerbated by bile acid sequestrants. *Facial flushing* - **Facial flushing** is a common adverse effect primarily associated with **niacin (nicotinic acid)**, another lipid-lowering agent. - Niacin causes vasodilation, but this mechanism is not shared by bile acid sequestrants. *Fat malabsorption* - **Bile acid sequestrants** can interfere with the absorption of fat-soluble vitamins (A, D, E, K) due to their binding of bile acids. - While some gastrointestinal upset can occur, significant **fat malabsorption** leading to steatorrhea is less common with typical doses and is primarily associated with conditions severely impairing bile flow or pancreatic function.

Question 24: A 27-year-old woman comes to the physician because of poor sleep for the past 8 months. She has been gradually sleeping less because of difficulty initiating sleep at night. She does not have trouble maintaining sleep. On average, she sleeps 4–5 hours each night. She feels tired throughout the day but does not take naps. She was recently diagnosed with social anxiety disorder and attends weekly psychotherapy sessions. Mental status examination shows an anxious mood. The patient asks for a sleeping aid but does not want to feel drowsy in the morning because she has to drive her daughter to kindergarten. Short-term treatment with which of the following drugs is the most appropriate pharmacotherapy for this patient's symptoms?

• A. Triazolam
• B. Phenobarbital
• C. Doxepin
• D. Suvorexant (Correct Answer)
• E. Flurazepam

Explanation: ***Suvorexant*** - This patient presents with **insomnia**, specifically **difficulty initiating sleep**, and requires an agent with a quick onset for short-term use, minimal morning sedation, and suitability for co-morbid **anxiety**. Suvorexant, an **orexin receptor antagonist**, works by blocking wakefulness-promoting signals, providing a good sleep aid without residual daytime drowsiness reported in other classes. - Its mechanism of action specifically targets wakefulness rather than generally depressing the CNS, making it appropriate for patients who need to function normally the next day, like driving. *Triazolam* - **Triazolam** is a short-acting **benzodiazepine** that acts quickly but carries a higher risk of **rebound insomnia** and potential for dependence with prolonged use. - While it helps with sleep initiation, its anxiolytic properties might be appealing, but the patient's concern about morning sedation makes it less ideal, as benzodiazepines can have residual effects. *Phenobarbital* - **Phenobarbital** is a **barbiturate** and a potent CNS depressant primarily used as an anticonvulsant; its use as a sleep aid is highly discouraged due to its **sedative effects**, risk of dependence, and narrow therapeutic index. - It would cause significant morning drowsiness and is generally not indicated for routine insomnia due to its severe side effect profile. *Doxepin* - **Doxepin** is a **tricyclic antidepressant** with strong **antihistaminic** properties at low doses, which can be useful for sleep maintenance, but it has a long half-life and can lead to significant **daytime sedation** and anticholinergic side effects. - Its long half-life makes it unsuitable for a patient who needs to avoid morning drowsiness for driving. *Flurazepam* - **Flurazepam** is a long-acting **benzodiazepine** with a prolonged half-life, meaning it would likely cause significant **next-day sedation** and impairment, making it unsuitable for someone who needs to drive in the morning. - Its long duration of action would counteract the patient's need for a drug without residual daytime effects.

Question 25: A 24-year-old woman is brought into the emergency department by an ambulance after swallowing a bottle of pain medication in a suicide attempt. According to her parents, she recently had a fight with her boyfriend and was acting very depressed. She claims to not remember what she had taken. Further inquiry reveals she is experiencing nausea and feeling quite dizzy. She also repeatedly asks if anyone else can hear a ringing sound. Her pulse is 105/min, respirations are 24/min, and temperature is 38.2°C (100.8°F). Examination reveals mild abdominal tenderness. The patient is visibly agitated and slightly confused. The following lab values are obtained: Arterial blood gas analysis pH 7.35 Po2 100 mm Hg Pco2 20 mm Hg HCO3- 12 mEq/L Which of the following pain medications did this patient most likely take?

• A. Codeine
• B. Indomethacin
• C. Gabapentin
• D. Aspirin (Correct Answer)
• E. Acetaminophen

Explanation: ***Aspirin*** - The patient's symptoms of **tinnitus (ringing sound)**, **nausea**, **dizziness**, **tachycardia**, **tachypnea**, **fever**, and **metabolic acidosis with respiratory alkalosis (pH 7.35, PCO2 20, HCO3 12)** are classic for **salicylate toxicity**. - Aspirin overdose leads to direct stimulation of the respiratory center, causing **hyperventilation** and **respiratory alkalosis**, while also uncoupling oxidative phosphorylation, leading to **lactic acidosis** and **metabolic acidosis**. *Codeine* - Codeine is an **opioid** and overdose typically causes **respiratory depression**, **miosis (pinpoint pupils)**, and potentially **narcosis (stupor)**, which are not seen here. - The patient exhibits tachypnea and agitation, which contradict opioid toxicity. *Indomethacin* - Indomethacin is an **NSAID**; overdose can cause **gastrointestinal upset**, **CNS effects** like headache or confusion, and potentially **renal impairment**. - It does not typically cause the classic tinnitus or the specific mixed acid-base derangement seen in this patient. *Gabapentin* - Gabapentin overdose usually results in **drowsiness**, **ataxia**, **dizziness**, and occasionally **slurred speech**. - It does not cause tinnitus, fever, or the characteristic acid-base imbalance observed in this clinical scenario. *Acetaminophen* - Acetaminophen overdose often presents with **nausea**, **vomiting**, and later **hepatotoxicity** (elevated liver enzymes). - It does not cause tinnitus, fever, or the specific mixed acid-base disorder characteristic of salicylate poisoning.

Question 26: A 55-year-old woman comes to the emergency room 30 minutes after the sudden onset of chest pain radiating to the left shoulder. Prior to the onset of her symptoms, she was lying in bed because of a migraine headache. Episodes of similar chest pain usually resolved after a couple of minutes. She has smoked one pack of cigarettes daily for 20 years. Her only medication is sumatriptan. An ECG shows ST-segment elevations in the anterior leads. Serum troponins are negative on two successive blood draws and ECG shows no abnormalities 30 minutes later. Administration of which of the following is most likely to prevent further episodes of chest pain in this patient?

• A. Aspirin
• B. Clopidogrel
• C. Propranolol
• D. Diltiazem (Correct Answer)
• E. Ramipril

Explanation: ***Diltiazem*** - This patient presents with symptoms highly suggestive of **Prinzmetal angina** (vasospastic angina), characterized by sudden-onset chest pain, often at rest or with migraine, transient ST-segment elevations, and negative troponins. - **Calcium channel blockers** like diltiazem are the cornerstone of treatment for Prinzmetal angina as they effectively prevent coronary artery spasm. *Aspirin* - **Aspirin** is an antiplatelet agent used to prevent arterial thrombosis in patients with atherosclerotic disease. - It does not directly prevent coronary artery spasms, which are the underlying cause of Prinzmetal angina. *Clopidogrel* - **Clopidogrel** is an antiplatelet agent similar to aspirin, primarily used to prevent arterial thrombosis. - It would not prevent coronary spasms and is therefore not the most appropriate treatment for Prinzmetal angina. *Propranolol* - **Beta-blockers** like propranolol can sometimes worsen vasospastic angina by inhibiting beta-2 mediated vasodilation, leaving alpha-1 vasoconstriction unopposed. - Their use is generally contraindicated or approached with caution in patients with Prinzmetal angina. *Ramipril* - **Ramipril** is an ACE inhibitor, primarily used for hypertension, heart failure, and renal protection. - It does not directly address coronary artery spasms and would not be effective in preventing episodes of Prinzmetal angina.

Question 27: A healthy 48-year-old presents for a well-patient visit. He has no symptoms and feels well. Past medical history is significant for asthma, chronic sinusitis, and nasal polyps. He occasionally takes diphenhydramine for allergies. Both of his parents and an elder brother are in good health. Today, his blood pressure is 119/81 mm Hg, heart rate is 101/min, respiratory rate is 21/min, and temperature 37°C (98.6°F). Routine screening blood work reveals elevated total cholesterol. The patient asks if he should take low-dose aspirin to reduce his risk of stroke and heart attack. Of the following, which is the best response?

• A. Have you had a reaction to aspirin in the past? (Correct Answer)
• B. No, because aspirin does not help reduce the risk of stroke and heart attack.
• C. Yes, aspirin therapy is recommended.
• D. Yes, but only every other day.
• E. No, because all chronic sinusitis carries aspirin-complications.

Explanation: ***Have you had a reaction to aspirin in the past?*** - This is the most crucial initial question as the patient's history of **asthma, chronic sinusitis, and nasal polyps** strongly suggests a risk of **aspirin-exacerbated respiratory disease (AERD)**. - Asking about past reactions helps identify potential contraindications and avoid a severe, potentially life-threatening reaction if aspirin were prescribed. *No, because aspirin does not help reduce the risk of stroke and heart attack.* - This statement is incorrect as **low-dose aspirin** is known to **reduce the risk of cardiovascular events**, including stroke and heart attack, in appropriate patients through its antiplatelet effects. - The decision to prescribe aspirin depends on a careful assessment of individual risk factors and comorbidities, not a blanket dismissal of its efficacy. *Yes, aspirin therapy is recommended.* - Recommending aspirin therapy outright without assessing for contraindications is dangerous given the patient's history of **asthma, chronic sinusitis, and nasal polyps**, which is a classic triad for **aspirin-exacerbated respiratory disease (AERD)**. - Aspirin could precipitate a severe **bronchospasm** or **anaphylactoid reaction** in such individuals. *Yes, but only every other day.* - While aspirin dosing regimens vary, the frequency (every other day) is secondary to determining if the patient can safely take aspirin at all, especially with his medical history. - The fundamental concern is the potential for **aspirin-exacerbated respiratory disease (AERD)**, which would make aspirin contraindicated regardless of the dosing frequency. *No, because all chronic sinusitis carries aspirin-complications.* - This statement is an **overgeneralization** as not all cases of chronic sinusitis are associated with aspirin sensitivity or **aspirin-exacerbated respiratory disease (AERD)**. - While there is an association, especially in patients with the triad of asthma, sinusitis, and nasal polyps, it's not a universal complication for all individuals with chronic sinusitis.

Question 28: An 82-year-old man comes to the physician complaining of frequent urination, especially at night, and difficulty initiating urination. However, he points out that his symptoms have improved slightly since he started terazosin 2 months ago. He has a history of stable angina. Other medications include nitroglycerin, metoprolol, and aspirin. His blood pressure is 125/70 mm Hg and pulse is 72/min. On examination, the urinary bladder is not palpable. He has a normal anal sphincter tone and a bulbocavernosus muscle reflex. Digital rectal exam shows a prostate size equivalent to three finger pads without fluctuance or tenderness. The 24-hour urinary volume is 2.5 liters. Laboratory studies show: Urine Protein negative RBC none WBC 1–2/hpf Hemoglobin negative Bacteria none Ultrasonography shows an estimated prostate size of 50 grams, a post-void residual volume of 120 mL, and urinary bladder wall trabeculation without any hydronephrosis. In addition to controlled fluid intake, which of the following is the most appropriate additional pharmacotherapy at this time?

• A. Finasteride (Correct Answer)
• B. Oxybutynin
• C. Tadalafil
• D. Tamsulosin
• E. No additional pharmacotherapy at this time

Explanation: ***Finasteride*** - This patient exhibits symptoms of **benign prostatic hyperplasia (BPH)** with a prostate size of 50 grams and a post-void residual volume of 120 mL, indicating an enlarged prostate contributing to his lower urinary tract symptoms (LUTS) - **Finasteride**, a **5-alpha reductase inhibitor**, reduces prostate size by inhibiting the conversion of testosterone to dihydrotestosterone, making it an appropriate addition to his current alpha-blocker therapy - Given his stable angina and current medications including nitroglycerin, finasteride works via a different mechanism than alpha-blockers and directly addresses the underlying prostate enlargement - Combination therapy with an alpha-blocker and 5-alpha reductase inhibitor is recommended for patients with moderate-to-severe BPH symptoms and prostate enlargement >40 grams *Oxybutynin* - **Oxybutynin** is an **anticholinergic medication** used to treat **overactive bladder** symptoms like urgency and frequency - While the patient has frequency, his primary issue is bladder outflow obstruction from BPH, and anticholinergics can worsen urinary retention in patients with obstructive symptoms - Contraindicated in men with significant post-void residual volumes *Tadalafil* - **Tadalafil** is a **phosphodiesterase-5 (PDE5) inhibitor** FDA-approved for BPH treatment at lower doses - It acts by relaxing smooth muscle in the prostate and bladder neck, improving urinary flow - However, it does not reduce prostate size, which is significant in this patient (50 grams), and would not address the underlying progressive enlargement - Could be considered as an alternative but finasteride is more appropriate for size reduction in moderate-to-severe BPH *Tamsulosin* - **Tamsulosin** is a selective **alpha-1A blocker** that relaxes smooth muscle in the prostate and bladder neck - The patient is already on terazosin, another alpha-blocker, so adding tamsulosin would be redundant and not provide additional benefit through a different mechanism - Switching from terazosin to tamsulosin (more selective) could be considered but doesn't address the question of "additional pharmacotherapy" - Adding another alpha-blocker increases risk of orthostatic hypotension without targeting prostate size reduction *No additional pharmacotherapy at this time* - The patient's objective findings including a post-void residual volume of 120 mL (normal <50 mL) and 50-gram prostate indicate significant BPH requiring additional treatment - Although he has improved slightly on terazosin, the persistently elevated post-void residual suggests inadequate treatment response - Additional treatment targeting prostate size reduction is warranted to prevent complications like acute urinary retention, bladder decompensation, or renal compromise from chronic obstruction

Question 29: A 68-year-old man seeks evaluation at an office with a complaint of breathlessness of several months duration. He is able to do his daily tasks, but says that he is not as efficient as before. His breathlessness has been progressive with the recent onset of a dry cough. The past medical history is significant for a cardiac arrhythmia that is being treated with an anti-arrhythmic. He has never smoked cigarettes and is a social drinker. His pulse is 87/min and regular and the blood pressure is 135/88 mm Hg. Bilateral basal inspiratory crackles are present on auscultation of the chest from the back. A chest X-ray image shows peripheral reticular opacities with a coarse reticular pattern. A high-resolution CT scan of the chest reveals patchy bibasilar reticular opacities. Which of the following medications is most likely responsible for this patient’s condition?

• A. Verapamil
• B. Amiodarone (Correct Answer)
• C. Digoxin
• D. Lidocaine
• E. Sotalol

Explanation: ***Amiodarone*** - Amiodarone is a well-known antiarrhythmic drug that can cause **pulmonary toxicity**, leading to conditions like **pulmonary fibrosis**, which manifests as progressive breathlessness, dry cough, and basal crackles. - The imaging findings of **peripheral reticular opacities** and **bibasilar reticular opacities** on HRCT are classic for drug-induced interstitial lung disease, highly suggestive of amiodarone toxicity in this context. *Verapamil* - Verapamil, a calcium channel blocker, is used for arrhythmias but is not typically associated with **pulmonary fibrosis** or significant interstitial lung disease. - Its common side effects include constipation, bradycardia, and hypotension, not respiratory pathology like that described. *Digoxin* - Digoxin is a cardiac glycoside used for heart failure and arrhythmias, but it does not cause **interstitial lung disease** or pulmonary fibrosis. - Toxicity usually presents with gastrointestinal symptoms, visual disturbances, and cardiac arrhythmias. *Lidocaine* - Lidocaine is an antiarrhythmic often used intravenously for acute arrhythmias, but it is not linked to **chronic pulmonary toxicity** or fibrosis. - Side effects are primarily neurological (dizziness, seizures) and cardiovascular (arrhythmias, hypotension). *Sotalol* - Sotalol is a beta-blocker with potassium channel blocking properties used for arrhythmias, but it is not associated with **drug-induced pulmonary fibrosis**. - Its main side effects include bradycardia, fatigue, and potential for torsades de pointes.

Question 30: A 36-year-old woman is brought to the emergency department because of lightheadedness, weakness, and abdominal pain for 6 hours. Over the past 3 days, she has also had severe nausea, vomiting, and watery diarrhea. She was diagnosed with pulmonary sarcoidosis 2 years ago. Current medications include prednisone. Her temperature is 38.9°C (102.0°F), pulse is 112/min, and blood pressure is 85/50 mm Hg. Physical examination shows a round face with prominent preauricular fat pads. Her fingerstick blood glucose concentration is 48 mg/dL. Further evaluation is most likely to show which of the following laboratory changes?

• A. Decreased norepinephrine
• B. Decreased aldosterone
• C. Decreased corticotropin-releasing hormone
• D. Increased cortisol
• E. Increased adrenocorticotropic hormone (Correct Answer)

Explanation: ***Increased adrenocorticotropic hormone*** - This patient presents with **adrenal crisis** (hypotension, hypoglycemia, GI symptoms during acute illness). While she has been on chronic prednisone for sarcoidosis, the underlying cause of her adrenal insufficiency is likely **primary adrenal insufficiency** from **sarcoid infiltration of the adrenal glands**, rather than simple steroid-induced suppression. - In **primary adrenal insufficiency**, the adrenal glands themselves fail to produce cortisol and aldosterone. This leads to **loss of negative feedback** on the hypothalamus and pituitary, resulting in **compensatory elevation of ACTH**. - The Cushingoid features indicate chronic steroid exposure, but the acute decompensation during illness with severe hypotension and hypoglycemia suggests the **adrenal glands can no longer respond** adequately, even to endogenous or therapeutic steroids. This points to primary adrenal failure (Addison's disease) secondary to sarcoidosis. - Sarcoidosis can cause **granulomatous infiltration of the adrenal glands**, leading to primary adrenal insufficiency in 1-5% of cases. *Decreased norepinephrine* - In states of hypotension and shock, the sympathetic nervous system is activated to **increase norepinephrine** release to maintain blood pressure. - Decreased norepinephrine would worsen hypotension and is not expected in adrenal crisis. *Decreased aldosterone* - While aldosterone is indeed **decreased in primary adrenal insufficiency** and contributes to hypotension and hyperkalemia, this is a direct consequence of adrenal gland failure, not a compensatory pituitary response. - The question asks for the most likely laboratory finding on "further evaluation," which typically refers to the **diagnostic hormonal changes** - elevated ACTH is the key finding that distinguishes primary from secondary adrenal insufficiency. *Decreased corticotropin-releasing hormone* - In primary adrenal insufficiency, **CRH and ACTH are both elevated** due to loss of negative feedback from cortisol. - Decreased CRH would only occur in tertiary adrenal insufficiency (hypothalamic dysfunction) or in cases of chronic exogenous steroid use causing **secondary** adrenal insufficiency - but the severity of this patient's presentation suggests primary adrenal failure. *Increased cortisol* - Cortisol levels are **low or undetectable** in adrenal crisis, which is the underlying pathophysiology causing hypotension, hypoglycemia, and inability to respond to stress. - Increased cortisol would contradict the diagnosis of adrenal crisis.

Question 31: A 65-year-old woman presents with complaints of difficulty sleeping due to discomfort in her legs for the past 6 months. She is unable to describe the discomfort, but says it is an unpleasant, creeping and crawling feeling that is not painful. She feels an irresistible urge to move her legs to decrease the discomfort. The unpleasant sensation in her legs often occurs at night when she is lying in bed. She is recently divorced and lives alone. She denies any changes in appetite, weight loss, low mood, or suicidal thoughts. The physical examination is unremarkable except for signs of mild pallor. Laboratory test results show microcytic anemia with hemoglobin of 9.8 g/dL and decreased serum iron and ferritin levels. Apart from correcting her anemia, which additional drug would you prescribe for her symptoms?

• A. Ropinirole (Correct Answer)
• B. Paroxetine
• C. Lithium
• D. Haloperidol
• E. Propranolol

Explanation: ***Ropinirole*** - The patient's symptoms are classic for **Restless Legs Syndrome (RLS)**: an unpleasant, creepy-crawly sensation, an irresistible urge to move legs, and symptom relief with movement, occurring predominantly at night. - **Dopamine agonists** like ropinirole are first-line treatments for RLS, especially when conservative measures and iron supplementation (for associated anemia) are insufficient. *Paroxetine* - **Paroxetine** is a Selective Serotonin Reuptake Inhibitor (SSRI) used for depression and anxiety. - SSRIs can sometimes **worsen RLS symptoms** due to their impact on dopamine pathways, making them an inappropriate choice. *Lithium* - **Lithium** is a mood stabilizer primarily used in the treatment of bipolar disorder. - It has no established role in the treatment of Restless Legs Syndrome. *Haloperidol* - **Haloperidol** is a typical antipsychotic that blocks dopamine receptors. - **Dopamine blockers** can significantly exacerbate RLS symptoms and are contraindicated. *Propranolol* - **Propranolol** is a beta-blocker used for conditions such as hypertension, anxiety, and tremors. - It is not indicated for the treatment of Restless Legs Syndrome.

Question 32: A 42-year-old man is brought to the emergency department by police. He was found obtunded at a homeless shelter. The patient has a past medical history of alcohol abuse, intravenous (IV) drug use, schizophrenia, hepatitis C, and anxiety. His current medications include disulfiram, intramuscular haloperidol, thiamine, and clonazepam. The patient is non-compliant with his medications except for his clonazepam. His temperature is 99.5°F (37.5°C), blood pressure is 110/67 mmHg, pulse is 100/min, respirations are 16/min, and oxygen saturation is 96% on room air. On physical exam, the patient is covered in bruises, and his nose is bleeding. The patient's abdomen is distended and positive for a fluid wave. IV fluids are started, and the patient is also given thiamine, folic acid, and magnesium. It is noted by the nursing staff that the patient seems to be bleeding at his IV sites. Laboratory values are ordered and return as below: Hemoglobin: 10 g/dL Hematocrit: 25% Leukocyte count: 7,500 cells/mm^3 with normal differential Platelet count: 65,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 102 mEq/L K+: 4.1 mEq/L HCO3-: 24 mEq/L BUN: 24 mg/dL Glucose: 77 mg/dL Creatinine: 1.4 mg/dL Ca2+: 9.9 mg/dL D-dimer: < 250 ng/mL AST: 79 U/L ALT: 52 U/L Which of the following is most likely to help with this patient's bleeding?

• A. Desmopressin
• B. Platelet transfusion (Correct Answer)
• C. Fresh frozen plasma
• D. Factor VIII concentrate
• E. Phytonadione

Explanation: ***Platelet transfusion*** - The patient's **platelet count is significantly low (65,000/mm^3)**, and he is actively bleeding (nosebleed, bleeding at IV sites). - Given his history of **cirrhosis** (suggested by alcohol abuse, Hepatitis C, distended abdomen, fluid wave, slightly elevated AST/ALT), **thrombocytopenia** is a common complication due to **splenomegaly** and reduced thrombopoietin production. *Desmopressin* - **Desmopressin (DDAVP)** is primarily used to treat **mild hemophilia A** or **Type 1 von Willebrand disease** by increasing the release of factor VIII and von Willebrand factor from endothelial cells. - It is not indicated for **thrombocytopenia** as the primary cause of bleeding, which is the case here. *Fresh frozen plasma* - **Fresh frozen plasma (FFP)** provides **clotting factors**, and would be appropriate for deficiencies in these factors, such as in severe liver disease with prolonged **PT/INR** or **APTT**. - While this patient has liver disease, his most critical and direct cause of bleeding listed is severe thrombocytopenia, not a coagulation factor deficiency, and D-dimer is normal, suggesting no DIC. *Factor VIII concentrate* - **Factor VIII concentrate** is used to treat **hemophilia A**, which is a deficiency in factor VIII. - This patient's presentation and laboratory findings (low platelets, normal D-dimer) do not suggest hemophilia A. *Phytonadione* - **Phytonadione (Vitamin K)** is used to **reverse the effects of warfarin** or treat **Vitamin K deficiency**, which impairs the synthesis of factors II, VII, IX, and X. - While liver disease can lead to vitamin K malabsorption or impaired synthesis of these factors, the most immediate and treatable cause of bleeding highlighted by the labs is severe thrombocytopenia, and there's no direct evidence of prolonged PT/INR due to vitamin K deficiency.

Question 33: A 7-year-old boy presents with frequent episodes of blanking out or daydreaming. Each episode lasts for less than 10 seconds. During the episode, he is unaware of what is going on around him and does not respond to questions or calling his name. After the episode, he continues whatever he was doing before. An EEG is performed during one of these episodes, which shows generalized 3–4 Hz 'spike-and-dome' wave complexes. What is the mechanism of action of the drug recommended to treat this patient’s condition?

• A. Inhibits neuronal GABA receptors
• B. Inhibits voltage-gated sodium channels
• C. Potentiates GABA transmission
• D. Inhibits voltage-gated calcium channels (Correct Answer)
• E. Inhibits release of excitatory amino acid glutamate

Explanation: ***Inhibits voltage-gated calcium channels*** - The clinical presentation of **absence seizures** (brief blanking out, unawareness, rapid recovery) combined with the EEG finding of **3–4 Hz spike-and-wave complexes** is characteristic of childhood absence epilepsy. - The first-line treatment for absence seizures is **ethosuximide**, which primarily works by blocking **T-type calcium channels** in the thalamus, reducing oscillatory thalamic activity responsible for the seizures. *Inhibits neuronal GABA receptors* - This mechanism would typically lead to **proconvulsant effects** by reducing inhibitory neurotransmission, rather than treating seizures. - Drugs that inhibit GABA receptors are not used in the treatment of absence seizures. *Inhibits voltage-gated sodium channels* - Drugs that inhibit **voltage-gated sodium channels** (e.g., carbamazepine, phenytoin, lamotrigine) are effective for **focal seizures** and **tonic-clonic seizures**. - These drugs are generally **not effective** for absence seizures and can sometimes exacerbate them. *Potentiates GABA transmission* - Drugs that potentiate GABA transmission (e.g., **benzodiazepines**, **valproate**) can be used for various seizure types, including absence seizures (valproate being a broad-spectrum AED). - However, for absence seizures specifically, **ethosuximide** is often preferred as a first-line agent, and its primary mechanism directly targets thalamic T-type calcium channels, not GABA potentiation. *Inhibits release of excitatory amino acid glutamate* - Inhibiting the release of **glutamate** is a mechanism of action for some antiseizure drugs (e.g., lamotrigine, levetiracetam). - While this can be effective for various seizure types, it is not the primary mechanism of action for the most effective first-line treatment for classic absence seizures (ethosuximide).

Question 34: A previously healthy 9-year-old boy is brought to the physician by his mother because of a 3-month history of episodic abdominal pain. During this time, he has been more tired than usual. For the past 2 months, he has also had bulky stools that are difficult to flush. His maternal aunt has systemic lupus erythematosus. The boy is at the 31st percentile for height and 5th percentile for weight. Vital signs are within normal limits. Examination shows scattered ecchymoses across bilateral knees, the left forearm, and the upper back. The abdomen is mildly distended; bowel sounds are hyperactive. Laboratory studies show: Hemoglobin 11.1 g/dL Leukocyte count 4,500/mm3 Platelet count 243,000/mm3 Mean corpuscular volume 78 μm3 Bleeding time 5 minutes Prothrombin time 24 seconds Partial thromboplastin time 45 seconds Further evaluation is most likely to show which of the following?

• A. Impaired platelet-to-platelet aggregation
• B. Increased activity of protein S
• C. Deficiency of clotting factor VIII
• D. Increased serum anti-phospholipid antibodies
• E. Deficiency of clotting factor II (Correct Answer)

Explanation: ***Deficiency of clotting factor II*** - The patient presents with **malabsorption** (low weight, bulky stools, abdominal distention) and **bleeding dysfunction** (ecchymoses, prolonged PT and PTT). This constellation of symptoms, especially in a child with malabsorption, suggests **vitamin K deficiency**. - **Vitamin K is essential for the gamma-carboxylation of clotting factors II (prothrombin), VII, IX, and X, as well as proteins C and S**. A deficiency in factor II (also known as prothrombin) would lead to prolonged PT and PTT, as observed. *Impaired platelet-to-platelet aggregation* - This would lead to a **prolonged bleeding time** and potentially petechiae, but it typically does not affect PT or PTT. - The patient's bleeding time is normal, and his symptoms involve deeper bleeding (ecchymoses) rather than mucosal or superficial bleeding characteristic of aggregation defects. *Increased activity of protein S* - **Protein S is a natural anticoagulant**, and increased activity would predispose to bleeding, not clotting. It would prolong PT and PTT. - However, the patient's symptoms are more consistent with a global deficiency in vitamin K-dependent factors, and increased protein S activity typically isn't associated with malabsorption or the specific pattern of laboratory findings seen here. *Deficiency of clotting factor VIII* - A deficiency in Factor VIII causes **Hemophilia A**, which primarily leads to a **prolonged PTT** with a normal PT and bleeding time. - While it can cause ecchymoses, the additional finding of a prolonged PT and signs of malabsorption make this diagnosis less likely. *Increased serum anti-phospholipid antibodies* - Anti-phospholipid antibodies can cause a **paradoxical prolongation of PTT** (due to interference with phospholipid-dependent clotting assays) in vitro, but in vivo, they are associated with a **thrombotic diathesis** (increased clotting), not bleeding. - The patient's symptoms are related to bleeding and malabsorption, making a thrombotic disorder less likely.

Question 35: A 58-year-old female comes to the physician because of generalized fatigue and malaise for 3 months. Four months ago, she was treated for a urinary tract infection with trimethoprim-sulfamethoxazole. She has hypertension, asthma, chronic lower back pain, and chronic headaches. Current medications include hydrochlorothiazide, an albuterol inhaler, naproxen, and an aspirin-caffeine combination. Examination shows conjunctival pallor. Laboratory studies show: Hemoglobin 8.9 g/dL Serum Urea nitrogen 46 mg/dL Creatinine 2.4 mg/dL Calcium 9.8 mg/dL Urine Protein 1+ Blood 1+ RBCs none WBCs 9-10/hpf Urine cultures are negative. Ultrasound shows shrunken kidneys with irregular contours and papillary calcifications. Which of the following is the most likely underlying mechanism of this patient's renal failure?

• A. Hypersensitivity reaction
• B. Inhibition of prostaglandin I2 production (Correct Answer)
• C. Overproduction of light chains
• D. Precipitation of drugs within the renal tubules
• E. Infection with an acid-fast bacillus

Explanation: ***Inhibition of prostaglandin I2 production*** - Chronic use of **NSAIDs** (naproxen) inhibits **prostaglandin synthesis**, leading to **afferent arteriolar constriction** and reduced renal blood flow, which can cause acute kidney injury or exacerbate chronic kidney disease, especially in patients with comorbidities like hypertension. - The patient's **shrunken kidneys** with **irregular contours** and **papillary calcifications** are consistent with **analgesic nephropathy**, a form of chronic interstitial nephritis often caused by prolonged NSAID use. *Hypersensitivity reaction* - While drug-induced interstitial nephritis can be caused by hypersensitivity reactions (e.g., to trimethoprim-sulfamethoxazole), this typically presents with acute kidney injury, eosinophilia, fever, and rash, which are not prominent features here. - The imaging findings of **shrunken kidneys** and **papillary calcifications** are more indicative of chronic, rather than acute, damage. *Overproduction of light chains* - This mechanism is characteristic of **multiple myeloma**, which causes **cast nephropathy** and typically presents with hypercalcemia, anemia due to marrow infiltration, and large amounts of protein (Bence-Jones proteins) in the urine. - The patient's calcium is normal, and while she has anemia, the overall picture of chronic kidney changes and NSAID use points elsewhere. *Precipitation of drugs within the renal tubules* - This can occur with certain medications like **acyclovir** or **sulfonamides** (trimethoprim-sulfamethoxazole) leading to **obstructive nephropathy**. - However, the patient's exposure to trimethoprim-sulfamethoxazole was 4 months prior, and the imaging findings of **shrunken kidneys** and **papillary calcifications** are not typical of acute tubular obstruction but rather chronic damage from analgesic use. *Infection with an acid-fast bacillus* - This refers to **renal tuberculosis**, which can cause chronic kidney disease, but it usually presents with sterile pyuria and can lead to calcifications and strictures. - However, there is no information in the vignette to suggest exposure to tuberculosis or other symptoms often associated with it, and **analgesic nephropathy** is a more common cause given the patient's medication history.

Question 36: A 32-year-old man presents with excessive urination. He reports that he urinates 10 times a day and wakes up multiple times a night to pee. He complains that this is affecting both his social life and his ability to concentrate at work. He states that he always has an “active bladder,” but his symptoms worsened when he started meeting with a physical trainer last month who told him he should increase his water intake to prevent dehydration. The patient has a history of migraines and bipolar I disorder. His medications include metoprolol, lithium, and naproxen as needed. A basic metabolic panel is performed, and the results are shown below: Serum: Na+: 149 mEq/L Cl-: 102 mEq/L K+: 3.4 mEq/L HCO3-: 26 mEq/L Urea nitrogen: 12 mg/dL Creatinine: 1.0 mg/dL Glucose: 78 mg/dL Ca2+: 9.5 mg/dL A urinalysis is obtained, which reveals pale-colored urine with a specific gravity of 0.852 and a urine osmolarity of 135 mOsm/L. The patient undergoes a water deprivation test. The patient’s urine specific gravity increases to 0.897 and urine osmolarity is now 155 mOsm/L. The patient is given an antidiuretic hormone analogue. Urine osmolarity rises to 188 mOsm/L. Which of the following is the best initial management for the patient’s most likely condition?

• A. Lithium cessation (Correct Answer)
• B. Calcitonin and zoledronic acid
• C. Hydrochlorothiazide
• D. Furosemide
• E. Desmopressin

Explanation: ***Lithium cessation*** - The patient exhibits symptoms of **nephrogenic diabetes insipidus (NDI)**, including polyuria, nocturia, and dilute urine with low specific gravity and osmolarity, despite mild hypernatremia. **Lithium** is a known cause of acquired NDI, blocking the action of ADH in the collecting ducts. - Given that lithium is the likely cause and the patient started having worsening symptoms after increasing water intake (which can unmask NDI), the best initial management is to **discontinue lithium**, if clinically feasible, especially since his symptoms worsened with increased fluid intake which stresses the affected renal tubules further. *Calcitonin and zoledronic acid* - **Calcitonin and zoledronic acid** are used to treat hypercalcemia, which is not present in this patient; his calcium level is normal. - These medications have no direct role in the management of diabetes insipidus. *Hydrochlorothiazide* - **Hydrochlorothiazide** is sometimes used in NDI, as it can induce mild volume depletion, increasing proximal tubular reabsorption of water and sodium and thereby reducing urine output. - However, in cases of drug-induced NDI, especially from lithium, discontinuing the offending agent is the **first-line and most effective initial step**. *Furosemide* - **Furosemide** is a loop diuretic that inhibits water reabsorption in the ascending loop of Henle, leading to increased urine output. - This would **worsen polyuria** and dehydration in a patient with diabetes insipidus, thus it is contraindicated. *Desmopressin* - **Desmopressin** is an ADH analog used to treat central diabetes insipidus, where there is insufficient ADH production. - In **nephrogenic diabetes insipidus (NDI)**, the kidneys are resistant to ADH, so desmopressin would be ineffective or only minimally effective, as demonstrated by the limited increase in urine osmolarity after its administration (155 mOsm/L to 188 mOsm/L, which is still very low).

Question 37: An anesthesiologist is preparing a patient for a short surgical procedure. The physician would like to choose a sedating agent that can be given intravenously and will have a quick onset of action and short half-life. Which of the following agents would be ideal for this purpose?

• A. Hydromorphone
• B. Succinylcholine
• C. Isoflurane
• D. Propofol (Correct Answer)
• E. Sodium thiopental

Explanation: ***Propofol*** - This is the **ideal IV anesthetic** for short procedures with **rapid onset** (30-45 seconds) and **short duration of action**. - Has a **very short half-life** due to rapid redistribution and metabolism, allowing for quick recovery. - Currently the **most commonly used agent** for induction and maintenance of anesthesia in short surgical procedures. - Provides excellent sedation with smooth induction and emergence. *Sodium thiopental* - This **barbiturate** historically was used for rapid induction and had a quick onset due to high lipid solubility. - While it would fit the description, **sodium thiopental has been discontinued** in the United States and is no longer available for clinical use in most countries. - Its short duration was due to **redistribution** from the brain to other tissues, not rapid metabolism. *Hydromorphone* - This is an **opioid analgesic** used for pain relief, not typically as the primary agent for surgical sedation. - While it has analgesic properties, it does not provide the sedation and amnesia required for surgical procedures. *Succinylcholine* - This is a **neuromuscular blocker** used to induce muscle paralysis, not a sedative. - It would not provide sedation or loss of consciousness; the patient would remain fully aware but unable to move or breathe. *Isoflurane* - This is an **inhaled anesthetic**, not administered intravenously. - While effective for anesthesia, the question specifically asks for an IV agent, making this inappropriate for the scenario.

Question 38: A 57-year-old woman presents to her physician for a checkup. The past medical history is significant for diabetes mellitus type 2, and a history of myocardial infarction. The current medications are aspirin, lisinopril, metoprolol, atorvastatin, and metformin. The patient’s HbA1c is 7.9%, and her fasting blood glucose is 8.9 mmol/L (160 mg/dL). Which of the following statements regarding the use of exenatide in this patient is most correct?

• A. It cannot be used in combination with metformin
• B. It requires daily subcutaneous injection
• C. It has a high risk of causing severe hypoglycemia when used alone
• D. It is contraindicated in patients with a history of myocardial infarction
• E. It is associated with weight loss in most patients (Correct Answer)

Explanation: ***It is associated with weight loss in most patients*** - Exenatide and other **GLP-1 receptor agonists** are consistently associated with **modest weight loss** (typically 2-5 kg) in the majority of patients. - This occurs through multiple mechanisms: **delayed gastric emptying**, **increased satiety**, and **reduced appetite** via central nervous system effects. - Weight loss is a significant **clinical benefit** in overweight diabetic patients and is one reason these agents are preferred in this population. *It cannot be used in combination with metformin* - Exenatide is **commonly combined with metformin** and this is an FDA-approved combination. - They have **complementary mechanisms**: metformin reduces hepatic glucose production while exenatide enhances glucose-dependent insulin secretion. - This combination is a **standard therapeutic approach** for type 2 diabetes management. *It requires daily subcutaneous injection* - The original exenatide formulation (Byetta) requires **twice-daily subcutaneous injections**, not once daily. - An **extended-release formulation** (Bydureon) is available as a **once-weekly injection**. - The statement is imprecise and not universally applicable to all exenatide formulations. *It has a high risk of causing severe hypoglycemia when used alone* - GLP-1 receptor agonists have a **low risk of hypoglycemia** when used as monotherapy because their insulinotropic effect is **glucose-dependent**. - Insulin secretion only occurs when glucose levels are elevated, providing a **built-in safety mechanism**. - Hypoglycemia risk increases when combined with **sulfonylureas or insulin**, but not with metformin alone. *It is contraindicated in patients with a history of myocardial infarction* - This is **FALSE**. Exenatide is **NOT contraindicated** in patients with prior MI. - In fact, several GLP-1 receptor agonists have demonstrated **cardiovascular benefits** in outcome trials (LEADER, SUSTAIN-6). - Current **ADA/ACC guidelines recommend** GLP-1 agonists in diabetic patients with established cardiovascular disease for risk reduction. - The only absolute contraindication for exenatide is personal or family history of **medullary thyroid carcinoma** or **MEN 2 syndrome**.

Question 39: A 71-year-old female presents to the clinic with frequent and voluminous urination for 2 weeks. She is a new patient and does not have any medical records as she recently moved to the US from Europe to live with her grandson. When asked about any prior health issues, she looks confused and shows some medications that she takes every day which includes aspirin, omeprazole, naproxen, and lithium. Her grandson is accompanying her and adds that he has requested a copy of her medical records from her previous physician in Europe. The grandson states that she has been drinking about 4–5 L of water every day. Her temperature is 37°C (98.6°F), respirations are 15/min, pulse is 107/min, and blood pressure is 92/68 mm Hg. The physical examination is significant for dry mucous membranes. Laboratory evaluation reveals the following: Plasma osmolarity (Posm) 310 mOsm/kg Urine osmolarity (Uosm) 270 mOsm/kg After 6 hours of water deprivation: Plasma osmolarity (Posm) 320 mOsm/kg Urine osmolarity (Uosm) 277 mOsm/kg After administration of desmopressin acetate (DDAVP): Plasma osmolarity (Posm) 318 mOsm/kg Urine osmolarity (Uosm) 280 mOsm/kg What is the most likely cause of this patient's condition?

• A. Pituitary adenoma
• B. Primary polydipsia
• C. Lithium (Correct Answer)
• D. Aspirin
• E. Omeprazole

Explanation: ***Lithium*** - The patient's inability to concentrate urine, even after water deprivation and desmopressin administration, indicates **nephrogenic diabetes insipidus**. - **Lithium** is a known cause of acquired **nephrogenic diabetes insipidus**, often leading to symptoms like polyuria and polydipsia, consistent with the patient's presentation and medication history. *Pituitary adenoma* - A pituitary adenoma could cause **central diabetes insipidus** by impairing ADH production. - However, in central DI, urine osmolarity would significantly increase after desmopressin, which is not observed here, ruling out significant ADH deficiency at the pituitary level. *Primary polydipsia* - In primary polydipsia, the initial plasma and urine osmolalities would typically be **lower** due to chronic water overload. - After water deprivation, urine osmolality would eventually increase significantly as the body attempts to conserve water, which is contrary to the findings in this case. *Aspirin* - **Aspirin** and other NSAIDs (including naproxen, which the patient is also taking) primarily act as anti-inflammatory agents and are not implicated in causing diabetes insipidus. - While NSAIDs can rarely cause acute interstitial nephritis or reduce GFR, they do not directly lead to the pattern of impaired urine concentration characteristic of nephrogenic diabetes insipidus. *Omeprazole* - **Omeprazole** is a proton pump inhibitor used for acid reduction and does not have a known association with diabetes insipidus or its symptoms. - Its mechanism of action is unrelated to renal water handling or ADH pathways.

Question 40: A 64-year-old woman with osteoarthritis presents to the emergency room with a 2-day history of nausea and vomiting. Over the past few weeks, the patient has been taking painkillers to control worsening knee pain. Physical examination reveals scleral icterus and tender hepatomegaly. The patient appears confused. Laboratory investigations reveal the following enzyme levels: Serum alanine aminotransferase (ALT) 845 U/L Aspartate aminotransferase (AST) 798 U/L Alkaline phosphatase 152 U/L Which of the following is the most appropriate antidote for the toxicity seen in this patient?

• A. N-acetylmuramic acid
• B. N-acetyl-p-benzoquinoneimine
• C. N-acetylcysteine (Correct Answer)
• D. N-acetylaspartic acid
• E. N-acetylglucosamine

Explanation: ***N-acetylcysteine*** - The patient's presentation with nausea, vomiting, confusion, scleral icterus, tender hepatomegaly, and significantly elevated **ALT** and **AST** levels (in the hundreds) after taking painkillers strongly suggests **acetaminophen (paracetamol) toxicity** leading to acute liver failure. - **N-acetylcysteine (NAC)** is the specific antidote for acetaminophen overdose; it works by replenishing hepatic **glutathione** stores, which are crucial for detoxifying the toxic metabolite **N-acetyl-p-benzoquinone imine (NAPQI)**. *N-acetylmuramic acid* - This compound is a component of **bacterial cell walls** and is not involved in human metabolism or toxicology. - It has no role as an antidote for drug-induced liver injury or any known human toxicity. *N-acetyl-p-benzoquinoneimine* - This is the highly reactive and **toxic metabolite of acetaminophen (NAPQI)** that causes liver damage when glutathione stores are depleted. - It is the substance that NAC helps to detoxify, not an antidote itself. *N-acetylaspartic acid* - This molecule is concentrated in the **brain** and is involved in neuronal osmoregulation and energy metabolism. - It is not an antidote for drug toxicity and is primarily associated with neurological conditions like Canavan disease. *N-acetylglucosamine* - This is a **monosaccharide derivative** involved in the biosynthesis of glycoproteins and proteoglycans. - It has no established role as an antidote for acetaminophen toxicity or any other acute poisoning.

Question 41: A 45-year-old man comes to the physician because of numbness and tingling in his fingers and toes for the past month. He also describes difficulty with balance while walking. Laboratory studies show a hemoglobin concentration of 9.5 g/dL. Serum homocysteine and methylmalonic acid levels are elevated. Peripheral blood smear shows hypersegmented neutrophils. Which of the following is most likely to have prevented this patient's condition?

• A. Folic acid supplementation
• B. Avoidance of lead-based paint
• C. Cyanocobalamin supplementation (Correct Answer)
• D. Avoidance of canned foods
• E. Pyridoxine supplementation

Explanation: ***Cyanocobalamin supplementation*** - The patient's symptoms (numbness, tingling, difficulty with balance, anemia) and lab findings (**elevated homocysteine** and **methylmalonic acid**, **hypersegmented neutrophils**) are classic for **vitamin B12 deficiency**. - **Cyanocobalamin** is vitamin B12, and supplementation would prevent the development of these signs and symptoms. *Folic acid supplementation* - While folic acid deficiency also causes **macrocytic anemia** and **elevated homocysteine**, it does not lead to elevated methylmalonic acid or the neurological symptoms described. - Supplementing folic acid without addressing vitamin B12 deficiency can mask the hematological signs of B12 deficiency while allowing neurological damage to progress. *Avoidance of lead-based paint* - **Lead poisoning** can cause anemia and neurological symptoms (e.g., peripheral neuropathy), but it typically presents with microcytic or normocytic anemia, not macrocytic anemia, and would not cause elevated methylmalonic acid. - Hypersegmented neutrophils are not characteristic of lead poisoning. *Avoidance of canned foods* - **Botulism** (often associated with improperly canned foods) causes neurological symptoms like paralysis but does not cause anemia or elevated homocysteine and methylmalonic acid. - It's an acute toxin-mediated illness, not a deficiency state. *Pyridoxine supplementation* - **Pyridoxine (vitamin B6) deficiency** can cause microcytic anemia (sideroblastic anemia), peripheral neuropathy, and cheilosis and glossitis, but it would not lead to macrocytic anemia, elevated methylmalonic acid, or hypersegmented neutrophils. - Elevated homocysteine can occur but is not as characteristic as in B12 or folate deficiency.

Question 42: A 54-year-old woman presents to the emergency department with sudden shortness of breath. A CT scan shows multiple nodules in her left lung. She reports that for the past 6 months, she has been feeling tired and depressed. She also has frequently felt flushed, which she presumed is a symptom of getting closer to menopause. On physical examination, a nodule with a size of 2.5 cm is palpable in the left lobe of the thyroid gland; the nodule is firm and non-tender. Cervical lymphadenopathy is present. Cytology obtained by fine needle aspiration indicates a high likelihood of thyroid carcinoma. Laboratory findings show a serum basal calcitonin of 620 pg/mL. A thyroidectomy is performed but the patient presents again to the ER with flushing and diarrhea within 6 weeks. Considering this patient, which of the following treatment options should be pursued?

• A. Observation
• B. Tamoxifen
• C. Vandetanib (Correct Answer)
• D. Radioactive iodine (radioiodine)
• E. Thyroid-stimulating hormone (TSH) suppression

Explanation: ***Vandetanib*** - This patient's presentation with **thyroid nodule**, **elevated calcitonin**, and symptoms like flushing and diarrhea, combined with lung metastases, is highly suggestive of **medullary thyroid carcinoma (MTC)**. The recurrence of flushing and diarrhea post-thyroidectomy indicates **persistent or metastatic disease**. - **Vandetanib** is a multi-kinase inhibitor specifically approved for the treatment of **symptomatic or progressive medullary thyroid carcinoma** that is unresectable or metastatic. It targets key pathways involved in MTC proliferation and angiogenesis, offering a systemic treatment option for advanced disease. *Observation* - **Observation** is not appropriate for metastatic medullary thyroid carcinoma, especially given the patient's persistent and symptomatic disease with lung metastases and systemic symptoms. - MTC is an aggressive cancer, and untreated metastatic disease would lead to continued progression and worsening symptoms. *Tamoxifen* - **Tamoxifen** is a selective estrogen receptor modulator primarily used in the treatment of **estrogen receptor-positive breast cancer**. - It has no role or efficacy in the treatment of medullary thyroid carcinoma. *Radioactive iodine (radioiodine)* - **Radioactive iodine (RAI) therapy** is effective for differentiated thyroid cancers (papillary and follicular) because these cancers retain the ability to absorb iodine. - **Medullary thyroid carcinoma** originates from parafollicular C cells and does not take up iodine, rendering RAID therapy ineffective. *Thyroid-stimulating hormone (TSH) suppression* - **TSH suppression therapy** is used in differentiated thyroid cancers to reduce the growth stimulus provided by TSH, thereby reducing recurrence risk. - **Medullary thyroid carcinoma** does not arise from TSH-dependent thyroid follicular cells, so TSH suppression therapy is not effective for MTC.

Question 43: A 35-year-old woman comes to the physician because of a 3-month history of headache, palpitations, diarrhea, and weight loss. She takes no medications. Her pulse is 110/min and blood pressure is 125/70 mm Hg. Examination shows warm, moist skin and diffuse hyperreflexia. An MRI of the brain shows a sellar mass. The underlying cause of this patient's condition is best explained by binding of a ligand to which of the following?

• A. Nonreceptor tyrosine kinase
• B. Intracytosolic nuclear receptor
• C. Receptor tyrosine kinase
• D. Membrane-bound guanylate cyclase
• E. G protein-coupled receptors (Correct Answer)

Explanation: ***G protein-coupled receptors*** - The patient's symptoms (tachycardia, diarrhea, weight loss, warm moist skin, hyperreflexia) are highly suggestive of **hyperthyroidism**. The sellar mass on MRI points to a **TSH-secreting pituitary adenoma (secondary hyperthyroidism)**, which leads to excessive activation of **TSH receptors** on thyroid follicular cells. - TSH receptors are a classic example of **G protein-coupled receptors**. When TSH binds, it activates an associated G protein, leading to an intracellular signaling cascade (typically through adenylyl cyclase and cAMP) that stimulates thyroid hormone synthesis and release. *Nonreceptor tyrosine kinase* - This class of receptors (e.g., for **cytokines** like growth hormone or interferons) often involves **JAK-STAT pathways** and does not typically mediate the effects of TSH. - While involved in various cellular processes, they are not the primary mechanism by which TSH exerts its effects on the thyroid gland. *Intracytosolic nuclear receptor* - **Steroid hormones** (like cortisol, estrogen, testosterone) and **thyroid hormones (T3/T4)** themselves bind to intracytosolic or nuclear receptors, which then translocate to the nucleus to regulate gene transcription. - TSH, being a polypeptide hormone, cannot directly cross the cell membrane to bind to an intracytosolic receptor; it acts via a cell-surface receptor. *Receptor tyrosine kinase* - These receptors (e.g., for **insulin** or **growth factors** like EGF, PDGF) directly possess intrinsic tyrosine kinase activity or are tightly associated with one upon ligand binding. - While they mediate many growth and metabolic effects, TSH signaling primarily occurs through G protein-coupled receptors, not receptor tyrosine kinases. *Membrane-bound guanylate cyclase* - This type of receptor, such as the receptor for **atrial natriuretic peptide (ANP)**, directly catalyzes the formation of **cGMP** upon ligand binding. - While other membrane-bound receptors exist, the TSH receptor specifically functions as a G protein-coupled receptor linked to the adenylyl cyclase system, not directly activating guanylate cyclase.

Question 44: A 58-year-old woman with type 2 diabetes mellitus comes to the physician because of a 3-month history of right lower extremity pain and burning while walking. The pain subsides with rest. She has smoked one pack of cigarettes daily for the past 30 years. Her current medications include metformin, atorvastatin, and aspirin. Examination shows a lack of hair and decreased skin temperature over the right foot. The right pedal pulse is not palpable. The physician adds a drug to her regimen that causes vasodilation and inhibits the aggregation of platelets and the proliferation of smooth muscle cells. Which of the following drugs was most likely added?

• A. Cilostazol (Correct Answer)
• B. Bosentan
• C. Eptifibatide
• D. Dabigatran
• E. Clopidogrel

Explanation: ***Cilostazol*** - **Cilostazol** is a **phosphodiesterase-3 (PDE3) inhibitor** approved specifically for the treatment of **intermittent claudication**, a symptom of peripheral arterial disease (PAD). - Its mechanism of action involves **vasodilation** via increased cAMP and **inhibition of platelet aggregation** and smooth muscle cell proliferation. *Bosentan* - **Bosentan** is an **endothelin receptor antagonist** used primarily for the treatment of **pulmonary arterial hypertension**. - Its main effect is **vasodilation** in the pulmonary vasculature, and it is not indicated for peripheral arterial disease. *Eptifibatide* - **Eptifibatide** is a **glycoprotein IIb/IIIa inhibitor** that primarily blocks the final common pathway of **platelet aggregation**, used in acute coronary syndromes or during PCI. - It does not significantly promote vasodilation and is not a first-line treatment for chronic symptoms of PAD. *Dabigatran* - **Dabigatran** is a **direct thrombin inhibitor** used to prevent stroke in atrial fibrillation and to treat/prevent deep vein thrombosis and pulmonary embolism. - While it inhibits coagulation, it does not exert significant vasodilatory effects or directly modify smooth muscle cell proliferation in the context of PAD. *Clopidogrel* - **Clopidogrel** is a **P2Y12 platelet inhibitor** that prevents platelet aggregation, often used for acute coronary syndromes, stroke prevention, and in PAD. - While it effectively inhibits platelet aggregation, it does not have significant vasodilatory properties that would directly alleviate claudication symptoms by increasing blood flow.

Question 45: A newborn male, delivered by emergency Cesarean section during the 28th week of gestation, has a birth weight of 1.2 kg (2.5 lb). He develops rapid breathing 4 hours after birth. Examination of the respiratory system reveals a respiratory rate of 80/min, expiratory grunting, intercostal and subcostal retractions with nasal flaring. His chest radiograph shows bilateral diffuse reticulogranular opacities and poor lung expansion. His echocardiography suggests a diagnosis of patent ductus arteriosus with left-to-right shunt and signs of fluid overload. The pediatrician administers intravenous indomethacin to facilitate closure of the duct. Which of the following effects best explains the mechanism of action of this drug in the management of this neonate?

• A. Increased synthesis of prostaglandin E2
• B. Inhibition of cyclooxygenase (Correct Answer)
• C. Decreased blood flow in the vasa vasorum of the ductus arteriosus
• D. Induction of endothelial nitric oxide synthase
• E. Increased synthesis of platelet-derived growth factor (PDGF)

Explanation: ***Inhibition of cyclooxygenase*** - **Indomethacin** is a potent **cyclooxygenase (COX) inhibitor** (both COX-1 and COX-2), which is the primary mechanism for PDA closure in neonates. - COX inhibition leads to **decreased synthesis of prostaglandin E2 (PGE2)**, which normally maintains ductal patency in utero. - With reduced PGE2 levels, the **ductal smooth muscle constricts**, leading to closure of the patent ductus arteriosus. - This is the standard mechanism taught for indomethacin use in PDA closure and is well-established in **neonatal pharmacology**. *Decreased blood flow in the vasa vasorum of the ductus arteriosus* - While decreased blood flow in the vasa vasorum may occur as a **secondary consequence** of prolonged ductal constriction, this is not the primary mechanism of action of indomethacin. - The immediate pharmacological effect is **COX inhibition and PGE2 reduction**, not a direct effect on vasa vasorum blood flow. - This represents a downstream anatomical consequence rather than the drug's mechanism of action. *Induction of endothelial nitric oxide synthase* - **Nitric oxide** is a potent vasodilator that would promote ductal patency, not closure. - Indomethacin does not induce nitric oxide synthase; its action is to **inhibit prostaglandin synthesis** through COX inhibition. - This would have the opposite therapeutic effect. *Increased synthesis of prostaglandin E2* - **PGE2 maintains ductal patency** during fetal life by causing smooth muscle relaxation. - Increasing PGE2 would **prevent closure** and worsen the PDA—this is the opposite of the desired effect. - Indomethacin **decreases** PGE2 synthesis, not increases it. *Increased synthesis of platelet-derived growth factor (PDGF)* - While PDGF plays a role in vascular remodeling and long-term structural changes, it is not the mechanism by which indomethacin acutely closes the ductus arteriosus. - The primary action is **prostaglandin inhibition**, not growth factor modulation. - PDGF changes are not a significant acute effect of indomethacin therapy.

Question 46: A 39-year-old man comes to the physician because of a 3-month history of fatigue, decreased sexual desire, and difficulty achieving an erection. He has no past medical history except for a traumatic brain injury he sustained in a motor vehicle accident 4 months ago. At that time, neuroimaging studies showed no abnormalities. Physical examination shows bilateral gynecomastia and a thin white nipple discharge. Decreased production of which of the following is the most likely underlying cause of this patient's current condition?

• A. Gonadotropin-releasing hormone
• B. Thyrotropin-releasing hormone
• C. Luteinizing hormone
• D. Growth hormone
• E. Dopamine (Correct Answer)

Explanation: ***Dopamine*** - The patient's symptoms (fatigue, decreased sexual desire, erectile dysfunction, gynecomastia, galactorrhea) following a **traumatic brain injury (TBI)** are indicative of **hypopituitarism**, specifically affecting dopamine's inhibitory control over prolactin. - **Dopamine** is produced in the hypothalamus and tonically inhibits **prolactin secretion** from the anterior pituitary; a decrease in dopamine can lead to elevated prolactin, causing the observed symptoms. *Gonadotropin-releasing hormone* - While TBI can cause **hypogonadism** due to GnRH deficiency, this would primarily lead to decreased LH/FSH and subsequent low testosterone, causing sexual dysfunction but not necessarily **galactorrhea** or **gynecomastia**. - Decreased GnRH would result in low levels of LH and FSH, but the direct cause of gynecomastia and nipple discharge in this case is likely **hyperprolactinemia**. *Thyrotropin-releasing hormone* - TRH stimulates TSH release; a deficiency would lead to **central hypothyroidism** (fatigue, cold intolerance, weight gain), but it does not directly explain **gynecomastia** or **galactorrhea**. - While TRH can stimulate prolactin secretion, a primary TRH deficiency would more prominently feature symptoms of hypothyroidism, which are not mentioned as the primary concern. *Luteinizing hormone* - A decrease in LH would lead to **decreased testosterone production** and symptoms like low sexual desire and erectile dysfunction. However, it does not directly cause **galactorrhea** or **gynecomastia** as seen in this patient. - LH primarily acts on Leydig cells to produce testosterone; while low testosterone can cause gynecomastia, the nipple discharge points more strongly to **hyperprolactinemia**. *Growth hormone* - Growth hormone deficiency in adults can cause fatigue, decreased muscle mass, and central obesity but is not typically associated with **gynecomastia** or **galactorrhea**. - A decrease in GH does not explain the breast-related symptoms observed in this patient.

Question 47: A 64-year-old man presents to the emergency department with acute onset of chest pain. He says the pain is substernal and radiates to his left arm. He has a history of hypertension, diabetes mellitus, erectile dysfunction, benign prostate hyperplasia, and panic disorder. He takes aspirin, lisinopril, metformin, sildenafil, prazosin, and citalopram. An electrocardiogram shows new ST-elevations in the lateral leads. He undergoes catherization, which reveals a complete blockage of the left circumflex artery. A stent is placed, and the patient is discharged with clopidogrel and isosorbide mononitrate. Five days later the patient presents to the emergency department complaining of fainting spells. The patient’s temperature is 97°F (37.2°C), blood pressure is 89/53 mmHg, and pulse is 90/min. Physical examination is unremarkable. An electrocardiogram reveals lateral Q waves without ST or T wave abnormalities. Which of the following is the most likely cause of the patient’s presentation?

• A. Stent thrombosis
• B. Fibrinous pericarditis
• C. Myocardial wall rupture
• D. Papillary muscle rupture
• E. Medication interaction (Correct Answer)

Explanation: ***Medication interaction*** - The patient experienced **hypotension and fainting spells** after being prescribed **isosorbide mononitrate** (a nitrate) following his myocardial infarction. The patient also takes **sildenafil** (a PDE5 inhibitor) for erectile dysfunction, which when combined with nitrates can lead to severe and prolonged hypotension. - Both **nitrates and sildenafil mediate nitric oxide (NO)-induced vasodilation**, leading to a synergistic effect on blood pressure reduction which caused his syncopal episodes. *Stent thrombosis* - This would typically present with a **recurrence of acute chest pain, ST-elevations, and signs of myocardial ischemia** due to re-occlusion of the stented artery. - The patient's symptoms are primarily **fainting spells and hypotension**, without signs of recurrent ischemia on ECG (lateral Q waves indicate prior infarction, but no acute changes). *Fibrinous pericarditis* - This complication typically occurs **2-4 days post-MI** and presents with **pleuritic chest pain that is positional** (worse when lying flat, better when leaning forward) and can be associated with a pericardial friction rub. - The patient's primary complaint is fainting spells and hypotension, not pleuritic chest pain. *Myocardial wall rupture* - A myocardial wall rupture is a catastrophic complication that typically presents with **sudden severe chest pain, profound hypotension, and often rapid death** due to cardiac tamponade. - The patient's presentation of fainting spells without acute severe chest pain or immediate life-threatening collapse makes complete myocardial wall rupture less likely. *Papillary muscle rupture* - This complication primarily presents with acute onset of **severe mitral regurgitation**, leading to **acute pulmonary edema, dyspnea, and cardiogenic shock**. - While hypotension can be present, the dominant symptoms are usually respiratory distress and signs of heart failure, which are not described in this patient's fainting spells.

Question 48: A 27-year-old woman comes to her primary care physician complaining of palpitations. She reports that for the past 2 months she has felt anxious and states that her heart often feels like it’s “racing.” She also complains of sweating and unintentional weight loss. Physical examination reveals symmetrical, non-tender thyroid enlargement and exophthalmos. After additional testing, the patient is given an appropriate treatment for her condition. She returns 2 weeks later complaining of worsening of her previous ocular symptoms. Which of the following treatments did the patient most likely receive?

• A. Radioactive iodine (Correct Answer)
• B. Propranolol
• C. Methimazole
• D. Propylthiouracil
• E. Thyroidectomy

Explanation: ***Radioactive iodine*** - The constellation of **palpitations, anxiety, racing heart, sweating, unintentional weight loss, symmetrical non-tender thyroid enlargement**, and **exophthalmos** points to **Graves' disease**. - This treatment is known to exacerbate ophthalmopathy due to the release of thyroid antigens following radiation-induced thyroid cellular damage, triggering an immune response. *Propranolol* - **Propranolol** is a **beta-blocker** used to manage the adrenergic symptoms of hyperthyroidism (e.g., palpitations, tremors, anxiety) but does not treat the underlying thyroid overproduction. - It would not worsen ocular symptoms, as it primarily targets cardiovascular effects. *Methimazole* - **Methimazole** is an **antithyroid drug** that inhibits thyroid hormone synthesis and would improve both systemic and ocular symptoms over time by reducing the hyperthyroid state. - It is a primary treatment for Graves' disease and would generally lead to improvement rather than worsening of symptoms. *Propylthiouracil* - **Propylthiouracil (PTU)** is another **antithyroid drug** that inhibits thyroid hormone synthesis and also blocks the conversion of T4 to T3. - Similar to methimazole, PTU would alleviate hyperthyroid symptoms, including ocular manifestations, and not worsen them. *Thyroidectomy* - **Thyroidectomy** removes the thyroid gland, effectively treating hyperthyroidism and reducing the immune response over time. - While it can sometimes be associated with a transient worsening of ophthalmopathy in some patients, it is less common and less pronounced than with radioactive iodine, and the long-term goal is improvement.

Question 49: A 56-year-old male with history of CHF presents to a trauma center following a motor vehicle accident. On arrival, his Glasgow Coma Scale score is 8, and he is found to have increased intracranial pressure. Mannitol is administered. Which of the following side effects of the drug would you most likely observe in this patient?

• A. Pulmonary edema (Correct Answer)
• B. Seizures
• C. Restrictive cardiomyopathy
• D. Arrhythmias
• E. Blood dyscrasias

Explanation: ***Pulmonary edema*** - **Mannitol** is an osmotic diuretic that initially draws fluid from the interstitial space into the intravascular compartment, causing **transient hypervolemia** before diuresis occurs. - In patients with **congestive heart failure (CHF)**, the heart has limited ability to handle this acute increase in preload, making **pulmonary edema the most likely complication** during mannitol administration. - This is a well-recognized risk that requires careful monitoring, especially in patients with compromised cardiac function. The fluid overload can precipitate acute decompensation before the diuretic effect provides relief. - Mannitol should be used cautiously in CHF patients, with slow administration and close monitoring of volume status. *Arrhythmias* - While mannitol can cause electrolyte disturbances (**hypokalemia**, **hyponatremia**, or **hyperkalemia** from renal effects) that may precipitate arrhythmias, this is less immediately likely than pulmonary edema. - Electrolyte shifts typically develop over time with repeated dosing or in the setting of renal dysfunction, rather than as an acute complication after initial administration. - CHF patients may be more susceptible to arrhythmias from electrolyte imbalances, but this is not the most immediate concern. *Seizures* - Seizures are not a typical direct side effect of mannitol administration. - They can result from the underlying **cerebral edema** or neurological injury that mannitol is being used to treat. - Rarely, **rebound cerebral edema** from rapid osmotic shifts or very high doses could theoretically worsen neurological status, but seizures are not a recognized direct adverse effect. *Blood dyscrasias* - **Blood dyscrasias** (disorders affecting blood cell production or function) are not associated with mannitol. - This adverse effect is characteristic of medications affecting **bone marrow function**, such as chemotherapeutic agents or certain antibiotics. *Restrictive cardiomyopathy* - **Restrictive cardiomyopathy** is a chronic structural heart disease characterized by impaired ventricular filling due to rigid myocardium. - This is not an acute side effect of mannitol, which primarily affects **fluid and electrolyte balance** without causing structural cardiac changes.

Question 50: A 52-year-old man presents his primary care physician for follow-up. 3 months ago, he was diagnosed with type 2 diabetes mellitus and metformin was started. Today, his HbA1C is 7.9%. The physician decides to add pioglitazone for better control of hyperglycemia. Which of the following is a contraindication to pioglitazone therapy?

• A. Pancreatitis
• B. Renal impairment
• C. Sulfa allergy
• D. Genital mycotic infection
• E. History of bladder cancer (Correct Answer)

Explanation: ***History of bladder cancer*** - **Pioglitazone** has been associated with an increased risk of **bladder cancer**, and therefore, it is **contraindicated** in patients with a history of bladder cancer or active bladder cancer. - The risk appears to be dose and duration-dependent, making prior bladder cancer a significant safety concern. - **Note**: The most critical contraindication to pioglitazone is **heart failure (NYHA Class III-IV)**, which carries an FDA black box warning due to fluid retention and worsening heart failure. Among the options provided, history of bladder cancer is the documented contraindication. *Pancreatitis* - While some diabetes medications, like **GLP-1 receptor agonists** and **DPP-4 inhibitors**, have been linked to pancreatitis, **pioglitazone (a thiazolidinedione)** is not directly associated with this condition to the extent of being a contraindication. - The primary concerns with pioglitazone are fluid retention, heart failure, and bladder cancer risk—not pancreatitis. *Renal impairment* - **Pioglitazone** is primarily metabolized in the **liver**, and its elimination is not significantly dependent on renal function. - Therefore, it can generally be used in patients with renal impairment, unlike some other antidiabetic drugs (e.g., metformin, SGLT2 inhibitors at advanced stages). - No dose adjustment is required for renal impairment. *Sulfa allergy* - **Pioglitazone** is not a **sulfonamide derivative**, unlike sulfonylureas (e.g., glyburide, glipizide). - Therefore, a sulfa allergy is not a contraindication for pioglitazone use. *Genital mycotic infection* - **Genital mycotic infections** are a common side effect of **SGLT2 inhibitors** (e.g., empagliflozin, canagliflozin) due to increased urinary glucose excretion. - Pioglitazone does not work via this mechanism and is not specifically contraindicated for patients with a history of these infections.

Question 51: A 40-year-old male in West Virginia presents to the emergency room complaining that his vision has deteriorated within the past several hours to the point that he can no longer see. He explains that some acquaintances sold him some homemade liquor and stated that it was pure as it burned with a "yellow flame." Which of the following if administered immediately after drinking the liquor would have saved his vision?

• A. Methylene blue
• B. Succimer
• C. Ethanol (Correct Answer)
• D. Amyl nitrite
• E. Atropine

Explanation: ***Ethanol*** - The patient's symptoms (sudden vision loss) and history (homemade liquor burning with a "yellow flame") are highly suggestive of **methanol poisoning**. Methanol is metabolized by **alcohol dehydrogenase (ADH)** to **formaldehyde**, then to **formic acid**, which is highly toxic to the optic nerve and retina, causing blindness. - **Ethanol** acts as a competitive substrate for **ADH**, which has higher affinity for ethanol than methanol. By administering ethanol, the metabolism of methanol to toxic metabolites is blocked, allowing time for methanol to be excreted unchanged via the kidneys, thus preventing further damage. - **Note**: While **fomepizole** (4-methylpyrazole) is now the preferred first-line ADH inhibitor due to fewer side effects, **ethanol remains an acceptable alternative** when fomepizole is unavailable, particularly in emergency settings or rural areas. *Methylene blue* - **Methylene blue** is used in the treatment of **methemoglobinemia**, a condition where the iron in hemoglobin is oxidized to the ferric state (Fe³⁺), reducing oxygen-carrying capacity. - This patient's symptoms are not consistent with methemoglobinemia (which presents with cyanosis unresponsive to oxygen), and methylene blue would not address the **methanol toxicity**. *Succimer* - **Succimer** (DMSA) is a chelating agent primarily used for the treatment of **lead poisoning** and other heavy metal toxicities (mercury, arsenic). - It would not be effective in treating methanol poisoning, which is a metabolic toxicity requiring competitive enzyme inhibition, not chelation. *Amyl nitrite* - **Amyl nitrite** is used in the treatment of **cyanide poisoning** by inducing methemoglobinemia, which then binds cyanide ions. - Its mechanism of action and indications are unrelated to methanol poisoning, which involves toxic organic acid accumulation rather than cellular respiration blockade. *Atropine* - **Atropine** is an anticholinergic medication used to treat **organophosphate/carbamate poisoning** (by blocking excess acetylcholine) and symptomatic bradycardia. - It would have no therapeutic effect on methanol toxicity and is unrelated to alcohol dehydrogenase or formic acid metabolism.

Question 52: A 32-year-old woman presents to the clinic for routine follow-up. She recently discovered that she is pregnant and is worried about taking medications throughout her pregnancy. She has a history of hypothyroidism and takes levothyroxine daily. Her vital signs are unremarkable. Her physical exam is consistent with the estimated 11-week gestation time. Which of the following statements regarding levothyroxine use during pregnancy is correct?

• A. Well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. (Correct Answer)
• B. Levothyroxine use in pregnancy is contraindicated, and its use should be discontinued.
• C. Levothyroxine can be safely used in the first trimester of pregnancy but should be discontinued in the second and third trimesters.
• D. Pregnant women will need to reduce the dose of levothyroxine to prevent congenital malformations.
• E. Animal studies have shown an adverse effect to the fetus, but there are no adequate and well-controlled studies in humans.

Explanation: ***Well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.*** - Many studies indicate that **levothyroxine** is safe and essential for managing **maternal hypothyroidism** throughout all trimesters of pregnancy. - Adequate maternal thyroid hormone levels are crucial for **fetal neurological development** and **preventing complications** in pregnancy. - **Levothyroxine is considered safe** throughout pregnancy with extensive human data supporting its use. *Levothyroxine use in pregnancy is contraindicated, and its use should be discontinued.* - **Discontinuing levothyroxine** during pregnancy in a hypothyroid patient would lead to **maternal and fetal hypothyroidism**, causing severe adverse outcomes. - **Hypothyroidism during pregnancy** is associated with increased risks of **preeclampsia**, **gestational hypertension**, **preterm birth**, and impaired fetal cognitive development. *Levothyroxine can be safely used in the first trimester of pregnancy but should be discontinued in the second and third trimesters.* - **Thyroid hormone requirements typically increase** throughout pregnancy, often necessitating a higher dose of levothyroxine rather than discontinuation in later trimesters. - Maintaining **euthyroid state** is important throughout the entire pregnancy to ensure optimal fetal growth and development. *Pregnant women will need to reduce the dose of levothyroxine to prevent congenital malformations.* - Pregnant women with hypothyroidism most often require an **increase in their levothyroxine dosage** (typically 25-50% higher) to maintain euthyroidism due to increased thyroid hormone demands. - **Hypothyroidism**, not appropriate levothyroxine doses, is associated with adverse pregnancy outcomes and potential fetal malformations. *Animal studies have shown an adverse effect to the fetus, but there are no adequate and well-controlled studies in humans.* - This statement does not apply to levothyroxine, which has **extensive human data** demonstrating safety in pregnancy. - **Well-controlled studies in pregnant women** have established the safety and necessity of levothyroxine during pregnancy in hypothyroid women.

Question 53: A 61-year-old female with a history of breast cancer currently on chemotherapy is brought by her husband to her oncologist for evaluation of a tremor. She reports that she developed a hand tremor approximately six months ago, prior to the start of her chemotherapy. The tremor is worse at rest and decreases with purposeful movement. She has experienced significant nausea and diarrhea since the start of her chemotherapy. Her past medical history is also notable for diabetes and hypertension treated with metformin and lisinopril, respectively. She takes no other medications. On examination, there is a tremor in the patient’s left hand. Muscle tone is increased in the upper extremities. Gait examination reveals difficulty initiating gait and shortened steps. Which of the following medications is contraindicated in the management of this patient’s nausea and diarrhea?

• A. Diphenhydramine
• B. Ondansetron
• C. Metoclopramide (Correct Answer)
• D. Loperamide
• E. Benztropine

Explanation: ***Metoclopramide*** - This patient presents with symptoms consistent with **Parkinson’s disease** (resting tremor, rigidity, bradykinesia indicated by gait initiation difficulty and shortened steps). **Metoclopramide** is a dopamine receptor antagonist that can worsen **extrapyramidal symptoms** and is therefore contraindicated. - While metoclopramide is used to treat nausea and vomiting, its **dopamine blocking effects** on the central nervous system would exacerbate the patient's existing Parkinsonian symptoms. *Diphenhydramine* - **Diphenhydramine** is an antihistamine with anticholinergic properties that can be used to treat nausea and can also reduce **tremor**, making it potentially beneficial rather than contraindicated. - Its anticholinergic effects can actually help alleviate some Parkinsonian symptoms, particularly tremor, though it is not a primary treatment. *Ondansetron* - **Ondansetron** is a **5-HT3 receptor antagonist** and is a first-line antiemetic for chemotherapy-induced nausea and vomiting. It does not affect dopamine pathways. - It would not worsen this patient's Parkinsonian symptoms, making it a safe choice for nausea management. *Loperamide* - **Loperamide** is an **opioid receptor agonist** used to treat diarrhea. It acts on opioid receptors in the gut to slow motility. - It does not have known interactions that would worsen Parkinson's disease or its symptoms. *Benztropine* - **Benztropine** is an **anticholinergic medication** used to treat Parkinson's disease symptoms, particularly tremor and rigidity. - It would be *therapeutic* for the patient's Parkinsonian symptoms, not contraindicated.

Question 54: A 65-year-old man with a history of myocardial infarction is admitted to the hospital for treatment of atrial fibrillation with rapid ventricular response. He is 180 cm (5 ft 11 in) tall and weighs 80 kg (173 lb). He is given an intravenous bolus of 150 mg of amiodarone. After 20 minutes, the amiodarone plasma concentration is 2.5 mcg/mL. Amiodarone distributes in the body within minutes, and its elimination half-life after intravenous administration is 30 days. Which of the following values is closest to the volume of distribution of the administered drug?

• A. 60 L (Correct Answer)
• B. 80 L
• C. 150 L
• D. 17 L
• E. 10 L

Explanation: ***60 L*** - The **volume of distribution (Vd)** is calculated using the formula: **Vd = Dose / Plasma Concentration**. - Given: Dose = 150 mg (150,000 mcg), Plasma concentration = 2.5 mcg/mL - Calculation: Vd = 150,000 mcg / 2.5 mcg/mL = 60,000 mL = **60 L** - Note: This calculation represents a simplified scenario. In clinical practice, amiodarone has an extremely large volume of distribution (60-100 L/kg or ~4,800-8,000 L in this patient) due to extensive tissue distribution, but the question tests the ability to apply the basic pharmacokinetic formula. *80 L* - This value would result if the plasma concentration were 1.875 mcg/mL (150,000 mcg / 80,000 mL), not the given 2.5 mcg/mL. - This represents a common calculation error when working with pharmacokinetic parameters. *150 L* - This value would require a plasma concentration of 1 mcg/mL (150,000 mcg / 150,000 mL), which is lower than the measured 2.5 mcg/mL. - This error might occur if the dose value were confused with the volume of distribution. *17 L* - This value would be obtained with a plasma concentration of approximately 8.8 mcg/mL (150,000 mcg / 17,000 mL), significantly higher than the measured 2.5 mcg/mL. - This represents a significant underestimation of Vd and would suggest limited drug distribution. *10 L* - This value would require a plasma concentration of 15 mcg/mL (150,000 mcg / 10,000 mL), which is 6-fold higher than the given 2.5 mcg/mL. - Such a small Vd would suggest drug confined primarily to plasma, which is inappropriate for lipophilic drugs with extensive tissue distribution.

Question 55: A 10-year-old boy comes to the physician for a follow-up examination. He was diagnosed with asthma one year ago and uses an albuterol inhaler as needed. His mother reports that he has had shortness of breath on exertion and a dry cough 3–4 times per week over the past month. Pulmonary examination shows expiratory wheezing in all lung fields. Treatment with low-dose inhaled mometasone is initiated. Which of the following recommendations is most appropriate to prevent complications from this treatment?

• A. Oral rinsing after medication administration (Correct Answer)
• B. Pantoprazole use prior to meals
• C. Weight-bearing exercise three times weekly
• D. Trimethoprim-sulfamethoxazole use three times weekly
• E. Minimizing use of a spacer

Explanation: ***Oral rinsing after medication administration*** - **Oral rinsing** after using an inhaled corticosteroid like mometasone helps to remove medication residue from the mouth and throat. - This significantly reduces the risk of local side effects such as **oral candidiasis (thrush)** and **dysphonia**. *Pantoprazole use prior to meals* - **Pantoprazole** is a proton pump inhibitor used to treat acid reflux or GERD. - While GERD can sometimes exacerbate asthma, there is no direct link between inhaled mometasone use and the need for prophylactic pantoprazole. *Weight-bearing exercise three times weekly* - **Weight-bearing exercises** are beneficial for bone health and overall fitness, particularly important for long-term oral corticosteroid use which can cause skeletal complications. - However, inhaled corticosteroids like mometasone have minimal systemic absorption and therefore have a negligible effect on bone mineral density in typical therapeutic doses. *Trimethoprim-sulfamethoxazole use three times weekly* - **Trimethoprim-sulfamethoxazole** is an antibiotic used for preventing or treating bacterial infections, particularly in immunocompromised individuals. - Inhaled corticosteroids do not typically cause significant systemic immunosuppression requiring prophylactic antibiotics. *Minimizing use of a spacer* - A **spacer** is a device used with metered-dose inhalers that helps improve drug delivery to the lungs and reduces deposition in the oropharynx. - Maximizing, not minimizing, the use of a spacer is recommended to enhance efficacy and reduce local side effects of inhaled corticosteroids.

Question 56: A 40-year-old man is bitten by a copperhead snake, and he is successfully treated with sheep hyperimmune Fab antivenom. Six days later, the patient develops an itchy abdominal rash and re-presents to the emergency department for medical care. He works as a park ranger. His medical history is significant for gout, hypertension, hypercholesterolemia, diabetes mellitus type II, and multiple basal cell carcinomas on his face and neck. He currently smokes 1 pack of cigarettes per day, drinks a 6-pack of beer per day, and currently denies any illicit drug use. His vital signs include: temperature 40.0°C (104.0°F), blood pressure 126/74 mm Hg, heart rate 111/min, and respiratory rate 23/min. On physical examination, his gait is limited by diffuse arthralgias, and he has clear breath sounds bilaterally and normal heart sounds. There is also a pruritic abdominal serpiginous macular rash which has spread to involve the back, upper trunk, and extremities. Of the following options, which best describes the mechanism of his reaction?

• A. Type IV–cell-mediated (delayed) hypersensitivity reaction
• B. Type I–anaphylactic hypersensitivity reaction
• C. Type II–cytotoxic hypersensitivity reaction
• D. Type III–immune complex-mediated hypersensitivity reaction (Correct Answer)
• E. Type I and IV–mixed anaphylactic and cell-mediated hypersensitivity reactions

Explanation: ***Type III–immune complex-mediated hypersensitivity reaction*** - The patient's symptoms (fever, rash, arthralgias) developing several days after receiving **sheep hyperimmune Fab antivenom** are classic for **serum sickness**, a type III hypersensitivity reaction. - This reaction occurs when **antibody-antigen complexes** form and deposit in tissues, activating complement and causing inflammation. *Type IV–cell-mediated (delayed) hypersensitivity reaction* - This type of reaction is mediated by **T-cells** and typically involves a delayed response (24-72 hours), seen in reactions like **contact dermatitis** or PPD tests, but does not usually present with fever and widespread rash as described. - While there is a delayed component, the systemic symptoms of fever and arthralgias point away from a purely cell-mediated response. *Type I–anaphylactic hypersensitivity reaction* - Type I reactions are **IgE-mediated**, rapid-onset reactions (minutes to hours) characterized by **urticaria**, angioedema, bronchospasm, and hypotension. - The delayed onset of symptoms (six days later) rules out an acute anaphylactic reaction. *Type II–cytotoxic hypersensitivity reaction* - Type II reactions involve **antibodies directed against antigens on cell surfaces**, leading to cell destruction (e.g., **hemolytic transfusion reactions**, autoimmune hemolytic anemia). - The patient's presentation with a widespread rash and arthralgias is not consistent with cell-specific destruction. *Type I and IV–mixed anaphylactic and cell-mediated hypersensitivity reactions* - While mixed reactions can occur, the specific combination of symptoms and the delayed onset strongly favor a single, well-defined mechanism: **Type III serum sickness**. - There is no clinical evidence to support an acute IgE-mediated (Type I) component or a primary cell-mediated (Type IV) process as the main cause of the widespread systemic illness.

Question 57: A 9-year-old boy with cerebral palsy is about to undergo a femoral osteotomy. An intravenous catheter needs to be placed; however, given prior experience the boy is extremely anxious and does not want to be stuck with a needle while awake. The decision is made to administer appropriate anesthesia by mask first before any other procedures are performed. An inhalation agent that would anesthetize most quickly has which of the following characteristics?

• A. Low blood solubility (Correct Answer)
• B. High blood solubility
• C. High cerebrospinal fluid solubility
• D. Low lipid solubility
• E. High lipid solubility

Explanation: ***Low blood solubility*** - An inhalation agent with **low blood solubility** has a fast **onset of action** because less anesthetic dissolves in the blood, leading to a quicker rise in the partial pressure of the anesthetic gas in the brain. - This rapid equilibration between the inhaled gas and the brain allows for a quick induction of anesthesia, which is desirable for anxious pediatric patients. *High blood solubility* - An inhalation agent with **high blood solubility** has a slow **onset of action** because a large amount of the anesthetic dissolves in the blood before equilibrium with the brain is achieved. - This delays the rise in brain partial pressure of the anesthetic, prolonging the induction period. *High cerebrospinal fluid solubility* - While cerebrospinal fluid (CSF) solubility can affect the duration of action and recovery from anesthesia by influencing the brain's internal environment, it does not primarily dictate the **speed of initial induction**. - The critical factor for rapid induction is the rate at which the anesthetic reaches the brain itself, primarily governed by blood-brain partial pressure gradients. *Low lipid solubility* - Most inhalation agents exert their primary effects by dissolving in the **lipid bilayers** of neuronal membranes in the brain to alter their function. - A low lipid solubility would mean that the agent would have difficulty crossing the **blood-brain barrier** and partitioning into neuronal membranes, leading to poor anesthetic efficacy. *High lipid solubility* - While **high lipid solubility** is important for an anesthetic agent to effectively cross the blood-brain barrier and partition into the brain tissue, it does not directly correlate with a **fast onset of action** for induction. - An agent with high lipid solubility but also high blood solubility would still have a slow onset because it would be extensively taken up by the blood before reaching the brain.

Question 58: A 53-year-old woman presents to a medical clinic complaining of diarrhea. She also has episodes during which her face becomes red and she becomes short of breath. These symptoms have been ongoing for the past few months. Five years ago she had an appendectomy. The medical history is otherwise not significant. On physical examination, her vital signs are normal. Wheezing is heard at the bases of the lungs bilaterally. A CT scan reveals multiple small nodules in the liver. A 24-hr urine collection reveals increased 5-hydroxyindoleacetic acid (5-HIAA). Which of the following is the next best step in the management of the patient?

• A. Explain to the patient that this condition would resolve spontaneously
• B. Start the patient on propranolol
• C. Perform a liver nodule excision with wide margins
• D. Start the patient on octreotide to manage the symptoms (Correct Answer)
• E. Test for serum chromogranin A (CgA)

Explanation: ***Start the patient on octreotide to manage the symptoms*** - The patient's symptoms (diarrhea, facial redness/flushing, shortness of breath/wheezing), elevated **5-HIAA**, and liver nodules are classic for **carcinoid syndrome**, likely from a neuroendocrine tumor that has metastasized to the liver. - **Octreotide**, a somatostatin analog, is the mainstay of treatment for symptomatic control in carcinoid syndrome by inhibiting the release of peptide hormones, including serotonin, from neuroendocrine tumors. *Explain to the patient that this condition would resolve spontaneously* - **Carcinoid syndrome** due to metastatic disease, as indicated by liver nodules and elevated 5-HIAA, is a progressive condition and **does not resolve spontaneously**. - Without treatment, symptoms will likely worsen, and the disease can lead to significant morbidity and mortality, particularly due to **carcinoid heart disease**. *Start the patient on propranolol* - **Propranolol** is a non-selective beta-blocker that could potentially worsen **bronchospasm** (indicated by wheezing) in patients with carcinoid syndrome, as serotonin can cause bronchial constriction. - While beta-blockers might be used for specific cardiac manifestations of carcinoid syndrome, they are not the initial or primary symptomatic treatment for the constellation of symptoms presented. *Perform a liver nodule excision with wide margins* - While surgical resection of liver metastases can be considered in some cases, especially for **debulking** or disease control, it is not the *next best step* for immediate **symptom management** in a patient with active carcinoid syndrome. - The primary goal at this stage is to control the hormonal symptoms, for which octreotide is highly effective. Excision would be a later consideration, often after initial medical stabilization. *Test for serum chromogranin A (CgA)* - While **serum chromogranin A (CgA)** is a useful tumor marker for **neuroendocrine tumors**, the diagnosis of carcinoid syndrome is already strongly established by the clinical picture, elevated 5-HIAA, and liver metastases. - Obtaining CgA would confirm the diagnosis but would not be the *next best step* for immediate management of the patient's severe symptoms. **Symptomatic control** is the priority.

Question 59: A 54-year-old man presents to the office for consultation regarding the results of recent laboratory studies. Medical history includes stage 3 chronic kidney disease, diabetes mellitus type 2, and hypertension, which is currently well controlled with lisinopril and furosemide. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 87/min, and respiratory rate 17/min. On physical examination, the heart sounds show a grade 3/6 holosystolic murmur heard best at the left upper sternal border, breath sounds are clear, no abnormal abdominal findings, and 2+ pedal edema of the bilateral lower extremities up to the knee. The patient has a 23-pack-year history of cigarette smoking. The results of the laboratory studies of serum include the following: ALT 20 U/L AST 19 U/L Total cholesterol 249 mg/dL LDL 160 mg/dL HDL 41 mg/dL Triglycerides 101 mg/dL Initiation of therapy with which of the following agents is most appropriate for the management of hyperlipidemia in this patient?

• A. Simvastatin (Correct Answer)
• B. Fenofibrate
• C. Fish oil
• D. Ezetimibe
• E. Niacin

Explanation: ***Simvastatin*** - This patient has **diabetes mellitus type 2**, a **history of smoking**, and **HTN**, which are all significant risk factors for **atherosclerotic cardiovascular disease (ASCVD)**. High cholesterol levels (total cholesterol 249 mg/dL, LDL 160 mg/dL) necessitate **statin therapy** for ASCVD risk reduction. - **Simvastatin** is a **moderate-intensity statin** appropriate for reducing ASCVD risk by lowering LDL cholesterol. Despite existing **CKD stage 3**, simvastatin can be safely initiated at an appropriate dosage, as it's generally well-tolerated and effective even with moderate renal impairment. - Among the options provided, simvastatin is the most appropriate **first-line therapy** for this patient's elevated LDL cholesterol. *Fenofibrate* - Fenofibrate is primarily used to lower **triglycerides** and to a lesser extent, increase HDL. This patient's triglyceride level (101 mg/dL) is within the normal range. - While fenofibrate can also affect cholesterol, the primary goal here is significant **LDL reduction** in a high-risk patient, for which statins are first-line therapy. *Fish oil* - **Fish oil** supplements, rich in **omega-3 fatty acids**, are primarily used to lower significantly elevated **triglyceride levels** (typically >500 mg/dL). - This patient's triglyceride level is normal (101 mg/dL), and fish oil is not indicated as a primary therapy for **LDL reduction** in high-risk patients. *Ezetimibe* - **Ezetimibe** is a cholesterol absorption inhibitor that primarily lowers LDL-C. It is typically used as an **add-on therapy** when statins alone do not achieve target LDL-C levels or in patients who are **statin-intolerant**. - Given that a statin has not yet been initiated, ezetimibe would not be the first-line choice for initial management in this high-risk patient. *Niacin* - **Niacin** (nicotinic acid) can lower LDL cholesterol and triglycerides while raising HDL, but it is associated with significant side effects such as **flushing** and **hepatotoxicity**. - Its use has declined due to lack of evidence showing improved cardiovascular outcomes when added to statin therapy, and it is not considered first-line for **ASCVD prevention**.

Question 60: A 56-year-old man comes to the physician for evaluation of gradually worsening fatigue, increased urinary frequency, and blurry vision for 5 months. He has not seen a doctor in several years. Physical examination shows decreased vibratory sense and proprioception in the lower extremities. His hemoglobin A1c is 10.4%. Treatment for his condition with an appropriate medication is begun. In response to this drug, pancreatic islet cells begin producing increasing amounts of secretory granules. The patient was most likely treated with which of the following drugs?

• A. Glimepiride (Correct Answer)
• B. Metformin
• C. Insulin
• D. Pioglitazone
• E. Acarbose

Explanation: ***Glimepiride*** - **Glimepiride** is a sulfonylurea that stimulates pancreatic beta cells to increase **insulin secretion**, leading to an increase in secretory granules. - The patient's symptoms (fatigue, polyuria, blurry vision, neurological deficits) and **high HbA1c (10.4%)** are consistent with poorly controlled **Type 2 Diabetes Mellitus**, for which sulfonylureas are an appropriate treatment. *Metformin* - **Metformin** primarily reduces **hepatic glucose production** and improves insulin sensitivity in peripheral tissues, rather than directly increasing insulin secretion or secretory granules from beta cells. - While it is a common first-line treatment for Type 2 Diabetes, its mechanism of action does not involve increasing pancreatic islet cell secretory granules. *Insulin* - While insulin would effectively lower blood glucose, it is an **exogenous hormone** and does not stimulate the patient's own pancreatic beta cells to produce more secretory granules. - Insulin therapy is often used in cases of beta-cell exhaustion or severe hyperglycemia, but the question specifies a drug that increases **pancreatic islet cell production** of granules. *Pioglitazone* - **Pioglitazone** is a thiazolidinedione that improves **insulin sensitivity** in peripheral tissues by activating PPAR-gamma receptors. - It does not directly stimulate the pancreas to increase insulin secretion or the number of secretory granules. *Acarbose* - **Acarbose** is an alpha-glucosidase inhibitor that works by delaying **carbohydrate absorption** in the gut, thereby reducing postprandial glucose spikes. - Its mechanism does not involve any direct effect on pancreatic islet cell insulin production or secretory granules.

Question 61: An investigator is studying the principles of cell-to-cell signaling of the autonomic nervous system. It is found that the adrenal medulla has receptors that, when activated, result in the immediate opening of Na+, Ca2+, and K+ channels, which subsequently leads to the secretion of epinephrine and norepinephrine. These receptors are structurally most similar to which of the following receptors?

• A. Alpha 1 receptors of the bladder neck
• B. D2 receptors of the basal ganglia
• C. M2 receptors of heart
• D. NM receptors of the quadriceps femoris muscle (Correct Answer)
• E. H2 receptors of the stomach

Explanation: ***NM receptors of the quadriceps femoris muscle*** - The adrenal medulla's chromaffin cells are modified **postganglionic sympathetic neurons** that release catecholamines upon stimulation by preganglionic neurons. - The activation of **Na+, Ca2+, and K+ channels** leading to rapid depolarization and neurotransmitter release is characteristic of **nicotinic acetylcholine receptors (NM type)**, which are ligand-gated ion channels. *Alpha 1 receptors of the bladder neck* - **Alpha-1 receptors** are **G-protein coupled receptors** that primarily activate phospholipase C, leading to increased intracellular calcium and smooth muscle contraction. - Their activation does not directly result in the immediate opening of Na+, Ca2+, and K+ channels. *D2 receptors of the basal ganglia* - **D2 receptors** are **G-protein coupled receptors**, specifically inhibitory (Gi-coupled), that decrease adenylyl cyclase activity and reduce intracellular cAMP. - They do not function as direct ligand-gated ion channels. *M2 receptors of heart* - **M2 receptors** are **G-protein coupled receptors** (Gi-coupled) that decrease heart rate by inhibiting adenylyl cyclase and opening potassium channels indirectly via G-protein subunits. - While they affect ion channels, this is an indirect G-protein mediated process, not a direct ligand-gated ion channel mechanism. *H2 receptors of the stomach* - **H2 receptors** are **G-protein coupled receptors** (Gs-coupled) that increase adenylyl cyclase activity, leading to increased cAMP and stimulation of gastric acid secretion. - They are not ligand-gated ion channels and do not directly open Na+, K+, and Ca2+ channels.

Question 62: A 36-year-old woman is brought to the emergency department after a high-speed motor vehicle collision. Her temperature is 36.5°C (97.7°F), pulse is 120/min, respirations are 24/min, and blood pressure is 100/65 mm Hg. Examination shows second and third-degree burns covering 30% of the surface area of her body. Intravenous fluids are administered. 30 minutes later, the patient develops respiratory distress and requires intubation. Administration of succinylcholine during the procedure is most likely to increase this patient's risk of developing which of the following laboratory abnormalities?

• A. Hyperkalemia (Correct Answer)
• B. Hypermagnesemia
• C. Hypernatremia
• D. Hyperglycemia
• E. Hyperphosphatemia

Explanation: ***Hyperkalemia*** - Succinylcholine, a **depolarizing neuromuscular blocker**, can cause an acute, life-threatening release of potassium from muscle cells, especially in patients with burns, trauma, denervation, or prolonged immobilization. - This is due to an upregulation of **extrajunctional nicotinic acetylcholine receptors** on the muscle surface following burn injury or muscle damage, leading to an exaggerated potassium efflux when activated by succinylcholine. - **Clinical timing**: The risk of hyperkalemia is greatest from **24-48 hours post-burn through several months**, though succinylcholine should generally be avoided in burn patients due to this potentially fatal complication. - The serum potassium can rise acutely by 5-10 mEq/L, causing **cardiac arrhythmias and cardiac arrest**. *Hypermagnesemia* - **Hypermagnesemia** is typically seen in patients with renal failure or those receiving excessive magnesium administration (e.g., in preeclampsia treatment). - It does not directly result from succinylcholine administration, nor is it a common complication of burns unless exogenous magnesium is given. *Hypernatremia* - **Hypernatremia** is usually caused by conditions like dehydration, diabetes insipidus, or excessive intake of sodium. - Succinylcholine does not directly affect serum sodium levels to cause hypernatremia. *Hyperglycemia* - **Hyperglycemia** can occur in trauma and burn patients due to increased stress hormones (e.g., cortisol, catecholamines) and insulin resistance. - While stress-induced hyperglycemia is a possibility in this patient, succinylcholine itself does not directly cause hyperglycemia. *Hyperphosphatemia* - **Hyperphosphatemia** is usually associated with **renal failure**, rhabdomyolysis, or tumor lysis syndrome. - Succinylcholine is not known to cause a significant increase in serum phosphate levels.

Question 63: A 36-year-old man comes to the physician for a routine health maintenance examination. He has a 20-year history of seizure disorder characterized by sudden-onset, periodic, jerking movements of both arms and lip smacking. He has a history of intravenous cocaine use. His temperature is 37.1°C (98.8°F), pulse is 80/min, respirations are 13/min, and blood pressure is 130/75 mm Hg. Examination shows gingival tissue covering the upper third of the teeth. There is bleeding of the gums when touched with a fine instrument. The remainder of the examination shows no abnormalities. Which of the following is the most likely cause of this patient's symptoms?

• A. Nifedipine
• B. Phenytoin (Correct Answer)
• C. Phenobarbital
• D. Carbamazepine
• E. Topiramate

Explanation: ***Phenytoin*** - The patient's history of a **seizure disorder** treated with medication, combined with **gingival hyperplasia** and bleeding gums, strongly suggests chronic **phenytoin use**. - Phenytoin is a well-known cause of **gingival overgrowth** (occurs in ~50% of patients), which is a **dose-independent side effect** related to altered collagen metabolism. - The overgrowth is exacerbated by poor oral hygiene and commonly presents with bleeding on probing. *Nifedipine* - While nifedipine, a **calcium channel blocker**, can cause gingival hyperplasia, it is primarily used for **hypertension** or **angina**, not seizure disorder. - The patient's primary condition is a seizure disorder, making nifedipine an unlikely cause of his oral symptoms in this context. *Phenobarbital* - Phenobarbital is an **antiepileptic drug** but is not typically associated with **gingival hyperplasia**. - Its more common side effects include **sedation**, **cognitive impairment**, and dependence. *Carbamazepine* - Carbamazepine is another **antiepileptic drug** that can be used for seizure disorders, but **gingival hyperplasia** is not a characteristic side effect. - It is more commonly associated with side effects such as **dizziness**, **ataxia**, and **bone marrow suppression** (aplastic anemia). *Topiramate* - Topiramate is an **antiepileptic drug** often used for various seizure types, but it does not cause **gingival hyperplasia**. - Common side effects include **cognitive slowing**, **paresthesias**, and **weight loss**.

Question 64: A 39-year-old man presents to the primary care physician complaining of 6 months of increasing dyspnea and non-productive cough. He has a past medical history of asthma, hypertension, obesity, and hypercholesterolemia. On examination, you notice that he takes shallow breaths and the respiratory rate is 22/min. On auscultation, you notice bibasilar rales, wheezes, and a grade 2/6 holosystolic murmur. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, and heart rate 74/min. He then undergoes an outpatient high-resolution chest computed tomography (CT) scan which reveals bibasilar honeycombing, a calcified granuloma, and a mildly enlarged mediastinal lymph node. Which of the following medications can cause or contribute to this man’s lung disease?

• A. Amiodarone (Correct Answer)
• B. Candesartan
• C. Verapamil
• D. Propranolol
• E. Prednisone

Explanation: ***Amiodarone*** - **Amiodarone** is a known cause of **pulmonary fibrosis**, characterized by dyspnea, non-productive cough, and bibasilar rales, as seen in the patient. - The CT findings of **bibasilar honeycombing** are consistent with interstitial lung disease, which can be induced by amiodarone. - Amiodarone pulmonary toxicity can occur with chronic use and presents with the structural changes seen on this patient's CT scan. *Candesartan* - **Candesartan** is an **angiotensin receptor blocker (ARB)** primarily used for hypertension and heart failure. - It is not typically associated with causing or contributing to pulmonary fibrosis or interstitial lung disease. *Verapamil* - **Verapamil** is a **calcium channel blocker** used for hypertension, angina, and arrhythmias. - It is not known to cause pulmonary fibrosis or significant lung disease. *Propranolol* - **Propranolol** is a **non-selective beta-blocker** that can exacerbate bronchospasm in patients with asthma or COPD, potentially worsening respiratory symptoms. - However, it does **not cause the structural lung changes** (honeycombing, interstitial fibrosis) seen on this patient's CT scan. - While it could worsen his asthma symptoms, it does not explain the CT findings that indicate drug-induced pulmonary fibrosis. *Prednisone* - **Prednisone** is a **corticosteroid** often used to *treat* inflammatory lung conditions, including some types of interstitial lung disease. - It does not cause pulmonary fibrosis; rather, it is broadly anti-inflammatory, and its long-term use can lead to other complications but not the fibrotic lung damage described.

Question 65: A 50-year-old man presents to an ophthalmologist with progressive decrease in his visual acuity over the last 6 months. He also mentions that he has become excessively sensitive to light over the same duration. Past medical history is significant for schizophrenia diagnosed in early adulthood which has been managed with an antipsychotic medication for the past 20 years. The ophthalmologist performs a slit lamp examination and notes discrete brown deposits on the corneal epithelium in both eyes. Which of the following antipsychotic drugs has this patient most likely been taking?

• A. Chlorpromazine (Correct Answer)
• B. Clozapine
• C. Thioridazine
• D. Haloperidol
• E. Ziprasidone

Explanation: ***Chlorpromazine*** - **Chlorpromazine** is known to cause **corneal and lenticular opacities** due to drug accumulation, presenting as **discrete brown deposits** on the **corneal epithelium** and lens. - This side effect can lead to **decreased visual acuity** and **photosensitivity**, matching the patient's symptoms. *Clozapine* - Clozapine is primarily associated with **agranulocytosis** and **myocarditis**, not significant ocular deposits. - While it can cause blurry vision, it does not typically manifest as discrete brown corneal deposits. *Thioridazine* - **Thioridazine** is notorious for causing **retinal pigmentation** (retinopathy), particularly at higher doses, leading to **visual impairment**. - However, it does not typically cause the **corneal epithelial deposits** described in the patient. *Haloperidol* - **Haloperidol** is a potent typical antipsychotic with a high risk of **extrapyramidal symptoms**. - It is not prominently associated with ocular side effects like corneal deposits or significant photosensitivity. *Ziprasidone* - **Ziprasidone** is an atypical antipsychotic with a risk of **QT prolongation** and metabolic side effects. - It does not cause the specific corneal and lenticular changes seen with chlorpromazine.

Question 66: A 68-year-old male with congestive heart failure recently had his medication regimen adjusted to better control his hypertension. Three weeks later, laboratory analysis shows his serum calcium and magnesium levels have both decreased. The diuretic used in this patient acts predominantly on which nephron segment:

• A. Distal tubule
• B. Descending loop of Henle
• C. Proximal tubule
• D. Thick ascending loop of Henle (Correct Answer)
• E. Cortical collecting duct

Explanation: ***Thick ascending loop of Henle*** - Diuretics acting on the **thick ascending loop of Henle** (e.g., **furosemide**) inhibit the **Na+-K+-2Cl- cotransporter**, reducing the reabsorption of these ions. - This also significantly reduces the **lumen-positive transepithelial potential difference**, which is the driving force for **paracellular reabsorption of calcium and magnesium**, leading to their increased excretion and decreased serum levels. *Distal tubule* - Diuretics acting on the **distal tubule** (e.g., **thiazides**) inhibit the **Na+-Cl- cotransporter**. - While they cause natriuresis, they paradoxically **increase calcium reabsorption** by enhancing activity of the basolateral Na+-Ca++ exchanger, leading to hypercalcemia, not hypocalcemia. *Descending loop of Henle* - The **descending loop of Henle** is primarily permeable to **water** but not solutes. - Diuretics that affect this segment (e.g., ADH antagonists) would primarily impact water reabsorption without directly altering calcium and magnesium reabsorption in a way that causes hypocalcemia and hypomagnesemia. *Proximal tubule* - The **proximal tubule** is responsible for reabsorbing a large proportion of filtered calcium and magnesium, but diuretics acting here (e.g., **acetazolamide**) primarily inhibit bicarbonate reabsorption. - While they can increase calcium and magnesium excretion to some degree, they are not typically associated with the pronounced hypocalcemia and hypomagnesemia seen with loop diuretics. *Cortical collecting duct* - The **cortical collecting duct** is targeted by **potassium-sparing diuretics** (e.g., **spironolactone**, **amiloride**). - These diuretics inhibit sodium reabsorption and potassium secretion, but they do not significantly impact calcium or magnesium levels; in fact, some may even slightly increase calcium reabsorption.

Question 67: A 47-year-old man with alcoholic cirrhosis is brought to the emergency department by ambulance 20 minutes after being involved in a high-speed motor vehicle collision. His pulse is 120/min, respirations are 28/min and labored, and blood pressure is 70/40 mm Hg. Physical examination shows ecchymoses over the trunk and abdomen. In preparation for an exploratory laparotomy, atracurium is administered as an anesthetic. Which of the following characteristics is the most likely reason that this drug was chosen over other drugs in the same class?

• A. Quickest onset of action
• B. Highest potency
• C. Prolonged depolarization
• D. Organ-independent elimination (Correct Answer)
• E. Low risk of bleeding

Explanation: ***Organ-independent elimination*** - **Atracurium** is metabolized by **Hofmann elimination** and **ester hydrolysis**, which are independent of renal or hepatic function. - This is crucial for a patient with **alcoholic cirrhosis** and **hemodynamic instability**, where liver and kidney function may be compromised, preventing drug accumulation. *Quickest onset of action* - While a rapid onset is desirable in an emergency, atracurium does not have the **quickest onset of action** among neuromuscular blockers; **succinylcholine** is faster. - The primary selection criterion here relates to the patient's underlying liver pathology and the drug's elimination profile. *Highest potency* - **Potency** refers to the dose required to produce a given effect, and while important, it is not the **most critical factor** in selecting atracurium for this patient. - The patient's severe medical condition necessitates drug selection based on **metabolic profile** to minimize adverse effects. *Prolonged depolarization* - Atracurium is a **non-depolarizing neuromuscular blocker**, meaning it does not cause prolonged depolarization. - **Succinylcholine** is a depolarizing agent, and its use might be contraindicated or require careful consideration in trauma patients with potential electrolyte imbalances. *Low risk of bleeding* - The risk of bleeding is generally not a direct characteristic of **neuromuscular blocking agents** themselves. - The patient's **cirrhosis** and **trauma** are the primary factors contributing to a high risk of bleeding, which is managed independently of muscle relaxant choice.

Question 68: A 52-year-old woman with hypertension and type 2 diabetes mellitus comes to the physician because of a 1-day history of severe pain and swelling of her left great toe. She has had similar episodes sporadically over the past 3 years. She drinks 6 beers daily. She does not smoke or use illicit drugs. She is allergic to hydrochlorothiazide and glipizide. Her current medications are amlodipine and metformin. Examination shows erythema, warmth, and tenderness of the left first metatarsophalangeal joint and a nodule over the right elbow. The most appropriate next step in treatment is the administration of a drug that has which of the following mechanisms of action?

• A. Selective inhibition of cyclooxygenase-2
• B. Increased renal excretion of uric acid
• C. Irreversible inhibition of cyclooxygenase
• D. Reversible inhibition of prostaglandin synthesis (Correct Answer)
• E. Irreversible inhibition of xanthine oxidase

Explanation: ***Reversible inhibition of prostaglandin synthesis*** - The patient presents with classic symptoms of an acute **gout flare**, including severe pain, swelling, erythema, and tenderness of the left great toe (podagra), with a history of similar episodes and an elbow nodule (tophi). - **NSAIDs** (e.g., indomethacin, ibuprofen, naproxen) are first-line agents for acute gout attacks due to their rapid anti-inflammatory effects through the **reversible inhibition of cyclooxygenase (COX-1 and COX-2)**, thereby blocking prostaglandin synthesis. *Selective inhibition of cyclooxygenase-2* - **COX-2 selective inhibitors** (coxibs) can be used for acute gout flares, particularly in patients at higher risk of gastrointestinal bleeding. - However, they are generally not preferred over non-selective NSAIDs due to potential cardiovascular risks, and the question asks for the **most appropriate** general mechanism, which broadly encompasses prostaglandin synthesis inhibition by non-selective NSAIDs as well. *Increased renal excretion of uric acid* - This mechanism describes **uricosuric agents** (e.g., probenecid, lesinurad), which are used for **long-term management of hyperuricemia** to prevent future gout flares, not for treating an acute attack. - They work by inhibiting uric acid reabsorption in the renal tubules and are contraindicated in patients with a history of kidney stones. *Irreversible inhibition of cyclooxygenase* - This mechanism refers primarily to **aspirin** (acetylsalicylic acid), particularly at low doses. - While aspirin is an NSAID, it is generally **avoided in acute gout** because it can both inhibit uric acid excretion (at low doses) and compete with uric acid for secretion, potentially worsening hyperuricemia or triggering a flare. *Irreversible inhibition of xanthine oxidase* - This mechanism describes **xanthine oxidase inhibitors** (e.g., allopurinol, febuxostat), which are used for **long-term management of hyperuricemia** by reducing uric acid production. - These drugs are typically initiated after an acute flare has resolved, as they can sometimes precipitate a flare if started during an acute attack.

Question 69: A 20-year-old premedical student travels abroad for a global health service semester and presents to the local clinic with palpitations. She initially dismissed these symptoms as a side effect of working too hard; however, she has been noticing that these episodes have increased in frequency. Otherwise, she has had headaches and episodes of sweating, but she says that many members of her family have migraines. In the clinic, her temperature is 99°F (37°C), blood pressure is 170/120 mmHg, pulse is 105/min, respirations are 20/min. Other laboratory testing is not available. The doctor provides an older medication that he says does not bind to the relevant receptor but instead blocks an upstream process. The drug provided most likely has which of the following mechanisms of action?

• A. Cleavage of vesicular SNAP proteins
• B. Inhibition of vesicular transporters
• C. Replacement of vesicular contents
• D. Inhibition of metabolite conversion (Correct Answer)
• E. Inhibition of reuptake pathways

Explanation: ***Inhibition of metabolite conversion*** - This patient's symptoms (palpitations, headaches, sweating, hypertension) point to a **pheochromocytoma**, which overproduces **catecholamines**. The drug described as not binding to the relevant receptor but blocking an upstream process, suggests it inhibits an enzyme involved in catecholamine synthesis, such as **tyrosine hydroxylase** or **dopamine beta-hydroxylase**. - **Metyrosine** is an example of such a drug; it inhibits **tyrosine hydroxylase**, thereby reducing the synthesis of catecholamines and managing symptoms associated with pheochromocytoma. *Cleavage of vesicular SNAP proteins* - This mechanism is associated with **botulinum toxin**, which cleaves **SNARE proteins** like SNAP-25, synaptobrevin, and syntaxin, preventing the release of acetylcholine. - This would lead to muscle paralysis and is not relevant to the management of catecholamine excess. *Inhibition of vesicular transporters* - This mechanism involves drugs like **reserpine**, which inhibits the **vesicular monoamine transporter (VMAT)**, preventing the uptake and storage of norepinephrine and other monoamines into synaptic vesicles. - While it reduces catecholamine release, the question states the drug "blocks an upstream process" rather than vesicular transport specifically, and reserpine directly impacts vesicular contents. *Replacement of vesicular contents* - This mechanism describes drugs like **clonidine** or **alpha-methyldopa**, which act as **false neurotransmitters** or agonists that lead to reduced sympathetic outflow. Alpha-methyldopa is converted to alpha-methylnorepinephrine, which is then stored in vesicles displacing natural norepinephrine. - While relevant to hypertension, this is a replacement, not an inhibition of an upstream synthetic process. *Inhibition of reuptake pathways* - This mechanism is characteristic of **tricyclic antidepressants (TCAs)** or **selective serotonin reuptake inhibitors (SSRIs)**, which increase the concentration of neurotransmitters in the synaptic cleft by blocking their reuptake into the presynaptic neuron. - This would *increase* the effects of catecholamines, worsening the patient's symptoms, and is generally not used for chronic hypertension, especially in the context of pheochromocytoma.

Question 70: A 76-year-old man is brought to the emergency department by his daughter because he has been feeling lightheaded and almost passed out during dinner. Furthermore, over the past few days he has been experiencing heart palpitations. His medical history is significant for well-controlled hypertension and diabetes. Given this presentation, an electrocardiogram is performed showing an irregularly irregular tachyarrhythmia with narrow QRS complexes. The patient is prescribed a drug that decreases the slope of phase 0 of the ventricular action potential but does not change the overall duration of the action potential. Which of the following drugs is consistent with this mechanism of action?

• A. Procainamide
• B. Mexiletine
• C. Propranolol
• D. Dofetilide
• E. Propafenone (Correct Answer)

Explanation: ***Propafenone*** - **Propafenone** is a **Class IC antiarrhythmic drug** that strongly blocks fast **sodium channels**, thereby decreasing the slope of phase 0 depolarization. - Class IC drugs significantly slow conduction velocity but have **minimal effect on action potential duration (APD)** or effective refractory period (ERP). *Procainamide* - **Procainamide** is a **Class IA antiarrhythmic drug**. It blocks sodium channels and also prolongs repolarization by blocking potassium channels. - This prolongation of repolarization leads to an **increased action potential duration (APD)**, which is contrary to the question stem. *Mexiletine* - **Mexiletine** is a **Class IB antiarrhythmic drug**. It blocks sodium channels but with **fast on-off kinetics**, leading to minimal effect at normal heart rates. - Class IB drugs typically **shorten the action potential duration (APD)**, especially in ischemic tissue, by blocking inactivated sodium channels and affecting potassium currents. *Propranolol* - **Propranolol** is a **Class II antiarrhythmic drug (beta-blocker)**. It primarily acts by blocking beta-adrenergic receptors, reducing automaticity and slowing AV nodal conduction. - Beta-blockers affect phase 4 (spontaneous depolarization) and prolong the effective refractory period of the AV node, but they do not primarily decrease the slope of phase 0 of the ventricular action potential without changing APD. *Dofetilide* - **Dofetilide** is a **Class III antiarrhythmic drug**. It selectively blocks **potassium channels**, thereby *prolonging repolarization* and the action potential duration (APD). - Prolongation of APD is a characteristic feature of Class III drugs, which is contrary to the drug mechanism described in the question.

Question 71: A 45-year-old male presents to your office with complaints of chronic insomnia. After reviewing his medical history, you decide to prescribe zolpidem. Which of the following is a valid reason to choose zolpidem over a benzodiazepine?

• A. Zolpidem has a lower risk of tolerance and dependence (Correct Answer)
• B. Zolpidem has a slow onset of action
• C. Zolpidem is a potent anticonvulsant
• D. Zolpidem does not bind to the GABA receptor
• E. Zolpidem is a potent muscle relaxant

Explanation: ***Zolpidem has a lower risk of tolerance and dependence*** - While both zolpidem and benzodiazepines enhance GABAergic activity, **zolpidem** is a **selective GABAA receptor modulator** (specifically targeting the α1-subunit). This selectivity theoretically contributes to a lower risk of tolerance and dependence compared to non-selective benzodiazepines. - Benzodiazepines, by binding to a broader range of GABA-A receptor subunits, are associated with a higher potential for **physical dependence**, **withdrawal symptoms**, and the need for dose escalation over time to achieve the same hypnotic effect (tolerance). *Zolpidem has a slow onset of action* - Zolpidem actually has a **rapid onset of action**, typically within 15-30 minutes, which is beneficial for initiating sleep. - A slow onset would make it less effective for patients needing to fall asleep quickly. *Zolpidem is a potent anticonvulsant* - While zolpidem has some **sedative-hypnotic properties** similar to benzodiazepines, it is a relatively weak anticonvulsant and is not typically prescribed for controlling seizures. - **Benzodiazepines** like clonazepam or lorazepam are well-established for their potent anticonvulsant effects. *Zolpidem does not bind to the GABA receptor* - This statement is incorrect; **zolpidem is a GABAA receptor agonist**, meaning it binds to a specific site on the GABAA receptor complex. - Its mechanism of action involves enhancing the inhibitory effects of GABA, leading to sedation and sleep induction. *Zolpidem is a potent muscle relaxant* - Zolpidem possesses some **muscle relaxant properties**, similar to benzodiazepines, but these are generally less pronounced. - **Benzodiazepines** are more commonly used for their significant muscle relaxant effects due to their broader interactions with GABAA receptor subunits throughout the central nervous system.

Question 72: A 60-year-old man with a 1-year history of recurrent aspiration pneumonia is brought to the emergency department by his daughter after being found unconscious and gasping for air in his bed. Despite resuscitative efforts, the patient dies. Autopsy of the patient shows degeneration of the corticospinal tracts and anterior horn cells of the upper cervical cord. There is asymmetrical atrophy of the limb muscles, the diaphragm, and the intercostal muscles. Which of the following drugs would have most likely slowed the progression of this patient's condition?

• A. Inactivated virus vaccine
• B. Corticosteroids
• C. Glatiramer acetate
• D. Riluzole (Correct Answer)
• E. Nusinersen

Explanation: ***Riluzole*** - This patient's presentation with **recurrent aspiration pneumonia**, progressive muscle weakness, and eventual respiratory failure, along with autopsy findings of **degeneration of corticospinal tracts and anterior horn cells**, is highly suggestive of **amyotrophic lateral sclerosis (ALS)**. - **Riluzole** is a glutamate inhibitor that is the only drug approved to extend survival and delay the need for tracheostomy in patients with ALS, primarily by reducing excitotoxic damage to motor neurons. *Inactivated virus vaccine* - An inactivated virus vaccine is used to prevent viral infections, and while aspiration pneumonia can be complicated by infections, it does not address the underlying **neurodegenerative process** described. - Vaccinations, such as the flu vaccine, might prevent some types of pneumonia but would not slow the progression of a condition like ALS. *Corticosteroids* - **Corticosteroids** are potent anti-inflammatory and immunosuppressive agents often used in autoimmune diseases but are generally not effective and can even be detrimental in conditions like ALS due to potential side effects like myopathy. - They have no proven benefit in altering the course or slowing the progression of ALS. *Glatiramer acetate* - **Glatiramer acetate** is an immunomodulator specifically used in the treatment of **multiple sclerosis (MS)**. - It works by mimicking myelin basic protein and diverting immune responses away from myelin, a mechanism irrelevant to the pathophysiology of ALS. *Nusinersen* - **Nusinersen** is an antisense oligonucleotide used to treat **spinal muscular atrophy (SMA)**, a genetic motor neuron disease. - While both ALS and SMA involve motor neuron degeneration, they are distinct conditions with different genetic and molecular pathology; Nusinersen is not indicated for ALS.

Question 73: A 38-year-old woman comes to the physician because of a 1-month history of palpitations. She does not smoke or drink alcohol. Her pulse is 136/min and irregularly irregular. An ECG shows irregularly spaced QRS complexes with no distinct P waves. Treatment is started with a drug that slows atrioventricular node conduction velocity and prevents voltage-dependent calcium entry into myocytes. The patient is at greatest risk for which of the following adverse effects?

• A. Bronchospasm
• B. Peripheral edema (Correct Answer)
• C. Dry mouth
• D. Tinnitus
• E. Gingival hyperplasia

Explanation: ***Peripheral edema*** - The patient's symptoms (irregularly irregular pulse, no distinct P waves) suggest **atrial fibrillation**. The drug described, which slows AV nodal conduction velocity and prevents voltage-dependent calcium entry into myocytes, is a **non-dihydropyridine calcium channel blocker** such as **verapamil** or **diltiazem**. - While **peripheral edema** occurs more commonly with **dihydropyridine calcium channel blockers** (e.g., nifedipine, amlodipine), it can also occur with **non-dihydropyridine CCBs** due to their **vasodilatory effects** on peripheral arterioles. Among the options provided, this is the most likely adverse effect. - Other common adverse effects of non-dihydropyridine CCBs include **constipation** (especially with verapamil), **bradycardia**, and **AV block**. *Bronchospasm* - **Bronchospasm** is a common adverse effect of **beta-blockers** due to their blockade of β₂-adrenergic receptors in the airways. - Calcium channel blockers do not cause bronchospasm and may actually have bronchodilatory effects. *Dry mouth* - **Dry mouth** is often associated with **anticholinergic medications** (e.g., tricyclic antidepressants, antihistamines) due to their inhibition of salivary secretions. - This is not a characteristic adverse effect of calcium channel blockers. *Tinnitus* - **Tinnitus** (ringing in the ears) can be an adverse effect of various drugs, including **aspirin** (especially at high doses), **loop diuretics**, and some **aminoglycoside antibiotics**. - It is not typically associated with calcium channel blockers. *Gingival hyperplasia* - **Gingival hyperplasia** is a well-known adverse effect of **dihydropyridine calcium channel blockers** (like nifedipine), as well as **phenytoin** and **cyclosporine**. - While it can rarely occur with **non-dihydropyridine CCBs**, it is much less commonly associated with verapamil or diltiazem compared to dihydropyridines.

Question 74: An otherwise healthy 13-year-old boy is brought to the physician because of asthma attacks that have been increasing in frequency and severity over the past 4 weeks. He was first diagnosed with asthma 6 months ago. Current medications include high-dose inhaled fluticasone and salmeterol daily, with additional albuterol as needed. He has required several courses of oral corticosteroids. A medication is added to his therapy regimen that results in downregulation of the high-affinity IgE receptor (FcεRI) on mast cells and basophils. Which of the following drugs was most likely added to the patient's medication regimen?

• A. Infliximab
• B. Theophylline
• C. Zileuton
• D. Nedocromil
• E. Omalizumab (Correct Answer)

Explanation: ***Omalizumab*** - **Omalizumab** is a **monoclonal antibody** that targets and binds to free IgE, preventing its binding to **FcεRI receptors** on mast cells and basophils. - By reducing free IgE, it leads to a **downregulation of FcεRI receptors**, thereby decreasing mediator release and reducing asthma symptoms in severe, persistent asthma. *Infliximab* - **Infliximab** is an **anti-TNF-α monoclonal antibody** used primarily in inflammatory conditions like **rheumatoid arthritis**, **Crohn's disease**, and **ankylosing spondylitis**. - It does not directly affect IgE or its receptors, thus it is not indicated for the treatment of **asthma**. *Theophylline* - **Theophylline** is a **phosphodiesterase inhibitor** that causes bronchodilation by increasing intracellular cAMP. - It does not modulate IgE or its receptors, and its use is limited by a narrow **therapeutic index** and potential for side effects. *Zileuton* - **Zileuton** is a **5-lipoxygenase inhibitor** that blocks the synthesis of **leukotrienes**, potent bronchoconstrictors and inflammatory mediators in asthma. - While effective in some asthma patients, it does not act on IgE or its receptors. *Nedocromil* - **Nedocromil** is a **mast cell stabilizer** that inhibits the release of inflammatory mediators from mast cells. - It does not directly impact IgE levels or the expression of **FcεRI receptors** on mast cells and basophils, making it less suitable for severe, refractory asthma requiring IgE-pathway modulation.

Question 75: A 64-year-old man presents to his physician 6 months after experiencing a myocardial infarction. The patient currently denies any symptoms and is only in for a check up. The patient's past medical history is notable for diabetes (type II), obesity, hypertension and cyclothymia. His current medications are hydrochlorothiazide, metoprolol, metformin, insulin, fluoxetine, and fish oil. On physical exam you note a calm elderly man who is moderately obese and in no current distress. The patient's cardiovascular exam is notable for a S4 heart sound. The patients lab work is below. Serum: Na+: 140 mEq/L Cl-: 100 mEq/L K+: 4.4 mEq/L HCO3-: 23 mEq/L BUN: 20 mg/dL Glucose: 120 mg/dL Creatinine: 1.6 mg/dL Ca2+: 10.1 mg/dL AST: 11 U/L ALT: 9 U/L Cholesterol: 190 mg/dL Triglycerides: 150 mg/dL High density lipoprotein associated cholesterol: 11 mg/dL Low density lipoprotein associated cholesterol: 149 mg/dL The physician updates the patient's medication regimen after this visit. The patient returns 2 weeks later and presents his blood glucose diary to you demonstrating a mean blood glucose of 167 mg/dL. He is also complaining of flushing that occurs occasionally but otherwise is doing well. Which of the following is most likely to alleviate this patient's current symptom?

• A. Irreversible inactivation of cyclooxygenase (Correct Answer)
• B. Inhibition of angiotensin II formation
• C. GLUT-4 insertion in cell membranes
• D. Decreased inhibition of HMG CoA reductase
• E. Discontinue diuretic that inhibits Na/Cl cotransporter

Explanation: ***Irreversible inactivation of cyclooxygenase*** - The patient is likely experiencing **flushing** due to **niacin** (nicotinic acid) therapy, which is often used to lower **LDL-C** and **triglycerides** and raise **HDL-C**. Niacin-induced flushing is mediated by **prostaglandins**, specifically **PGD2**, which can be alleviated by irreversible inactivation of COX with **aspirin**. - Given his history of **myocardial infarction**, poorly controlled diabetes, and dyslipidemia (HDL-C of 11 mg/dL, LDL-C 149 mg/dL), a lipid-modifying agent like niacin would be a reasonable addition to his regimen. *Inhibition of angiotensin II formation* - This refers to the mechanism of **ACE inhibitors** or **ARBs**, which are used to manage hypertension and protect the kidneys, especially in patients with diabetes and post-MI. - While beneficial for this patient's overall cardiovascular health, it does not directly address the symptom of **flushing**. *GLUT-4 insertion in cell membranes* - This mechanism is associated with **thiazolidinediones (TZDs)**, a class of antidiabetic drugs that improve **insulin sensitivity**. - While improved glucose control (mean 167 mg/dL) is needed for this patient, GLUT-4 insertion does not alleviate flushing. *Decreased inhibition of HMG CoA reductase* - This response implies stopping or reducing the dose of a **statin**, which inhibits **HMG-CoA reductase** and is crucial for lowering LDL-C. - The patient's LDL-C of 149 mg/dL is still elevated, and statins are a cornerstone of post-MI therapy; thus, decreasing their inhibition would be detrimental to his cardiovascular risk. *Discontinue diuretic that inhibits Na/Cl cotransporter* - The patient is currently on **hydrochlorothiazide**, which inhibits the **Na/Cl cotransporter** in the distal convoluted tubule and helps manage his hypertension. - Discontinuing this medication would likely worsen his blood pressure and has no direct effect on flushing.

Question 76: A 50-year-old man presents to the emergency department for evaluation of a pulsatile headache, palpitations, chest pain, and anxiety. The vital signs include: heart rate 90/min, blood pressure 211/161 mm Hg, and respiration rate 18/min. His fundoscopic exam is remarkable for papilledema. An urgent urinalysis reveals increased protein and red blood cells (RBCs). Further evaluation reveals elevated plasma metanephrines. What is the 1st step in the definitive treatment of this patient’s underlying disorder?

• A. Calcium channel blockers
• B. Hydralazine
• C. Beta-blockers followed by alpha-blockers
• D. Emergent surgery
• E. Alpha-blockers followed by beta-blockers (Correct Answer)

Explanation: ***Alpha-blockers followed by beta-blockers*** - This patient presents with symptoms highly suggestive of a **pheochromocytoma** (pulsatile headache, palpitations, chest pain, anxiety, severe hypertension, papilledema, and elevated plasma metanephrines). The first step in managing a pheochromocytoma, especially before surgery, is to start with **alpha-blockade** to control blood pressure and prevent a hypertensive crisis. - After adequate alpha-blockade (typically for 7-14 days), **beta-blockers** can be added to control tachycardia and arrhythmias. Using beta-blockers before alpha-blockers can lead to unopposed alpha-adrenergic stimulation, causing a further rise in blood pressure. *Calcium channel blockers* - While calcium channel blockers can be used to manage hypertension, they are **not the primary or initial treatment** for a pheochromocytoma. - They do not address the root cause of the catecholamine excess and are less effective in preventing a hypertensive crisis in this specific context. *Hydralazine* - Hydralazine is a **direct arterial vasodilator** and can be used in hypertensive emergencies. - However, it is not the preferred initial agent for pheochromocytoma given the need for comprehensive alpha-blockade to manage the effects of excessive catecholamines. *Beta-blockers followed by alpha-blockers* - Administering **beta-blockers before alpha-blockers** in a patient with pheochromocytoma is contraindicated and dangerous. - This sequence can lead to **unopposed alpha-adrenergic stimulation**, resulting in profound vasoconstriction and a life-threatening hypertensive crisis. *Emergent surgery* - While surgery is the definitive treatment for pheochromocytoma (removal of the tumor), it is **not the 1st step in treatment**. - Proper **preoperative medical management** with alpha-blockade (and subsequent beta-blockade) is critical to stabilize the patient and prevent complications during surgery.

Question 77: A 26-year-old woman presents to the clinic with complaints of missing her 'monthlies'. She usually has her menses around the 15th of every month and they last for about 4 days. She is not on any birth control and has recently gotten into a relationship with her boyfriend from college. She is on lithium for maintenance therapy of her bipolar disorder. She once took herself off of lithium, but she became so depressed that she had a suicide attempt shortly after. She is concerned about how lithium use might affect her fetus if she were pregnant. What is the single most appropriate recommendation?

• A. Supplement her treatment with 3-4 mg of folate per day.
• B. The lithium should be discontinued immediately.
• C. Discontinue the lithium after delivery and before breastfeeding.
• D. Add another drug to the regime but decrease each drug’s dosage.
• E. Continue her lithium monotherapy. (Correct Answer)

Explanation: ***Continue her lithium monotherapy.*** - Maintaining **lithium monotherapy** is crucial given her history of severe depression and suicide attempt when off lithium, prioritizing maternal mental health during pregnancy. - While lithium carries some fetal risks (e.g., Ebstein's anomaly), these risks are dose-dependent and careful monitoring can mitigate them, justifying continued therapy over abrupt discontinuation. *Supplement her treatment with 3-4 mg of folate per day.* - While **folate supplementation** is generally recommended in pregnancy to prevent neural tube defects, it does not directly address the specific fetal risks associated with lithium exposure or the patient's need for mood stabilization. - The standard dose for women with no previous affected pregnancies is 0.4-0.8mg daily. Higher doses are usually reserved for women with a history of neural tube defects or who are on **anti-epileptics**. *The lithium should be discontinued immediately.* - **Abrupt discontinuation** of lithium carries a very high risk of relapse into severe depression or mania, which could pose a significant danger to both the mother and the fetus. - Given her history of a suicide attempt when off lithium, this action could lead to detrimental maternal mental health outcomes. *Discontinue the lithium after delivery and before breastfeeding.* - This recommendation addresses neither the immediate mental health needs during pregnancy nor the potential fetal exposure risks during the most critical developmental stages. - Discontinuing lithium only after delivery and before breastfeeding still exposes the fetus to lithium throughout pregnancy, while also interrupting critical postpartum mood stability for the mother. *Add another drug to the regime but decrease each drug’s dosage.* - Adding another drug would introduce additional fetal exposure risks without clear evidence of benefit over carefully managed monotherapy, especially with a history of effective lithium use. - **Polypharmacy** during pregnancy is generally avoided due to increased complexity and potential for drug interactions, and simply decreasing dosages might not maintain therapeutic levels.

Question 78: A 68-year-old man presents to his primary care physician with complaints of intermittent dysuria, pain with ejaculation, mild lower abdominal pain, and difficulty voiding for the last four months. There is no weight loss or change in stools. He has no known family history of cancer. His past medical history is notable for irritable bowel syndrome and hypertension. On examination, he is well-appearing but mildly uncomfortable. There are no abdominal or rectal masses appreciated; the prostate is mildly tender to palpation, but with normal size, texture, and contour. Urinalysis reveals trace leukocyte esterase and negative nitrite, negative blood, and no bacteria on microscopy. Which of the following is the most appropriate treatment?

• A. Duloxetine
• B. Finasteride
• C. Ciprofloxacin
• D. Tamsulosin and ciprofloxacin
• E. Tamsulosin (Correct Answer)

Explanation: ***Tamsulosin*** - The patient's symptoms (dysuria, pain with ejaculation, difficulty voiding, lower abdominal pain) are suggestive of **chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)**, particularly in the absence of infection. **Alpha-blockers like tamsulosin** relax smooth muscle in the prostate and bladder neck, improving urinary flow and reducing pain. - The **mildly tender prostate** and **urinalysis showing trace leukocyte esterase but negative nitrites and bacteria** rule out acute bacterial prostatitis and indicate inflammation without overt infection, strengthening the diagnosis of CP/CPPS. *Duloxetine* - This medication is a **serotonin-norepinephrine reuptake inhibitor (SNRI)**, primarily used for depression, anxiety, and neuropathic pain. - While CP/CPPS can involve neuropathic-like pain, duloxetine is **not a first-line treatment** and does not address the underlying urinary flow issues. *Finasteride* - **Finasteride is a 5-alpha-reductase inhibitor** used to treat **benign prostatic hyperplasia (BPH)** by reducing prostate size. - The patient's prostate is described as having **normal size, texture, and contour**, making BPH less likely as the primary cause of his symptoms, and finasteride would not directly relieve the inflammatory or ejaculatory pain. *Ciprofloxacin* - **Ciprofloxacin is an antibiotic** effective against many urinary pathogens. - However, the **urinalysis showed negative nitrites and no bacteria on microscopy**, making a bacterial infection (acute or chronic bacterial prostatitis) unlikely. Therefore, empirical antibiotic monotherapy is not indicated. *Tamsulosin and ciprofloxacin* - While tamsulosin is appropriate, the addition of **ciprofloxacin is not justified** given the lack of evidence for bacterial infection (negative nitrites and no bacteria on microscopy). - Combining these would expose the patient to unnecessary antibiotic side effects without clear benefit for an infection that doesn't appear to be present.

Question 79: A 75-year-old man with a seizure disorder is brought to the emergency department by a friend because of progressive confusion over the past two weeks. He is unable to provide any history. His vital signs are within normal limits. He appears lethargic and is only oriented to person. Oral mucosa is moist. There is no jugular venous distention. A basic metabolic panel shows a serum sodium concentration of 115 mEq/L but is otherwise normal. Serum osmolality is low and antidiuretic hormone level is elevated. X-ray of the chest shows no abnormalities. Which of the following is the most likely cause of this patient’s hyponatremia?

• A. Aldosterone deficiency
• B. Medication effect (Correct Answer)
• C. Low cardiac output
• D. Insulin deficiency
• E. Excess cortisol

Explanation: ***Medication effect*** - This patient's **hyponatremia** with **appropriately low serum osmolality** and **elevated antidiuretic hormone (ADH)** levels, in the absence of signs of hypovolemia or fluid overload, points to the **syndrome of inappropriate ADH secretion (SIADH)**. - Many medications, including anti-epileptic drugs like carbamazepine or oxcarbazepine (commonly used for seizure disorders), as well as selective serotonin reuptake inhibitors (SSRIs), can cause SIADH. *Aldosterone deficiency* - **Aldosterone deficiency** would likely lead to **hyperkalemia** and metabolic acidosis, which are not mentioned in the basic metabolic panel as being abnormal. - While it can cause hyponatremia due to inability to retain sodium, the elevated ADH level with normal volume status points away from primary aldosterone deficiency. *Low cardiac output* - **Low cardiac output** can lead to hyponatremia by decreased renal perfusion and activation of the renin-angiotensin-aldosterone system and ADH release. - However, this patient has **normal vital signs** and **no jugular venous distention**, making significant low cardiac output and resultant hypovolemia less likely. *Insulin deficiency* - **Insulin deficiency** (as seen in uncontrolled diabetes) typically leads to **hyperglycemia** and can cause a **pseudohyponatremia** due to osmotic effects, or true hyponatremia due to polyuria and volume depletion. - The basic metabolic panel is otherwise normal, suggesting no significant hyperglycemia or electrolyte abnormalities consistent with insulin deficiency. *Excess cortisol* - **Excess cortisol** (Cushing's syndrome) typically leads to **hyperglycemia**, hypertension, and features of fat redistribution, muscular weakness, and thin skin, none of which are detailed here. - It does not directly cause hyponatremia; conversely, cortisol has some mineralocorticoid effects and typically opposes ADH action, so severe excess would more likely cause hypernatremia or normal sodium levels.

Question 80: A 49-year-old woman with a long-standing history of a seizure disorder presents with fatigue, weight gain, and hair loss. The patient reports that the symptoms have gradually worsened over the past month and have not improved. Past medical history is significant for a seizure disorder diagnosed 10 years ago, for which she recently switched medications. She currently takes phenytoin 300 mg orally daily and a multivitamin. Review of systems is significant for decreased appetite, recent constipation, and cold intolerance. Her temperature is 37.0°C (98.6°F), the blood pressure is 100/80 mm Hg, the pulse is 60/min, the respiratory rate is 16/min, and the oxygen saturation is 98% on room air. On physical exam, the patient is slow to respond but cooperative. Cardiac exam is normal. Lungs are clear to auscultation. Skin is coarse and dry. Mild to moderate hair loss is present over the entire body, and the remaining hair is brittle. Which of the following additional findings would you expect to see in this patient?

• A. Spasticity
• B. Hyperreflexia
• C. Impaired memory (Correct Answer)
• D. Decreased vibration sense and proprioception
• E. Tardive dyskinesia

Explanation: ***Impaired memory*** - The patient's symptoms of **fatigue**, **weight gain**, **hair loss**, **constipation**, **cold intolerance**, and **slow responsiveness** are characteristic of **hypothyroidism**. - **Cognitive impairment**, including **impaired memory** and **poor concentration**, is a common neurological manifestation of hypothyroidism due to reduced thyroid hormone levels affecting brain function. *Spasticity* - **Spasticity** is typically associated with upper motor neuron lesions and presents as increased muscle tone and hyperreflexia, which are not typical features of hypothyroidism. - Hypothyroidism is more likely to cause **muscle weakness** and **delayed relaxation of deep tendon reflexes**, rather than spasticity. *Hyperreflexia* - **Hyperreflexia** indicates an exaggerated reflex response, often seen in conditions like hyperthyroidism or upper motor neuron lesions. - In contrast, **hypothyroidism** is characterized by **hyporeflexia** or **delayed relaxation of deep tendon reflexes** such as the Achilles reflex. *Decreased vibration sense and proprioception* - **Decreased vibration sense** and **proprioception** are hallmark signs of **peripheral neuropathy**, often associated with conditions like **diabetes mellitus** or vitamin B12 deficiency. - While severe, long-standing hypothyroidism can rarely lead to neuropathy, the more prominent cognitive and systemic symptoms point away from this as an expected primary neurological finding in this presentation. *Tardive dyskinesia* - **Tardive dyskinesia** is a movement disorder characterized by involuntary, repetitive body movements, typically associated with long-term use of dopamine receptor-blocking medications, such as antipsychotics. - This patient's symptoms and medication history (phenytoin for seizures) do not suggest a risk for tardive dyskinesia, and it is not a feature of hypothyroidism.

Question 81: A 45-year-old female presents to her primary care physician with a chief complaint of easy bruising and bleeding over the last 6 months. She has also noticed that she has been having fatty, foul smelling stools. Past history is significant for cholecystectomy a year ago to treat a long history of symptomatic gallstones. Based on clinical suspicion a coagulation panel was obtained showing a prothrombin time (PT) of 18 seconds (normal range 9-11 seconds), a partial thromboplastin time (PTT) of 45 seconds (normal 20-35 seconds), with a normal ristocetin cofactor assay (modern equivalent of bleeding time). Which of the following is the most likely cause of this patient's bleeding?

• A. Idiopathic Thrombocytopenic Purpura (ITP)
• B. Rat poison ingestion
• C. Hemophilia
• D. Von Willebrand disease
• E. Vitamin K deficiency (Correct Answer)

Explanation: ***Vitamin K deficiency*** - This patient's symptoms of **easy bruising**, **bleeding**, and **fatty, foul-smelling stools** (steatorrhea) combined with a history of **cholecystectomy** strongly suggest **fat malabsorption**. - **Vitamin K is a fat-soluble vitamin** essential for the synthesis of coagulation factors II, VII, IX, and X. Malabsorption leads to its deficiency, prolonging both PT and PTT, which aligns with the lab results (PT 18s, PTT 45s). *Idiopathic Thrombocytopenic Purpura (ITP)* - ITP is characterized by **thrombocytopenia** (low platelet count), leading to mucocutaneous bleeding and bruising. - While ITP causes easy bruising and bleeding, it would present with a **normal PT and PTT**, as these tests measure coagulation factor activity, not platelet count. *Rat poison ingestion* - Rat poisons often contain **warfarin**, a **vitamin K antagonist**, which would also lead to prolonged PT and PTT. - However, there is **no clinical history or other indication** of rat poison ingestion. *Hemophilia* - Hemophilia is an **X-linked recessive disorder** primarily affecting males, resulting in a deficiency of factor VIII (Hemophilia A) or factor IX (Hemophilia B). - Both forms primarily cause a **prolonged PTT with a normal PT**, which does not match the patient's presentation of both prolonged PT and PTT. *Von Willebrand disease* - Von Willebrand disease is the **most common inherited bleeding disorder** affecting primary hemostasis (platelet plug formation). - It would typically cause a **prolonged bleeding time** (or abnormal ristocetin cofactor assay), which is noted as normal in this patient, and often a normal PT and PTT unless Factor VIII levels are severely reduced.

Question 82: A 59-year-old man presents with intense, sharp pain in his toe for the past hour. He reports similar symptoms in the past and this is his 2nd visit to the emergency department this year with the same complaint. The patient is afebrile and the vital signs are within normal limits. On physical examination, there is significant erythema, swelling, warmth, and moderate pain on palpation of the right 1st toe. The remainder of the examination is unremarkable. A plain radiograph of the right foot reveals no abnormalities. Joint arthrocentesis of the inflamed toe reveals urate crystals. Laboratory studies show: Serum glucose (random) 170 mg/dL Sodium 140 mEq/L Potassium 4.1 mEq/L Chloride 100 mEq/L Uric acid 7.2 mg/dL Serum creatinine 0.8 mg/dL Blood urea nitrogen 9 mg/dL Cholesterol, total 170 mg/dL HDL-cholesterol 43 mg/dL LDL-cholesterol 73 mg/dL Triglycerides 135 mg/dL HDL: high-density lipoprotein; LDL: low-density lipoprotein Ibuprofen is prescribed for the acute treatment of this patient's symptoms. He is also put on chronic therapy to prevent the recurrence of future attacks. Which of the following drugs is 1st-line for chronic therapy of gout?

• A. Methotrexate
• B. Indomethacin
• C. Probenecid
• D. Colchicine
• E. Allopurinol (Correct Answer)

Explanation: ***Allopurinol*** - Allopurinol is a **xanthine oxidase inhibitor** that reduces uric acid production, making it the **first-line therapy** for **chronic gout management**. - It effectively **lowers serum uric acid levels** to prevent recurrent attacks and dissolution of urate crystals. *Methotrexate* - Methotrexate is a **disease-modifying antirheumatic drug (DMARD)** primarily used in conditions like **rheumatoid arthritis** and **psoriasis**. - It is **not indicated for gout** as it does not target uric acid metabolism. *Indomethacin* - Indomethacin is an **NSAID** commonly used for the **acute treatment of gout flares** due to its potent anti-inflammatory effects. - It is **not suitable for chronic management** or prevention of gout due to potential long-term side effects and lack of effect on uric acid levels. *Probenecid* - Probenecid is a **uricosuric agent** that increases renal excretion of uric acid. - While it lowers uric acid, it is typically considered a **second-line agent** for chronic gout, especially in patients with underexcretion of uric acid, or as an alternative to allopurinol if it cannot be tolerated. *Colchicine* - Colchicine is used for both **acute gout flares** and as **prophylaxis** during the initiation of uric acid-lowering therapy to prevent flares. - It is **not a first-line drug for chronic gout management** as it does not lower uric acid levels; it primarily reduces inflammation.

Question 83: A 57-year-old man presents with episodic left periorbital pain that radiates to the left frontotemporal side of his head for the last 2 weeks. The episodes are severe and are usually present for 1–2 hours before bedtime. During these episodes, he has also noticed lacrimation on the left side and a runny nose. He has tried over-the-counter analgesics with no relief. He currently has a headache. He denies any cough, seizure, nausea, vomiting, photophobia, phonophobia, or visual disturbances. His past medical history is significant for a myocardial infarction 1 year ago, with residual angina with exertion. The patient has a 10 pack-year history of smoking, but no alcohol or recreational drug use. His vital signs include: blood pressure 155/90 mm Hg, pulse 90/min, and respiratory rate 15/min. Physical examination is significant for a left-sided Horner’s syndrome. Which of the following is the next best step in the acute management of this patient’s most likely condition?

• A. Sumatriptan
• B. Ibuprofen
• C. Ergotamine
• D. 100% oxygen (Correct Answer)
• E. Verapamil

Explanation: ***100% oxygen*** - The patient's symptoms — **episodic, severe periorbital pain**, **lacrimation**, **runny nose**, occurrence around bedtime, and **Horner's syndrome** — are classic for a **cluster headache**. - **100% oxygen** via a non-rebreather mask is the **first-line acute treatment** for cluster headaches due to its rapid onset and efficacy in aborting attacks. *Sumatriptan* - While **subcutaneous sumatriptan** can be effective for cluster headaches, it is contraindicated in patients with a history of **myocardial infarction** or **coronary artery disease** due to its vasoconstrictive properties. - The patient's history of MI one year ago makes sumatriptan a risky choice, despite its proven efficacy in abortive treatment. *Ibuprofen* - **NSAIDs** like ibuprofen are generally ineffective for the severe, acute pain of **cluster headaches**. - They lack the rapid onset and potent analgesic effect required for this condition. *Ergotamine* - **Ergotamine** is a historical treatment for cluster headaches but has largely been replaced by more effective and safer options like oxygen and triptans. - It also carries contraindications, especially in patients with **cardiovascular disease**, similar to triptans, making it unsuitable for this patient. *Verapamil* - **Verapamil** is the **first-line prophylactic treatment** for cluster headaches, not an acute abortive treatment. - It is used to prevent future attacks, but it will not alleviate the current headache.

Question 84: A 43-year-old female presents to her endocrinologist for a new patient appointment. She initially presented three months ago as a referral for a new diagnosis of type II diabetes mellitus. At that time, her HbA1c was found to be 8.8%, and she was started on metformin. Her metformin was quickly uptitrated to the maximum recommended dose. At the same visit, her body mass index (BMI) was 31 kg/m^2, and the patient was counseled on the importance of diet and exercise for achieving better glycemic control. Today, the patient reports complete adherence to metformin as well as her other home medications of atorvastatin and lisinopril. She also started a daily walking routine and has lost two pounds. Her HbA1c today is 7.6%, and her BMI is stable from her last visit. The patient is discouraged by her slow weight loss, and she would like to lose an additional 5-10 pounds. Which of the following would be the best choice as a second agent in this patient?

• A. Repaglinide
• B. Sitagliptin
• C. Glipizide
• D. Exenatide (Correct Answer)
• E. Pioglitazone

Explanation: ***Exenatide*** - **Exenatide** is a **GLP-1 receptor agonist** that promotes **weight loss**, a desired outcome for this patient, in addition to lowering HbA1c. - It also has a low risk of **hypoglycemia** and offers cardiovascular benefits, making it an excellent choice for this patient with **type 2 diabetes** and **obesity**. *Repaglinide* - This **meglitinide** can lead to **weight gain** and carries a higher risk of **hypoglycemia**, which would be counterproductive to the patient's goals. - It primarily targets post-prandial glucose and is less effective at lowering HbA1c compared to other agents, especially as a second-line therapy. *Sitagliptin* - **Sitagliptin**, a **DPP-4 inhibitor**, is generally weight-neutral and has a modest effect on **HbA1c reduction** compared to **GLP-1 agonists**. - While it's a good add-on with a low risk of **hypoglycemia**, it does not address the patient's desire for further weight loss. *Glipizide* - This **sulfonylurea (SU)** medication is known for causing **weight gain** and having a significant risk of **hypoglycemia**. - These side effects are undesirable for a patient actively trying to lose weight and seeking to avoid hypoglycemic events. *Pioglitazone* - **Pioglitazone**, a **thiazolidinedione (TZD)**, is associated with **weight gain** and **fluid retention**, which would hinder the patient's weight loss efforts. - It also carries risks such as **heart failure exacerbation** and **osteoporosis**, which make it a less favorable option given the patient's current profile.

Question 85: Thirty minutes after surgical nasal polyp removal for refractory rhinitis, a 40-year-old man has retrosternal chest tightness and shortness of breath in the post-anesthesia care unit. The surgical course was uncomplicated and the patient was successfully extubated before arrival to the unit. He received 0.5 L of lactated Ringer's solution intraoperatively. The patient was given morphine and ketorolac for postoperative pain. He has a history of obstructive sleep apnea, asthma, hypertension, and sensitivity to aspirin. His daily medications include metoprolol and lisinopril. He has smoked a pack of cigarettes daily for 20 years. Pulse oximetry shows an oxygen concentration of 97% with support of 100% oxygen via face mask. Bilateral wheezes are heard in both lungs. Breath sounds are decreased. The patient's face appears flushed. ECG shows no abnormalities. Which of the following is the most likely underlying cause of this patient's symptoms?

• A. Prinzmetal angina
• B. Alveolar rupture
• C. Bradykinin-induced bronchial irritation
• D. Excessive beta-adrenergic blockade
• E. Pseudoallergic reaction (Correct Answer)

Explanation: ***Pseudoallergic reaction*** - The patient's history of **aspirin sensitivity**, asthma, nasal polyps, and development of bronchospasm and flushing post-operatively strongly suggests a **pseudoallergic reaction**. Conditions like **aspirin-exacerbated respiratory disease (AERD)** involve abnormal arachidonic acid metabolism and mast cell activation, which can be triggered by NSAIDs (like ketorolac) and cause asthma, rhinitis, and nasal polyps. - The use of **ketorolac**, a non-steroidal anti-inflammatory drug (NSAID), can induce severe bronchospasm in patients with **aspirin sensitivity** or AERD due to its effect on the **cyclooxygenase pathway**, leading to increased leukotriene production. *Prinzmetal angina* - **Prinzmetal angina** typically presents as episodic chest pain at rest, caused by **coronary artery vasospasm**, and would likely show **ECG changes** during the event, which are absent here. - While chest tightness is present, the accompanying **shortness of breath, wheezing, and flushing** are not typical features of Prinzmetal angina. *Alveolar rupture* - **Alveolar rupture** would likely manifest as a **pneumothorax**, characterized by sudden severe dyspnea and often unilateral absent or decreased breath sounds, which is not fully consistent with the **bilateral wheezing** and decreased breath sounds described. - While decreased breath sounds can occur, the presence of **bilateral wheezing** and overall clinical picture points away from primary alveolar rupture. *Bradykinin-induced bronchial irritation* - **Bradykinin-induced effects**, such as angioedema or cough, can occur with ACE inhibitors like lisinopril, but the onset of these symptoms typically doesn't directly follow NSAID administration in this acute manner with severe bronchospasm and flushing. - Although the patient is on lisinopril, bradykinin-mediated bronchoconstriction alone is less likely to cause this acute, severe constellation of symptoms following NSAID administration in a patient with a history of aspirin sensitivity and asthma. *Excessive beta-adrenergic blockade* - While the patient is on **metoprolol**, an excessive beta-adrenergic blockade itself would likely exacerbate asthma symptoms but wouldn't directly cause a sudden, severe reaction leading to flushing and bronchospasm like a pseudoallergic reaction triggered by ketorolac. - Although beta-blockers can worsen asthma, the acute onset and specific constellation of symptoms, especially with the history of aspirin sensitivity and NSAID use, make **pseudoallergy** a more targeted diagnosis.

Question 86: A 43-year-old man presents with a severe, throbbing, left-sided headache for the last 2 hours. He says that the pain has been progressively worsening and is aggravated by movement. The patient says he has had similar episodes in the past and would take acetaminophen and ‘sleep it off’. He also complains that the light in the room is intolerably bright, and he is starting to feel nauseous. No significant past medical history and no current medications. Vital signs include: pulse 110/min, respiratory rate 15/min, and blood pressure 136/86 mm Hg. Physical examination reveals mild conjunctival injection in the left eye. Intraocular pressure (IOP) is normal. The rest of the examination is unremarkable. The patient is given a medication which relieves his symptoms. During discharge, he wants more of this medication to prevent episodes in future but he is told that the medication is only effective in terminating acute attacks but not for prevention. Which of the following receptors does the drug given to this patient bind to?

• A. Muscarinic receptors
• B. Angiotensin II receptors
• C. β-adrenergic receptors
• D. 5-hydroxytryptamine type 2 (5-HT2) receptors
• E. 5-hydroxytryptamine type 1 (5-HT1) receptors (Correct Answer)

Explanation: ***5-hydroxytryptamine type 1 (5-HT1) receptors*** - The patient's symptoms (unilateral, throbbing headache, phonophobia, photophobia, nausea) are characteristic of a **migraine attack**. The reference to a medication that terminates acute attacks but isn't for prevention points to **triptans**. - **Triptans** (e.g., sumatriptan) are selective agonists that bind to **5-HT1B** and **5-HT1D receptors**. This binding causes **vasoconstriction of intracranial blood vessels** and inhibition of neuropeptide release, interrupting the migraine pathway. *Muscarinic receptors* - **Muscarinic receptors** are part of the **cholinergic system** and are involved in parasympathetic functions. - Drugs acting on muscarinic receptors (e.g., atropine, pilocarpine) are not used for acute migraine treatment. *Angiotensin II receptors* - **Angiotensin II receptors** are involved in blood pressure regulation and fluid balance, primarily targeted by **ARBs (Angiotensin Receptor Blockers)** for hypertension and heart failure. - These drugs do not have a direct role in the acute termination of migraine headaches. *β-adrenergic receptors* - **Beta-blockers** (antagonists of β-adrenergic receptors) like propranolol are commonly used for **migraine prophylaxis (prevention)**, not for acute treatment. - Beta-agonists are not used for migraine management. *5-hydroxytryptamine type 2 (5-HT2) receptors* - Antagonists of **5-HT2 receptors** (e.g., cyproheptadine, methysergide) have historically been used for **migraine prophylaxis**, but not for acute termination. - Agonists of 5-HT2 receptors are generally not indicated for migraine treatment and can even trigger headaches in some cases.

Question 87: A 22-year-old man presents with a painful right arm. He says the pain started several hours ago after he fell on his right shoulder while playing college football. He says that he felt a stinging sensation running down his right arm when he fell. On physical examination, there is a reduced range of motion of the right arm. Plain radiographs of the right shoulder confirm the presence of a shoulder dislocation. A detailed examination yields no evidence of neurovascular problems, and a decision is made to reduce the shoulder using ketamine. Which of the following side effects will be most likely seen in this patient after administering ketamine?

• A. Renal failure
• B. Increased appetite
• C. Diplopia (Correct Answer)
• D. Cough
• E. Fever

Explanation: ***Diplopia*** - **Ketamine** can cause **ophthalmological side effects** such as **diplopia**, nystagmus, and blurred vision due to its dissociative effects on the central nervous system. - These visual disturbances are typically transient and resolve as the drug wears off. *Renal failure* - **Ketamine** is not known to directly cause acute **renal failure** as a common or immediate side effect. - While chronic, high-dose ketamine abuse has been linked to **ketamine-induced cystitis** and upper urinary tract damage, this is distinct from acute renal failure. *Increased appetite* - **Ketamine** typically causes a transient **reduction in appetite** or no significant change during its acute effects, rather than an increase. - An increase in appetite is not a recognized immediate side effect of ketamine administration. *Cough* - **Ketamine** is generally associated with **bronchodilation** and can be beneficial in patients with reactive airway disease, making **cough** less likely. - It can, however, increase **salivation and secretions**, which in rare cases might lead to coughing if not managed with anticholinergics. *Fever* - **Fever** is not a common or expected immediate side effect of **ketamine** administration. - While some individuals may experience a mild increase in body temperature with certain anesthetics, frank fever is rare and usually points to an underlying infection or other medical condition.

Question 88: A 68-year-old man presents to the emergency department with shortness of breath for the past 2 hours. He mentions that he had a cough, cold, and fever for the last 3 days and has taken an over-the-counter cold preparation. He is hypertensive and has had coronary artery disease for the last 7 years. His regular medications include aspirin and ramipril. On physical examination, temperature is 36.9°C (98.4°F), pulse is 120/min, blood pressure is 118/80 mm Hg, and respiratory rate is 24/min. Pulse oximetry shows an oxygen saturation of 99%. Pitting edema is present bilaterally over the ankles and pretibial regions, and the peripheral extremities are warm to touch. On auscultation of the lung fields, pulmonary crackles are heard over the lung bases bilaterally. Auscultation of the precordium reveals a third heart sound. On examination of the abdomen, mild tender hepatomegaly is present. The chest radiograph is not suggestive of consolidation. Which of the following medications is the drug of choice for initial management of this patient?

• A. Milrinone
• B. Digoxin
• C. Nitroglycerin
• D. Furosemide (Correct Answer)
• E. Dobutamine

Explanation: ***Furosemide*** - The patient exhibits classic signs of **acute decompensated heart failure** with fluid overload, including **shortness of breath**, **peripheral edema**, **pulmonary crackles**, **S3 heart sound**, and **tender hepatomegaly**. - **Furosemide**, a **loop diuretic**, is the initial drug of choice to rapidly reduce fluid overload by increasing renal excretion of sodium and water, thereby decreasing **preload** and alleviating pulmonary and systemic congestion. *Milrinone* - **Milrinone** is a **phosphodiesterase inhibitor** with **inotropic** and **vasodilatory** effects, typically reserved for patients with severe heart failure refractory to standard therapy, particularly those with reduced cardiac output. - Its use in initial management of acute decompensated heart failure with significant congestion is not preferred over diuretics due to potential for hypotension and arrhythmias. *Digoxin* - **Digoxin** is a **positive inotrope** that also slows heart rate, primarily used in chronic heart failure with **reduced ejection fraction** or for rate control in **atrial fibrillation**. - It does not offer the rapid relief of fluid overload needed in this acute presentation and has a narrow therapeutic index. *Nitroglycerin* - **Nitroglycerin** is a **vasodilator** that reduces preload and, at higher doses, afterload, primarily used for acute coronary syndromes and acute heart failure with significant hypertension or severe pulmonary congestion. - While it helps reduce preload, **furosemide** directly addresses the underlying fluid overload more effectively as a first-line agent, especially given the signs of systemic congestion. *Dobutamine* - **Dobutamine** is a **beta-1 agonist** with **positive inotropic** effects, used in acute heart failure when there is evidence of **hypoperfusion** (cardiogenic shock) despite adequate fluid status. - This patient presents with signs of fluid overload and preserved blood pressure, not hypoperfusion, making dobutamine an inappropriate initial choice.

Question 89: Twelve hours after undergoing a right hip revision surgery for infected prosthesis, a 74-year-old man has numbness in his fingertips and around the lips. His surgery was complicated by severe blood loss. He underwent a total right hip replacement 2 years ago. He has hypertension and type 2 diabetes mellitus. His father had hypoparathyroidism. The patient has smoked one pack of cigarettes daily for 40 years. His current medications include metformin and captopril. He appears uncomfortable. His temperature is 37.3°C (99.1°F), pulse is 90/min, and blood pressure is 110/72 mm Hg. Examination shows an adducted thumb, flexed metacarpophalangeal joints and wrists, and extended fingers. Tapping the cheeks 2 cm ventral to the ear lobes leads to contraction of the facial muscles. The remainder of the examination shows no abnormalities. Which of the following is the most likely cause of this patient's symptoms?

• A. Multiple blood transfusions (Correct Answer)
• B. Cerebrovascular event
• C. Hypoparathyroidism
• D. Vitamin B12 deficiency
• E. Peripheral nerve injury

Explanation: ***Multiple blood transfusions*** - This patient's symptoms, including **perioral numbness**, **fingertip numbness**, and **carpal spasm** (**Trousseau's sign**), along with a positive **Chvostek's sign** (facial muscle contraction upon tapping the facial nerve), are classic signs of **hypocalcemia**. - In the context of severe blood loss and subsequent **multiple blood transfusions**, the most likely cause of hypocalcemia is **citrate toxicity**. Citrate, an anticoagulant used in stored blood, chelates calcium in the patient's blood, leading to decreased ionized calcium levels. *Cerebrovascular event* - While a cerebrovascular event can cause neurological deficits, the patient's symptoms are characteristic of a **diffuse neuromuscular irritability**, rather than focal neurological signs typically seen in stroke. - The **symmetrical nature** of numbness (fingertips, around lips) and the specific signs of Trousseau's and Chvostek's are not typical presentations of a stroke. *Hypoparathyroidism* - Although the patient's father had hypoparathyroidism, this patient has not displayed symptoms until now, after a significant surgical event. - **Primary hypoparathyroidism** is a chronic condition and would likely have presented earlier in life, or at least not acutely in direct response to a surgery requiring transfusions. *Vitamin B12 deficiency* - **Vitamin B12 deficiency** can cause neurological symptoms, including paresthesias and numbness, particularly in the extremities, but typically has a more **gradual onset** and is associated with **megaloblastic anemia** and sometimes **subacute combined degeneration** of the spinal cord. - It does not explain the acute onset of carpal spasm (Trousseau's sign) or Chvostek's sign, which are specific for hypocalcemia. *Peripheral nerve injury* - A **peripheral nerve injury** would typically present with symptoms in the distribution of the affected nerve. - The **generalized numbness** affecting fingertips and perioral region, along with the specific signs of Trousseau's and Chvostek's, are inconsistent with a single peripheral nerve injury but are rather indicative of a **systemic metabolic derangement**.

Question 90: A 13-year-old male presents to his primary care provider with joint pain in his right knee. He has had multiple episodes of pain and effusion in both knees throughout his life as well as easy bruising. Most of these episodes followed minor trauma, including accidentally hitting his knee on a coffee table, but they occasionally occurred spontaneously. Both his uncle and grandfather have had similar problems. The patient denies any recent trauma and reports that his current pain is dull in nature. The patient is a long distance runner and jogs frequently. He is currently training for an upcoming track and field meet. On physical exam, the joint is warm and nonerythematous and with a large effusion. The patient endorses pain on both passive and active range of motion. Which of the following prophylactic treatments could have prevented this complication?

• A. Cryoprecipitate
• B. Desmopressin
• C. Fresh frozen plasma
• D. Additional rest between symptomatic episodes
• E. Factor concentrate (Correct Answer)

Explanation: ***Factor concentrate*** - This patient presents with symptoms highly suggestive of **hemophilia**, including recurrent joint effusions, easy bruising, and a family history of similar bleeding issues (X-linked recessive inheritance pattern). - Prophylactic treatment with **factor concentrate** (either factor VIII for hemophilia A or factor IX for hemophilia B) can prevent bleeding episodes and subsequent joint complications characteristic of hemophilia. *Cryoprecipitate* - While cryoprecipitate contains **factor VIII**, it is not the primary prophylactic treatment for hemophilia due to its variable factor VIII content and higher risk of transfusion reactions. - Its use is generally reserved for situations where factor concentrate is unavailable or in specific types of von Willebrand disease. *Desmopressin* - **Desmopressin (DDAVP)** is effective in managing bleeding in **mild hemophilia A** and **Type 1 von Willebrand disease** by increasing the release of factor VIII and von Willebrand factor from endothelial cells. - However, it is generally ineffective for moderate to severe hemophilia A, hemophilia B, or other types of von Willebrand disease, which this patient's severe symptoms and family history suggest. *Fresh frozen plasma* - **Fresh frozen plasma (FFP)** contains all clotting factors, but its use for hemophilia prophylaxis is limited by the large volumes required to achieve therapeutic factor levels and the associated risks of fluid overload and allergic reactions. - Factor concentrates offer a more targeted and safer approach for prophylaxis. *Additional rest between symptomatic episodes* - While rest is important during acute bleeding episodes to prevent further injury, it does not address the underlying clotting factor deficiency. - Resting alone would not prevent future spontaneous or post-traumatic bleeding events in a patient with hemophilia; **factor replacement therapy** is necessary for true prophylaxis.

Question 91: A 65-year-old woman is brought to the emergency department because of left wrist pain and swelling that began after she fell from a seated position. Menopause occurred 15 years ago. Her serum parathyroid hormone level is within normal limits. An x-ray of the left wrist shows a nondisplaced fracture of the distal radial metaphysis and decreased bone mineral density. The patient would likely benefit from an agent with a structure analogous to which of the following substances?

• A. Hydroxyapatite
• B. Inositol
• C. Pyrophosphate (Correct Answer)
• D. Nitric oxide
• E. Keratan sulfate

Explanation: **Pyrophosphate** - The patient presents with a **fragility fracture** (distal radial metaphysis from a seated fall) and **decreased bone mineral density** (osteoporosis), likely post-menopausal, indicating a need for an anti-resorptive agent. - **Bisphosphonates** are the first-line treatment for osteoporosis; their structure is analogous to **pyrophosphate**, allowing them to inhibit osteoclast activity by binding to hydroxyapatite in bone. *Hydroxyapatite* - **Hydroxyapatite** is the primary mineral component of bone, consisting of calcium and phosphate crystals. - While bisphosphonates bind to hydroxyapatite, they do not have an analogous structure or provide a therapeutic benefit when administered directly in this context. *Inositol* - **Inositol** is a sugar alcohol involved in various cellular signaling pathways, including insulin signaling. - It has no direct role in the treatment of osteoporosis or bone mineral density regulation. *Nitric oxide* - **Nitric oxide** is a signaling molecule involved in vasodilation, neurotransmission, and immune responses. - It is not used as a pharmacological agent to treat osteoporosis or improve bone density. *Keratan sulfate* - **Keratan sulfate** is a glycosaminoglycan found in cartilage and cornea, contributing to tissue structure. - It is not involved in bone metabolism or the treatment of osteoporosis.

Question 92: A 25-year-old woman presents to her primary care physician with complaints of chronic congestion. She notes that she has always had trouble breathing through her nose, and her new husband has told her that she breathes loudly when she sleeps. She denies frequent infections or allergies. She has no chronic medical problems and takes no medications. Family history is also insignificant. The blood pressure is 124/78 mm Hg, heart rate is 74/min, and respiratory rate is 14/min. On physical examination, her lungs are clear to auscultation bilaterally. Intranasal inspection reveals a deviated septum. She is referred to an otolaryngologist for surgical evaluation. When discussing the surgical options for this condition, she asks if she will be given propofol for anesthesia. Which of the following is the most appropriate classification of anesthesia primarily achieved with intravenous propofol?

• A. Regional anesthesia
• B. Dissociation
• C. Deep sedation (Correct Answer)
• D. Epidural anesthesia
• E. Minimal sedation

Explanation: ***Deep sedation*** - **Propofol** is commonly used for **deep sedation** due to its rapid onset and short duration of action, allowing for quick recovery. - In deep sedation, patients are not easily aroused but respond purposefully to **repeated or painful stimulation**, and their airway may require intervention. *Regional anesthesia* - This involves injecting local anesthetics near nerves to **numb a specific region** of the body, such as an arm or leg, while the patient remains conscious or lightly sedated. - While propofol can be used for **conscious sedation during regional anesthesia**, it is not the primary anesthetic agent for the regional block itself. *Dissociation* - **Dissociative anesthesia**, typically achieved with **ketamine**, involves a trance-like state characterized by profound analgesia and amnesia, with the patient appearing awake but unresponsive to pain. - Propofol does not produce this specific dissociative state; it causes general central nervous system depression. *Epidural anesthesia* - This is a form of **regional anesthesia** where local anesthetics are injected into the **epidural space** to block nerve impulses, commonly used for labor pain or lower limb surgery. - While a patient might receive **mild sedation** with propofol during an epidural procedure, it is not considered the primary anesthetic for the epidural itself. *Minimal sedation* - In **minimal sedation (anxiolysis)**, patients respond normally to verbal commands, and cognitive function and coordination may be impaired, but ventilatory and cardiovascular functions are unaffected. - While propofol can be used in very low doses to achieve minimal sedation, it is most commonly associated with **moderate to deep sedation** due to its potent hypnotic effects.

Question 93: A 33-year-old man comes to the physician for evaluation of progressive hair loss from his scalp. He first noticed receding of the hairline over the bitemporal regions of his scalp 5 years ago. Since then, his hair has gradually become thinner over the crown of his head. He is otherwise healthy and takes no medications. Examination shows diffuse, nonscarring hair loss over the scalp with a bitemporal pattern of recession. Administration of which of the following drugs is most appropriate to treat this patient's hair loss?

• A. Clomipramine
• B. Finasteride (Correct Answer)
• C. Flutamide
• D. Triamcinolone
• E. Levothyroxine

Explanation: ***Finasteride*** - This patient presents with **androgenetic alopecia** (male-pattern baldness), characterized by progressive, nonscarring hair loss in a bitemporal and crown pattern, which is a classic presentation. - **Finasteride** is a **5-alpha-reductase inhibitor** that blocks the conversion of testosterone to **dihydrotestosterone (DHT)**, the primary androgen responsible for miniaturization of hair follicles in androgenetic alopecia. *Clomipramine* - **Clomipramine** is a **tricyclic antidepressant** primarily used to treat **obsessive-compulsive disorder** and certain anxiety disorders. - It does not have any direct indication or established efficacy for treating hair loss. *Flutamide* - **Flutamide** is an **androgen receptor antagonist** used in the treatment of **prostate cancer**. - While it blocks androgen action, it is not used for androgenetic alopecia due to its potential for severe **hepatotoxicity** and other adverse effects. *Triamcinolone* - **Triamcinolone** is a **corticosteroid** used to treat inflammatory conditions, including some forms of **alopecia areata** (an autoimmune hair loss condition). - It is not indicated for **androgenetic alopecia**, which is a hormonal and genetic condition, not primarily inflammatory. *Levothyroxine* - **Levothyroxine** is a synthetic thyroid hormone used to treat **hypothyroidism**. - While **thyroid dysfunction** can cause hair loss (telogen effluvium), this patient's presentation of progressive, patterned hair loss is characteristic of androgenetic alopecia, and he is otherwise healthy, suggesting normal thyroid function.

Question 94: A 35-year-old woman with irritable bowel syndrome comes to the physician because of increased diarrhea. She has not had any fever, bloody stools, nausea, or vomiting. The increase in stool frequency began when she started a new job. She is started on loperamide, and her symptoms improve. Which of the following is the primary mechanism of action of this drug?

• A. Acetylcholine receptor antagonism
• B. H2 receptor antagonism
• C. Physical protection of stomach mucosa
• D. 5-HT3 receptor antagonism
• E. μ-opioid receptor agonism (Correct Answer)

Explanation: ***μ-opioid receptor agonism*** - **Loperamide** is an **opioid receptor agonist** that acts on **μ-opioid receptors** in the intestine, reducing gut motility and secretion. - This action allows for increased water and electrolyte absorption from the gut lumen, leading to thicker, less frequent stools. *Acetylcholine receptor antagonism* - **Acetylcholine receptor antagonists** (anticholinergics) like dicyclomine can also reduce gut motility, but loperamide's primary mechanism is not via this pathway. - These drugs can have broader systemic anticholinergic side effects compared to the peripherally acting loperamide. *H2 receptor antagonism* - **H2 receptor antagonists** like ranitidine or famotidine primarily reduce gastric acid secretion in the stomach. - They are used for conditions like GERD or ulcers and have no significant direct effect on intestinal motility or diarrhea. *Physical protection of stomach mucosa* - Medications that physically protect the stomach mucosa, such as **bismuth subsalicylate** or **sucralfate**, form a protective barrier. - While bismuth subsalicylate can have antidiarrheal effects, its primary mechanism involves mucosal protection and anti-inflammatory properties, not similar to loperamide. *5-HT3 receptor antagonism* - **5-HT3 receptor antagonists** like ondansetron primarily reduce nausea and vomiting by blocking serotonin receptors in the chemoreceptor trigger zone and GI tract. - While some 5-HT3 antagonists (e.g., alosetron) are used for diarrhea-predominant IBS, their mechanism is distinct from loperamide.

Question 95: A 41-year-old woman arrives to her primary care physician with abnormal labs. She states that 1 week ago she had laboratory work done as part of her company’s health initiative. During the past month, she has been walking 3 miles a day and has increased the amount of fruits and vegetables in her diet. Her medical history is significant for obesity, hypertension, and obstructive sleep apnea. She takes hydrochlorothiazide and wears a continuous positive airway pressure machine at night. Her recent labs are shown below: Serum: Na+: 140 mEq/L K+: 4.1 mEq/L Cl-: 101 mEq/L BUN: 16 mg/dL Glucose: 95 mg/dL Creatinine: 0.9 mg/dL Total cholesterol: 255 mg/dL (normal < 200 mg/dL) Low-density lipoprotein (LDL) cholesterol: 115 mg/dL (normal < 100 mg/dL) High-density lipoprotein (HDL) cholesterol: 40 (normal > 50 mg/dL) Triglycerides: 163 mg/dL (normal < 150 mg/dL) The patient is started on atorvastatin. Which of the following is the most common adverse effect of the patient’s new medication?

• A. Rhabdomyolysis
• B. Flushing
• C. Elevated liver enzymes
• D. Myalgia (Correct Answer)
• E. Cholesterol gallstones

Explanation: ***Myalgia*** - **Myalgia (muscle pain/aches)** is the most common adverse effect of statins like atorvastatin, occurring in approximately 5-10% of patients. - Patients may experience muscle pain, weakness, or discomfort, typically without significant CK elevation. - This side effect is dose-dependent and often manageable by dose reduction or switching to a different statin. *Elevated liver enzymes* - **Elevated transaminases** occur in approximately 0.5-2% of statin users, making this less common than myalgia. - Liver function tests should be checked at baseline and monitored periodically, but routine monitoring is no longer recommended by most guidelines. - Elevations are usually mild, asymptomatic, and reversible upon discontinuation. *Rhabdomyolysis* - While **rhabdomyolysis** is a serious and well-known adverse effect of statins, it is quite rare (0.01-0.1% of patients). - Characterized by severe muscle breakdown with markedly elevated **creatine kinase** (typically >10x upper limit of normal), myoglobinuria, and potential acute kidney injury. - Risk factors include higher statin doses, drug interactions (especially with CYP3A4 inhibitors), and concurrent use of fibrates. *Cholesterol gallstones* - **Cholesterol gallstones** are not a common adverse effect of statins. Statins actually decrease hepatic cholesterol synthesis. - **Fibrates**, another class of lipid-lowering drugs, are associated with increased risk of gallstones due to increased biliary cholesterol secretion. *Flushing* - **Flushing** and pruritus are characteristic side effects of **niacin (nicotinic acid)**, caused by prostaglandin-mediated cutaneous vasodilation. - This is not a typical adverse effect of statin therapy.

Question 96: A preterm neonate, born at 28 weeks of gestation, is in the neonatal intensive care unit as he developed respiratory distress during the 4th hour after birth. On the 2nd day of life, he required ventilator support. Today, on the 5th day of life, he developed generalized purpura and a hemorrhagic aspirate from the stomach. His laboratory workup is suggestive of thrombocytopenia, prolonged prothrombin time, and prolonged activated partial thromboplastin time. Which of the following statements is correct regarding the coagulation system of this patient?

• A. There is a physiologic increase in levels of antithrombin III in neonates.
• B. Administration of vitamin K to the mother during labor results in a reduction in the incidence of widespread subcutaneous ecchymosis that may be seen immediately after birth in otherwise normal premature infants.
• C. An extremely premature infant has markedly elevated levels of protein C, as compared to an adult.
• D. Serum levels of fibrinogen in a preterm infant born at 32 weeks of gestation are typically normal, as compared to an adult. (Correct Answer)
• E. A transient increase in serum levels of factor VII is seen in almost all neonates, which returns to normal levels by the 7th–10th day of life.

Explanation: ***Serum levels of fibrinogen in a preterm infant born at 32 weeks of gestation are typically normal, as compared to an adult.*** * **Fibrinogen** levels in preterm infants, especially those born after 30-32 weeks, are often comparable to adult levels, as fibrinogen synthesis matures relatively early in gestation. * This normalcy in fibrinogen levels stands in contrast to other coagulation factors which are often reduced in prematurity. *There is a physiologic increase in levels of antithrombin III in neonates.* * **Antithrombin III (ATIII)** levels are generally lower in neonates, particularly preterm infants, compared to adults. * Lower ATIII levels contribute to the **procoagulant state** often seen in neonates. *Administration of vitamin K to the mother during labor results in a reduction in the incidence of widespread subcutaneous ecchymosis that may be seen immediately after birth in otherwise normal premature infants.* * **Prenatal vitamin K administration** to the mother does not effectively prevent **vitamin K deficiency bleeding (VKDB)** in the neonate because of poor placental transfer. * **Postnatal vitamin K administration** directly to the neonate is the standard of care for preventing VKDB. *An extremely premature infant has markedly elevated levels of protein C, as compared to an adult.* * Levels of **Protein C**, an important natural anticoagulant, are significantly **lower** in premature infants compared to adults, not elevated. * This deficiency contributes to the neonatal predisposition for **thrombosis**. *A transient increase in serum levels of factor VII is seen in almost all neonates, which returns to normal levels by the 7th–10th day of life.* * Most vitamin K-dependent factors, including **Factor VII**, are generally **reduced** in neonates, particularly preterm infants, rather than transiently increased. * This is due to the immature hepatic synthesis and relative **vitamin K deficiency** in newborns.

Question 97: A 35-year-old woman is brought to the emergency department by her husband after she lost consciousness 30 minutes ago. The patient's husband says that she has been in a bad mood lately and getting upset over small things. He also says she has been crying a lot and staying up late at night. Her husband mentions that her mother died earlier this year, and she hasn't been coping well with this loss. He says that he came home an hour ago and found her lying on the floor next to a bottle of pills. The patient's husband knows that they were a bottle of her migraine prevention pills (propranolol) but cannot remember the exact name of the medication. On examination, the patient's blood pressure is 75/50 mm Hg, the pulse is 50/min, and the respiratory rate is 12/min. Which of the following is the best course of treatment for this patient?

• A. Glucagon (Correct Answer)
• B. Beta-agonist
• C. Sodium bicarbonate
• D. Insulin
• E. N-Acetylcysteine

Explanation: ***Glucagon*** - This patient presents with **hypotension** and **bradycardia** after an overdose of migraine prevention pills, which her husband identifies as **propranolol**. This clinical picture is highly suggestive of **beta-blocker overdose**. - **Glucagon** is the antidote for beta-blocker overdose as it activates adenylate cyclase independently of the beta-adrenergic receptor, increasing intracellular cAMP and thus improving cardiac contractility and heart rate. *Beta-agonist* - While beta-agonists increase heart rate and contractility, their effect is mediated through **beta-adrenergic receptors**. - In cases of severe **beta-blocker overdose**, these receptors are blocked, rendering beta-agonists less effective or ineffective. *Sodium bicarbonate* - **Sodium bicarbonate** is primarily used to treat **tricyclic antidepressant overdose** by alkalinizing the blood and reducing the binding of the drug to myocardial sodium channels. - It does not have a direct role in reversing the cardiovascular effects of **beta-blocker overdose**. *Insulin* - **High-dose insulin therapy** (with glucose) is used for severe calcium channel blocker overdose, as it enhances myocardial glucose uptake and contractility. - While it can be considered in refractory beta-blocker overdose after other measures fail, it is not the primary or best initial treatment. *N-Acetylcysteine* - **N-Acetylcysteine** (NAC) is the specific antidote for **acetaminophen overdose**, replenishing glutathione stores and preventing hepatotoxicity. - It has no role in the management of **beta-blocker overdose**.

Question 98: A 25-year-old man is brought to the emergency department by his fiancée for altered mental status. She states that they got in a fight that morning. She later got a text from him at work that said he was going to kill himself. She rushed back home and found him unconscious on the living room floor surrounded by his prescription pill bottles. The patient is sedated but conscious and states that he thinks he swallowed “a bunch of pills” about 2 hours ago. He also complains of nausea. The patient’s medical history is significant for bipolar disorder and chronic back pain from a motor vehicle accident. He takes lithium and oxycodone. The patient’s temperature is 99°F (37.2°C), blood pressure is 130/78 mmHg, pulse is 102/min, and respirations are 17/min with an oxygen saturation of 97% on room air. On physical exam, the patient is drowsy, and his speech is slurred, but he is fully oriented. He has horizontal nystagmus, is diffusely hyperreflexic, and has a mild tremor. His initial electrocardiogram shows sinus tachycardia. Labs are obtained, as shown below: Serum: Na: 143 mEq/L K+: 4.3 mEq/L Cl-: 104 mEq/L HCO3-: 24 mEq/L BUN: 18 mg/dL Creatinine: 1.5 mg/dL Glucose: 75 mg/dL Lithium level: 6.8 mEq/L (normal 0.6 mEq/L – 1.2 mEq/L) An intravenous bolus of 1 liter normal saline is given. Which of the following is the next step in management?

• A. Naloxone
• B. Activated charcoal
• C. Hemodialysis (Correct Answer)
• D. Gastric lavage
• E. Sodium bicarbonate

Explanation: ***Hemodialysis*** - The patient presents with severe **lithium toxicity** (lithium level of 6.8 mEq/L) evidenced by altered mental status, slurred speech, nystagmus, hyperreflexia, and tremor. Given the severe symptoms and extremely high lithium level, **hemodialysis** is the most effective and rapid method to remove lithium from the body. - Indications for emergent hemodialysis in lithium toxicity include lithium levels > 4 mEq/L (or >2.5 mEq/L with severe symptoms), seizures, cardiac arrhythmias, and renal failure, all of which are severe presentations. *Naloxone* - Naloxone is an **opioid antagonist** used to reverse opioid overdose, which presents with **respiratory depression**, miosis, and sedation. - While the patient takes oxycodone, his current presentation does not align with opioid overdose; he is tachycardic, and his respiratory rate and oxygen saturation are within normal limits. *Activated charcoal* - **Activated charcoal** is effective for many oral poisonings by binding to toxins in the gastrointestinal tract, but it is **not effective for lithium** due to lithium's poor absorption by charcoal. - It would also be less effective given the presumed ingestion occurred 2 hours prior, as its utility significantly decreases beyond 1 hour post-ingestion. *Gastric lavage* - **Gastric lavage** involves flushing the stomach to remove unabsorbed toxins, but it is generally **not recommended for lithium toxicity** due to its limited efficacy and potential complications, especially if more than 1 hour has passed since ingestion. - The procedure also carries a risk of aspiration in patients with altered mental status. *Sodium bicarbonate* - **Sodium bicarbonate** is used to alkalinize urine in certain toxicities to promote drug excretion (e.g., salicylates, phenobarbital), and it is also used for QRS widening in tricyclic antidepressant overdose. - It is **not indicated for lithium toxicity** as it does not enhance lithium elimination and can worsen electrolyte imbalances.

Question 99: A 27-year-old male presents to his primary care physician with lower back pain. He notes that the pain started over a year ago but has become significantly worse over the past few months. The pain is most severe in the mornings. His past medical history is unremarkable except for a recent episode of right eye pain and blurry vision. Radiographs of the spine and pelvis show bilateral sacroiliitis. Which of the following is the most appropriate treatment for this patient?

• A. Methotrexate
• B. Oral prednisone
• C. Cyclophosphamide
• D. Indomethacin (Correct Answer)
• E. Bed rest

Explanation: ***Indomethacin*** - This patient's symptoms (chronic inflammatory back pain, morning stiffness, uveitis, and sacroiliitis on imaging) are highly suggestive of a **spondyloarthritis**, likely **ankylosing spondylitis**. - **NSAIDs**, such as indomethacin, are the **first-line treatment** for pain and stiffness in spondyloarthritis, providing symptomatic relief and often improving function. *Methotrexate* - **Methotrexate** is a disease-modifying antirheumatic drug (DMARD) used in inflammatory arthritis but is generally **ineffective for axial (spinal) inflammation** in spondyloarthritis. - It is more commonly used in peripheral arthritis or psoriasis associated with spondyloarthritis but not as a primary treatment for isolated axial disease. *Oral prednisone* - While oral corticosteroids like **prednisone** can reduce inflammation, their use in chronic spondyloarthritis is limited due to **significant side effects** with long-term use. - They are typically reserved for acute symptom flares or as a bridge therapy, not for sustained management. *Cyclophosphamide* - **Cyclophosphamide** is a potent immunosuppressant used for severe autoimmune conditions or vasculitis, not typically indicated for the initial or routine treatment of spondyloarthritis. - Its use is associated with considerable **toxicity** and side effects, making it unsuitable for this clinical presentation. *Bed rest* - **Bed rest** is generally **contraindicated** in inflammatory back conditions like spondyloarthritis, as inactivity can actually worsen stiffness and pain. - Regular exercise and activity that improves spinal mobility are encouraged, along with pharmacological interventions.

Question 100: An investigator is studying the regulation of adrenal hormone synthesis in rats. The investigator measures serum concentrations of different hormones before and after intravenous administration of metyrapone, which inhibits adrenal 11β-hydroxylase. The serum concentration of which of the following hormones is most likely to be increased after administration of this agent?

• A. Aldosterone
• B. 17-hydroxyprogesterone
• C. 11-deoxycortisol (Correct Answer)
• D. Adrenocorticotropic hormone (ACTH)
• E. Cortisol

Explanation: ***11-deoxycortisol*** - Metyrapone inhibits **11β-hydroxylase**, which catalyzes the conversion of **11-deoxycortisol to cortisol** in the zona fasciculata. - **11-deoxycortisol** is the **direct substrate** for this enzyme, so when 11β-hydroxylase is blocked, 11-deoxycortisol accumulates dramatically in the serum. - This principle forms the basis of the **metyrapone stimulation test**, used clinically to assess ACTH reserve and diagnose adrenal insufficiency. *17-hydroxyprogesterone* - 17-hydroxyprogesterone is converted to **11-deoxycortisol** by **21-hydroxylase**, not by 11β-hydroxylase. - Since 21-hydroxylase is **not inhibited** by metyrapone, 17-hydroxyprogesterone continues to be converted downstream to 11-deoxycortisol. - While there may be a minor accumulation due to increased flux through the pathway, it is **not the primary hormone that accumulates**. *Aldosterone* - Aldosterone synthesis occurs predominantly in the **zona glomerulosa** and involves aldosterone synthase (CYP11B2). - Although 11β-hydroxylase (CYP11B1) is involved in cortisol synthesis, metyrapone primarily affects the zona fasciculata pathway. - Aldosterone levels typically **remain stable or decrease slightly**, rather than increase. *Adrenocorticotropic hormone (ACTH)* - Metyrapone blocks cortisol synthesis, leading to **decreased cortisol levels**. - This reduces **negative feedback** on the **hypothalamic-pituitary-adrenal (HPA) axis**. - The pituitary responds by **increasing ACTH secretion** as a compensatory mechanism. - While ACTH does increase, the question asks about the **most direct hormonal effect** of enzyme inhibition, which is accumulation of the enzyme's substrate (11-deoxycortisol). *Cortisol* - **Cortisol** is the product of the 11β-hydroxylase reaction. - When this enzyme is inhibited, cortisol synthesis is **blocked**, resulting in **decreased** serum cortisol concentration.

Question 101: A 54-year-old male with a history of hypertension, coronary artery disease status post 3-vessel coronary artery bypass surgery 5 years prior, stage III chronic kidney disease and a long history of uncontrolled diabetes presents to your office. His diabetes is complicated by diabetic retinopathy, gastroparesis with associated nausea, and polyneuropathy. He returns to your clinic for a medication refill. He was last seen in your clinic 1 year ago and was living in Thailand since then and has recently moved back to the United States. He has been taking lisinopril, amlodipine, simvastatin, aspirin, metformin, glyburide, gabapentin, metoclopramide and multivitamins during his time abroad. You notice that he is constantly smacking his lips and moving his tongue in and out of his mouth in slow movements. His physical exam is notable for numbness and decreased proprioception of feet bilaterally. Which of the following medications most likely is causing his abnormal movements?

• A. Gabapentin
• B. Aspirin
• C. Amlodipine
• D. Metoclopramide (Correct Answer)
• E. Glyburide

Explanation: ***Metoclopramide*** - The patient's presentation with **lip smacking** and **tongue movements** is highly indicative of **tardive dyskinesia**, a movement disorder often triggered by dopamine receptor blocking agents. - **Metoclopramide** is a prokinetic agent and **dopamine D2 receptor antagonist** commonly associated with **extrapyramidal symptoms**, including tardive dyskinesia, especially with chronic use. *Gabapentin* - **Gabapentin** is an anticonvulsant and neuropathic pain medication that primarily acts on voltage-gated calcium channels. - While it can cause side effects like dizziness and somnolence, it is **not known to cause tardive dyskinesia** or similar abnormal movements. *Aspirin* - **Aspirin** is an antiplatelet agent and NSAID primarily used for cardiovascular disease prevention and pain relief. - Its side effects include gastrointestinal upset and bleeding, but it **does not cause movement disorders** such as tardive dyskinesia. *Amlodipine* - **Amlodipine** is a calcium channel blocker used to treat hypertension and angina. - Common side effects include edema, headache, and flushing, but it is **not associated with extrapyramidal symptoms** or tardive dyskinesia. *Glyburide* - **Glyburide** is a sulfonylurea used to treat type 2 diabetes by stimulating insulin release from the pancreas. - Its primary side effects are hypoglycemia and weight gain, and it **does not cause neurological movement disorders**.

Question 102: An 89-year-old woman is admitted to the neurology intensive care unit following a massive cerebral infarction. She has a history of hypertension, ovarian cancer, and lung cancer. Her medications include lisinopril and aspirin. She has smoked a few cigarettes each day for the last 60 years. She does not drink alcohol or use drugs. An arterial line and intraventricular pressure monitor are placed. You decide to acutely lower intracranial pressure by causing cerebral vasoconstriction. Which of the following methods could be used for this effect?

• A. Elevating head position
• B. Mannitol infusion
• C. Glucocorticoids
• D. Mechanical hyperventilation (Correct Answer)
• E. Mechanical hypoventilation

Explanation: ***Mechanical hyperventilation*** - **Mechanical hyperventilation** acutely lowers **PaCO2**, leading to cerebral **vasoconstriction** and a reduction in cerebral blood volume, thereby decreasing intracranial pressure (ICP). - This effect is rapid but **transient**, as the brain can adapt to changes in PaCO2 within hours, and excessive vasoconstriction can lead to **cerebral ischemia**. *Elevating head position* - Elevating the head of the bed to 30 degrees can help improve **venous outflow** from the brain, which can mildly reduce ICP. - However, it does not achieve ICP reduction through **cerebral vasoconstriction**. *Mannitol infusion* - **Mannitol** is an **osmotic diuretic** that draws water from brain tissue into the intravascular space, reducing brain edema and ICP. - It does not primarily induce ICP reduction via **cerebral vasoconstriction**. *Glucocorticoids* - **Glucocorticoids** like dexamethasone are effective in reducing ICP primarily in cases of **vasogenic edema** associated with brain tumors. - They work by stabilizing the **blood-brain barrier** and reducing inflammation, not through cerebral vasoconstriction. *Mechanical hypoventilation* - **Mechanical hypoventilation** would increase **PaCO2**, leading to **cerebral vasodilation** and an increase in cerebral blood volume. - This would **raise intracranial pressure**, which is the opposite of the desired effect.

Question 103: A 64-year-old man comes to the physician for a follow-up examination. Four months ago, he underwent a renal transplantation for end-stage renal disease. Current medications include sirolimus, tacrolimus, and prednisolone. Physical examination shows no abnormalities. Serum studies show a creatinine concentration of 2.7 mg/dL. A kidney allograft biopsy specimen shows tubular vacuolization without parenchymal changes. Which of the following is the most likely cause of this patient's renal injury?

• A. Sirolimus toxicity
• B. Preformed antibody-mediated rejection
• C. T cell-mediated rejection
• D. Prednisolone toxicity
• E. Tacrolimus toxicity (Correct Answer)

Explanation: ***Tacrolimus toxicity*** - **Tacrolimus** is a **calcineurin inhibitor** known to cause nephrotoxicity, and its signature histological finding is **tubular vacuolization**. - The elevated **creatinine** level in the presence of this specific biopsy finding strongly suggests tacrolimus-induced renal injury, especially in a transplant patient on this medication. *Sirolimus toxicity* - **Sirolimus** is an **mTOR inhibitor** that can cause nephrotoxicity, but it typically presents with different histological findings, such as **thrombotic microangiopathy** or **proteinuria**, rather than isolated tubular vacuolization. - While it can contribute to renal dysfunction, the specific biopsy finding points away from sirolimus as the primary cause. *Preformed antibody-mediated rejection* - **Antibody-mediated rejection (AMR)** typically presents with **glomerulitis**, **peritubular capillaritis**, and C4d deposition in the biopsy, rather than isolated tubular vacuolization. - It usually occurs acutely post-transplant, often with severe renal dysfunction, but the specific histologic changes seen here are not characteristic of AMR. *T cell-mediated rejection* - **T cell-mediated rejection (TCMR)** is characterized by **tubulitis** (inflammation of the tubules with infiltrating lymphocytes) and **interstitial inflammation**, sometimes with vascular involvement. - The biopsy mentions "tubular vacuolization without parenchymal changes," which does not fit the typical histological picture of TCMR. *Prednisolone toxicity* - **Prednisolone** (a corticosteroid) is generally nephroprotective and does not directly cause renal injury with tubular vacuolization. - While chronic steroid use can have various side effects, direct acute renal toxicity with this specific histological finding is not characteristic of prednisolone.

Question 104: A 58-year-old man presents to the emergency department with worsening shortness of breath, cough, and fatigue. He reports that his shortness of breath was worst at night, requiring him to sit on a chair in order to get some sleep. Medical history is significant for hypertension, hypercholesterolemia, and coronary heart disease. His temperature is 98.8°F (37.1°C), blood pressure is 146/94 mmHg, pulse is 102/min, respirations are 20/min with an oxygen saturation of 89%. On physical examination, the patient's breathing is labored. Pulmonary auscultation reveals crackles and wheezes, and cardiac auscultation reveals an S3 heart sound. After appropriate imaging and labs, the patient receives a non-rebreather facemask, and two intravenous catheters. Drug therapy is initiated. Which of the following is the site of action of the prescribed drug used to relieve this patient's symptoms?

• A. Descending loop of Henle
• B. Collecting tubule
• C. Proximal tubule
• D. Ascending loop of Henle (Correct Answer)
• E. Distal tubule

Explanation: ***Ascending loop of Henle*** - The patient's symptoms (orthopnea, crackles, S3 heart sound, history of coronary heart disease) are consistent with **acute decompensated heart failure** with pulmonary edema. - The most effective drug class for rapid symptom relief is a **loop diuretic** (e.g., furosemide), which acts on the **Na-K-2Cl cotransporter** in the thick ascending loop of Henle. - Loop diuretics promote potent diuresis and rapid reduction of pulmonary congestion, making them the first-line choice in acute heart failure with volume overload. *Descending loop of Henle* - This segment is primarily permeable to **water** and largely impermeable to solutes. - There are **no major diuretic drug targets** in the descending loop of Henle. *Collecting tubule* - This is the primary site of action for **potassium-sparing diuretics** (e.g., spironolactone, amiloride), which are less potent than loop diuretics and not typically used for initial rapid diuresis in acute heart failure. - **Vasopressin** also acts here to regulate water reabsorption, but its antagonists are not first-line for acute pulmonary edema. *Proximal tubule* - The **proximal tubule** is where most reabsorption of solutes (e.g., Na+, Cl-, HCO3-) and water occurs. - **Carbonic anhydrase inhibitors** (e.g., acetazolamide) act here, but they are relatively weak diuretics and not used for acute heart failure symptoms. *Distal tubule* - This segment is the primary site of action for **thiazide diuretics**, which inhibit the Na-Cl cotransporter. - While effective for long-term hypertension and heart failure management, thiazides are **less potent** than loop diuretics and have a slower onset of action, making them unsuitable for emergency relief of acute pulmonary edema.

Question 105: A 48-year-old man presents to his primary care physician with a complaint of lower back pain that has developed over the past week. He works in construction but cannot recall a specific injury or incident that could have led to this pain. He denies any pain, weakness, or change/loss of sensation in his legs. The patient also reports no episodes of incontinence and confirms that he has not noted any changes in his bowel movements or urination. His temperature is 97.6°F (36.4°C), blood pressure is 133/82 mmHg, pulse is 82/min, respirations are 15/min, and oxygen saturation is 98% on room air. Physical examination reveals no focal spine tenderness and demonstrates 5/5 strength and intact sensation to light touch throughout the lower extremities. Which of the following is the most appropriate next step in management?

• A. CT spine
• B. Ibuprofen and bed rest
• C. CRP level
• D. MRI spine
• E. Naproxen and activity as tolerated (Correct Answer)

Explanation: ***Naproxen and activity as tolerated*** - This patient presents with **acute, uncomplicated low back pain** with no signs of neurological deficits, radiculopathy, or cauda equina syndrome. Initial management should focus on symptom relief with **NSAIDs** (like naproxen) and encouraging **activity as tolerated**, as prolonged bed rest can worsen outcomes. - Given the absence of "red flag" symptoms (e.g., fever, weight loss, progressive neurological deficits, history of cancer, recent trauma, IV drug use, saddle anesthesia, bowel/bladder dysfunction), imaging is generally not indicated within the first 4-6 weeks of symptom onset. *CT spine* - **CT imaging** exposes the patient to significant radiation and is typically reserved for cases where bony abnormalities or fractures are suspected or as a follow-up to plain radiographs. - It is not the initial imaging modality of choice for uncomplicated back pain, especially without specific trauma or "red flag" symptoms. *Ibuprofen and bed rest* - While **NSAIDs like ibuprofen** are appropriate for pain relief, **prolonged bed rest** is generally discouraged for acute low back pain. - Evidence suggests that maintaining activity as tolerated leads to better outcomes compared to strict bed rest. *CRP level* - **CRP (C-reactive protein)** is a marker of inflammation and could be elevated in various conditions, including infection, inflammatory arthropathies, or malignancy. - However, in cases of uncomplicated acute low back pain without specific "red flag" signs of inflammatory or infectious etiology, routinely measuring CRP is generally not helpful for initial management and can lead to unnecessary investigations. *MRI spine* - **MRI is a sensitive imaging modality** for visualizing soft tissues (discs, nerves, spinal cord) and is indicated for suspected radiculopathy, cauda equina syndrome, spinal cord compression, or when "red flag" symptoms suggest infection, tumor, or fracture. - In this patient, the absence of any neurological deficits, radicular symptoms, or other red flags makes an MRI unnecessary and potentially misleading in the initial management of acute, uncomplicated low back pain.

Question 106: A 78-year-old man is brought to the emergency department by ambulance 30 minutes after the sudden onset of speech difficulties and right-sided arm and leg weakness. Examination shows paralysis and hypoesthesia on the right side, positive Babinski sign on the right, and slurred speech. A CT scan of the head shows a hyperdensity in the left middle cerebral artery and no evidence of intracranial bleeding. The patient's symptoms improve rapidly after pharmacotherapy is initiated and his weakness completely resolves. Which of the following drugs was most likely administered?

• A. Alteplase (Correct Answer)
• B. Heparin
• C. Prasugrel
• D. Rivaroxaban
• E. Warfarin

Explanation: ***Alteplase*** - The patient experienced an **acute ischemic stroke** given the sudden onset of neurological deficits and CT findings consistent with a **thrombus (hyperdensity in the M1 segment of the left Middle Cerebral Artery)** and no intracranial bleeding. - **Alteplase**, a **thrombolytic agent**, is indicated for acute ischemic stroke when administered within the therapeutic window (typically 3-4.5 hours from symptom onset), leading to rapid clot dissolution and resolution of symptoms. *Heparin* - **Heparin** is an anticoagulant used to prevent new clot formation or extension of existing clots, but it does not actively dissolve existing clots rapidly enough to explain the immediate resolution of symptoms in an acute setting. - It is typically used for conditions like DVT, PE, or to prevent stroke in high-risk patients but not as a primary treatment for acute ischemic stroke to restore perfusion quickly. *Prasugrel* - **Prasugrel** is an antiplatelet medication that inhibits platelet aggregation. It is used to prevent arterial thrombosis, particularly in patients with acute coronary syndromes undergoing PCI. - While it helps prevent stroke recurrence, it does not dissolve an existing thrombus in an acute ischemic event, nor would it lead to the rapid symptom resolution seen here. *Rivaroxaban* - **Rivaroxaban** is a direct oral anticoagulant (DOAC) that inhibits Factor Xa. It is used for stroke prevention in atrial fibrillation and treatment of DVT/PE. - Like heparin, it prevents new clot formation or growth, but it is not a thrombolytic and would not cause the rapid resolution of acute ischemic stroke symptoms. *Warfarin* - **Warfarin** is a vitamin K antagonist, an anticoagulant used for long-term prevention of thromboembolic events. Its onset of action is slow, taking several days to reach therapeutic levels. - It is not suitable for the acute treatment of an ischemic stroke where rapid clot dissolution is required.

Question 107: A 33-year-old comes to her dermatologist complaining of a rash that recently started appearing on her face. She states that over the past three months, she has noticed that her cheeks have been getting darker, which has been causing her psychological distress. She has attempted using skin lighteners on her cheeks, but recently noticed more dark spots on her forehead. Aside from a first-trimester miscarriage 5 years ago and a 15-year history of migraines, she has no other past medical history. She is currently taking ibuprofen and rizatriptan for her migraines, and is also on oral contraceptives. Her mother has a history of thyroid disease and migraines but was otherwise healthy. On exam, the patient’s temperature is 99.1°F (37.3°C), blood pressure is 130/88 mmHg, pulse is 76/min, and respirations are 12/min. The patient has Fitzpatrick phototype III skin and marked confluent hyperpigmented patches over her cheeks without scarring. Her forehead is also notable for hyperpigmented macules that have not yet become confluent. There are no oral ulcers nor any other visible skin lesion. The patient has a negative pregnancy test, and her ANA is negative. Which of the following is the most likely cause of this patient’s disease?

• A. Medication (Correct Answer)
• B. Post-inflammatory changes
• C. Autoantibodies
• D. Hypersensitivity reaction
• E. Enzyme inhibition

Explanation: ***Medication*** - The patient's **oral contraceptive use** is a significant risk factor for **melasma**, presenting as hyperpigmented patches on the face. - Exposure to **estrogen and progesterone** can stimulate melanocyte activity, leading to increased melanin production. *Post-inflammatory changes* - **Post-inflammatory hyperpigmentation** typically follows an inflammatory skin condition (e.g., acne, eczema, injury), which is not described. - The patient's rash appeared spontaneously without a prior inflammatory event or trauma to the skin leading to hyperpigmentation. *Autoantibodies* - While some autoimmune conditions can cause skin changes, the patient's **negative ANA** and lack of other systemic symptoms make an autoantibody-mediated disease less likely. - Melasma is primarily related to hormonal and sun exposure factors, not typically to autoimmune phenomena. *Hypersensitivity reaction* - A hypersensitivity reaction would usually present with **erythema, pruritus, or urticaria**, none of which are noted in the patient's presentation. - The **progressive hyperpigmentation without inflammatory signs** is not consistent with an allergic or hypersensitivity response. *Enzyme inhibition* - While some skin conditions involve enzyme pathways, melasma is primarily due to **increased melanocyte activity and melanin production**, not typically a direct result of enzyme inhibition. - There is no clinical indication in the patient's history or physical exam to suggest an enzyme inhibition disorder.

Question 108: A 21-year-old man presents for a pre-employment medical check-up. He has a history of persistent asthma and regularly uses inhaled fluticasone for prophylaxis. For the last week, he has been experiencing increasing symptoms, such as night time cough and wheezing on exertion. Because his albuterol metered-dose inhaler ran out, he has been taking oral albuterol 3 times a day for the last 3 days, which has improved his symptoms. The physician performs a complete physical examination and orders laboratory tests. Which of the following findings is most likely to be present on his physical examination or laboratory studies?

• A. Serum magnesium is 2.4 mEq/L (1.2 mmol/L)
• B. Upbeat nystagmus
• C. Myoclonus
• D. Pulse rate is 116/min (Correct Answer)
• E. Serum potassium is 5.5 mEq/L (5.5 mmol/L)

Explanation: ***Pulse rate is 116/min*** - Oral **albuterol** is a **beta-2 adrenergic agonist** that can cause systemic side effects, including **tachycardia** and palpitations, especially when taken in higher or more frequent doses. - The patient's increased albuterol use as an oral formulation, rather than a metered-dose inhaler, leads to higher systemic absorption and a greater likelihood of adverse effects like a **fast heart rate**. *Serum magnesium is 2.4 mEq/L (1.2 mmol/L)* - This value is within the normal range for serum magnesium, and albuterol use is not typically associated with changes in magnesium levels. - While magnesium can be used in acute severe asthma, it is not an expected side effect of albuterol to significantly alter serum magnesium. *Upbeat nystagmus* - **Upbeat nystagmus** is a neurological sign often associated with **brainstem lesions** or certain drug toxicities (e.g., lithium, carbamazepine, alcohol) but is not a typical side effect of albuterol. - Albuterol's primary effects are on the **sympathetic nervous system** and smooth muscle in the airways, not directly on vestibular or brainstem function to cause nystagmus. *Myoclonus* - **Myoclonus** (brief, involuntary twitching of a muscle or group of muscles) is not a common side effect of albuterol. - While high doses of **beta-agonists** can cause tremors, myoclonus specifically suggests a different neurological pathology or drug toxicity. *Serum potassium is 5.5 mEq/L (5.5 mmol/L)* - This value indicates **hyperkalemia**, while **beta-2 agonists** like albuterol are known to cause a shift of potassium *into* cells, leading to **hypokalemia**, not hyperkalemia. - Therefore, a finding of hyperkalemia would be inconsistent with albuterol use and instead might suggest kidney dysfunction or other underlying conditions.

Question 109: A 76-year-old male presents to his primary care physician because he is concerned about changes in urination. Over the last few months, he has noticed increased urinary frequency as well as difficulty with initiating and stopping urination. He denies having pain with urination. Physical exam reveals a uniformly enlarged and non-tender prostate. Lab tests showed that the prostate specific antigen (PSA) was within normal limits. The patient did not tolerate an alpha blocker due to episodes of syncope so another medication is prescribed that affects testosterone metabolism. Which of the following disorders can also be treated with the medication most likely prescribed in this case?

• A. Prostate adenocarcinoma
• B. Male pattern baldness (Correct Answer)
• C. Hypogonadism
• D. Erectile dysfunction
• E. Polycystic ovarian syndrome (PCOS)

Explanation: ***Male pattern baldness*** - The patient's symptoms (urinary frequency, difficulty initiating/stopping urination, uniformly enlarged prostate, normal PSA) are consistent with **benign prostatic hyperplasia (BPH)**. Since he couldn't tolerate alpha-blockers, a **5-alpha reductase inhibitor** like **finasteride** or **dutasteride** would likely be prescribed, which works by blocking the conversion of testosterone to dihydrotestosterone (DHT). - **Male pattern baldness (androgenetic alopecia)** is also caused by DHT and can be treated with 5-alpha reductase inhibitors such as finasteride. *Prostate adenocarcinoma* - While 5-alpha reductase inhibitors can reduce the risk of prostate cancer, they are **not a primary treatment** for established prostate adenocarcinoma. - Prostate adenocarcinoma is typically managed with surgery, radiation, or more aggressive hormonal therapies if advanced. *Hypogonadism* - Hypogonadism is characterized by **low testosterone levels**; 5-alpha reductase inhibitors actually decrease the conversion of testosterone to DHT, which could potentially worsen symptoms associated with low testosterone if used inappropriately. - The primary treatment for hypogonadism is **testosterone replacement therapy**. *Erectile dysfunction* - Erectile dysfunction is often treated with **phosphodiesterase-5 inhibitors (PDE5i)** like sildenafil or tadalafil, which improve blood flow to the penis. - While BPH can sometimes contribute to ED, 5-alpha reductase inhibitors are **not a first-line treatment** for primary ED and can even have ED as a side effect. *Polycystic ovarian syndrome (PCOS)* - PCOS is a hormonal disorder affecting women, characterized by **elevated androgen levels** and ovarian cysts. - While anti-androgens can be used in PCOS to manage symptoms like hirsutism, **5-alpha reductase inhibitors are not a standard treatment** for the overall syndrome and this medication is prescribed for a male patient.

Question 110: A 40-year-old male presents to the clinic. The patient has begun taking large doses of vitamin E in order to slow down the aging process and increase his sexual output. He has placed himself on this regimen following reading a website that encouraged this, without consulting a healthcare professional. He is interested in knowing if it is alright to continue his supplementation. Which of the following side-effects should he be concerned about should he continue his regimen?

• A. Retinopathy
• B. Hemorrhage (Correct Answer)
• C. Peripheral neuropathy
• D. Deep venous thrombosis
• E. Night blindness

Explanation: ***Hemorrhage*** - High doses of **vitamin E** can inhibit **vitamin K-dependent coagulation factors**, leading to an increased risk of bleeding or **hemorrhage**. - This effect is particularly pronounced when vitamin E is taken in conjunction with **anticoagulant medications** like warfarin. *Retinopathy* - **Retinopathy** is not a common side effect associated with high-dose vitamin E supplementation. - It is more typically linked to conditions like **diabetes** or **hypertension**. *Peripheral neuropathy* - **Peripheral neuropathy** is primarily associated with deficiencies in other vitamins, such as **vitamin B12** or **B6 toxicity**, not with vitamin E supplementation. - Excessive vitamin E intake does not directly cause nerve damage in the periphery. *Deep venous thrombosis* - **Deep venous thrombosis (DVT)** is a condition involving blood clot formation, and vitamin E supplementation is generally **not associated with an increased risk of DVT**. - In fact, vitamin E's anticoagulant properties might theoretically reduce clot formation, though this is not a primary clinical indication for its use. *Night blindness* - **Night blindness** is a classic symptom of **vitamin A deficiency**, which is unrelated to vitamin E intake. - Vitamin E overdose does not cause vision impairment such as night blindness.

Question 111: A 23-year-old man is brought to the emergency department by the police for impaired cognition and agitation after being struck in the head at a local nightclub. The patient refuses to respond to questions and continues to be markedly agitated. An alcoholic smell is noted. His temperature is 36.9°C (98.4°F), pulse is 104/min, respirations are 24/min, and blood pressure is 148/95 mm Hg. He is confused and oriented only to person. Neurological examination shows miosis and nystagmus but is quickly aborted after the patient tries to attack several members of the care team. CT scan of the head shows no abnormalities. Ingestion of which of the following substances most likely explains this patient's symptoms?

• A. Lysergic acid diethylamide
• B. Phencyclidine (Correct Answer)
• C. Alcohol
• D. Heroin
• E. Methamphetamine

Explanation: ***Phencyclidine*** - **Phencyclidine (PCP)** intoxication is characterized by a combination of severe **agitation**, **aggression**, impaired cognition, nystagmus (vertical or horizontal), and miotic pupils, which precisely matches the patient's presentation. - The patient's violent behavior and refusal to cooperate with examination despite an initial head injury also align with the dissociative and stimulant effects of PCP. *Lysergic acid diethylamide* - **LSD** typically causes hallucinations, altered perceptions, and dilated pupils (**mydriasis**), rather than the miotic pupils and marked aggression seen in this patient. - While agitation can occur with LSD, the extreme violence and neurological signs like nystagmus point away from it as the primary cause. *Alcohol* - While alcohol can cause impaired cognition and agitation, the presence of **miosis** and **nystagmus** in this agitated state, especially given the degree of disorientation and aggression, is more characteristic of other substances. - The "alcoholic smell" could be a red herring or co-ingestion, but the overall clinical picture is not solely attributable to acute alcohol intoxication. *Heroin* - **Heroin (opioid)** overdose typically causes **sedation**, respiratory depression, and pinpoint pupils (**miosis**), which is contrary to the agitation, aggression, and elevated vital signs described. - The patient's high blood pressure and pulse are inconsistent with opioid effects. *Methamphetamine* - **Methamphetamine** intoxication leads to agitation, paranoia, and elevated vital signs (tachycardia, hypertension), but typically causes **mydriasis (dilated pupils)**, not miosis. - Although agitation and aggression are significant features, the pupillary findings help differentiate it from PCP.

Question 112: A previously healthy 5-year-old girl is brought to the emergency department because of difficulty breathing and vomiting that began 1 hour after she took an amoxicillin tablet. She appears anxious. Her pulse is 140/min, respirations are 40/min, and blood pressure is 72/39 mmHg. She has several well-circumscribed, raised, erythematous plaques scattered diffusely over her trunk and extremities. Pulmonary examination shows diffuse, bilateral wheezing. Which of the following is the most appropriate initial pharmacotherapy?

• A. Norepinephrine
• B. Dobutamine
• C. Methylprednisolone
• D. Epinephrine (Correct Answer)
• E. Diphenhydramine

Explanation: ***Epinephrine*** - This patient presents with **anaphylaxis** due to amoxicillin, characterized by rapidly developing **respiratory distress** (wheezing, tachypnea), **circulatory compromise** (hypotension, tachycardia), and **cutaneous manifestations** (urticaria). - **Epinephrine** is the first-line treatment for anaphylaxis because it stabilizes mast cells, causes **vasoconstriction** to improve blood pressure, and promotes **bronchodilation** to alleviate respiratory symptoms. *Norepinephrine* - **Norepinephrine** is a potent **vasopressor** primarily used for septic shock or conditions requiring significant vasoconstriction. - It lacks the bronchodilatory effects and mast cell-stabilizing properties that are crucial in managing the respiratory and systemic inflammatory components of anaphylaxis. *Dobutamine* - **Dobutamine** is a **beta-1 adrenergic agonist** primarily used to increase cardiac contractility and heart rate in cases of cardiogenic shock or heart failure. - It would not address the systemic vasodilation, bronchospasm, or immune-mediated aspects of anaphylaxis effectively. *Methylprednisolone* - **Methylprednisolone** is a **corticosteroid** that acts to reduce inflammation and prevent biphasic anaphylactic reactions. - While important in the overall management of anaphylaxis, it has a delayed onset of action and is not the appropriate initial therapy for acute life-threatening symptoms; **epinephrine** is critical for immediate stabilization. *Diphenhydramine* - **Diphenhydramine** is an **antihistamine** that blocks histamine H1 receptors, helping to reduce symptoms such as urticaria and pruritus. - It does not address the life-threatening aspects of anaphylaxis, such as hypotension and bronchospasm, and should be used as an adjunct rather than initial monotherapy.

Question 113: A 32-year-old man is brought to the emergency department because he was found stumbling in the street heedless of oncoming traffic. On arrival, he is found to be sluggish and has slow and sometimes incoherent speech. He is also drowsy and falls asleep several times during questioning. Chart review shows that he has previously been admitted after getting a severe cut during a bar fight. Otherwise, he is known to be intermittently homeless and has poorly managed diabetes. Serum testing reveals the presence of a substance that increases the duration of opening for an important channel. Which of the following symptoms may be seen if the most likely substance in this patient is abruptly discontinued?

• A. Tremors
• B. Insomnia
• C. Delayed delirium
• D. Piloerection
• E. Seizures (Correct Answer)

Explanation: ***Seizures*** - This patient presents with symptoms of **central nervous system (CNS) depression** (sluggish, incoherent speech, drowsiness) and a history suggestive of **substance abuse** (homelessness, bar fight). - The key clue is that the substance **increases the duration of opening** of the GABA-A receptor channel, which specifically describes **barbiturates** (benzodiazepines increase the **frequency** of opening, not duration). - Abrupt discontinuation of barbiturates can lead to life-threatening **withdrawal seizures** due to CNS hyperexcitability when GABAergic inhibition is suddenly removed [1]. - This is the most critical and potentially fatal complication of barbiturate withdrawal. *Tremors* - While **tremors** can occur during withdrawal from CNS depressants, they are a less severe symptom compared to seizures. - Tremors are common in withdrawal syndromes but do not represent the most life-threatening risk in acute barbiturate withdrawal. *Insomnia* - **Insomnia** is a common symptom of withdrawal from CNS depressants due to rebound CNS hyperactivity [1]. - However, compared to seizures, insomnia is not life-threatening and is a less critical feature of barbiturate withdrawal. *Delayed delirium* - **Delirium** can occur during severe withdrawal, particularly **delirium tremens** in alcohol withdrawal. - While delirium may develop, the most immediate and severe risk for barbiturate withdrawal is seizures, which can occur within hours to days of cessation. *Piloerection* - **Piloerection** (goosebumps) is a classic symptom of **opioid withdrawal**, resulting from sympathetic nervous system activation. - This symptom is **not** characteristic of withdrawal from barbiturates or other GABAergic substances, making it an incorrect choice.

Question 114: A 33-year-old man comes to the physician because of a 2-month history of burning epigastric pain, dry cough, and occasional regurgitation. The pain is aggravated by eating and lying down. Physical examination shows a soft, non-tender abdomen. Upper endoscopy shows hyperemia in the distal third of the esophagus. Which of the following drugs is most likely to directly inhibit the common pathway of gastric acid secretion?

• A. Pirenzepine
• B. Ranitidine
• C. Lansoprazole (Correct Answer)
• D. Aluminum hydroxide
• E. Octreotide

Explanation: ***Lansoprazole*** - **Lansoprazole** is a **proton pump inhibitor (PPI)** that irreversibly blocks the **H+/K+-ATPase (proton pump)** in gastric parietal cells, the final common pathway for gastric acid secretion. - By inhibiting this pump, PPIs effectively reduce acid production, providing significant relief for symptoms like **burning epigastric pain** and **regurgitation** as seen in **gastroesophageal reflux disease (GERD)**. *Pirenzepine* - **Pirenzepine** is a **muscarinic M1 receptor antagonist** that selectively inhibits gastric acid secretion stimulated by acetylcholine. - While it reduces acid, it does not directly target the final common pathway (the proton pump) and is less potent than PPIs. *Ranitidine* - **Ranitidine** is an **H2 receptor antagonist** that blocks histamine-mediated acid secretion from parietal cells. - Although it reduces acid production, it does not inhibit the proton pump directly, which is the common pathway for all acid secretagogues. *Aluminum hydroxide* - **Aluminum hydroxide** is an **antacid** that neutralizes existing stomach acid by acting as a buffer. - It does not inhibit acid secretion but rather works on the acid that has already been secreted. *Octreotide* - **Octreotide** is a **somatostatin analog** that inhibits various gastrointestinal hormones, including gastrin, thereby indirectly reducing acid secretion. - It is primarily used for conditions like **variceal bleeding** or **neuroendocrine tumors** like **gastrinomas**, not for routine GERD treatment.

Question 115: A 59-year-old man is brought to the emergency department one hour after developing shortness of breath and “squeezing” chest pain that began while he was mowing the lawn. He has asthma, hypertension, and erectile dysfunction. Current medications include salmeterol, amlodipine, lisinopril, and vardenafil. His pulse is 110/min and blood pressure is 122/70 mm Hg. Physical examination shows diaphoresis. An ECG shows sinus tachycardia. Sublingual nitroglycerin is administered. Five minutes later, his pulse is 137/min and his blood pressure is 78/40 mm Hg. Which of the following is the most likely mechanism of this patient's hypotension?

• A. Bradykinin accumulation
• B. Cyclic GMP elevation (Correct Answer)
• C. Decreased nitric oxide production
• D. Calcium channel antagonism
• E. Alpha-1 receptor antagonism

Explanation: ***Cyclic GMP elevation*** - The patient's severe hypotension after nitroglycerin administration is likely due to an interaction with **vardenafil**, a **phosphodiesterase-5 (PDE5) inhibitor**. - Both nitroglycerin and vardenafil increase levels of **cyclic guanosine monophosphate (cGMP)**, leading to excessive systemic vasodilation and profound hypotension. *Bradykinin accumulation* - This is a well-known side effect of **ACE inhibitors (e.g., lisinopril)**, manifesting primarily as a dry cough or angioedema. - While the patient is on lisinopril, bradykinin accumulation does not immediately cause severe hypotension following nitroglycerin administration in this manner. *Decreased nitric oxide production* - Nitric oxide (NO) is a **vasodilator**; decreased production would typically lead to vasoconstriction and *increased* blood pressure, not hypotension. - Nitroglycerin, in fact, works by **increasing NO production** or release to induce vasodilation. *Calcium channel antagonism* - **Amlodipine** is a calcium channel blocker, which can cause vasodilation and lower blood pressure. - However, the sudden and severe drop in blood pressure observed *after* nitroglycerin is not primarily due to an additive effect of amlodipine in the way PDE5 inhibitors interact. *Alpha-1 receptor antagonism* - Alpha-1 receptor antagonists (e.g., prazosin, doxazosin) cause **vasodilation** by blocking norepinephrine's action on blood vessels. - While they can cause orthostatic hypotension, the patient is not on such a medication, and this mechanism does not explain the acute, severe drop seen after nitroglycerin.

Question 116: A 40-year-old homeless man is brought to the emergency department after police found him in the park lying on the ground with a minor cut at the back of his head. He is confused with slurred speech and fails a breathalyzer test. Pupils are normal in size and reactive to light. A bolus of intravenous dextrose, thiamine, and naloxone is given in the emergency department. The cut on the head is sutured. Blood and urine are drawn for toxicology screening. The blood-alcohol level comes out to be 200 mg/dL. Liver function test showed an AST of 320 U/L, ALT of 150 U/L, gamma-glutamyl transferase of 100 U/L, and total and direct bilirubin level are within normal limits. Which additional physical examination finding is most likely to be present in this patient?

• A. Pin point pupil
• B. Vertical nystagmus
• C. Ataxic gait (Correct Answer)
• D. Increased appetite
• E. High blood pressure

Explanation: ***Ataxic gait*** - Chronic alcohol abuse, suggested by elevated AST, ALT, and GGT levels, leads to **cerebellar degeneration** which manifests as an **ataxic gait**. - **Alcohol intoxication** itself can cause disequilibrium and staggering, contributing to an ataxic presentation. *Pin point pupil* - **Pinpoint pupils** are typically associated with **opioid intoxication** or pontine hemorrhage, neither of which is indicated here. - The patient's pupils are specifically noted as **normal in size and reactive to light**, ruling out this finding. *Vertical nystagmus* - **Vertical nystagmus** is often a sign of **brainstem dysfunction** or certain drug toxicities (e.g., phencyclidine, phenytoin), rather than typical alcohol intoxication or chronic alcoholic effects. - While nystagmus can occur with alcohol, it's more commonly horizontal; vertical nystagmus would suggest a different or additional pathology. *Increased appetite* - **Increased appetite** is not a characteristic symptom of acute alcohol intoxication or chronic alcoholism. - Chronic alcoholics often experience **malnutrition** and **decreased appetite** due to the metabolic effects of alcohol and associated organ damage. *High blood pressure* - While chronic alcoholism can lead to **hypertension** over time, acute alcohol intoxication typically causes **vasodilation and hypotension**. - This patient's presentation with acute intoxication would more likely involve a lower, rather than higher, blood pressure.

Question 117: A 72-year-old woman with metastatic ovarian cancer is brought to the physician by her son because she is in immense pain and cries all the time. On a 10-point scale, she rates the pain as an 8 to 9. One week ago, a decision to shift to palliative care was made after she failed to respond to 2 years of multiple chemotherapy regimens. She is now off chemotherapy drugs and has been in hospice care. Current medications include 2 mg morphine intravenously every 2 hours and 650 mg of acetaminophen every 4 to 6 hours. The son is concerned because he read online that increasing the dose of morphine would endanger her breathing. Which of the following is the most appropriate next step in management?

• A. Counsel patient and continue same opioid dose
• B. Increase dosage of morphine (Correct Answer)
• C. Change morphine to a non-opioid analgesic
• D. Initiate palliative radiotherapy
• E. Initiate cognitive behavioral therapy

Explanation: ***Increase dosage of morphine*** - The patient is experiencing severe, **uncontrolled pain** (8-9/10), indicating her current morphine dose is inadequate. In palliative care, the goal is to provide maximum comfort, and **opioid dose escalation** is appropriate to achieve this. - While respiratory depression is a concern with opioids, in patients with chronic pain who are already on opioids, **tolerance to respiratory depressant effects** develops more quickly than tolerance to analgesic effects. Careful titration and monitoring can safely increase pain relief. *Counsel patient and continue same opioid dose* - The patient's pain is severe and unmanaged, so simply counseling her without addressing the **inadequate analgesia** would be inappropriate and unethical. - Continuing the same dose would perpetuate her suffering, as the current regimen is clearly **insufficient for pain control**. *Change morphine to a non-opioid analgesic* - For severe cancer pain (8-9/10), **non-opioid analgesics** alone are typically ineffective. - Switching to a non-opioid would likely lead to even poorer pain control and increased suffering, as opioids are the **cornerstone of severe cancer pain management**. *Initiate palliative radiotherapy* - While **radiotherapy** can be effective for localized pain caused by bone metastases, its onset of action is not immediate, and the primary issue here is urgent, **uncontrolled systemic pain**. - It is not an appropriate initial step for immediate pain relief in a patient already in hospice with widespread metastatic disease and severe current pain. *Initiate cognitive behavioral therapy* - **Cognitive behavioral therapy (CBT)** can be a useful adjunct in chronic pain management to help with coping strategies and psychological distress. - However, it does not directly address the severe, acute physical pain the patient is experiencing and is not a substitute for **pharmacological pain control** in this context.

Question 118: A well-dressed couple presents to the emergency department with sudden onset of headache, a sensation of floating, and weakness of arms and legs after eating a plate of shellfish 2 hours ago. They mention that they had experienced tingling of the lips and mouth within 15 minutes of ingesting the shellfish. They also complain of mild nausea and abdominal discomfort. On physical examination, their vital signs are within normal limits. Their neurological examination reveals decreased strength in all extremities bilaterally and hyporeflexia. After detailed laboratory evaluation, the physician confirms the diagnosis of paralysis due to the presence of a specific toxin in the shellfish they had consumed. Which of the following mechanisms best explains the action of the toxin these patients had consumed?

• A. Inactivation of syntaxin
• B. Increased opening of presynaptic calcium channels
• C. Blockade of voltage-gated fast sodium channels (Correct Answer)
• D. Inactivation of synaptobrevin
• E. Inhibition of acetylcholinesterase

Explanation: ***Blockade of voltage-gated fast sodium channels*** - The symptoms described, particularly **tingling of the lips and mouth**, **sensation of floating**, **weakness**, and **paralysis** after consuming shellfish, are classic for **paralytic shellfish poisoning (PSP)** caused by **saxitoxin**. - Saxitoxin acts by **blocking voltage-gated fast sodium channels** in excitable membranes (neurons and muscles), preventing depolarization and impulse propagation. *Inactivation of syntaxin* - **Syntaxin** is a **SNARE protein** involved in the fusion of synaptic vesicles with the presynaptic membrane, essential for neurotransmitter release. - Toxins like **botulinum neurotoxins** (specifically serotypes C1, A, E) can cleave syntaxin, leading to **flaccid paralysis** by preventing acetylcholine release. However, the onset and nature of symptoms (e.g., tingling, sensation of floating) differ from botulism. *Increased opening of presynaptic calcium channels* - Increased opening of **presynaptic calcium channels** would lead to **exaggerated neurotransmitter release**, resulting in symptoms like **spasms** or **tetany**, not flaccid paralysis or weakness. - Examples include **black widow spider venom** (alpha-latrotoxin), which causes a massive influx of presynaptic calcium and widespread acetylcholine release. *Inactivation of synaptobrevin* - **Synaptobrevin** (also known as VAMP) is another **SNARE protein** located on synaptic vesicles, crucial for neurotransmitter release. - **Tetanus toxin** and **other botulinum neurotoxins** (serotypes B, D, F, G) specifically cleave synaptobrevin, preventing vesicle fusion and neurotransmitter release, leading to **spastic paralysis** (tetanus) or **flaccid paralysis** (botulism). *Inhibition of acetylcholinesterase* - **Acetylcholinesterase inhibitors** prevent the breakdown of **acetylcholine** in the synaptic cleft, leading to an **accumulation of acetylcholine** and continuous stimulation of cholinergic receptors. - This would result in symptoms like **salivation, lacrimation, urination, defecation, gastrointestinal upset, emesis (SLUDGE)**, muscle fasciculations, and eventually paralysis due to prolonged depolarization block, which is not consistent with the primary symptoms experienced by the patients.

Question 119: A 64-year-old woman comes to the physician because of gradually worsening blurry vision in both eyes for 5 months. She has also had intermittent headaches for the past 2 months. She has type 2 diabetes mellitus, osteoarthritis, second-degree heart block, and presbyopia. Her current medications include metformin, lisinopril, and ibuprofen. Examination shows bilateral equal and reactive pupils. The best-corrected visual acuity in each eye is 20/40. There is narrowing of her visual fields bilaterally. Fundoscopic examination shows bilateral narrowing of the outer rim of the optic nerve head and cupping of the optic disk. Intraocular pressure by applanation tonometry is 27 mm Hg in the right eye and 26 mm Hg in the left eye (N=10–21 mm Hg). Gonioscopy shows no abnormalities. Which of the following is the most appropriate next step in management?

• A. Surgical trabeculectomy
• B. Topical pilocarpine therapy
• C. Topical latanoprost therapy (Correct Answer)
• D. Laser iridotomy
• E. Topical timolol

Explanation: ### ***Topical latanoprost therapy*** - This patient's presentation, including elevated **intraocular pressure**, **bilateral visual field narrowing**, and **optic disc cupping**, is highly suggestive of **primary open-angle glaucoma (POAG)**. - **Topical prostaglandin analogs** like latanoprost are the **first-line treatment** for POAG due to their efficacy in reducing intraocular pressure by increasing **uveoscleral outflow**. - Latanoprost is particularly appropriate for this patient given her **second-degree heart block**, as it avoids the cardiac effects associated with beta-blockers. ### *Surgical trabeculectomy* - **Trabeculectomy** is a surgical procedure typically reserved for cases where medical therapy fails to adequately control intraocular pressure or when there is progressive visual field loss despite maximal medical treatment. - It is generally not the initial management step for newly diagnosed **primary open-angle glaucoma (POAG)**. ### *Topical pilocarpine therapy* - **Pilocarpine** is a **miotic agent** that increases **trabecular outflow** but is generally considered a second or third-line agent for glaucoma due to its significant side effects, such as **ciliary spasm**, **brow ache**, and **miosis**, which can impair vision, especially in older patients. - It is not the preferred initial therapy over prostaglandin analogs or beta-blockers. ### *Laser iridotomy* - **Laser iridotomy** is the definitive treatment for **angle-closure glaucoma** where the iris blocks the trabecular meshwork. - The patient's **gonioscopy showed no abnormalities**, indicating an **open-angle**, ruling out angle-closure glaucoma. ### *Topical timolol* - **Topical timolol**, a **beta-blocker**, lowers intraocular pressure by **decreasing aqueous humor production**. While it is an effective first-line agent for POAG, it should be used with caution in patients with **second-degree heart block** due to potential cardiac effects from systemic absorption. - Latanoprost is preferred in this patient given her cardiac comorbidity, as it offers once-daily dosing and avoids beta-blocker-related cardiac risks.

Question 120: A 14-year-old boy is admitted to the emergency department with acute onset of confusion, malaise, diffuse abdominal pain, nausea, and a single episode of vomiting. He denies ingestion of any suspicious foods, fevers, respiratory symptoms, or any other symptoms preceding his current condition. However, he notes an increase in his liquid consumption and urinary frequency over the last 6 months. On physical examination, he is responsive but somnolent. His blood pressure is 90/50 mm Hg, heart rate is 101/min, respiratory rate is 21/min, temperature is 36.0°C (96.8°F), and SpO2 is 96% on room air. He has facial pallor and dry skin and mucous membranes. His lungs are clear to auscultation, and heart sounds are normal. His abdomen is soft with no rebound tenderness on palpation. Neurological examination is significant for 1+ deep tendon reflexes in all extremities. A dipstick test shows 3+ for ketones and glucose. The patient’s blood tests show the following findings: RBCs 4.1 million/mm3 Hb 13.7 mg/dL Hematocrit 56% Leukocyte count 7,800/mm3 Platelet count 321,000/mm3 Glucose 565 mg/dL Potassium 5.8 mEq/L Sodium 136 mEq/L ALT 15 U/L AST 17 U/L Amylase 88 U/L Bicarbonate 19 mEq/L BE −3 mEq/L pH 7.3 pCO2 37 mm Hg pO2 66 mm Hg Which of the medications listed below should be administered to the patient intravenously?

• A. Insulin detemir
• B. Regular insulin (Correct Answer)
• C. Cefazolin
• D. Potassium chloride
• E. Isophane insulin

Explanation: **Regular insulin** - The patient presents with **diabetic ketoacidosis (DKA)**, characterized by **hyperglycemia** (glucose 565 mg/dL), **ketonuria** (ketones 3+), and **metabolic acidosis** (pH 7.3, bicarbonate 19 mEq/L, BE -3 mEq/L). **Intravenous regular insulin** is the cornerstone of DKA treatment to lower blood glucose and resolve ketosis. - Regular insulin is the only type of insulin that can be administered intravenously and has a **rapid onset** and **short duration of action**, allowing for precise titration and quick correction of severe hyperglycemia and acidosis. *Insulin detemir* - **Insulin detemir** is a **long-acting insulin analog** primarily used for basal insulin replacement, not for acute management of severe hyperglycemia or DKA. - It has a **slow onset of action** (1-2 hours) and a prolonged duration (up to 24 hours), making it unsuitable for the urgent and rapid correction required in DKA. *Cefazolin* - **Cefazolin** is a **first-generation cephalosporin antibiotic** used to treat bacterial infections. - This patient's symptoms are consistent with DKA, not a bacterial infection, and there is no indication for antibiotic therapy. *Potassium chloride* - Despite the patient's **hyperkalemia** (potassium 5.8 mEq/L) at presentation, DKA treatment with insulin will shift potassium intracellularly, leading to **hypokalemia**. - **Potassium chloride** is typically added to IV fluids **after insulin therapy has begun and potassium levels start to drop**, to prevent severe hypokalemia, not as an initial treatment when levels are already high. *Isophane insulin* - **Isophane insulin (NPH)** is an **intermediate-acting insulin** that is administered subcutaneously. - It has a **delayed onset of action** (2-4 hours) and cannot be given intravenously, making it inappropriate for the acute management of DKA.

Question 121: A 25-year-old woman comes into her family doctor’s clinic confused as to how she failed her work-required urine drug test. The patient has no significant past medical history and takes no medications. She states that she does not smoke and denies ever using any alcohol or recreational drugs. The patient’s social history reveals a recent change in her diet. For the past 2-weeks, she was experimenting with a ketogenic diet and using poppy seed bagels as her only source of carbohydrates. Her vital signs and physical examination are within normal limits. Which of the following physical exam findings might be present had this patient really been abusing the class of drug for which she most likely tested positive?

• A. Tachypnea
• B. Myalgia
• C. Anhidrosis
• D. Conjunctival injection
• E. Miosis (Correct Answer)

Explanation: ***Miosis*** - Poppy seeds can cause a false positive for **opiates** (morphine/codeine) on urine drug screens. Acute opiate intoxication typically causes **miosis** (pinpoint pupils) due to parasympathetic stimulation. - Other signs of acute opiate intoxication include **respiratory depression** and **CNS depression**. *Tachypnea* - **Tachypnea** (increased respiratory rate) is not a typical sign of acute opiate intoxication; rather, **bradypnea** or **respiratory depression** is characteristic. - Tachypnea is more commonly seen with stimulant abuse, anxiety, or metabolic acidosis. *Myalgia* - **Myalgia** (muscle pain) is a common symptom of **opiate withdrawal**, not acute intoxication. - During acute opiate use, patients more commonly experience analgesia. *Anhidrosis* - The class of drugs involved here is **opiates**, which typically cause **diaphoresis** (sweating), not anhidrosis (absence of sweating). - Anhidrosis can be a symptom of certain neurological conditions or anticholinergic toxicity. *Conjunctival injection* - **Conjunctival injection** (red eyes) is more commonly associated with **cannabis use**. - Opiate intoxication typically causes **miosis** and sometimes mild conjunctival changes but not prominent injection.

Question 122: A 32-year-old woman comes to the clinic with concerns related to her medication. She recently learned that she is pregnant and wants to know if she needs to change anything. She is taking levothyroxine for hypothyroidism. She does not take any other medication. A urine pregnancy test is positive. What should this patient be advised about her medication during pregnancy?

• A. She can continue taking her medication at the usual dose
• B. She should be switched to an alternative medication
• C. Her medication dose should be increased by 30% (Correct Answer)
• D. She should stop taking her medication immediately
• E. The decision should be based on an evaluation of fetal risks and maternal benefits

Explanation: ***Her medication dose should be increased by 30%*** - During pregnancy, **levothyroxine** requirements typically increase by **25-50%** due to increased maternal metabolism, estrogen-induced increases in thyroid-binding globulin, and fetal thyroid hormone needs. - An increase of approximately **30%** is a common initial adjustment, with further titration based on TSH levels. *She can continue taking her medication at the usual dose* - Continuing the usual dose of **levothyroxine** without adjustment is likely to result in **suboptimal thyroid hormone levels**, as pregnancy significantly increases the demand for thyroid hormones. - **Maternal hypothyroidism** during pregnancy is associated with adverse outcomes for both the mother and the fetus, including pre-eclampsia, preterm birth, and impaired neurodevelopment in the child. *She should be switched to an alternative medication* - **Levothyroxine** is the **treatment of choice** for hypothyroidism during pregnancy and is considered safe for both mother and fetus. - There is typically no medical reason to switch to an alternative medication for treating hypothyroidism during pregnancy. *She should stop taking her medication immediately* - Discontinuing **levothyroxine** immediately would lead to uncontrolled **maternal hypothyroidism**, which poses a significant risk to the developing fetus, impacting neurodevelopment and increasing the risk of obstetric complications. - **Thyroid hormone** is crucial for proper fetal growth and development, especially in the first trimester before the fetal thyroid gland is fully functional. *The decision should be based on an evaluation of fetal risks and maternal benefits* - While evaluating fetal risks and maternal benefits is generally prudent for medication decisions in pregnancy, for **levothyroxine**, the **benefits overwhelmingly outweigh any risks**, and maintaining optimal thyroid function is critical. - The primary decision regarding **levothyroxine** in pregnancy is not whether to continue but rather how to **adjust the dose** to meet increased physiological demands.

Question 123: A 48-year-old man is brought to the emergency department 20 minutes after being rescued from a house fire. He reports headache, metallic taste, abdominal pain, and nausea. He appears confused and agitated. His pulse is 125/min, respirations are 33/min, and blood pressure is 100/65 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 98%. Physical examination shows a bright red color of the skin. His breath smells of bitter almonds. Hyperbaric oxygen therapy and appropriate pharmacotherapy are initiated. The expected beneficial effect of this drug is most likely due to which of the following mechanisms?

• A. Synthesis of 2,3-bisphosphoglycerate
• B. Formation of methemoglobin (Correct Answer)
• C. Inhibition of cytochrome c oxidase
• D. Dissociation of carboxyhemoglobin
• E. Reduction of ferric iron

Explanation: ***Formation of methemoglobin*** - This patient's symptoms (headache, confusion, bright red skin, bitter almond breath, high pulse oximetry despite severe symptoms) are classic for **cyanide poisoning**. - Many antidotes for cyanide poisoning, such as **nitrites**, work by forming **methemoglobin**, which has a higher affinity for cyanide than cytochrome c oxidase, thus detaching cyanide from the enzyme and allowing cellular respiration to resume. *Synthesis of 2,3-bisphosphoglycerate* - **2,3-bisphosphoglycerate (2,3-BPG)** helps regulate oxygen release from hemoglobin in red blood cells. - While important for oxygen delivery, increasing 2,3-BPG is not a direct therapeutic mechanism for **cyanide poisoning**. *Inhibition of cytochrome c oxidase* - **Cyanide** itself inhibits cytochrome c oxidase, leading to cellular hypoxia despite adequate oxygen supply. - The therapeutic goal is to reverse this inhibition, not to further inhibit the enzyme. *Dissociation of carboxyhemoglobin* - **Carbon monoxide poisoning**, not cyanide poisoning, causes carboxyhemoglobin formation and presents with cherry-red skin, but there is no foul-smelling breath. - Dissociating carboxyhemoglobin is relevant for carbon monoxide poisoning, not cyanide poisoning. *Reduction of ferric iron* - Reducing ferric iron (Fe3+) back to ferrous iron (Fe2+) would reverse **methemoglobinemia**, which is often a side effect of some cyanide antidotes. - The therapeutic strategy for cyanide poisoning involves *inducing* methemoglobinemia to sequester cyanide.

Question 124: A 71-year-old man is brought to the emergency department by his wife because of increasing confusion, weakness, and vomiting for 1 day. He has had 5 episodes of vomiting and blurry vision; he told his wife that "everything appears in different colors." He has been unable to recall his wife's name or their address. His wife reports that his drug regimen was adjusted because of worsening tibial edema 1 week ago. He has congestive heart failure, atrial fibrillation, hypothyroidism, and osteoarthritis. Current medications include rivaroxaban, metoprolol, digoxin, levothyroxine, spironolactone, and furosemide. His temperature is 36.7°C (98°F), pulse is 56/min, and blood pressure is 98/68 mm Hg. He is confused and oriented only to person. Neurologic examination shows no focal findings. The abdomen is soft, and there is tenderness to palpation of both lower quadrants without guarding or rebound. There is 1+ pitting edema of both ankles. This patient is most likely to have which of the following ECG findings?

• A. Low QRS voltage
• B. Increased PR interval (Correct Answer)
• C. Mobitz type 2 atrioventricular block
• D. Prolonged QT interval
• E. Peaked T waves

Explanation: ***Increased PR interval*** - The patient's symptoms (confusion, weakness, vomiting, blurry vision with "everything appears in different colors," bradycardia) are classic signs of **digoxin toxicity**. Digoxin primarily affects the **AV node**, leading to slowed conduction and thus an **increased PR interval** on ECG. - The recent adjustment of his diuretic regimen (spironolactone and furosemide) for worsening edema suggests possible **hypokalemia** or **renal impairment**, which can precipitate digoxin toxicity even at therapeutic levels. *Low QRS voltage* - **Low QRS voltage** is typically associated with conditions like **pericardial effusion**, severe hypothyroidism, or diffuse myocardial disease, which are not directly suggested by the patient's acute presentation. - While the patient has hypothyroidism, acute digoxin toxicity does not primarily cause low QRS voltage. *Mobitz type 2 atrioventricular block* - While digoxin toxicity can cause various arrhythmias, **Mobitz type 2 AV block** (characterized by constant PR interval before a dropped beat) usually indicates issues deeper in the His-Purkinje system. - **First-degree AV block** (increased PR interval) and **Wenckebach (Mobitz type 1) AV block** are more common manifestations of digoxin's direct inhibitory effect on the AV node. *Prolonged QT interval* - A **prolonged QT interval** is associated with an increased risk of **Torsades de Pointes** and can be caused by certain antiarrhythmics (e.g., amiodarone, sotalol) or electrolyte imbalances, but it is not a direct or typical ECG finding of digoxin toxicity. - Digoxin toxicity is more commonly associated with a **shortened QT interval** or "scooping" of the ST segment. *Peaked T waves* - **Peaked T waves** are a hallmark of **hyperkalemia**, an electrolyte disturbance that can cause cardiac arrhythmias and muscle weakness. - While electrolyte imbalances can contribute to digoxin toxicity, peaked T waves themselves are not a direct consequence of digoxin.

Question 125: An 81-year-old man is admitted to the hospital due to acute decompensated heart failure. He has type 2 diabetes mellitus, hypertension, coronary artery disease, and congestive heart failure. Current medications include lisinopril, metformin, and low-dose aspirin. He has smoked one pack of cigarettes daily for 45 years. His temperature is 37.6°C (99.7°F), pulse is 105/min and regular, respirations are 21/min, and blood pressure is 103/64 mm Hg. Laboratory studies show: Hemoglobin 13.7 g/dL Leukocyte count 8200/mm3 Serum Na+ 128 mEq/L Cl- 98 mEq/L K+ 4.9 mEq/L Urea nitrogen 58 mg/dL Glucose 200 mg/dL Creatinine 2.2 mg/dL Which of the following changes in the medication regimen is most appropriate in this patient at this time?

• A. Begin vancomycin therapy
• B. Discontinue aspirin therapy
• C. Begin nitroprusside therapy
• D. Discontinue metformin therapy (Correct Answer)
• E. Begin hydrochlorothiazide therapy

Explanation: ***Discontinue metformin therapy*** - The patient has **acute decompensated heart failure** with **acute kidney injury** (creatinine 2.2 mg/dL, BUN 58 mg/dL). Metformin is **contraindicated in acute kidney injury** due to the significantly increased risk of **lactic acidosis**. - With renal failure, metformin excretion is impaired, leading to drug accumulation and dangerous elevations in lactic acid levels. **Immediate discontinuation** is critical to prevent this life-threatening complication. - Current guidelines recommend avoiding metformin when eGFR <30 mL/min or creatinine >1.5 mg/dL in males. *Begin vancomycin therapy* - There is **no indication of bacterial infection** (normal leukocyte count 8200/mm³, only mild temperature elevation to 37.6°C, no localizing signs). - Initiating broad-spectrum antibiotics like vancomycin without clear evidence of infection contributes to **antibiotic resistance** and potential adverse effects. *Discontinue aspirin therapy* - The patient has a history of **coronary artery disease** and **congestive heart failure**, making him high risk for acute coronary events. - Aspirin provides crucial **antiplatelet therapy** for secondary prevention of cardiovascular events in this patient population and should be continued. *Begin nitroprusside therapy* - Nitroprusside is a potent vasodilator used in **hypertensive emergencies** or severe heart failure with elevated blood pressure. - This patient currently has **hypotension** (BP 103/64 mm Hg), and nitroprusside would further lower blood pressure, potentially causing cardiovascular collapse and end-organ hypoperfusion. *Begin hydrochlorothiazide therapy* - While diuretics are used in heart failure, hydrochlorothiazide is a **thiazide diuretic** primarily effective with preserved renal function (eGFR >30 mL/min). - This patient has **elevated creatinine (2.2 mg/dL)**, indicating acute kidney injury, which would significantly limit the efficacy of hydrochlorothiazide. **Loop diuretics** (furosemide) would be more appropriate if diuresis is needed in the setting of renal impairment.

Question 126: A 48-year-old woman comes to the physician because of recurrent right upper abdominal pain for 3 weeks. The pain usually occurs after meals and tends to radiate to the right shoulder. She reports that she otherwise feels well. She has more energy since she started an intermittent fasting diet and has rapidly lost 9.0 kg (20 lbs). She is 160 cm (5 ft 3 in) tall and weighs 100 kg (220 lb); BMI is 39.1 kg/m2. Physical examination shows a nontender abdomen. Abdominal ultrasonography shows several small stones in the gallbladder without calcification. When discussing treatment options, she states that she does not wish to undergo surgery and asks about other possibilities. Which of the following is the most appropriate pharmacotherapy to address the underlying cause of this patient's condition?

• A. Ezetimibe
• B. Hydromorphone
• C. Ursodeoxycholic acid (Correct Answer)
• D. Gemfibrozil
• E. Colestipol

Explanation: ***Ursodeoxycholic acid*** - This medication is a **bile acid** that can dissolve **cholesterol gallstones** by reducing cholesterol synthesis and secretion into bile, and by stabilizing the gallbladder membrane. - It is appropriate for patients with **symptomatic gallstones** who are poor surgical candidates or refuse surgery, especially when the stones are small and non-calcified. *Ezetimibe* - This drug works by inhibiting the absorption of **cholesterol** from the small intestine. - While it lowers cholesterol, it is not a primary treatment for dissolving existing **gallstones**. *Hydromorphone* - This is an **opioid analgesic** used for managing severe pain. - It would only mask the symptoms of gallstones and does not address the underlying pathology or dissolution of the stones. *Gemfibrozil* - This fibrate medication primarily lowers **triglycerides** and can also increase HDL cholesterol. - It works by activating peroxisome proliferator-activated receptor alpha (PPAR-alpha) but is not indicated for dissolving gallstones. *Colestipol* - This is a **bile acid sequestrant** that binds bile acids in the intestine, preventing their reabsorption and increasing their excretion. - While it lowers cholesterol, it can actually **increase the risk of gallstone formation** by altering bile composition rather than dissolving them.

Question 127: A 62-year-old Caucasian male receiving treatment for stable angina experiences intermittent throbbing headaches. What is the most likely cause?

• A. Transient ischemic attack
• B. Beta adrenergic inactivation
• C. Acute hemorrhage
• D. Vasodilation of cerebral arteries (Correct Answer)
• E. Elevated creatine kinase

Explanation: ***Vasodilation of cerebral arteries*** - Many medications used to treat **stable angina**, such as **nitrates**, achieve their therapeutic effect through **vasodilation**. - This vasodilation can extend to the **cerebral arteries**, leading to an increase in intracranial arterial pulsatility, which is often perceived as a **throbbing headache**. *Transient ischemic attack* - A TIA typically presents with **focal neurological deficits** (e.g., weakness, numbness, speech difficulties) that resolve within 24 hours, not primarily with isolated headaches. - While headache can occur, it's not the hallmark symptom and usually accompanies other transient neurological symptoms. *Beta adrenergic inactivation* - **Beta-blockers**, while used for angina, typically do not cause throbbing headaches; in fact, they are sometimes used to prevent migraines. - **Inactivation** or withdrawal of beta-blockers might cause rebound symptoms but regular use is not linked to this type of headache. *Acute hemorrhage* - An **acute hemorrhage**, especially in the brain, often causes a **sudden, severe "thunderclap" headache** accompanied by neurological deficits, altered mental status, or signs of meningeal irritation, which are not described here as intermittent or mild. - The description of "intermittent throbbing headaches" does not fit the typical presentation of an acute intracranial hemorrhage. *Elevated creatine kinase* - **Elevated creatine kinase (CK)** indicates muscle damage and is not directly related to headaches. - While some medications (e.g., statins) can cause myopathy and elevated CK, this is not a common cause of headaches, particularly throbbing ones.

Question 128: A 6-year-old boy is brought to the physician by his mother for a follow-up examination. He has persistent bedwetting. Over the past year, his parents have attempted various methods to prevent him from wetting his bed, including fluid restriction in the evenings, sticker rewards, and bedwetting alarms, with no improvement. The patient wets his bed 2–3 times a week. He does not have problems going to the bathroom during the day. The physician prescribes an oral medication that successfully controls his symptoms. The most likely effect of this drug on the principal cells of the kidney is increased activity of which of the following?

• A. Phospholipase C
• B. Adenylate cyclase (Correct Answer)
• C. Steroid hormone response element
• D. Guanylate cyclase
• E. Tyrosine kinase

Explanation: ***Adenylate cyclase*** - The drug prescribed is likely **desmopressin** (DDAVP), an analog of **antidiuretic hormone** (ADH), used to treat **nocturnal enuresis** by reducing urine production during the night. - ADH binds to **V2 receptors** on the principal cells of the collecting ducts, activating **adenylate cyclase** to increase **cAMP** production, which then inserts **aquaporin-2 channels** into the apical membrane, leading to increased water reabsorption. *Phospholipase C* - **Phospholipase C** is typically activated by signaling pathways involving **Gq proteins**, leading to the production of **inositol triphosphate (IP3)** and **diacylglycerol (DAG)**, which then increase intracellular **calcium** and activate **protein kinase C**. - While some ADH receptors (V1) activate phospholipase C, the **V2 receptors** in the kidney responsible for water reabsorption primarily act through **adenylate cyclase**. *Steroid hormone response element* - **Steroid hormones** (e.g., aldosterone, cortisol) diffuse through the cell membrane and bind to **intracellular receptors**, which then translocate to the nucleus and bind to **steroid hormone response elements** on DNA to directly alter gene transcription. - This mechanism is associated with a slower, long-term effect on gene expression, rather than the rapid modulation of water reabsorption seen with ADH. *Guanylate cyclase* - **Guanylate cyclase** produces **cyclic GMP (cGMP)**, which is involved in various signaling pathways, notably those mediated by **nitric oxide (NO)** and **natriuretic peptides**. - cGMP signaling is more commonly associated with vasodilation and regulation of blood pressure, and it is not the primary mechanism of action for ADH in water reabsorption in the kidney. *Tyrosine kinase* - **Tyrosine kinase receptors** are often involved in growth factor signaling, insulin action, and cytokine responses, where ligand binding leads to receptor dimerization and phosphorylation of tyrosine residues on the receptor and downstream proteins. - This mechanism is distinct from the G protein-coupled receptor (GPCR) pathway utilized by ADH.

Question 129: A 19-year-old African American male with a history of bipolar I disorder presents to the psychiatrist for a follow-up visit. During the session, the patient explains that for the past 2 months he has felt significantly fatigued and constipated. He is always complaining of feeling cold and has gained several pounds although his diet has not changed. A blood sample was sent for analysis, revealing the following: TSH - 6 mIU/L (nl = 0.4-4.0 mIU/L), free T4 - 0.4 ng/dL (nl = 0.7-1.9 ng/dL), and serum T4 - 2.1 mcg/dL (nl = 4.6-12 mcg/dL). Which of the following is responsible for these abnormalities?

• A. Valproic acid
• B. Lamotrigine
• C. Lithium (Correct Answer)
• D. Olanzapine
• E. Carbamazepine

Explanation: ***Lithium*** - The patient's symptoms (fatigue, constipation, cold intolerance, weight gain) and lab results (**elevated TSH** and **low free T4/T4**) are consistent with **hypothyroidism**. - **Lithium** is a known mood stabilizer used in bipolar disorder that can induce hypothyroidism by interfering with thyroid hormone synthesis and release. *Valproic acid* - Valproic acid can cause several side effects, including **hepatotoxicity**, **pancreatitis**, and **thrombocytopenia**, but it does not typically cause hypothyroidism. - It works by increasing GABA levels in the brain and is not known to directly affect thyroid function in a manner that would cause these symptoms and lab findings. *Lamotrigine* - Lamotrigine is an anticonvulsant and mood stabilizer primarily associated with dermatological side effects like **Stevens-Johnson syndrome (SJS)**. - It is not commonly linked to thyroid dysfunction or the development of hypothyroidism. *Olanzapine* - Olanzapine is an atypical antipsychotic known for metabolic side effects such as **weight gain**, **hyperglycemia**, and **dyslipidemia**. - While it can cause weight gain, it does not typically lead to the specific constellation of symptoms and thyroid hormone abnormalities seen in this patient. *Carbamazepine* - Carbamazepine is an anticonvulsant that can cause side effects like **hyponatremia** (due to SIADH) and **agranulocytosis**. - Although it can rarely lead to thyroid abnormalities, it’s less commonly associated with symptomatic hypothyroidism and the specific lab profile presented compared to lithium.

Question 130: A 14-year-old girl is brought by her parents to the physician because of recurrent episodes of shortness of breath and nonproductive cough over the past 3 months. She has had two episodes per week, which have resolved spontaneously with rest. Once a month, she wakes up at night with shortness of breath. Spirometry shows an FVC of 95% and an FEV1 of 85% of predicted. Treatment with inhaled budesonide-formoterol as needed is begun. Two weeks later, she is brought to the physician with acute onset of dyspnea and wheezing. Her pulse is 95/min and respirations are 32/min. Which of the following is the most appropriate initial pharmacotherapy?

• A. Salmeterol
• B. Guaifenesin
• C. Montelukast sodium
• D. Fluticasone
• E. Albuterol (Correct Answer)

Explanation: ***Albuterol*** - The girl is experiencing an acute asthma exacerbation, characterized by **dyspnea** and **wheezing** despite current therapy. - **Albuterol** is a **short-acting beta-2 agonist (SABA)**, which provides rapid bronchodilation and is the most appropriate first-line treatment for acute asthma symptoms. *Salmeterol* - **Salmeterol** is a **long-acting beta-2 agonist (LABA)**, used for maintenance therapy, not for acute symptom relief. - LABAs should always be used in combination with an inhaled corticosteroid (ICS) for long-term control. *Guaifenesin* - **Guaifenesin** is an **expectorant** used to thin mucus and relieve cough, but it does not address the underlying bronchospasm of asthma. - It is not indicated for the management of acute dyspnea and wheezing in asthma. *Montelukast sodium* - **Montelukast** is a **leukotriene receptor antagonist** used for long-term asthma control and prevention of exercise-induced bronchoconstriction. - It is not effective for acute asthma exacerbations requiring immediate bronchodilation. *Fluticasone* - **Fluticasone** is an **inhaled corticosteroid (ICS)** used for long-term asthma control to reduce airway inflammation. - While crucial for maintenance, it does not provide rapid relief during an acute asthma attack.

Question 131: An 18-year-old man is brought to the emergency department by his girlfriend because of a pruritic rash on his penis that has been present for the past hour. The rash developed shortly after the patient had protected sexual intercourse with his girlfriend for the first time. His girlfriend does not have any symptoms. Five days ago, the patient visited a friend who was complaining of intense pruritus on her elbows, wrists, groin, and axillae. The friend subsequently underwent treatment that required her to wash her bedding, clothing, and towels in hot water. Two years ago, the patient developed an itchy rash around his mouth after blowing up balloons at a birthday party. He is breathing comfortably. Vitals signs are within normal limits. Examination shows multiple well-circumscribed, raised, erythematous plaques with mild excoriations that extend from the base to the glans of the penis. The remainder of the examination shows no abnormalities. Administration of which of the following is the most appropriate next step in management?

• A. Oral cromolyn sodium
• B. Intravenous acyclovir
• C. Subcutaneous epinephrine
• D. Oral cetirizine (Correct Answer)
• E. Oral famotidine

Explanation: ***Correct Option: Oral cetirizine*** - The patient presents with **pruritic, raised, erythematous plaques** consistent with **acute urticaria (hives)**, likely triggered by an allergic reaction (probably **latex allergy** from the condom, given his history of developing a rash after blowing up latex balloons). - **Oral antihistamines** like cetirizine (an H1 receptor blocker) are the **first-line treatment** for acute urticaria to alleviate pruritus and reduce swelling by blocking histamine effects. - The patient is **hemodynamically stable** with a **localized reaction**, making oral antihistamines appropriate. *Incorrect Option: Oral cromolyn sodium* - This medication is a **mast cell stabilizer** used primarily for **asthma prophylaxis** and some allergic conditions (e.g., allergic conjunctivitis, mastocytosis). - It is **not effective as an acute treatment** for urticaria because it prevents histamine release rather than blocking its effects once released. - Cromolyn must be used prophylactically, not for acute symptoms. *Incorrect Option: Intravenous acyclovir* - Acyclovir is an **antiviral agent** used to treat **herpes simplex virus (HSV) infections**. - The patient's rash consists of urticarial plaques, not the characteristic **grouped vesicles on an erythematous base** or **painful ulcers** seen in genital HSV. - The acute onset immediately after exposure and the morphology are inconsistent with HSV. *Incorrect Option: Subcutaneous epinephrine* - **Epinephrine** is indicated for **anaphylaxis** with signs of airway compromise, bronchospasm, hypotension, or widespread systemic symptoms. - The patient is **breathing comfortably with stable vitals**, indicating this is a **localized allergic reaction (urticaria)**, not anaphylaxis. - There is no indication for epinephrine in isolated cutaneous reactions without systemic involvement. *Incorrect Option: Oral famotidine* - Famotidine is an **H2 receptor blocker** typically used to reduce gastric acid in conditions like **GERD or peptic ulcers**. - While H2 blockers **can be used as adjunctive therapy** with H1 blockers in refractory or chronic urticaria, they are **not first-line monotherapy**. - **H1 antihistamines are more effective** for acute urticaria and should be tried first.

Question 132: A 6-year-old boy is brought to the physician because of a 2-week history of frequent episodes of unresponsiveness. During these episodes, he stares blankly, rhythmically nods his head, and does not respond to verbal stimulation for several seconds. Hyperventilation for 30 seconds precipitates an episode of unresponsiveness and head nodding that lasts for 7 seconds. He regains consciousness immediately afterward. An electroencephalogram shows 3-Hz spikes and waves. Which of the following best describes the mechanism of action of the most appropriate pharmacotherapy for this patient's condition?

• A. Inhibition of GABA reuptake into presynaptic neurons
• B. Increased frequency of GABAA channel opening
• C. Irreversible inhibition of GABA transaminase
• D. Increased duration of GABAA channel opening
• E. Blockade of thalamic T-type calcium channels (Correct Answer)

Explanation: ***Blockade of thalamic T-type calcium channels*** - The patient's presentation with **staring spells**, rhythmic head nodding, and precipitation by **hyperventilation** is classic for **absence epilepsy**. The EEG findings of **3-Hz spikes and waves** confirm this diagnosis. - **Ethosuximide** is the first-line treatment for absence seizures. It works by selectively blocking **T-type calcium channels** in the thalamus, which are crucial for generating the 3-Hz spike-and-wave discharges. *Inhibition of GABA reuptake into presynaptic neurons* - This mechanism of action is characteristic of **tiagabine**, an antiepileptic drug primarily used as an add-on therapy for **focal seizures**. - While GABAergic mechanisms are involved in epilepsy, tiagabine is not a primary treatment for absence seizures and does not target the specific thalamic pathways involved. *Increased frequency of GABAA channel opening* - This is the mechanism of action of **benzodiazepines**, such as **lorazepam** or **diazepam**, which enhance the inhibitory effects of GABA. - Benzodiazepines are typically used for acute seizure management (e.g., **status epilepticus**) or as adjunct therapy, but not as first-line monotherapy for absence seizures due to sedation and tolerance issues. *Irreversible inhibition of GABA transaminase* - This mechanism describes **vigabatrin**, an antiepileptic drug that increases GABA levels by inhibiting its breakdown. - Vigabatrin is primarily used for **infantile spasms** and **refractory focal seizures**, and it is associated with a risk of **visual field defects**, making it unsuitable for absence epilepsy. *Increased duration of GABAA channel opening* - This mechanism is characteristic of **barbiturates**, such as **phenobarbital**, which also enhance GABAergic inhibition like benzodiazepines but by increasing the duration of chloride channel opening. - Barbiturates are older antiepileptic drugs with significant side effects (e.g., sedation) and are generally not preferred for absence seizures.

Question 133: Drug A is an experimental compound being investigated for potential use as a protectant against venous thrombosis. Binding assays reveal that the drug’s primary mechanism of action is to block carboxylation of glutamic acid residues in certain serum proteins. Drug A is most similar to which of the following:

• A. Streptokinase
• B. Bivalirudin
• C. Warfarin (Correct Answer)
• D. Heparin
• E. Rivaroxaban

Explanation: ***Warfarin*** - Warfarin inhibits **vitamin K epoxide reductase**, enzyme responsible for regenerating active vitamin K. - Active vitamin K is a cofactor for the **gamma-carboxylation of glutamic acid residues** on factors II, VII, IX, X and protein C and S. Thus, warfarin blocks their activation, inhibiting coagulation. *Steptokinase* - **Streptokinase** is a **thrombolytic drug** that catalyzes the conversion of **plasminogen to plasmin**, an enzyme that degrades fibrin clots. - Its mechanism of action is focused on **breaking down existing clots**, rather than preventing their formation by affecting coagulation factor synthesis. *Bivalirudin* - **Bivalirudin** is a direct **thrombin inhibitor**, binding directly to the active site and exosite I of thrombin to prevent its action. - It does not interfere with the **carboxylation of glutamic acid residues** but rather directly inhibits the final common pathway of coagulation. *Heparin* - **Heparin** works by potentiating the action of **antithrombin III**, which in turn inactivates thrombin and factor Xa. - Its mechanism involves accelerating the natural anticoagulant system, rather than inhibiting the **synthesis or activation of coagulation factors** through carboxylation. *Rivaroxaban* - **Rivaroxaban** is a **direct factor Xa inhibitor**, which blocks the activity of free and clot-bound factor Xa. - It directly interferes with the coagulation cascade downstream of the carboxylation step, and does not affect the **vitamin K-dependent carboxylation process**.

Question 134: An 11-year-old boy presents to his pediatrician for a wellness checkup. The child is an immigrant, and this is his first visit. The patient is in the 99th percentile for height and 50th percentile for weight. The child is struggling in school, and basic cognitive testing suggests he is moderately mentally disabled. His temperature is 99.5°F (37.5°C), blood pressure is 107/68 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. Laboratory values are obtained and shown below. Hemoglobin: 9 g/dL Hematocrit: 30% MCV: 110 fL Leukocyte count: 5,500/mm^3 with normal differential Platelet count: 192,000/mm^3 Serum: Na+: 140 mEq/L Cl-: 101 mEq/L K+: 4.4 mEq/L HCO3-: 24 mEq/L BUN: 20 mg/dL Glucose: 90 mg/dL Creatinine: 1.0 mg/dL Ca2+: 10.0 mg/dL AST: 12 U/L ALT: 10 U/L The patient is started on vitamin B9 and B12. Which of the following interventions could decrease the risk for cardiac complications the most in this patient?

• A. Folic acid supplementation
• B. Homocysteine level monitoring
• C. Iron supplementation
• D. Pyridoxine (Vitamin B6) (Correct Answer)
• E. No additional interventions needed

Explanation: ***Pyridoxine (Vitamin B6)*** - This patient has **homocystinuria** (tall stature, mental disability, macrocytic anemia) and is already on **folate (B9) and B12** supplementation - **Pyridoxine (B6)** is the most important additional intervention because it is a cofactor for **cystathionine β-synthase**, the enzyme deficient in classical homocystinuria - Approximately **50% of homocystinuria patients are B6-responsive**, meaning pyridoxine can dramatically reduce homocysteine levels - The complete treatment regimen for homocystinuria includes **B6, B9 (folate), and B12** - since B9 and B12 are already started, **B6 is the critical missing intervention** - Reducing homocysteine levels decreases risk of **thromboembolism, stroke, and cardiovascular disease**, which are the major causes of morbidity and mortality in homocystinuria *Folic acid supplementation* - The patient is **already receiving vitamin B9 (folic acid)** as stated in the question stem - While folic acid is essential for lowering homocysteine through the remethylation pathway, it is already being administered - This option would be redundant *Homocysteine level monitoring* - Monitoring homocysteine is important for **assessing treatment response** but is a diagnostic tool, not an intervention - It does not directly decrease cardiac risk, though it helps guide therapy - The question asks for an intervention that decreases risk, not a monitoring strategy *Iron supplementation* - The patient has **macrocytic anemia (MCV 110 fL)**, not microcytic anemia - Macrocytic anemia suggests **folate/B12 deficiency**, not iron deficiency - Iron supplementation would not address the underlying cause (elevated homocysteine) or reduce cardiac complications - In fact, unnecessary iron supplementation can cause harm *No additional interventions needed* - This is incorrect because the standard treatment for homocystinuria requires **all three B vitamins: B6, B9, and B12** - Since only B9 and B12 have been started, **pyridoxine (B6) is still needed** to optimally reduce homocysteine and cardiac risk - B6 is particularly important as it addresses the underlying enzyme deficiency in many patients

Question 135: Seven days after undergoing bilateral total knee arthroplasty, a 65-year-old man comes to the physician with a dark discoloration and blisters on his abdomen. Current medications include simvastatin, aspirin, and low molecular weight heparin. His vital signs are within normal limits. Examination of the skin shows multiple coalescing blisters with areas of necrosis around the umbilicus. Laboratory studies show a platelet count of 32,000/mm3. Which of the following is the most likely underlying cause of this patient's symptoms?

• A. Antibody-platelet antigen complex formation
• B. Deficiency in ADAMTS13 activity
• C. Anti-desmoglein antibody formation
• D. Decreased production of GpIb
• E. Antibody formation against heparin-PF4 complex (Correct Answer)

Explanation: ***Antibody formation against heparin-PF4 complex*** - This clinical scenario describes **Heparin-Induced Thrombocytopenia (HIT) type II**, characterized by thrombocytopenia and paradoxical thrombosis or skin necrosis, often at the injection sites. - The **low molecular weight heparin (LMWH)** given post-surgery can induce antibodies against the heparin-platelet factor 4 (PF4) complex. - The activation of platelets by these antibodies leads to their consumption (thrombocytopenia) and pro-thrombotic activity, resulting in skin lesions (necrosis and blisters) and potential thrombotic events. *Antibody-platelet antigen complex formation* - This typically refers to **Immune Thrombocytopenic Purpura (ITP)**, where antibodies are formed against platelet glycoproteins, leading to their destruction. - ITP generally presents with mucocutaneous bleeding and does not typically cause the necrotic skin lesions seen here, nor is it directly linked to heparin administration. *Deficiency in ADAMTS13 activity* - This condition is characteristic of **Thrombotic Thrombocytopenic Purpura (TTP)**, presenting with microangiopathic hemolytic anemia, thrombocytopenia, renal failure, neurological symptoms, and fever (pentad). - While TTP involves thrombocytopenia, the presentation of localized necrotic skin lesions after heparin use is not typical for TTP. *Anti-desmoglein antibody formation* - This is the underlying mechanism of **pemphigus vulgaris**, an autoimmune blistering skin disease. - Pemphigus vulgaris causes widespread flaccid blisters and erosions but does not typically present with thrombocytopenia or necrosis related to heparin administration. *Decreased production of GpIb* - A defect in **glycoprotein Ib (GpIb)** is characteristic of **Bernard-Soulier syndrome**, a rare inherited bleeding disorder. - This genetic disorder presents with lifelong bleeding tendencies and giant platelets, not acute thrombocytopenia and necrotic lesions triggered by medication in an older adult.

Question 136: A 62-year-old man is referred to neurology by his primary care physician. He is accompanied by his wife. The patient reports having a resting tremor in his left hand for over a year and some “stiffness” in his left arm. His wife notes that he has started to walk "funny" as well. He has a history of hypertension and hyperlipidemia. He takes aspirin, amlodipine, and rosuvastatin. On physical examination, you notice a repetitive circular movement of his left index finger and thumb that resolves with active movement of the hand. Passive motion of the left upper extremity is partially limited by rigidity. Gait is slow and shuffling. The patient is prescribed the most effective treatment for his disorder. Which of the following is the mechanism of a second drug given to prevent adverse effects of this therapy?

• A. Inhibits monoamine oxidase-B
• B. Activates dopamine receptors
• C. Inhibits catechol-O-methyltransferase
• D. Inhibits aromatic L-amino acid decarboxylase (Correct Answer)
• E. Blocks muscarinic acetylcholine receptors

Explanation: ***Inhibits aromatic L-amino acid decarboxylase*** - The patient's symptoms (resting tremor, rigidity, shuffling gait, bradykinesia) are classical for **Parkinson's disease**, which is treated with **levodopa**. - Levodopa is often co-administered with a peripheral **aromatic L-amino acid decarboxylase (AADC) inhibitor** (e.g., carbidopa) to prevent its peripheral conversion to dopamine, reducing side effects and increasing levodopa's bioavailability in the brain. *Inhibits monoamine oxidase-B* - **Monoamine oxidase-B (MAO-B) inhibitors** (e.g., selegiline, rasagiline) are used in Parkinson's disease to reduce dopamine breakdown, but they are not primarily given to prevent adverse effects of levodopa itself; instead, they act to prolong the effect of available dopamine. - While they can be used adjunctively, their main role is to increase dopamine levels rather than directly mitigating levodopa's peripheral side effects. *Activates dopamine receptors* - **Dopamine receptor agonists** (e.g., pramipexole, ropinirole) are used in Parkinson's disease to directly stimulate dopamine receptors, either as monotherapy or adjunctively. - They are a treatment for the disease itself, not a co-medication specifically designed to prevent adverse effects of levodopa. *Inhibits catechol-O-methyltransferase* - **Catechol-O-methyltransferase (COMT) inhibitors** (e.g., entacapone, tolcapone) prolong the action of levodopa by blocking its peripheral metabolism by COMT. - While they prevent levodopa breakdown and enhance its central availability, they are typically used to extend the "on" time and manage motor fluctuations, rather than primarily preventing immediate peripheral adverse effects. *Blocks muscarinic acetylcholine receptors* - **Anticholinergics** (e.g., benztropine, trihexyphenidyl) block muscarinic acetylcholine receptors and are primarily used to treat the **tremor-dominant** form of Parkinson's disease. - They do not prevent the peripheral adverse effects of levodopa; their mechanism of action is distinct and targets a different neurochemical imbalance.

Question 137: An 83-year-old man with advanced-stage prostate cancer comes to the physician because of a 1-week history of worsening lower back and hip pain. The patient's analgesic regimen includes oxycodone, ibuprofen, and alendronic acid. Physical examination shows localized tenderness over the lumbar spine and right hip. His current pain management requires opioid dose escalation. Which of the following opioid side effects is most likely to remain unaffected by the mechanism underlying this patient's need for a higher drug dose?

• A. Pruritus
• B. Constipation (Correct Answer)
• C. Mydriasis
• D. Respiratory depression
• E. Nausea

Explanation: ***Constipation*** - **Opioid-induced constipation** is mediated by direct opioid receptor activation in the **enteric nervous system**, reducing gut motility. - Unlike most other opioid side effects, the body generally does not develop **tolerance** to this effect, meaning it persists even with chronic use and dose escalation. *Pruritus* - **Opioid-induced pruritus** is often due to **histamine release** from mast cells, which is a common side effect of opioid administration. - **Tolerance** can develop to pruritus over time, meaning it may lessen or resolve with chronic opioid use or dose escalation as the body adapts. *Mydriasis* - **Mydriasis** (pupil dilation) is not a typical opioid side effect; rather, **miosis** (pinpoint pupils) is characteristic of opioid use. - Furthermore, **miosis** itself can exhibit some degree of **tolerance** with chronic opioid use, though it is often one of the more persistent effects. *Respiratory depression* - **Respiratory depression** is a serious and dose-dependent opioid side effect caused by decreased sensitivity of the respiratory center in the brainstem to CO2. - While it is a dangerous effect, **tolerance** can develop to respiratory depression with chronic opioid use, reducing its severity over time. *Nausea* - **Opioid-induced nausea** is thought to be mediated by the **chemoreceptor trigger zone (CTZ)** in the brain and slowed gastric emptying. - The body often develops **tolerance** to opioid-induced nausea within a few days to weeks of consistent opioid use.

Question 138: A 54-year-old woman comes to the physician with abdominal distention and mild diffuse abdominal discomfort. She has not had nausea, vomiting, fever, or chills. She was diagnosed with alcoholic liver cirrhosis 2 years ago. Examination shows a protruding, distended abdomen that is dull to percussion with a positive fluid wave. Ultrasonography shows mild to moderate ascites. Appropriate treatment of the patient's condition is started. Four days later, the patient experiences palpitations and chest pain at home. She is brought to the emergency department, where her temperature is 37.3°C (99.1°F), pulse is 182/min, respirations are 18/min, and blood pressure is 82/50 mm Hg. An ECG shows ventricular tachycardia. Initial laboratory studies show: Serum Na+ 131 mEq/L K+ 2.9 mEq/L Cl- 92 mEq/L Bicarbonate 34 mEq/L Urea nitrogen 42 mg/dL Creatinine 4.8 mg/dL Glucose 90 mg/dL Ca2+ 8.1 mg/dL Mg2+ 1.5 mg/dL Phosphate 4.7 mg/dL Arterial Blood Gas pH 7.52 pCO2 45 mm Hg pO2 90.2 mm Hg She is successfully cardioverted to normal sinus rhythm. Which of the following treatments is most likely responsible for this patient's presentation?

• A. Lisinopril
• B. Acetazolamide
• C. Mannitol
• D. Furosemide (Correct Answer)
• E. Hydrochlorothiazide

Explanation: ***Furosemide*** - The patient's **hypokalemia (2.9 mEq/L)**, **hypomagnesemia (1.5 mg/dL)**, and **metabolic alkalosis (pH 7.52, bicarbonate 34 mEq/L)** are characteristic side effects of **loop diuretics** like furosemide. - These electrolyte imbalances, particularly **hypokalemia** and **hypomagnesemia**, can predispose to serious cardiac arrhythmias such as **ventricular tachycardia**, which the patient experienced. - Loop diuretics are commonly used in combination with spironolactone for management of cirrhotic ascites. *Lisinopril* - Lisinopril is an **ACE inhibitor** and would typically cause **hyperkalemia**, not hypokalemia, due to its effect on aldosterone. - It works by vasodilation and could potentially worsen hypotension, but it doesn't explain the patient's specific electrolyte disturbances or arrhythmia profile. *Acetazolamide* - Acetazolamide is a **carbonic anhydrase inhibitor** that can cause **metabolic acidosis** and hypokalemia but would not lead to the metabolic alkalosis observed here. - It increases bicarbonate excretion, which is the opposite of this patient's acid-base status. *Mannitol* - Mannitol is an **osmotic diuretic** primarily used for cerebral edema or acute glaucoma. - Its main effects relate to fluid shifts, and while it could cause electrolyte disturbances, it's not typically associated with this specific constellation of hypokalemia, hypomagnesemia, and metabolic alkalosis. *Hydrochlorothiazide* - Hydrochlorothiazide is a **thiazide diuretic** that can cause hypokalemia, hypomagnesemia, and metabolic alkalosis, similar to loop diuretics. - However, **thiazides are not used for cirrhotic ascites** because they are ineffective in treating significant fluid overload and can worsen complications of cirrhosis. The standard treatment is spironolactone (aldosterone antagonist) with or without a loop diuretic like furosemide for refractory cases.

Question 139: A 28-year-old man is brought to the emergency department after he was found half dressed and incoherent in the middle of the road. In the emergency department he states that he has not slept for 36 hours and that he has incredible ideas that will make him a billionaire within a few months. He also states that secret agents from Russia are pursuing him and that he heard one of them speaking through the hospital intercom. His past medical history is significant only for a broken arm at age 13. On presentation, his temperature is 102.2°F (39°C), blood pressure is 139/88 mmHg, pulse is 112/min, and respirations are 17/min. Physical exam reveals pupillary dilation and psychomotor agitation. Which of the following mechanisms is most likely responsible for this patient's symptoms?

• A. N-methyl-D-aspartate receptor antagonist
• B. Gamma-aminobutyric acid receptor agonist
• C. Increased biogenic amine release (Correct Answer)
• D. 5-HT receptor agonist
• E. Opioid receptor agonist

Explanation: ***Increased biogenic amine release*** - The patient exhibits a classic constellation of symptoms consistent with **stimulant intoxication**, including **psychomotor agitation**, **pupillary dilation**, **tachycardia**, **hyperthermia**, **insomnia**, **grandiosity**, and **paranoia**. - Stimulants like **amphetamines** and **cocaine** primarily exert their effects by increasing the release and inhibiting the reuptake of **biogenic amines** (dopamine, norepinephrine, serotonin) in the brain, leading to an exaggerated sympathetic response and altered mental status. *N-methyl-D-aspartate receptor antagonist* - **NMDA receptor antagonists** (e.g., phencyclidine - PCP, ketamine) are associated with dissociative symptoms, nystagmus, and sometimes aggression, but generally do not present with the prominent **hyperthermia** and grandiosity seen here. - While they can cause psychotic symptoms, the specific combination of signs points more strongly to **stimulant intoxication**. *Gamma-aminobutyric acid receptor agonist* - **GABA receptor agonists** (e.g., benzodiazepines, barbiturates) cause **CNS depression**, sedation, respiratory depression, and ataxia. - These effects are contrary to the patient's presentation of **agitation**, **increased heart rate**, and **hyperthermia**. *5-HT receptor agonist* - While drugs like **LSD** and **MDMA** (ecstasy) act as 5-HT receptor agonists and can cause hallucinations and altered perception, the prominent **paranoia**, **grandiosity**, and **significant hyperthermia** in this scenario are more characteristic of stimulant toxicity, which involves a broader increase in biogenic amine release beyond just serotonin. - MDMA, in particular, can cause hyperthermia, but the full clinical picture is more suggestive of traditional stimulants. *Opioid receptor agonist* - **Opioid receptor agonists** (e.g., heroin, morphine) typically cause **CNS depression**, **miosis** (pinpoint pupils), respiratory depression, and sedation. - These effects are the **opposite** of the patient's symptoms of pupillary dilation, agitation, and hyperthermia.

Question 140: A 59-year-old woman comes to the physician because of left leg swelling that started after a transcontinental flight. A duplex ultrasound of the left leg shows a noncompressible popliteal vein. A drug is prescribed that inhibits the coagulation cascade. Two weeks later, laboratory studies show: Platelet count 210,000/mm3 Partial thromboplastin time 28 seconds (normal: 25-35) Prothrombin time 12 seconds (normal: 11-13) Thrombin time 15 seconds (control: 15 seconds) Which of the following drugs was most likely prescribed?

• A. Unfractionated heparin
• B. Apixaban
• C. Aspirin
• D. Warfarin
• E. Low molecular weight heparin (Correct Answer)

Explanation: ***Low molecular weight heparin*** - **LMWH (e.g., enoxaparin) is the first-line treatment for acute DVT** in ambulatory patients and is the most likely drug prescribed in this outpatient scenario - LMWH enhances **antithrombin activity primarily against Factor Xa** (more than Factor IIa/thrombin), which is why it has **minimal effect on routine coagulation tests** (PT, PTT, TT) - **Monitoring of LMWH is done via anti-Xa levels**, not PTT, PT, or TT, explaining why all these values remain normal two weeks after initiation - The normal coagulation studies are **expected and consistent** with therapeutic LMWH use *Unfractionated heparin* - Unfractionated heparin (UFH) acts by enhancing **antithrombin activity against both Factor Xa and Factor IIa (thrombin)**, which significantly **prolongs PTT** (typically 1.5-2x control when therapeutic) - UFH requires **IV administration and hospital monitoring**, making it unlikely for this ambulatory post-flight DVT patient - If the patient were currently on UFH, the **PTT would be prolonged** (not normal as shown); if discontinued, this wouldn't be "the drug prescribed" for ongoing DVT treatment *Apixaban* - Apixaban is a **direct Factor Xa inhibitor** that would cause **mild prolongation of PT** and possibly PTT at therapeutic levels - While it's a reasonable outpatient DVT treatment, the completely normal PT argues against current apixaban use - Apixaban doesn't require routine monitoring, but when measured, coagulation times would typically show some abnormality *Warfarin* - Warfarin is a **vitamin K antagonist** that inhibits synthesis of factors II, VII, IX, and X, causing **significant PT/INR prolongation** (target INR 2-3 for DVT) - The **normal PT (12 seconds) excludes warfarin** as the current medication - Warfarin requires regular INR monitoring and would not show normal values at therapeutic doses *Aspirin* - Aspirin is an **antiplatelet agent** (COX-1 inhibitor) that affects platelet aggregation, **not the coagulation cascade** - It has **no effect on PT, PTT, or TT** and is **inadequate monotherapy for DVT treatment** - While it may have a role in extended VTE prevention, it would not be the primary drug prescribed for acute DVT

Question 141: A 32-year-old woman comes to the physician because of a 3-month history of irregular menses, milky discharge from her nipples, fatigue, and weight gain. Menses occur at irregular 25–40-day intervals and last 1–2 days with minimal flow. 5 months ago, she was started on clozapine for treatment of schizophrenia. She has hypothyroidism but has not been taking levothyroxine over the past 6 months. Visual field examination show no abnormalities. Her serum thyroid-stimulating hormone is 17.0 μU/mL and serum prolactin is 85 ng/mL. Which of the following is the most likely explanation for the nipple discharge in this patient?

• A. Prolactinoma
• B. Thyrotropic pituitary adenoma
• C. Ectopic prolactin production
• D. Hypothyroidism (Correct Answer)
• E. Adverse effect of medication

Explanation: ***Hypothyroidism*** - **Primary hypothyroidism** is the most likely cause of this patient's galactorrhea given her significantly elevated TSH (17.0 μU/mL) and 6-month non-compliance with levothyroxine. - In hypothyroidism, elevated **TRH (thyrotropin-releasing hormone)** stimulates both TSH and **prolactin release** from the anterior pituitary, commonly causing prolactin levels in the 50-100 ng/mL range. - The patient's prolactin level of **85 ng/mL is entirely consistent** with hypothyroidism-induced hyperprolactinemia. - Hypothyroidism also explains her other symptoms: **fatigue, weight gain, and menstrual irregularities**. *Adverse effect of medication* - While some antipsychotics cause significant hyperprolactinemia, **clozapine is notably prolactin-sparing** due to its weak D2 receptor antagonism and rapid dissociation from D2 receptors. - Clozapine is one of the **atypical antipsychotics with the lowest risk** of causing elevated prolactin levels. - Antipsychotics that commonly cause hyperprolactinemia include **risperidone, paliperidone, amisulpride, and typical antipsychotics** (e.g., haloperidol), but not clozapine. - Given the patient's untreated hypothyroidism, this is the less likely cause. *Prolactinoma* - A prolactinoma would typically present with **significantly higher prolactin levels** (usually >200 ng/mL for macroadenomas, though microprolactinomas may have levels 100-200 ng/mL). - The patient's prolactin of 85 ng/mL is **more consistent with secondary causes** like hypothyroidism or medications. - The absence of **visual field defects** makes a large macroadenoma less likely. *Thyrotropic pituitary adenoma* - A thyrotropic (TSH-secreting) pituitary adenoma causes **secondary hyperthyroidism** with elevated TSH and elevated thyroid hormones, not hypothyroidism. - This patient has **primary hypothyroidism** (elevated TSH with presumably low T4), which is the opposite presentation. - TSH-secreting adenomas are extremely rare (<1% of pituitary adenomas). *Ectopic prolactin production* - **Ectopic prolactin production** by non-pituitary tumors is exceedingly rare and usually associated with very high prolactin levels. - There are no clinical features suggesting an ectopic source or malignancy. - The patient's presentation is fully explained by her untreated hypothyroidism.

Question 142: A 68-year-old man comes to the physician because of a 6-week history of episodic tremors, headaches, and sweating. During this time, he has gained 2.5-kg (5 lb 8 oz). Two months ago, he was diagnosed with type 2 diabetes mellitus and treatment with an oral antidiabetic drug was initiated. The beneficial effect of the drug that was prescribed for this patient is most likely due to inhibition of which of the following?

• A. ATP-sensitive potassium channels (Correct Answer)
• B. Glycerophosphate dehydrogenase
• C. Sodium-glucose cotransporter-2
• D. Dipeptidyl peptidase-4
• E. Brush-border α-glucosidase

Explanation: ***ATP-sensitive potassium channels*** - The patient's symptoms of episodic tremors, headaches, sweating, and weight gain, along with a recent diagnosis of type 2 diabetes treated with an oral antidiabetic drug, suggest **hypoglycemia** as a side effect. - Sulfonylureas, a common class of oral antidiabetic drugs, exert their effect by **inhibiting ATP-sensitive potassium channels** on pancreatic beta cells, leading to insulin release and potentially hypoglycemia. *Glycerophosphate dehydrogenase* - This enzyme is involved in **glycerol metabolism** and is not a primary target for oral antidiabetic drugs that cause hypoglycemia. - Its inhibition would not directly lead to increased insulin secretion or the described pattern of symptoms. *Sodium-glucose cotransporter-2* - **SGLT2 inhibitors** (e.g., canagliflozin) work by blocking glucose reabsorption in the kidneys, leading to glucose excretion in urine. - While they can cause some weight loss, they are less likely to cause symptomatic hypoglycemia unless combined with other agents, and their mechanism does not involve ATP-sensitive potassium channels. *Dipeptidyl peptidase-4* - **DPP-4 inhibitors** (e.g., sitagliptin) prevent the breakdown of incretin hormones, thereby increasing insulin secretion in a glucose-dependent manner. - These drugs generally have a **low risk of hypoglycemia** because their effect on insulin release diminishes as blood glucose normalizes. *Brush-border α-glucosidase* - **Alpha-glucosidase inhibitors** (e.g., acarbose) delay carbohydrate absorption in the gut. - They primarily target **postprandial hyperglycemia** and, when used alone, cause very little risk of hypoglycemia because they do not directly stimulate insulin secretion.

Question 143: A 46-year-old premenopausal woman undergoes lumpectomy after a diagnosis of invasive ductal carcinoma of the breast is made. Pathologic examination of the surgical specimen shows that the breast cancer cells stain positive for estrogen receptor and progesterone receptor, and negative for human epidermal growth factor receptor 2. Which of the following characteristics applies to the most appropriate pharmacotherapy for this patient's condition?

• A. Monoclonal antibody against tyrosine kinase receptor
• B. Monoclonal antibody against vascular endothelial growth factor
• C. Selective agonist at progesterone receptors in mammary tissue
• D. Selective agonist at estrogen receptors in bone tissue
• E. Selective antagonist at estrogen receptors in mammary tissue (Correct Answer)

Explanation: ***Selective antagonist at estrogen receptors in mammary tissue*** - The patient's tumor is **estrogen receptor (ER) positive** and **progesterone receptor (PR) positive**. This indicates a **hormone-sensitive cancer**, making endocrine therapy the most appropriate pharmacotherapy. - A **selective antagonist at estrogen receptors** in mammary tissue, such as **tamoxifen** (a selective estrogen receptor modulator, SERM), is effective in blocking estrogen-mediated tumor growth in premenopausal patients. *Monoclonal antibody against tyrosine kinase receptor* - This therapy, typically targeting **HER2 (human epidermal growth factor receptor 2)**, would be appropriate if the tumor was **HER2-positive**. - The patient's tumor is **HER2-negative**, meaning this type of targeted therapy would not be beneficial. *Monoclonal antibody against vascular endothelial growth factor* - This class of drugs, like **bevacizumab**, targets **angiogenesis** by inhibiting VEGF, which is crucial for tumor blood supply. - While used in some cancers, it is not the primary or most appropriate pharmacotherapy based on the specific receptor status of this patient's breast cancer. *Selective agonist at progesterone receptors in mammary tissue* - An **agonist** at progesterone receptors would **promote growth** if the tumor is progesterone receptor-positive, which would be counterproductive for cancer treatment. - The goal of endocrine therapy for PR-positive tumors is to inhibit the effects of progesterone. *Selective agonist at estrogen receptors in bone tissue* - An agonist at estrogen receptors in bone tissue would **mimic estrogen's effects**, which is undesirable given the estrogen-sensitive nature of the breast cancer. - While some SERMs (like tamoxifen) can have agonist effects in bone (which can be beneficial for bone density), the primary therapeutic action for breast cancer is antagonism in mammary tissue.

Question 144: A 64-year-old woman is brought to the emergency department because of a 1-week history of progressive shortness of breath, lower extremity edema, and a 4-kg (9-lb) weight gain. She has ischemic cardiomyopathy and rheumatoid arthritis. Her respirations are 27/min. Examination shows pitting edema of the lower extremities and crackles over both lower lung fields. Therapy is initiated with intravenous furosemide. After 2 hours, urine output is minimal. Concomitant treatment with which of the following drugs is most likely to have contributed to treatment failure?

• A. Sulfasalazine
• B. Digoxin
• C. Prednisone
• D. Infliximab
• E. Diclofenac (Correct Answer)

Explanation: ***Diclofenac*** - **NSAIDs** like diclofenac can cause **sodium and water retention** and reduce the effectiveness of loop diuretics like furosemide by inhibiting prostaglandin synthesis in the kidneys. - This patient's symptoms of **heart failure exacerbation** (shortness of breath, edema, weight gain, crackles) and minimal urine output despite furosemide suggest drug-induced diuretic resistance. *Sulfasalazine* - This drug is used for **rheumatoid arthritis** and inflammatory bowel disease, but it does not typically interfere with diuretic action or cause fluid retention. - Its mechanism involves anti-inflammatory properties, not directly affecting renal hemodynamics or diuretic efficacy. *Digoxin* - Digoxin is used to improve **cardiac contractility** and does not directly cause fluid retention or diminish the effects of loop diuretics. - While it has a narrow therapeutic index, it does not antagonize furosemide's action. *Prednisone* - Prednisone is a **corticosteroid** that can cause **fluid retention** due to its mineralocorticoid effects, but it is not known to directly inhibit the action of loop diuretics to this extent. - Its use in rheumatoid arthritis would primarily suppress inflammation, not directly cause diuretic resistance in acute heart failure. *Infliximab* - Infliximab is a **TNF-alpha inhibitor** used in rheumatoid arthritis; it can rarely exacerbate heart failure by its mechanism of action but does not directly interfere with the efficacy of loop diuretics. - It does not cause fluid retention through renal mechanisms or reduce the renal response to furosemide.

Question 145: A 62-year-old man presents to his physician complaining of difficulty maintaining an erection over the past month. Otherwise he feels well. He has a history of hypertension and congestive heart failure. His current medications include metoprolol, amlodipine, furosemide, losartan, and aspirin. Three months ago, lisinopril was switched to losartan due to periodic cough. Two months ago, metoprolol and furosemide were added for better control of hypertension and edema, and the dose of amlodipine was reduced. He does not smoke. At the clinic, his blood pressure is 125/70 mm Hg, pulse is 58/min, and respirations are 14/min. Physical examination reveals clear lung sounds, a previously diagnosed systolic murmur, and mild pitting edema on the dorsum of both feet. Which of the following is the most appropriate modification in this patient’s medication?

• A. Increasing the amlodipine dose
• B. Discontinuing furosemide
• C. Reducing the metoprolol dose (Correct Answer)
• D. Adding indapamide
• E. Switching losartan to lisinopril

Explanation: ***Reducing the metoprolol dose*** - The patient's **bradycardia** (pulse 58/min) and **erectile dysfunction (ED)** are common side effects of **beta-blockers** like metoprolol. - Given his controlled blood pressure, reducing the metoprolol dose is the most appropriate step to mitigate these side effects while maintaining cardiovascular benefit. *Increasing the amlodipine dose* - Increasing amlodipine could worsen his **edema** and might lead to **hypotension**, especially with his current well-controlled blood pressure. - Amlodipine is less likely to cause ED compared to metoprolol and is usually not the primary cause in this context. *Discontinuing furosemide* - Furosemide is crucial for managing his **congestive heart failure** and **edema**, which is still present (mild pitting edema). - Discontinuing it could lead to worsening fluid overload and heart failure symptoms. *Adding indapamide* - Indapamide is a **thiazide-like diuretic** that could further lower blood pressure, but the patient's blood pressure is already well-controlled. - Adding another diuretic is unlikely to address his ED and could lead to electrolyte imbalances or dehydration. *Switching losartan to lisinopril* - The patient was switched from lisinopril to losartan due to a **cough**, which is a known side effect of **ACE inhibitors**. - Reintroducing lisinopril would likely cause the cough to return and does not address the current ED or bradycardia.

Question 146: A 75-year-old man presents with a tremor in his legs and arms. He says he has had the tremor for ‘many years’, but it has worsened in the last year. The tremor is more prominent at rest and nearly disappears on movement. He also says his family has mentioned that his movements have been slower, and he does feel like he has problem initiating movements. There is no significant past medical history. He says he often drinks wine, but this does not affect his tremors. The patient is afebrile and vital signs are within normal limits. On physical examination, the patient is hunched over and his face is expressionless throughout the examination. There is a ‘pill-rolling’ resting tremor that is accentuated when the patient is asked to clench the contralateral hand and alleviated by finger-nose testing. The patient is unable to play an imaginary piano with his fingers. There is the increased tone in the arm muscles bilaterally and resistance to passive movement at the elbow, knee, and hip joints is noted. When asked to walk across the room, the patient has difficulty taking the first step, has a stooped posture, and takes short rapid shuffling steps. Which of the following drugs would be the most effective treatment for this patient’s condition?

• A. Bromocriptine
• B. Entacapone
• C. Benztropine
• D. Selegiline
• E. Levodopa/carbidopa (Correct Answer)

Explanation: **Levodopa/carbidopa** - The patient's symptoms (resting tremor, bradykinesia, rigidity, postural instability, and shuffling gait) are classic for **Parkinson's disease**. **Levodopa/carbidopa** is the most effective treatment for the motor symptoms of Parkinson's disease, as levodopa is converted to dopamine in the brain, and carbidopa prevents its peripheral breakdown, allowing more to reach the brain. - It significantly improves **bradykinesia and rigidity**, which are prominent features in this patient, and can also help with tremor and gait difficulties. *Bromocriptine* - Bromocriptine is a **dopamine agonist** that directly stimulates dopamine receptors. While it can also treat Parkinson's symptoms, it is generally less effective than levodopa/carbidopa, especially in later stages or for severe symptoms. - It is more commonly used as an initial therapy in younger patients to delay levodopa use or as an adjunct therapy, but for a 75-year-old with advanced symptoms, levodopa/carbidopa is preferred. *Entacapone* - Entacapone is a **catechol-O-methyltransferase (COMT) inhibitor** that prolongs the action of levodopa by preventing its breakdown in the periphery. - It is not used as a monotherapy but rather as an **adjunct to levodopa/carbidopa** in patients experiencing "wearing off" phenomena, where levodopa's effects diminish before the next dose. *Benztropine* - Benztropine is an **anticholinergic medication** used primarily to treat tremor and dystonia in Parkinson's disease. - It is generally less effective for bradykinesia and rigidity and is often avoided in elderly patients due to potential side effects like confusion, hallucinations, and urinary retention. *Selegiline* - Selegiline is a **monoamine oxidase-B (MAO-B) inhibitor** that prevents the breakdown of dopamine in the brain. - It is used in early Parkinson's disease or as an adjunct to levodopa/carbidopa to extend its effects; however, its symptomatic efficacy is modest compared to levodopa/carbidopa.

Question 147: A 31-year-old woman comes to the physician because of headaches and nausea for 2 weeks. The headaches are worse on awakening and she describes them as 7 out of 10 in intensity. During this period, she has noticed brief episodes of visual loss in both eyes lasting several seconds, especially when she suddenly stands up or bends over. She is 165 cm (5 ft 5 in) tall and weighs 98 kg (216 lb); BMI is 36 kg/m2. Vital signs are within normal limits. Examination shows a visual acuity of 20/20 in both eyes with mild peripheral vision loss. Fundoscopic examination shows bilateral optic disc swelling. An MRI of the brain shows no abnormalities. A lumbar puncture is performed; opening pressure is 310 mm H2O. Cerebrospinal fluid analysis shows a leukocyte count of 4/mm3 (75% lymphocytes), a protein concentration of 35 mg/dL, and a glucose concentration of 45 mg/dL. Which of the following is the most appropriate next step in management?

• A. Prednisone therapy
• B. Optic nerve sheath fenestration
• C. Acetazolamide therapy (Correct Answer)
• D. Furosemide therapy
• E. Ventricular shunting

Explanation: ***Acetazolamide therapy*** - This patient presents with symptoms and signs consistent with **idiopathic intracranial hypertension (IIH)**: **headaches worse on awakening**, transient visual obscurations, **papilledema** on fundoscopic exam, elevated **BMI**, normal brain MRI, and **elevated CSF opening pressure** with normal CSF content. - **Acetazolamide** is the first-line medical treatment for IIH, working as a **carbonic anhydrase inhibitor** to decrease CSF production and thus lower intracranial pressure. *Prednisone therapy* - **Prednisone** is a corticosteroid that can reduce inflammation and edema, but it is **not the first-line treatment** for IIH and its prolonged use carries significant side effects. - While it may temporarily reduce intracranial pressure, it does not address the underlying pathophysiology of **CSF overproduction** or impaired absorption in IIH as effectively as acetazolamide. *Optic nerve sheath fenestration* - **Optic nerve sheath fenestration** is a surgical procedure considered for IIH patients with **progressive vision loss despite maximal medical therapy**, or those who cannot tolerate medical therapy. - It is an **invasive procedure** and not the initial management step for this patient, who has only mild peripheral vision loss and has not yet attempted medical treatment. *Furosemide therapy* - **Furosemide** is a loop diuretic that primarily reduces systemic fluid volume and can sometimes be used as an **adjunct** in resistant cases or to potentiate acetazolamide's effect in IIH. - However, it is **less effective than acetazolamide** in directly reducing CSF production and is not considered a first-line monotherapy for IIH. *Ventricular shunting* - **Ventricular shunting** (e.g., ventriculoperitoneal shunt) is a more invasive surgical option considered for severe, refractory cases of IIH, particularly those with **intractable headaches** or **severe, progressive vision loss** that has failed other treatments. - Given that this patient has not yet received initial medical therapy, **ventricular shunting is premature** as a next step in management.

Question 148: A 65-year-old man with hypertension and paroxysmal atrial fibrillation presents to his cardiologist for follow-up after recently starting metoprolol for rate control. His EKG shows an atrial rate of 260/min with ventricular rate of 50/min on an irregular baseline. An echocardiogram from his previous visit revealed no evidence of hypokinesis or hypertrophy with functionally intact valves. The patient does not drink alcohol and had no evidence of liver dysfunction in prior studies. What is the best medication for rhythm control in this patient?

• A. Amiodarone
• B. Flecainide (Correct Answer)
• C. Procainamide
• D. Verapamil
• E. Mexiletine

Explanation: ***Flecainide*** - **Flecainide** is a **Class IC antiarrhythmic** medication that is effective for rhythm control in patients with **paroxysmal atrial fibrillation** and no structural heart disease. - The patient's echocardiogram showed no evidence of hypokinesis or hypertrophy, with functionally intact valves, indicating the **absence of structural heart disease**, which is a prerequisite for using Class IC agents like flecainide. *Amiodarone* - **Amiodarone** is a potent antiarrhythmic but is associated with numerous significant **extracardiac side effects**, including **pulmonary fibrosis**, **thyroid dysfunction**, and liver toxicity. - It is generally reserved for patients with structural heart disease or those who have failed other antiarrhythmic therapies due to its extensive side effect profile. *Procainamide* - **Procainamide** is a **Class IA antiarrhythmic** that has a high incidence of side effects, including **drug-induced lupus**, and is typically used for acute management of arrhythmias, not long-term rhythm control in this setting. - Its use is limited by its short half-life and significant proarrhythmic potential, especially in patients with structural heart disease or LV dysfunction. *Verapamil* - **Verapamil** is a **non-dihydropyridine calcium channel blocker** primarily used for **rate control** in atrial fibrillation, not rhythm control. - The patient is already on metoprolol for rate control, and the question specifically asks for a medication for rhythm control. *Mexiletine* - **Mexiletine** is a **Class IB antiarrhythmic** agent primarily used for treating **ventricular arrhythmias**, particularly in the setting of myocardial infarction. - It is not typically used for rhythm control in atrial fibrillation and has limited efficacy in this context.

Question 149: A 35-year-old woman comes to the physician for the evaluation of fatigue over the past 6 months. During this period, she has also had fever, joint pain, and a recurrent skin rash on her face. She has smoked one pack of cigarettes daily for the past 15 years. Her temperature is 38.5°C (101.3°F), pulse is 90/min, and blood pressure is 130/80 mm Hg. Physical examination shows a facial rash that spares the nasolabial folds and several oral ulcers. Joints of the upper and lower extremities are tender with no reddening or swelling. Laboratory studies show anti-dsDNA antibodies. The patient is diagnosed with systemic lupus erythematosus and treatment of choice is initiated. Eight months later, the patient has weakness in her shoulders and hips. Examination shows slight weakness of the proximal muscles. Deep tendon reflexes are 2+ bilaterally. Laboratory studies show normal erythrocyte sedimentation rate and creatine kinase. Which of the following is the most likely underlying cause of this patient's symptoms?

• A. Dystrophin gene mutation
• B. Adverse effect of medication (Correct Answer)
• C. Upper and lower motor neuron degeneration
• D. Autoantibodies against postsynaptic acetylcholine receptors
• E. Autoantibodies against myelin

Explanation: ***Adverse effect of medication*** - The patient was diagnosed with **systemic lupus erythematosus (SLE)** and started on treatment. **Glucocorticoids** are a common treatment for SLE, and high doses can cause **proximal muscle weakness (steroid myopathy)**. - The combination of normal ESR and CK, along with symmetrical proximal weakness, is characteristic of steroid-induced myopathy. *Dystrophin gene mutation* - **Dystrophinopathies** (e.g., Duchenne or Becker muscular dystrophy) are typically **genetic disorders** that manifest much earlier in life with progressive muscle weakness and elevated CK. - This patient's symptoms developed acutely after SLE treatment and laboratory findings do not support a genetic muscular dystrophy. *Upper and lower motor neuron degeneration* - This describes conditions like **amyotrophic lateral sclerosis (ALS)**, which would feature both **upper motor neuron signs** (e.g., spasticity, hyperreflexia) and **lower motor neuron signs** (e.g., atrophy, fasciculations). - The patient only shows symmetrical proximal weakness with normal deep tendon reflexes, and no signs of either upper or lower motor neuron disease. *Autoantibodies against postsynaptic acetylcholine receptors* - This is the hallmark of **myasthenia gravis**, which causes **fluctuating muscle weakness** that worsens with activity and improves with rest, and often affects ocular and bulbar muscles. - Myasthenia gravis is less likely given the presentation of gradual, persistent proximal weakness following SLE treatment. *Autoantibodies against myelin* - This is characteristic of **demyelinating diseases** like **multiple sclerosis (MS)** or **Guillain-Barré syndrome (GBS)**. These conditions cause various neurological deficits including sensory disturbances, ataxia, or flaccid paralysis (GBS). - The patient's symptoms are confined to muscle weakness without other neurological signs, and normal deep tendon reflexes argue against these conditions.

Question 150: A 71-year-old male is brought to the emergency room by his caretaker and presents with difficulty breathing, muscle rigidity in the face, neck, back and upper extremities, and profuse sweating. The intern notes a large wound on his head near the back of his right ear which his caretaker had bandaged up. The caretaker explains that the wound was the result of a fall while walking in his backyard. The intern performs a quick physical exam and observes increased reflexes. The patient was intubated to assist in his breathing and was given diazepam, metronidazole, and an immunoglobulin after the blood work came back. Which of the following neurotransmitters is affected in this patient?

• A. Glycine (Correct Answer)
• B. Acetylcholine
• C. Serotonin
• D. Dopamine
• E. Epinephrine

Explanation: ***Glycine*** - The patient's symptoms (muscle rigidity, profuse sweating, increased reflexes, and difficulty breathing) are classic signs of **tetanus**, caused by *Clostridium tetani* toxin (tetanospasmin). The toxin inhibits the release of **both glycine and GABA**, which are inhibitory neurotransmitters in the spinal cord. Specifically, it blocks release from Renshaw cells and other inhibitory interneurons, leading to disinhibition of motor neurons and resulting in uncontrolled muscle spasms and rigidity. - The treatment with **metronidazole** (to kill *C. tetani*), **immunoglobulin** (to neutralize unbound toxin), and **diazepam** (a GABA agonist to reduce muscle spasms) further supports a diagnosis of tetanus, where **glycine's** inhibitory function is critically impaired. *Acetylcholine* - **Acetylcholine** is a primary excitatory neurotransmitter at the neuromuscular junction, responsible for muscle contraction. The pathology in tetanus is not an excess of acetylcholine, but rather a lack of inhibition by other neurotransmitters. - While muscle contraction is a symptom, the underlying defect isn't directly related to acetylcholine synthesis or release, but rather the loss of inhibitory input onto motor neurons. *Serotonin* - **Serotonin** primarily regulates mood, sleep, appetite, and pain perception in the central nervous system. - Dysregulation of serotonin is associated with conditions like depression and anxiety, not the severe muscle rigidity and spasms seen in this patient. *Dopamine* - **Dopamine** is involved in reward, motivation, motor control, and hormone release. Its deficiency is characteristic of Parkinson's disease, leading to bradykinesia and tremors. - Excess dopamine can be linked to psychotic disorders, but it does not cause the generalized muscle rigidity and hyperexcitability observed here. *Epinephrine* - **Epinephrine** (adrenaline) is a crucial neurotransmitter and hormone involved in the "fight or flight" response, increasing heart rate, blood pressure, and blood flow to muscles. - While profuse sweating suggests autonomic dysregulation, epinephrine's primary role is not in directly mediating the muscle rigidity and increased reflexes characteristic of tetanus.

Question 151: A 44-year-old female is admitted to the neurological service. You examine her chart and note that after admission she was started on nimodipine. Which of the following pathologies would benefit from this pharmacologic therapy?

• A. Thromboembolic stroke
• B. Subdural hematoma
• C. Epidural hematoma
• D. Pseudotumor cerebri
• E. Subarachnoid hemorrhage (Correct Answer)

Explanation: ***Subarachnoid hemorrhage*** - Nimodipine is a **calcium channel blocker** specifically used to prevent and treat **cerebral vasospasm** following a subarachnoid hemorrhage. - Vasospasm is a common and often devastating complication that can lead to delayed cerebral ischemia and poor neurological outcomes. *Thromboembolic stroke* - Treatment for thromboembolic stroke focuses on **reperfusion therapies** (e.g., tPA, thrombectomy) and antiplatelet/anticoagulant medications. - Nimodipine does not play a role in the acute management or prevention of tissue damage in ischemic stroke. *Subdural hematoma* - Subdural hematomas are collections of blood between the dura and arachnoid mater, usually resulting from **head trauma**. - Management typically involves **surgical evacuation** if symptomatic, and nimodipine is not indicated. *Epidural hematoma* - Epidural hematomas involve bleeding between the dura mater and the skull, often due to **arterial injury** from head trauma. - These are surgical emergencies, and nimodipine has no therapeutic role. *Pseudotumor cerebri* - Also known as **idiopathic intracranial hypertension**, this condition involves elevated intracranial pressure without a mass lesion. - Treatment focuses on reducing CSF pressure, often with diuretics (e.g., acetazolamide), and nimodipine is not part of the management.

Question 152: A 23-year-old active college student has a sudden loss of consciousness 40 minutes after he was playing basketball with his team. Cardiopulmonary resuscitation is administered by bystanders. On arrival of emergency medical professionals, he regains his consciousness. He has no past medical history. He does not smoke or drink alcohol. His family history is positive for a cousin who died suddenly in his youth. On physical examination, a systolic ejection murmur is audible on the left lower sternal border. ECG shows left ventricular hypertrophy and echocardiography shows asymmetric septal hypertrophy. Which of the following decreases the pressure gradient between the aorta and the left ventricle in this patient?

• A. Digoxin
• B. Metoprolol (Correct Answer)
• C. Nitroglycerin
• D. Forceful attempted exhalation against a closed airway
• E. High-dose diuretics

Explanation: ***Metoprolol*** - This patient presents with symptoms and signs consistent with **hypertrophic cardiomyopathy (HCM)**: sudden syncope during exertion, family history of sudden death, systolic ejection murmur, and asymmetric septal hypertrophy on echocardiography. - **Beta-blockers** like metoprolol decrease the **heart rate**, allowing for increased **diastolic filling time** and reducing the **contractility** of the left ventricle. This helps to reduce dynamic outflow obstruction and the pressure gradient. *Digoxin* - **Digoxin** is a **positive inotrope**, meaning it increases myocardial contractility. - In HCM, increasing contractility would worsen the **left ventricular outflow tract obstruction** and thereby increase the pressure gradient. *Nitroglycerin* - **Nitroglycerin** is a **vasodilator** that primarily reduces preload and, to a lesser extent, afterload. - Reducing **preload** can worsen the outflow tract obstruction in HCM by decreasing the left ventricular end-diastolic volume, leading to increased septal-mitral contact. *Forceful attempted exhalation against a closed airway* - This maneuver, known as the **Valsalva maneuver**, involves increased intra-thoracic pressure, which decreases **venous return to the heart** and subsequently reduces **preload**. - A reduction in preload would exacerbate the **left ventricular outflow tract obstruction** and thus increase the pressure gradient in HCM. *High-dose diuretics* - **Diuretics** decrease the **blood volume** and **preload**. - Similar to the Valsalva maneuver or nitroglycerin, a reduction in preload can worsen the dynamic outflow tract obstruction characteristic of HCM.

Question 153: A 42-year-old man is brought to the emergency department by the police after he was involved in a physical altercation at a friend’s home. Upon physical examination, the patient is disheveled. He is very agitated and actively strikes out at nurses and other hospital staff. A decision is made to place him in restraints. Head, eyes, ears, nose, and throat exam reveals temporal wasting, marked tooth decay, and healing and new ulcers in his mouth and on his lips. His pupils are dilated and minimally reactive to light. His skin shows dramatic diaphoresis as well as excoriations over his arms. Vital signs show pulse of 120/min, respirations of 12/min, temperature of 39.0°C (102.2°F), and blood pressure of 150/100 mm Hg. Urine drug screen is positive for an amphetamine. Which of the following is a life-threatening complication of the toxicity seen in this patient?

• A. Seizure
• B. Sudden cardiac arrest (Correct Answer)
• C. Heat stroke
• D. Respiratory depression
• E. Malignant hyperthermia

Explanation: ***Sudden cardiac arrest*** - **Amphetamine toxicity** causes immense **catecholamine release**, leading to severe **hypertension**, **tachycardia**, and **coronary vasospasm**, which can precipitate **myocardial ischemia** and **arrhythmias**, culminating in sudden cardiac arrest. - The patient's vital signs (pulse 120/min, BP 150/100 mm Hg, temperature 39.0°C) indicate **severe cardiovascular stress**, making sudden cardiac arrest a direct and life-threatening complication. *Seizure* - While **seizures** can occur with amphetamine toxicity due to its direct stimulant effect on the central nervous system, they are generally less immediately life-threatening than acute cardiovascular collapse. - The immediate threat posed by the described vital signs and the potential for fatal arrhythmias makes sudden cardiac arrest a more critical complication. *Heat stroke* - **Hyperthermia** is a known risk of amphetamine toxicity due to increased metabolic activity and impaired heat dissipation, but **heat stroke** specifically refers to hyperthermia with associated CNS dysfunction. - While the patient has an elevated temperature, heat stroke itself, while serious, is typically managed by cooling, whereas the direct cardiovascular effects can be acutely fatal before heat stroke progresses. *Respiratory depression* - **Amphetamines are stimulants**, so they typically cause **respiratory stimulation** (tachypnea) rather than depression. - Respiratory depression is more commonly associated with depressant drug overdoses, such as opioids. *Malignant hyperthermia* - **Malignant hyperthermia** is a genetic disorder triggered by certain anesthetic agents or succinylcholine, characterized by a rapid, uncontrolled increase in body temperature and muscle rigidity. - It is not directly caused by amphetamine toxicity, although both conditions involve severe hyperthermia, their etiologies are distinct.

Question 154: A 35-year-old patient is brought into the emergency department post motor vehicle crash. Stabilization of the patient in the trauma bay requires endotracheal intubation. The patient has a laceration on the femoral artery from shrapnel and seems to have lost large quantities of blood. The patient is transfused with 13 units of packed red blood cells. His vitals are T 96.5, HR 150, BP 90/40. Even with the direct pressure on the femoral artery, the patient continues to bleed. Results of labs drawn within the last hour are pending. Which of the following is most likely to stop the bleeding in this patient?

• A. Normal saline
• B. Fresh frozen plasma and platelets (Correct Answer)
• C. Whole blood
• D. Dextrose
• E. Cryoprecipitate

Explanation: ***Fresh frozen plasma and platelets*** - This patient is experiencing **dilutional coagulopathy** due to massive transfusion of packed red blood cells, which lack clotting factors and platelets. - **Fresh frozen plasma (FFP)** provides essential clotting factors, while **platelets** directly address thrombocytopenia, both crucial for **hemostasis**. - This represents **standard component therapy** readily available in emergency departments. *Normal saline* - Administering normal saline would further dilute the remaining clotting factors and platelets, potentially **worsening the coagulopathy**. - While essential for **volume resuscitation**, it does not provide any clotting components needed to stop bleeding. *Whole blood* - While **whole blood** contains red blood cells, plasma, and platelets in physiologic ratios, it is **not readily available** in most civilian trauma centers. - Modern practice uses **component therapy** (FFP + platelets + PRBCs) which is more widely accessible and allows for targeted resuscitation. - Low-titer O whole blood programs exist in some centers but are not universally available. *Dextrose* - **Dextrose solutions** primarily provide free water and glucose, used for hydration and hypoglycemia. - It has **no hemostatic properties** and would further dilute clotting factors, exacerbating the bleeding. *Cryoprecipitate* - **Cryoprecipitate** is rich in **fibrinogen, factor VIII, factor XIII, and von Willebrand factor**. - While useful for specific factor deficiencies or when fibrinogen is critically low in massive transfusions, it **does not replace all clotting factors or platelets** comprehensively as FFP and platelets would. - Typically used as **adjunctive therapy** when fibrinogen levels are known to be low.

Question 155: A 42-year-old woman comes to the physician because of urinary leakage over the last year. She reports involuntarily losing small amounts of urine after experiencing a sudden need to void. She has difficulty making it to the bathroom in time, and only feels comfortable going out into public if she has documented the location of all nearby restrooms. She also has begun to wake up at night to urinate. These symptoms have persisted despite 6 months of bladder training and weight loss and reducing soda and coffee intake. Physical examination shows no abnormalities. The most appropriate pharmacotherapy for this patient is a drug that has which of the following mechanisms of action?

• A. Agonism of muscarinic M2 receptors
• B. Antagonism of beta-3 adrenergic receptors
• C. Antagonism of alpha-1 adrenergic receptors
• D. Antagonism of muscarinic M3 receptors (Correct Answer)
• E. Agonism of beta-2 adrenergic receptors

Explanation: ***Antagonism of muscarinic M3 receptors*** - The patient's symptoms of **sudden urge to void**, difficulty making it to the bathroom, and nocturia, especially after conservative management failure, are classic for **urge incontinence** or overactive bladder. - Urge incontinence is caused by **detrusor muscle overactivity**, which is primarily mediated by **M3 muscarinic receptors**; thus, M3 antagonists (e.g., oxybutynin, solifenacin) relax the detrusor. *Agonism of muscarinic M2 receptors* - While M2 receptors are present in the bladder, their role in detrusor contraction is less prominent than M3 receptors. Agonism of M2 receptors would theoretically enhance bladder contraction, worsening symptoms. - No current pharmacotherapy for urge incontinence primarily targets M2 agonism for therapeutic benefit. *Antagonism of beta-3 adrenergic receptors* - **Beta-3 adrenergic receptor agonists** (e.g., mirabegron) are used to treat overactive bladder by relaxing the detrusor muscle, but antagonism of these receptors would promote detrusor contraction and worsen symptoms. - Antagonism of beta-3 receptors is counterproductive as it would increase bladder tone, exacerbating urinary urgency and frequency. *Antagonism of alpha-1 adrenergic receptors* - **Alpha-1 adrenergic receptors** are primarily located in the **bladder neck** and **urethra**, mediating smooth muscle contraction to maintain continence. - Antagonism of these receptors (e.g., with tamsulosin) is used to relax the bladder neck in conditions like benign prostatic hyperplasia to improve urine flow, but would worsen urge incontinence by reducing outflow resistance. *Agonism of beta-2 adrenergic receptors* - Beta-2 adrenergic receptors are present in the detrusor muscle, but their agonism has a relatively minor effect on detrusor relaxation compared to beta-3 agonists. - While beta-2 agonists can cause some detrusor relaxation, they are not the primary or most effective pharmacotherapeutic target for urge incontinence.

Question 156: A 4-year-old boy is brought by his mother to the emergency room after the child was bitten by a rattlesnake one hour prior to presentation. The child was reportedly playing in the backyard alone when his mother heard the child scream. She rushed out to her child and found a snake with a rattle on its tail slithering away from the child. On examination, the child has a bleeding bite mark and significant swelling over the dorsal aspect of his right hand. He is in visible distress and appears pale and diaphoretic. The child undergoes fluid resuscitation and is placed on supplemental oxygen. He is administered rattlesnake antivenom and is admitted for observation. He is subsequently discharged 24 hours later feeling better. However, 6 days after admission, he presents again to the emergency department with a temperature of 102°F (38.9°C), diffuse wheals, and knee and hip pain. This patient’s condition is caused by which of the following?

• A. IgE-mediated mast cell degranulation
• B. Antibodies directed against cell membrane antigens
• C. Antibody-antigen complex deposition (Correct Answer)
• D. Cell-mediated direct killing
• E. Antibodies directed against cell surface receptors

Explanation: ***Antibody-antigen complex deposition*** - This clinical scenario describes **serum sickness**, a **Type III hypersensitivity** reaction, which occurs due to the formation and deposition of **immune complexes** (antibody-antigen complexes) in tissues. - The antivenom, being a foreign protein, acts as an **antigen**, leading to an immune response and the subsequent development of symptoms like fever, urticaria (wheals), and arthralgia (joint pain) days after exposure. *IgE-mediated mast cell degranulation* - This describes a **Type I hypersensitivity** reaction, which typically has a much **faster onset** (minutes to hours) and can manifest as anaphylaxis, urticaria, or angioedema. - While an allergic reaction to antivenom is possible, the delayed onset (6 days) and specific symptoms (fever, arthralgia) are not typical for an immediate IgE-mediated response. *Antibodies directed against cell membrane antigens* - This mechanism describes a **Type II hypersensitivity** reaction, where antibodies bind to **antigens on cell surfaces**, leading to cell destruction (e.g., hemolytic anemia, thrombocytopenia). - The symptoms presented (fever, wheals, joint pain) are not characteristic of direct cellular destruction. *Cell-mediated direct killing* - This refers to a **Type IV hypersensitivity** reaction, involving **T lymphocytes** directly killing target cells or recruiting inflammatory cells, usually with a **delayed onset** of 24-72 hours. - Examples include contact dermatitis or graft-versus-host disease, which do not align with the diffuse systemic symptoms observed in this case. *Antibodies directed against cell surface receptors* - This is a specific subtype of **Type II hypersensitivity** where antibodies bind to and either stimulate or block cell surface receptors, interfering with cell function without necessarily causing cell destruction (e.g., Graves' disease, Myasthenia gravis). - The clinical presentation of fever, diffuse wheals, and joint pain is not consistent with this localized receptor-mediated dysfunction.

Question 157: A 10-year-old boy is brought to the emergency room after a fall from a horse. He has severe pain in his right forearm. He has a history of asthma and atopic dermatitis. His current medications include an albuterol inhaler and hydrocortisone cream. Examination shows an open fracture of the right forearm and no other injuries. The patient is given a parenteral infusion of 1 L normal saline, cefazolin, morphine, and ondansetron. The right forearm is covered with a splint. Informed consent for surgery is obtained. Fifteen minutes later, the patient complains of shortness of breath. He has audible wheezing. His temperature is 37.0°C (98.6°F), heart rate is 130/min, respiratory rate is 33/min, and blood pressure is 80/54 mm Hg. Examination shows generalized urticaria and lip swelling. There is no conjunctival edema. Scattered wheezing is heard throughout both lung fields. Which of the following is the most appropriate next step in management?

• A. Endotracheal intubation
• B. Administer intravenous diphenhydramine
• C. Administer intravenous methylprednisolone
• D. Administer vancomycin and piperacillin-tazobactam
• E. Administer intramuscular epinephrine (Correct Answer)

Explanation: ***Administer intramuscular epinephrine*** - The patient is presenting with signs of **anaphylaxis**, including **generalized urticaria**, **lip swelling**, **hypotension** (BP 80/54 mmHg), and **wheezing** (shortness of breath, audible wheezing over both lung fields). - **Epinephrine** is the first-line treatment for anaphylaxis as it acts on alpha- and beta-adrenergic receptors to reverse bronchospasm, vasodilation, and reduce angioedema. *Endotracheal intubation* - While the patient has **wheezing** and shortness of breath, **intubation** is a more aggressive measure usually reserved for impending or actual airway compromise that doesn't respond to initial treatment with epinephrine. - The immediate priority is to address the systemic allergic reaction with epinephrine, which can prevent the need for intubation by improving bronchospasm and laryngeal edema. *Administer intravenous diphenhydramine* - **Diphenhydramine**, an H1 antihistamine, can help with cutaneous symptoms like **urticaria** and itching but does not address the life-threatening aspects of anaphylaxis such as **bronchospasm** and **hypotension**. - It is used as an adjunct to epinephrine, not as a primary treatment for severe anaphylaxis. *Administer intravenous methylprednisolone* - **Corticosteroids** like **methylprednisolone** can help prevent protracted or biphasic anaphylactic reactions but have a delayed onset of action and are not effective in the acute, life-threatening phase of anaphylaxis. - They are used as an adjunct after epinephrine has been administered to stabilize the patient. *Administer vancomycin and piperacillin-tazobactam* - Administering **broad-spectrum antibiotics** like vancomycin and piperacillin-tazobactam would be appropriate for suspected **sepsis** or a severe bacterial infection. - The patient's symptoms (generalized urticaria, lip swelling, wheezing, and hypotension) are characteristic of **anaphylaxis**, not bacterial sepsis, making antibiotics an inappropriate immediate first-line treatment.

Question 158: A 37-year-old man with a history of schizophrenia, obesity, anxiety, recurrent pneumonia, and depression is brought to the emergency department. He was recently discharged from inpatient psychiatric care where he was treated for an acute psychotic episode with fluphenazine and started on a new antidepressant. One week after discharge, during a period of cold weather, he is found outdoors confused and poorly dressed. His rectal temperature is 93.2°F (34°C). Which of the following medications is most likely contributing to his hypothermia?

• A. Fluphenazine (Correct Answer)
• B. Valproic acid
• C. Diphenhydramine
• D. Fluoxetine
• E. Lithium

Explanation: **Fluphenazine** - **First-generation antipsychotics** like fluphenazine can impair the body's ability to **thermoregulate** by interfering with dopaminergic pathways in the hypothalamus, increasing susceptibility to hypothermia in cold environments. - Given the patient's recent discharge from inpatient care and exposure to cold weather while poorly dressed, the addition of an antipsychotic affecting thermoregulation strongly contributes to his hypothermia. *Valproic acid* - Valproic acid is an **anticonvulsant** and **mood stabilizer** primarily used for bipolar disorder and epilepsy. - While it can have various side effects, **hypothermia** is not a commonly reported or significant side effect of valproic acid. *Diphenhydramine* - Diphenhydramine is an **antihistamine** with significant **sedative** and **anticholinergic** properties. - While it can cause sedation and anticholinergic effects that might impact a patient's awareness or ability to seek shelter, it is not directly implicated in causing hypothermia through thermoregulatory dysfunction. *Fluoxetine* - Fluoxetine is a **selective serotonin reuptake inhibitor (SSRI)** commonly used for depression and anxiety. - While SSRIs can have various side effects, **hypothermia** is not a characteristic or significant side effect of fluoxetine. *Lithium* - Lithium is a **mood stabilizer** used primarily for bipolar disorder. - **Hypothyroidism** is a known side effect of long-term lithium use, which could theoretically contribute to an inability to maintain body temperature, but it is less likely to cause acute hypothermia compared to antipsychotics directly affecting thermoregulation.

Question 159: A 70-year-old male presents to his primary care provider complaining of decreased sexual function. He reports that over the past several years, he has noted a gradual decline in his ability to sustain an erection. He used to wake up with erections but no longer does. His past medical history is notable for diabetes, hyperlipidemia, and a prior myocardial infarction. He takes metformin, glyburide, aspirin, and atorvastatin. He drinks 2-3 drinks per week and has a 25 pack-year smoking history. He has been happily married for 40 years. He retired from his job as a construction worker 5 years ago and has been enjoying retirement with his wife. His physician recommends starting a medication that is also used in the treatment of pulmonary hypertension. Which of the following is a downstream effect of this medication?

• A. Increase cGMP degradation
• B. Increase cAMP production
• C. Increase PDE5 activity
• D. Decrease nitric oxide production
• E. Decrease cGMP degradation (Correct Answer)

Explanation: ***Decrease cGMP degradation*** - The medication described is likely a **phosphodiesterase-5 (PDE5) inhibitor** (e.g., sildenafil, tadalafil), used for erectile dysfunction and pulmonary hypertension. - These drugs work by inhibiting the enzyme PDE5, which is responsible for the breakdown of **cyclic GMP (cGMP)**, thereby increasing cGMP levels. *Increase cGMP degradation* - This is the **opposite** of the medication's intended effect, as it would lead to reduced cGMP levels and worsen erectile dysfunction. - An increase in cGMP degradation would diminish the **vasodilatory** effects necessary for erection. *Increase cAMP production* - This medication primarily affects the **cGMP pathway**, not directly boosting cyclic AMP (cAMP) production. - While cAMP also plays a role in vasodilation, it's regulated by different enzymes and pathways, such as **adenylyl cyclase**. *Increase PDE5 activity* - This would lead to a more **rapid breakdown of cGMP**, counteracting the goal of the medication and exacerbating erectile dysfunction. - The medication's mechanism is specifically designed to **inhibit PDE5 activity**. *Decrease nitric oxide production* - **Nitric oxide (NO)** production is a **precursor** to cGMP synthesis, as NO activates guanylate cyclase to produce cGMP. - Decreasing NO production would **reduce cGMP levels**, which is contrary to the action of PDE5 inhibitors.

Question 160: A 32-year-old man presents to his primary care physician because he has been experiencing intermittent episodes of squeezing chest pain and tightness. He says that the pain is 8/10 in severity, radiates to his left arm, and does not appear to be associated with activity. The episodes started 3 months ago and have been occurring about twice per month. His past medical history is significant for migraines for which he takes sumatriptan. Physical exam reveals no abnormalities and an EKG demonstrates sinus tachycardia with no obvious changes. An angiogram is performed to evaluate coronary artery blood flow. During the angiogram, a norepinephrine challenge is administered and blood flow is observed to decrease initially; however, after 2 minutes blood flow is observed to be increased compared to baseline. Which of the following substances is most likely responsible for the increased blood flow observed at this later time point?

• A. Angiotensin
• B. Thromboxane A2
• C. Epinephrine
• D. Adenosine (Correct Answer)
• E. Histamine

Explanation: ***Adenosine*** - The patient's symptoms (squeezing chest pain, radiation to the left arm, not activity-related, intermittent) are consistent with **vasospastic angina** (Prinzmetal's angina). The brief decrease in blood flow followed by an increase after a norepinephrine challenge suggests initial vasoconstriction followed by compensatory vasodilation. - **Adenosine** is a potent **endogenous vasodilator** in the coronary arteries. It is released by myocardial cells during periods of increased metabolic demand or hypoxia and also as a compensatory mechanism following vasoconstrictive challenges. Its release leads to an increase in blood flow to meet metabolic needs. *Angiotensin* - **Angiotensin II** is a potent **vasoconstrictor**, acting primarily through the AT1 receptor. - It would further reduce blood flow, not increase it, especially following a norepinephrine challenge. *Thromboxane A2* - **Thromboxane A2** is a potent **vasoconstrictor** and platelet aggregator. - Its primary role is to promote clotting and reduce blood flow, which would not explain the observed increase in flow. *Epinephrine* - **Epinephrine** has complex effects on vasculature depending on receptor distribution; however, at therapeutic concentrations, it generally causes **vasoconstriction** via alpha-1 adrenergic receptors in coronary arteries, especially when exogenous norepinephrine is already present. - While it can cause vasodilation via beta-2 receptors in some vascular beds, its net effect in this scenario would likely be vasoconstrictive or maintain constriction, not promote increased flow. *Histamine* - **Histamine** can cause vasodilation via H1 and H2 receptors, but its primary role is in **inflammatory and allergic responses**. - While it can cause increased blood flow, it is not typically the primary physiological compensatory mechanism for reversing vasoconstriction in the coronary arteries following a norepinephrine challenge in the context of angina.

Question 161: A 14-year-old boy is rushed to the emergency room after he became disoriented at home. His parents say that the boy was doing well until 2 days ago when he got sick and vomited several times. They thought he was recovering but today he appeared to be disoriented since the morning. His vitals are normal except shallow rapid breathing at a rate of 33/min. His blood sugar level is 654 mg/dL and urine is positive for ketone bodies. He is diagnosed with diabetic ketoacidosis and is managed with fluids and insulin. He responds well to the therapy. His parents are told that their son has type 1 diabetes and insulin therapy options are being discussed. Which of the following types of insulin can be used in this patient for the rapid action required during mealtimes?

• A. Insulin detemir
• B. Insulin degludec
• C. NPH insulin
• D. Insulin glargine
• E. Insulin lispro (Correct Answer)

Explanation: ***Insulin lispro*** - **Insulin lispro** is a **rapid-acting insulin analog** designed to be taken immediately before or with a meal, offering quick onset (5-15 minutes) and short duration of action. - Its rapid action helps to control **postprandial glucose spikes**, closely mimicking the physiological insulin response to food, which is crucial for mealtime coverage in **Type 1 diabetes**. *Insulin detemir* - **Insulin detemir** is a **long-acting insulin analog** used for basal insulin coverage, providing a relatively constant insulin level over an extended period (12-24 hours). - It is not suitable for **mealtime insulin coverage** due to its slow onset of action and prolonged duration, which would not effectively manage postprandial glucose excursions. *Insulin degludec* - **Insulin degludec** is an **ultra-long-acting basal insulin analog** with a duration of action exceeding 42 hours, providing stable basal coverage. - Its extremely slow onset and prolonged duration make it unsuitable for **prandial (mealtime) insulin**, as it cannot address the rapid rise in blood glucose following a meal. *NPH insulin* - **NPH (Neutral Protamine Hagedorn) insulin** is an **intermediate-acting insulin** that provides basal insulin coverage, with an onset of 2-4 hours and a peak effect around 6-10 hours. - Its slow onset and prolonged action make it unsuitable for **mealtime insulin coverage**, as it would not adequately prevent the rapid rise in blood sugar immediately after eating. *Insulin glargine* - **Insulin glargine** is a **long-acting insulin analog** used for **basal insulin coverage**, providing a relatively flat and peakless insulin profile over 24 hours. - It is not used for **prandial (mealtime) insulin** because its slow onset and sustained action would not effectively counteract the rapid rise in blood glucose following a meal.

Question 162: A 71-year-old man presents to his oncologist with nausea. He recently underwent chemotherapy for pancreatic cancer and has developed severe intractable nausea over the past week. He vomits several times a day. His past medical history is notable for gout, osteoarthritis, and major depressive disorder. He takes allopurinol and sertraline. He has a 15-pack-year smoking history and drinks 1 glass of wine per day. His temperature is 98.6°F (37°C), blood pressure is 148/88 mmHg, pulse is 106/min, and respirations are 22/min. On exam, he is lethargic but able to answer questions appropriately. He has decreased skin turgor and dry mucous membranes. He is started on a medication to treat nausea. However, 3 days later he presents to the emergency room with fever, agitation, hypertonia, and clonus. What is the most likely mechanism of action of the drug this patient was prescribed?

• A. 5-HT3 receptor antagonist (Correct Answer)
• B. M1 receptor antagonist
• C. Opiate receptor agonist
• D. D2 receptor antagonist
• E. H1 receptor antagonist

Explanation: ***5-HT3 receptor antagonist*** - The patient's symptoms of **fever**, **agitation**, **hypertonia**, and **clonus** after starting an antiemetic strongly suggest **serotonin syndrome**. - **Ondansetron**, a common 5-HT3 receptor antagonist used for chemotherapy-induced nausea, can precipitate serotonin syndrome, especially when used with **SSRIs** like **sertraline**. *M1 receptor antagonist* - **M1 receptor antagonists** (e.g., scopolamine, atropine) are anticholinergic agents that can cause dry mouth, blurred vision, urinary retention, and constipation. - They are not typically associated with the severe neuromuscular and autonomic hyperactivity seen in **serotonin syndrome**. *Opiate receptor agonist* - **Opiate receptor agonists** (e.g., morphine, fentanyl) primarily cause CNS depression, respiratory depression, constipation, and miosis. - They do not cause features like clonus, agitation, or hypertonia characteristic of **serotonin syndrome**. *D2 receptor antagonist* - **D2 receptor antagonists** (e.g., metoclopramide, prochlorperazine) can cause **extrapyramidal symptoms** (dystonia, akathisia) and **neuroleptic malignant syndrome** (NMS). - NMS also presents with fever and rigidity but lacks hyperreflexia and clonus, which are prominent in **serotonin syndrome**. *H1 receptor antagonist* - **H1 receptor antagonists** (e.g., promethazine, diphenhydramine) are used for nausea due to their sedative and anticholinergic effects. - Their side effects include sedation, dizziness, and anticholinergic effects, but not the specific constellation of symptoms indicative of **serotonin syndrome**.

Question 163: A 2-year-old boy is brought to his primary care physician for persistent failure to thrive. He has not been meeting normal motor developmental milestones. Further questioning reveals a family history of congenital kidney disorders, although the parents do not know details. Based on clinical suspicion a panel of lab tests are ordered which reveal a sodium of 129 mg/dL (normal range 136-145), a potassium of 3.1 mg/dL (normal range 3.5-5.0), a bicarbonate of 32 mg/dL (normal range 22-28) and a pH of 7.5 (normal range 7.35-7.45). Urinary calcium excretion is also found to be increased. Which of the following drugs has the most similar mechanism of action to the most likely diagnosis in this patient?

• A. Hydrochlorothiazide
• B. Furosemide (Correct Answer)
• C. Spironolactone
• D. Amiloride
• E. Acetazolamide

Explanation: **Furosemide** - The patient's presentation with **failure to thrive**, **motor developmental delay**, **hypokalemia**, **metabolic alkalosis**, and **hypercalciuria** is highly suggestive of **Bartter syndrome**. This condition is caused by a genetic defect in the **Na-K-2Cl cotransporter (NKCC2)** in the **thick ascending limb of the loop of Henle**. - **Furosemide** is a loop diuretic that works by inhibiting the **NKCC2 cotransporter**, thus mimicking the physiological effects seen in Bartter syndrome. *Hydrochlorothiazide* - This drug inhibits the **Na-Cl cotransporter** in the **distal convoluted tubule**, which is a different segment of the nephron and has a distinct mechanism of action from the defect in Bartter syndrome. - While it can cause hypokalemia, it typically causes **hypocalciuria**, which is opposite to the hypercalciuria seen in this patient. *Spironolactone* - This is an **aldosterone antagonist** that acts in the **collecting duct** to inhibit sodium reabsorption and potassium excretion. - Its primary mechanism of action is far removed from the defect in the thick ascending limb of the loop of Henle characteristic of Bartter syndrome. *Amiloride* - This is a **potassium-sparing diuretic** that directly inhibits **epithelial sodium channels (ENaC)** in the collecting duct. - This mechanism is unrelated to the Na-K-2Cl cotransporter defect found in Bartter syndrome. *Acetazolamide* - This drug is a **carbonic anhydrase inhibitor** that acts primarily in the **proximal tubule** to inhibit bicarbonate reabsorption. - It causes a **metabolic acidosis**, which is the opposite of the metabolic alkalosis seen in this patient.

Question 164: A 68-year-old man undergoes successful mechanical prosthetic aortic valve replacement for severe aortic valve stenosis. After the procedure, he is started on an oral medication and instructed that he should take for the rest of his life and that he should avoid consuming large amounts of dark-green, leafy vegetables. Which of the following laboratory parameters should be regularly monitored to guide dosing of this drug?

• A. D-dimer
• B. Anti-factor Xa activity
• C. Activated partial thromboplastin time
• D. Prothrombin time (Correct Answer)
• E. Thrombin time

Explanation: ***Prothrombin time*** - **Warfarin** is the standard chronic anticoagulant post-mechanical valve replacement, and its dosing is monitored using the **prothrombin time (PT)**, reported as the **International Normalized Ratio (INR)**. - The avoidance of dark-green, leafy vegetables indicates a **Vitamin K antagonist**, which is warfarin. *D-dimer* - **D-dimer** levels are primarily used to rule out **venous thromboembolism (VTE)** and are not used for routine monitoring of chronic anticoagulation. - Elevated D-dimer indicates recent or ongoing **fibrinolysis**, which is not directly targeted by warfarin therapy. *Anti-factor Xa activity* - **Anti-factor Xa activity** is used to monitor the anticoagulant effect of **low molecular weight heparins (LMWH)** or **direct oral anticoagulants (DOACs)** like rivaroxaban or apixaban. - This patient is on a vitamin K antagonist, not an anti-Xa inhibitor. *Activated partial thromboplastin time* - The **activated partial thromboplastin time (aPTT)** is used to monitor patients receiving **unfractionated heparin**, not warfarin. - While both heparin and warfarin are anticoagulants, they act on different parts of the coagulation cascade and are monitored differently. *Thrombin time* - **Thrombin time (TT)** measures the time it takes for plasma to clot after adding thrombin, and it is primarily used to detect inherited or acquired **fibrinogen disorders** or to monitor **direct thrombin inhibitors**. - It is not routinely used for monitoring warfarin therapy.

Question 165: A 50-year-old man with a history of atrial fibrillation presents to his cardiologist’s office for a follow-up visit. He recently started treatment with an anti-arrhythmic drug to prevent future recurrences and reports that he has been feeling well and has no complaints. The physical examination shows that the arrhythmia appears to have resolved; however, there is now mild bradycardia. In addition, the electrocardiogram recording shows a slight prolongation of the PR and QT intervals. Which of the following drugs was most likely used to treat this patient?

• A. Metoprolol
• B. Sotalol (Correct Answer)
• C. Propranolol
• D. Verapamil
• E. Carvedilol

Explanation: ***Sotalol*** - **Sotalol** is a **beta-blocker** and a **Class III antiarrhythmic** drug, meaning it blocks potassium channels. - This dual action explains the **bradycardia** (beta-blockade) and the **prolongation of the PR and QT intervals** (potassium channel blockade), which are characteristic side effects. *Metoprolol* - **Metoprolol** is a **selective beta-1 blocker** (Class II antiarrhythmic) that would cause **bradycardia** and **PR prolongation**, but it does not typically prolong the **QT interval**. - It primarily affects the heart rate and AV nodal conduction without significant potassium channel blocking properties. *Propranolol* - **Propranolol** is a **non-selective beta-blocker** (Class II antiarrhythmic) that would cause **bradycardia** and **PR prolongation**. - Similar to metoprolol, it does not typically prolong the **QT interval**. *Verapamil* - **Verapamil** is a **non-dihydropyridine calcium channel blocker** (Class IV antiarrhythmic) that causes **bradycardia** and **PR prolongation**. - However, it does not prolong the **QT interval**; instead, it can sometimes shorten it. *Carvedilol* - **Carvedilol** is a **non-selective beta-blocker** with **alpha-1 blocking properties** (Class II antiarrhythmic), leading to **bradycardia** and **PR prolongation**. - It does not have effects on potassium channels that would lead to **QT prolongation**.

Question 166: A 30-year-old male presents to a local clinic with a complaint of a stiff neck. The patient is known to be sporadic with follow-up appointments but was last seen recently for a regular depot injection. He initially presented with complaints of paranoid delusions and auditory hallucinations that lasted for 7 months and caused significant social and financial deterioration. He was brought into the clinic by his older brother, who provides social support. Because of the patient's tendency to be non-compliant with medications, the patient was placed on a specific drug to mitigate this pattern. Which of the following medications is responsible for the patient's movement disorder?

• A. Thioridazine
• B. Clozapine
• C. Haloperidol (Correct Answer)
• D. Olanzapine
• E. Benztropine

Explanation: ***Haloperidol*** - The patient's history of **paranoid delusions** and **auditory hallucinations** lasting 7 months, along with significant social and financial deterioration, is consistent with **schizophrenia**. - Given the patient's **non-compliance** and lack of social support, he was likely prescribed a **long-acting injectable antipsychotic**. **Haloperidol decanoate** is a first-generation antipsychotic often used in this scenario, known for its higher risk of **extrapyramidal symptoms (EPS)** like a **stiff neck (dystonia)** compared to second-generation agents. *Thioridazine* - **Thioridazine** is a **first-generation antipsychotic** but is associated with a **lower incidence of EPS** compared to other high-potency typical antipsychotics like haloperidol. - It also carries significant risks of **cardiac arrhythmias (QT prolongation)** and **retinal toxicity**, making it a less common choice for long-term management, especially with compliance issues. *Clozapine* - **Clozapine** is an atypical (second-generation) antipsychotic known for its efficacy in **treatment-resistant schizophrenia** and a very **low risk of EPS**. - However, it requires **weekly blood monitoring** due to the risk of **agranulocytosis**, which makes it unsuitable for a patient with compliance issues and lack of social support. *Olanzapine* - **Olanzapine** is a **second-generation antipsychotic** that is available as a **long-acting injection**. While it can cause some EPS, the risk is generally **lower than with haloperidol**. - It is more commonly associated with **metabolic side effects** such as weight gain, hyperglycemia, and dyslipidemia, rather than severe acute dystonia as the primary concern. *Benztropine* - **Benztropine** is an **anticholinergic medication** used to **treat the EPS induced by antipsychotics**, such as dystonia and parkinsonism. - If a patient is experiencing a stiff neck due to an antipsychotic, benztropine would be a treatment for the side effect, not the cause of it.

Question 167: A 28-year-old woman with a history of migraines presents to your office due to sudden loss of vision in her left eye and difficulty speaking. Two weeks ago she experienced muscle aches, fever, and cough. Her muscle aches are improving but she continues to have a cough. She also feels as though she has been more tired than usual. She had a similar episode of vision loss 2 years ago and had an MRI at that time. She has a family history of migraines and takes propranolol daily. On swinging light test there is decreased constriction of the left pupil relative to the right pupil. You repeat the MRI and note enhancing lesions in the left optic nerve. Which of the following is used to prevent progression of this condition?

• A. Dexamethasone
• B. Infliximab
• C. Methotrexate
• D. Adalimumab
• E. Natalizumab (Correct Answer)

Explanation: ***Natalizumab*** - This patient's presentation with recurrent optic neuritis, fatigue, and enhancing lesions on MRI, combined with a history of similar episodes, strongly suggests **multiple sclerosis (MS)**. Natalizumab is a **monoclonal antibody** that blocks the migration of lymphocytes across the blood-brain barrier, effectively preventing disease progression in MS. - It is a **highly effective disease-modifying therapy** for relapsing-remitting MS (RRMS) and is often used in patients who have failed other first-line treatments due to its efficacy in reducing relapse rates and preventing new lesions. *Dexamethasone* - While **corticosteroids** like dexamethasone are used to treat **acute exacerbations** or relapses in MS by reducing inflammation, they do not prevent long-term disease progression. - Its primary role is to **shorten the duration and severity of an acute attack**, rather than to modify the underlying disease course. *Infliximab* - Infliximab is an **anti-TNF-α biologic agent** primarily used in the treatment of **inflammatory bowel disease** (Crohn's disease, ulcerative colitis), rheumatoid arthritis, and other autoimmune conditions. - It is **contraindicated in MS** as it has been shown to worsen the disease and even induce demyelination in some patients. *Methotrexate* - Methotrexate is an **immunosuppressant** and **chemotherapeutic agent** used in conditions like rheumatoid arthritis, psoriasis, and certain cancers. - It is **not a primary treatment for MS** and has limited to no role in preventing its progression. *Adalimumab* - Adalimumab is another **anti-TNF-α agent** similar to infliximab, used for conditions such as rheumatoid arthritis, psoriatic arthritis, and inflammatory bowel disease. - Like infliximab, **TNF-α blockers are generally avoided in MS** due to concerns about exacerbating the disease.

Question 168: A 30-year-old woman is brought to the emergency department because of a 30-minute history of palpitations, dizziness, and chest discomfort. She has also not urinated since she woke up. She has a history of fibromyalgia treated with clomipramine. There is no family history of serious illness. She does not smoke or drink alcohol. Her temperature is 37°C (98.6°F), pulse is 120/min, and blood pressure is 90/60 mm Hg. On mental status examination, she is confused. Examination shows dilated pupils and dry skin. The abdomen is distended, there is tenderness to deep palpation of the lower quadrants with no guarding or rebound and dullness on percussion in the suprapubic region. An ECG shows tachycardia and a QRS complex width of 110 ms. Activated carbon is administered. The patient is intubated. Intravenous fluids and oxygenation are begun. Which of the following is the most appropriate pharmacotherapy for this patient?

• A. Cyproheptadine
• B. Lorazepam
• C. Naloxone
• D. Glucagon
• E. Sodium bicarbonate (Correct Answer)

Explanation: ***Sodium bicarbonate*** - The patient presents with symptoms and signs consistent with **tricyclic antidepressant (TCA) toxicity** (e.g., tachycardia, hypotension, dilated pupils, confusion, urinary retention, wide QRS complex on ECG), likely due to clomipramine. **Sodium bicarbonate** is the first-line treatment for TCA-induced cardiotoxicity and QRS widening. - It works by increasing extracellular sodium, overcoming the **sodium channel blockade** caused by TCAs, and by alkalinizing the blood, which reduces the binding of TCAs to myocardial cells. *Cyproheptadine* - **Cyproheptadine** is a serotonin antagonist used to treat **serotonin syndrome**, which presents with hyperthermia, muscle rigidity, and hyperreflexia, differentiating it from TCA toxicity. - While TCAs can contribute to serotonin syndrome, the primary concern in this case is **cardiac toxicity** and QRS widening due to sodium channel blockade. *Lorazepam* - **Lorazepam** is a benzodiazepine used to treat **seizures** and **agitation**, which can be associated with TCA overdose but are not the primary, life-threatening features requiring immediate pharmacotherapy here. - It does not address the **cardiac toxicity** (e.g., wide QRS, hypotension) that is the most critical aspect of this patient's presentation. *Naloxone* - **Naloxone** is an opioid antagonist used to reverse **opioid overdose**. - The patient's symptoms (dilated pupils, dry skin, wide QRS) are not consistent with opioid toxicity, which typically causes **miosis** (pinpoint pupils) and **respiratory depression**. *Glucagon* - **Glucagon** is used in cases of severe **beta-blocker or calcium channel blocker overdose** to improve cardiac contractility and heart rate. - While the patient has hypotension, glucagon does not address the specific mechanism of TCA toxicity involving **sodium channel blockade** and is not the primary treatment.

Question 169: A patient is receiving daily administrations of Compound X. Compound X is freely filtered in the glomeruli and undergoes net secretion in the renal tubules. The majority of this tubular secretion occurs in the proximal tubule. Additional information regarding this patient's renal function and the renal processing of Compound X is included below: Inulin clearance: 120 mL/min Plasma concentration of Inulin: 1 mg/mL PAH clearance: 600 mL/min Plasma concentration of PAH: 0.2 mg/mL Total Tubular Secretion of Compound X: 60 mg/min Net Renal Excretion of Compound X: 300 mg/min Which of the following is the best estimate of the plasma concentration of Compound X in this patient?

• A. 2 mg/mL (Correct Answer)
• B. 3 mg/mL
• C. There is insufficient information available to estimate the plasma concentration of Compound X
• D. 1 mg/mL
• E. 0.5 mg/mL

Explanation: ***2 mg/mL*** * The **net renal excretion of Compound X (300 mg/min)** is the sum of the filtered load and the net tubular secretion. * Given that Compound X is **freely filtered** and undergoes **net secretion (60 mg/min)**, we can calculate the filtered load and subsequently its plasma concentration. * **Net excretion = Filtered load + Net tubular secretion** * **300 mg/min = Filtered load + 60 mg/min** * **Filtered load = 300 mg/min - 60 mg/min = 240 mg/min** * Since **Filtered load = Glomerular Filtration Rate (GFR) * Plasma concentration (P_X)**, and GFR is estimated by **inulin clearance (120 mL/min)**: * **240 mg/min = 120 mL/min * P_X** * **P_X = 240 mg/min / 120 mL/min = 2 mg/mL**. *3 mg/mL* * This value would imply a significantly higher filtered load or a different contribution from tubular secretion. * Calculations using this plasma concentration would not align with the provided excretion and secretion rates. *There is insufficient information available to estimate the plasma concentration of Compound X* * The problem provides all necessary values: **Inulin clearance (GFR)**, **net tubular secretion of Compound X**, and **net renal excretion of Compound X**. * These parameters are sufficient to determine the filtered load and thus the plasma concentration of Compound X. *1 mg/mL* * A plasma concentration of 1 mg/mL would result in a lower filtered load than calculated and would not account for the observed net renal excretion. * **Filtered load = 120 mL/min * 1 mg/mL = 120 mg/min**. Total excretion would then be 120 mg/min + 60 mg/min = 180 mg/min, which contradicts the given 300 mg/min. *0.5 mg/mL* * This plasma concentration would lead to an even lower filtered load, making it impossible to achieve the *net renal excretion of Compound X* given the tubular secretion. * **Filtered load = 120 mL/min * 0.5 mg/mL = 60 mg/min**. Total excretion would be 60 mg/min + 60 mg/min = 120 mg/min, which is much lower than the given 300 mg/min.

Question 170: A 37-year-old female presents to the emergency room complaining of headaches and palpitations. She reports that she initially started experiencing these symptoms several months prior but attributed them to stress at work. The symptoms occur episodically. Her family history is notable for medullary thyroid cancer and hyperparathyroidism. Her temperature is 98.6°F (37°C), blood pressure is 165/90 mmHg, pulse is 105/min, and respirations are 18/min. On examination she appears tremulous. Urine metanephrines are elevated. Which of the following is the most appropriate first medication in the management of this patient’s condition?

• A. Atenolol
• B. Phentolamine
• C. Phenoxybenzamine (Correct Answer)
• D. Tamsulosin
• E. Propranolol

Explanation: ***Phenoxybenzamine*** - This patient presents with symptoms highly suggestive of **pheochromocytoma** (headaches, palpitations, hypertension, tremulousness, elevated urine metanephrines), further supported by the family history of **MEN2A syndrome** (medullary thyroid cancer and hyperparathyroidism). - **Alpha-blockade** with phenoxybenzamine (a non-selective, irreversible alpha-adrenergic antagonist) is the initial and crucial step in managing pheochromocytoma to control blood pressure and prevent a **hypertensive crisis** during surgical resection. *Atenolol* - **Beta-blockers** like atenolol are contraindicated as initial monotherapy in pheochromocytoma because blocking beta-2 receptors without prior alpha-blockade can lead to unopposed **alpha-1 mediated vasoconstriction**, worsening hypertension. - Beta-blockers can be added *after* adequate alpha-blockade has been achieved to control **tachycardia** or arrhythmias. *Phentolamine* - **Phentolamine** is an alpha-adrenergic blocker, but it is a **short-acting, reversible** agent, typically used for acute management of a **hypertensive crisis** in pheochromocytoma, rather than for chronic preoperative preparation. - While it has its role in emergency situations, it is not the most appropriate *first medication* for long-term preoperative stabilization. *Tamsulosin* - **Tamsulosin** is a **selective alpha-1a blocker** primarily used for benign prostatic hyperplasia (BPH) due to its uroselectivity. - It is not suitable for pheochromocytoma because it does not provide sufficient, widespread alpha-blockade to prevent a hypertensive crisis. *Propranolol* - Like atenolol, **propranolol** is a **beta-blocker** and should not be used as initial monotherapy in pheochromocytoma due to the risk of unopposed alpha-adrenergic vasoconstriction, which can exacerbate hypertension. - It may be used *after* alpha-blockade to manage tachycardia.

Question 171: A 28-year-old woman, gravida 1, para 0, at 32 weeks' gestation is evaluated for vaginal bleeding. Five days ago, she was admitted to the hospital and started on treatment for a deep vein thrombosis in the right leg. Her pulse is 125/min and blood pressure is 95/67 mm Hg. Physical examination shows large hematomas on the upper limbs and swelling in the right calf. There is a large amount of bright red blood in the vaginal vault. Laboratory studies show a hemoglobin of 8.9 mg/dL, platelet count of 185,000/mm3, and activated partial thromboplastin time of 160 seconds. Which of the following is the most appropriate pharmacotherapy to rapidly reverse this patient's coagulopathy?

• A. Vitamin K
• B. Prothrombin complex concentrate
• C. Fresh frozen plasma
• D. Protamine sulfate (Correct Answer)
• E. Alteplase

Explanation: ***Protamine sulfate*** - The patient's prolonged **aPTT (160 seconds)**, combined with recent treatment for DVT, strongly suggests **heparin overdose** or sensitivity. - **Protamine sulfate** is the specific antidote for **heparin**, forming a stable salt that neutralizes its anticoagulant effect. *Vitamin K* - **Vitamin K** is the antidote for **warfarin** and helps in the synthesis of clotting factors II, VII, IX, and X. - It would not reverse the effects of **heparin**, which works by activating antithrombin and inhibiting thrombin and factor Xa. *Prothrombin complex concentrate* - **PCC** contains factors II, VII, IX, and X and is used to rapidly reverse the effects of **warfarin** or in cases of severe bleeding due to factor deficiencies. - While it could theoretically help with general coagulopathy, it is not the specific or most direct antagonist for **heparin**. *Fresh frozen plasma* - **FFP** contains all coagulation factors and is used for broad reversal of coagulopathy, especially in cases of **liver disease**, DIC, or multiple factor deficiencies. - While it could provide factors, it would not directly antagonize the high levels of **heparin** that are likely causing the bleeding. *Alteplase* - **Alteplase** is a **thrombolytic agent** used to break down existing blood clots by converting plasminogen to plasmin. - Administering alteplase would worsen the patient's severe bleeding and is contraindicated in this scenario.

Question 172: A 30-year-old man presents to your clinic complaining of excessive thirst and frequent urination for the past few months. Urine testing reveals a low urine osmolarity, which fails to increase after subjecting the patient to a water deprivation test and injection of desmopressin. Further into the encounter, the patient reveals that he has been on a mood stabilizer for bipolar disorder for several years. Which of the following is the most likely cause of his polyuria?

• A. Nephrogenic diabetes insipidus (Correct Answer)
• B. Syndrome of inappropriate ADH secretion
• C. Primary polydipsia
• D. Central diabetes insipidus
• E. Urinary tract infection

Explanation: ***Nephrogenic diabetes insipidus*** - The patient's history of **excessive thirst and frequent urination** with **low urine osmolarity** indicates a problem with water reabsorption. - The failure of urine osmolarity to increase after both **water deprivation and desmopressin administration** strongly suggests **nephrogenic diabetes insipidus**, where the kidneys do not respond to ADH. His long-term use of a mood stabilizer (likely **lithium** for bipolar disorder) is a common cause of acquired nephrogenic DI. *Syndrome of inappropriate ADH secretion* - **SIADH** typically presents with **hyponatremia** and **concentrated urine** (high urine osmolarity) despite plasma hypo-osmolality, which is the opposite of this patient's findings. - This condition leads to **fluid retention** and *not* polyuria or excessive thirst. *Primary polydipsia* - In primary polydipsia, excessive fluid intake leads to polyuria, but the kidneys are still able to **concentrate urine** in response to water deprivation. - The patient's urine osmolarity would **increase** after water deprivation, unlike what is observed here. *Central diabetes insipidus* - While central DI also causes polyuria and low urine osmolarity, the urine osmolarity **would increase** significantly after the administration of **desmopressin** (synthetic ADH) because the kidneys are still responsive. - The lack of response to desmopressin rules out a central cause. *Urinary tract infection* - A UTI would typically present with symptoms such as **dysuria, urgency, frequency** (though polyuria can occur), and often **hematuria or pyuria**. - It would not explain the specific findings of **low urine osmolarity** and the **failure to respond to water deprivation and desmopressin** in this manner.

Question 173: A 69-year-old man with type 2 diabetes mellitus comes to the physician for a follow-up examination. His only medication is metformin. He has tried to lose weight for several years without success. He is 168 cm (5 ft 6 in) tall and weighs 110 kg (243 lb); BMI is 39 kg/m2. His hemoglobin A1c is 8.5%. Which of the following is the most appropriate antidiabetic drug to address both this patient's glucose control and weight?

• A. Nateglinide
• B. Rosiglitazone
• C. Liraglutide (Correct Answer)
• D. Miglitol
• E. Glipizide

Explanation: ***Liraglutide*** - **Liraglutide** is a **glucagon-like peptide-1 (GLP-1) receptor agonist** that improves glycemic control by increasing glucose-dependent insulin secretion, decreasing glucagon secretion, and slowing gastric emptying. - A significant side effect of GLP-1 agonists is **weight loss**, making it an ideal choice for this patient who is obese (BMI 39 kg/m2) and struggling with weight management while having suboptimal glycemic control (HbA1c 8.5%). *Nateglinide* - **Nateglinide** is a **meglitinide**, which stimulates insulin release from pancreatic beta cells, similar to sulfonylureas, but with a more rapid and short-lived effect. - While it helps in glucose control, it is often associated with **weight gain** and does not address the patient's desire for weight loss. *Rosiglitazone* - **Rosiglitazone** is a **thiazolidinedione (TZD)** that improves insulin sensitivity by acting on PPAR-gamma receptors. - TZDs are commonly associated with **weight gain** and fluid retention, which would be detrimental to this patient's weight management goals. *Miglitol* - **Miglitol** is an **alpha-glucosidase inhibitor** that delays the absorption of carbohydrates from the gut, reducing postprandial glucose excursions. - While it can help with glucose control and is weight-neutral or may cause modest weight loss, its efficacy in reducing HbA1c is generally lower compared to other agents, and it commonly causes **gastrointestinal side effects** like flatulence and diarrhea. *Glipizide* - **Glipizide** is a **sulfonylurea** that stimulates insulin secretion from pancreatic beta cells independently of glucose concentration. - It is associated with a risk of **hypoglycemia** and often leads to **weight gain**, which is not suitable for a patient who needs to lose weight.

Question 174: A 42-year-old man comes to the physician because of a 6-month history of progressively worsening shortness of breath with exertion. He was diagnosed with systemic sclerosis 5 years ago. Vital signs are within normal limits. Physical examination shows puffy, taut skin over the fingers. Pulmonary examination is unremarkable. There is no jugular venous distention. An x-ray of the chest shows enlargement of the pulmonary vessels and a prominent right heart border. Cardiac catheterization shows elevated right ventricular pressures and a mean pulmonary artery pressure of 55 mm Hg. Treatment with tadalafil is begun. The expected beneficial effect of this drug is most likely due to which of the following actions?

• A. Reduced transmembrane calcium current
• B. Enhanced activity of nitric oxide (Correct Answer)
• C. Increased activation of protein kinase A
• D. Blockade of endothelin-1 binding at the endothelin receptor
• E. Decreased smooth muscle sensitivity to norepinephrine

Explanation: ***Enhanced activity of nitric oxide*** - **Tadalafil** is a **phosphodiesterase-5 (PDE5) inhibitor** that prevents the degradation of **cGMP**, leading to increased cGMP levels. - Elevated cGMP levels result in vascular smooth muscle relaxation and **vasodilation**, mimicking and enhancing the effects of **nitric oxide**. *Reduced transmembrane calcium current* - This is the mechanism of action for **calcium channel blockers**, which can be used in pulmonary hypertension but is not the primary action of tadalafil. - While calcium plays a role in smooth muscle contraction, tadalafil's direct effect is not on calcium channels. *Increased activation of protein kinase A* - This effect is primarily mediated by **beta-adrenergic agonists** or **prostacyclin analogs**, which increase cAMP and subsequently activate protein kinase A. - Tadalafil's mechanism is through the cGMP pathway, not directly through cAMP or protein kinase A activation. *Blockade of endothelin-1 binding at the endothelin receptor* - This describes the action of **endothelin receptor antagonists** (e.g., bosentan, ambrisentan), which are another class of drugs used for pulmonary hypertension. - Tadalafil does not act on endothelin receptors; its mechanism is distinct. *Decreased smooth muscle sensitivity to norepinephrine* - This effect is typically achieved by **alpha-adrenergic blockers**, which are not the primary mechanism of action for tadalafil. - Tadalafil acts downstream of neurotransmitter receptors by affecting intracellular signaling pathways involving cGMP.

Question 175: A 55-year-old man with a history of repeated hospitalization for chronic pancreatitis comes to the physician because of difficulty walking and standing steadily. Neurological examination shows an unsteady, broad-based gait, distal muscle weakness, decreased deep tendon reflexes, and an abnormal Romberg test. His hemoglobin concentration is 11.9 g/dL, mean corpuscular volume is 89/μm3, and serum lactate dehydrogenase is 105 U/L. His serum haptoglobin is slightly decreased. A deficiency of which of the following substances is the most likely cause of this patient's findings?

• A. Niacin
• B. Folate
• C. Phytomenadione
• D. Tocopherol (Correct Answer)
• E. Pyridoxine

Explanation: ***Tocopherol*** - **Tocopherol (Vitamin E)** deficiency can cause neurological symptoms such as **ataxia**, **distal muscle weakness**, decreased deep tendon reflexes, and an **abnormal Romberg test** due to its role in nerve function and antioxidant properties. - **Chronic pancreatitis** often leads to **fat malabsorption** as pancreatic enzymes are crucial for fat digestion, which impairs the absorption of fat-soluble vitamins like Vitamin E. *Niacin* - **Niacin (Vitamin B3)** deficiency causes **pellagra**, characterized by the "3 Ds": **dermatitis**, **diarrhea**, and **dementia**, none of which are the primary presenting symptoms here. - While neurological symptoms can occur in severe cases, the specific presentation of ataxia and peripheral neuropathy points away from pellagra. *Folate* - **Folate (Vitamin B9)** deficiency primarily causes **megaloblastic anemia** with an elevated **mean corpuscular volume (MCV)**, which is normal in this patient (MCV 89/μm3). - While neurological symptoms can be present, they are less specific to folate deficiency compared to the classic presentation seen here. *Phytomenadione* - **Phytomenadione (Vitamin K)** deficiency leads to **coagulopathy** due to impaired synthesis of clotting factors, resulting in bleeding tendencies. - It does not typically cause neurological symptoms like ataxia or peripheral neuropathy. *Pyridoxine* - **Pyridoxine (Vitamin B6)** deficiency can cause **peripheral neuropathy** and **ataxia**, but it's often associated with **sideroblastic anemia** or seizures. - While some symptoms overlap, the strong history of chronic pancreatitis and fat malabsorption makes a fat-soluble vitamin deficiency more likely.

Question 176: A 61-year-old male is given acetazolamide to treat open-angle glaucoma. Upon diuresis, his urine is found to be highly alkaline. Which of the following accounts for the alkaline nature of this patient’s urine?

• A. Inhibition of bicarbonate reabsorption in the proximal tubule (Correct Answer)
• B. Inhibition of bicarbonate reabsorption in beta-intercalated cells
• C. Inhibition of acid secretion in alpha-intercalated cells
• D. Inhibition of chloride reabsorption in the distal convoluted tubule
• E. Inhibition of chloride reabsorption in the thick ascending loop of Henle

Explanation: ***Inhibition of bicarbonate reabsorption in the proximal tubule*** - **Acetazolamide** is a **carbonic anhydrase inhibitor** that primarily acts on the **proximal tubule** of the kidney. - Its action here prevents the reabsorption of **bicarbonate (HCO3-)**, leading to its increased excretion in the urine and thus making the urine alkaline. *Inhibition of chloride reabsorption in the distal convoluted tubule* - This effect is typically associated with **thiazide diuretics**, which inhibit the **Na-Cl cotransporter** in the distal convoluted tubule. - While it affects electrolyte balance, it does not directly lead to the observed **alkaline urine** in the manner described. *Inhibition of bicarbonate reabsorption in beta-intercalated cells* - **Beta-intercalated cells** in the collecting duct secrete bicarbonate, and their inhibition would lead to **acidic urine**, not alkaline. - They play a role in **bicarbonate secretion**, not reabsorption as seen with acetazolamide's primary action. *Inhibition of acid secretion in alpha-intercalated cells* - **Alpha-intercalated cells** secrete acid (H+) into the urine. Inhibiting their function would reduce acid excretion, making the urine less acidic or even alkaline. - However, the primary mechanism of acetazolamide's effect on urine pH is through **bicarbonate wasting** in the proximal tubule, not direct inhibition of acid secretion in the collecting duct. *Inhibition of chloride reabsorption in the thick ascending loop of Henle* - This is the mechanism of action for **loop diuretics** like furosemide, which inhibit the **Na-K-2Cl cotransporter**. - While loop diuretics cause significant diuresis, they do not directly lead to the pronounced **urinary alkalinization** seen with acetazolamide.

Question 177: A 6-month-old infant boy is brought to the clinic for a check-up by a couple who recently adopted him from foster care. The biological mother was from a rehabilitation facility and was found incompetent to care for the child, hence he was handed over to foster care. No other information is available regarding his prenatal or birth history. On examination, his weight is found to be below the 3rd percentile. Physical appearance is remarkable for midfacial hypoplasia with a flattened nasal bridge, smooth philtrum, and thin lips. Auscultation reveals a grade 3/6 holosystolic murmur at the left lower sternal border. Developmental delay is noted as well. Which of the following teratogens is most likely to be associated with the infant's presentation?

• A. Lithium
• B. Tobacco
• C. Phenytoin
• D. Alcohol (Correct Answer)
• E. Cocaine

Explanation: ***Alcohol*** - The combination of **facial dysmorphology** (midfacial hypoplasia, flattened nasal bridge, smooth philtrum, thin lips), **growth restriction** (weight below 3rd percentile), **cardiac defect** (holosystolic murmur), and **developmental delay** is highly characteristic of **Fetal Alcohol Syndrome (FAS)**. - The biological mother's history of being in a **rehabilitation facility** suggests a potential history of substance abuse, making maternal alcohol consumption during pregnancy a strong possibility. *Lithium* - Maternal lithium use is associated with **Ebstein's anomaly**, a specific congenital heart defect, but typically does not cause the widespread facial dysmorphism and growth restriction seen in this infant. - While it can cause cardiac defects, the overall constellation of findings points away from lithium as the primary teratogen. *Tobacco* - Maternal tobacco use is primarily associated with **low birth weight**, premature birth, and an increased risk of specific birth defects like **cleft lip and palate**. - It does not typically cause the characteristic facial features, significant cardiac anomalies, or widespread developmental delay observed in this case. *Phenytoin* - Phenytoin, an anticonvulsant, can cause **fetal hydantoin syndrome**, characterized by specific facial features (e.g., hypertelorism, short nose, cleft lip/palate), **digital hypoplasia**, and intellectual disability. - While it can cause some overlapping features like growth deficiency and developmental delay, the specific craniofacial features described for this infant are more typical of FAS. *Cocaine* - Cocaine exposure during pregnancy is associated with a range of problems including **preterm birth**, **placental abruption**, and **genitourinary defects**. - Its teratogenic effects often involve vascular disruption leading to limb defects or cerebral infarctions, rather than the characteristic facial dysmorphology and cardiac defects described in this infant.

Question 178: A 42-year-old man comes to the emergency department because of tingling in his hands and legs and palpitations for 1 week. He has also had severe cramping in his hands, feet, and abdomen during this period. Three months ago, he was hospitalized for acute pancreatitis. He discharged himself against medical advice at that time. There is no family history of illness. He does not smoke. He drinks 2–3 beers and a pint of vodka daily. He has a history of using intravenous heroin. He has not had a stable job for a year. He is only oriented to place and person. His temperature is 37.1°C (98.8°F), pulse is 90/min, and blood pressure is 110/96 mm Hg. There is a carpopedal spasm while measuring his blood pressure. Cardiopulmonary examination shows no abnormalities. Deep tendon reflexes are 4+ bilaterally. Neurologic examination shows no focal findings. Which of the following is the most appropriate pharmacotherapy?

• A. Magnesium sulfate (Correct Answer)
• B. Lorazepam
• C. Sodium bicarbonate
• D. Fomepizole
• E. Vitamin B1 (thiamine)

Explanation: ***Magnesium sulfate*** - The patient exhibits symptoms like **tingling**, **palpitations**, **severe cramping** (hands, feet, abdomen), **carpopedal spasm** (Trousseau's sign), and **hyperreflexia (4+)**, which are classic signs of **hypocalcemia** or **hypomagnesemia**. - Given his history of **alcohol abuse**, **intravenous drug use**, and recent **pancreatitis**, **hypomagnesemia** is a likely diagnosis, often leading to secondary hypocalcemia. **Magnesium sulfate** is the appropriate treatment. *Lorazepam* - Lorazepam is a **benzodiazepine** used to treat seizures, anxiety, and alcohol withdrawal. - While the patient has a history of alcohol use, his current symptoms are more indicative of electrolyte imbalance (hypomagnesemia/hypocalcemia) rather than acute alcohol withdrawal or seizures. *Sodium bicarbonate* - **Sodium bicarbonate** is used to treat metabolic acidosis or certain poisonings. - There is no indication of acidosis in the given clinical presentation; the symptoms are primarily related to neuromuscular irritability. *Fomepizole* - **Fomepizole** is an antidote used in cases of **methanol** or **ethylene glycol poisoning**. - The patient's presentation does not suggest ingestion of these toxic alcohols. *Vitamin B1 (thiamine)* - **Thiamine** is crucial for preventing and treating **Wernicke-Korsakoff syndrome** in patients with chronic alcohol abuse. - While appropriate for patients with alcohol abuse, it does not directly address the acute neuromuscular irritability and tetany symptoms (tingling, carpopedal spasm, hyperreflexia) observed in this patient.

Question 179: A 30-year-old female with a history of epilepsy becomes pregnant. Her epilepsy has been well controlled by taking a medication that inhibits GABA transaminase and blocks voltage-gated sodium and calcium channels. Her obstetrician informs her that her epilepsy medication has been shown to have teratogenic effects. Of the following, which teratogenic effect is this woman's medication most likely to cause?

• A. Limb defects
• B. Neural tube defect (Correct Answer)
• C. Renal damage
• D. Ebstein's anomaly
• E. Discolored teeth

Explanation: ***Neural tube defect*** - The medication described, which **inhibits GABA transaminase** and has multiple mechanisms including effects on voltage-gated channels, is **valproic acid** (valproate). - **Valproic acid** is the antiepileptic drug with the **highest risk of neural tube defects** (e.g., spina bifida), with an incidence of approximately 1-2% when taken during pregnancy. - This teratogenic effect occurs primarily during the first trimester and is believed to be due to interference with **folate metabolism** and **histone deacetylase inhibition**, which are crucial for proper neural tube closure. - Folic acid supplementation is recommended for women of childbearing age taking valproate. *Limb defects* - **Limb defects** (e.g., phocomelia, limb reduction defects) are classically associated with **thalidomide** exposure during early pregnancy. - While **phenytoin** (fetal hydantoin syndrome) can cause limb abnormalities including hypoplastic nails and distal phalanges, this is not the primary teratogenic concern with valproic acid. *Renal damage* - **Fetal renal damage** can be caused by medications such as **ACE inhibitors**, **ARBs**, and **NSAIDs** when taken during pregnancy. - This is not a characteristic teratogenic effect of valproic acid or other antiepileptic medications. *Ebstein's anomaly* - **Ebstein's anomaly**, a congenital heart defect characterized by apical displacement of the tricuspid valve, is most notably associated with **lithium exposure** during the first trimester of pregnancy. - This cardiac anomaly is not typically linked to valproic acid or other anticonvulsant medications. *Discolored teeth* - **Discolored teeth** (yellow-brown staining) and enamel hypoplasia are classic adverse effects of **tetracycline antibiotics** when administered during pregnancy (second and third trimesters) or early childhood. - This effect is not associated with antiepileptic medications.

Question 180: A 62-year-old man with a history of coronary artery disease comes to the emergency department with substernal chest pain for several hours. An ECG shows no abnormalities. Troponin T test results are negative. The patient is admitted to the hospital and treated with intravenous nitroglycerin, with an initial resolution of his symptoms. After 6 hours of continuous infusion of nitroglycerin, he reports increasing chest pain. The underlying cause of this patient's recurrent symptoms is most likely to also occur in treatment with which of the following drugs?

• A. Alprazolam
• B. Methicillin
• C. Phenylephrine (Correct Answer)
• D. Hydrocodone
• E. Levodopa

Explanation: ***Phenylephrine*** - The patient is experiencing **tachyphylaxis** to nitroglycerin, defined as rapidly decreasing response to a drug with continuous exposure (within hours). - **Phenylephrine** (alpha-1 adrenergic agonist) is well-known to cause **rapid tachyphylaxis** with continuous or repeated administration, particularly with IV infusions. - Both nitroglycerin and phenylephrine cause tachyphylaxis through **receptor desensitization and downregulation** with sustained exposure. - This is a classic pharmacology teaching point: **nitrates and direct-acting sympathomimetics** (like phenylephrine) share this mechanism of rapid tolerance. *Hydrocodone* - Hydrocodone is an **opioid analgesic** that can develop **tolerance** with chronic use. - However, opioid tolerance develops gradually over days to weeks, not the acute tachyphylaxis (hours) seen with nitroglycerin. - The mechanism and time course are distinct from the rapid receptor desensitization seen with nitrates. *Alprazolam* - Alprazolam is a **benzodiazepine** used for anxiety and can develop tolerance with long-term use. - This tolerance is a gradual process occurring over weeks to months, not the rapid tachyphylaxis seen here. - The mechanism involves changes in GABA receptor function, distinct from the acute desensitization with nitrates. *Methicillin* - Methicillin is a **beta-lactam antibiotic** that does not cause pharmacodynamic tachyphylaxis. - Bacterial resistance can develop through mutations and selection, which is an entirely different phenomenon from drug tachyphylaxis. *Levodopa* - Levodopa is used for **Parkinson's disease** and can lead to "wearing off" effects and motor fluctuations. - These phenomena are primarily due to disease progression and changes in striatal dopamine storage capacity, not acute tachyphylaxis. - The time course is over months to years, not hours like nitroglycerin tachyphylaxis.

Question 181: A 60-year-old woman is brought to the emergency department by paramedics after being found unresponsive. It is not possible to obtain a history. Her blood pressure is 75/30 mmHg and pulse is 108/min. Her extremities are cool and mottled. She is admitted to the intensive care unit (ICU) for further supportive care, where she is started on a norepinephrine intravenous drip. After several hours on this infusion, which of the following changes in vitals would be expected?

• A. Blood pressure decreases; pulse decreases
• B. Blood pressure increases; pulse increases
• C. Blood pressure decreases; pulse increases
• D. Blood pressure increases; pulse remains unchanged
• E. Blood pressure increases; pulse decreases (Correct Answer)

Explanation: ***Blood pressure increases; pulse decreases*** - **Norepinephrine** is a potent **vasoconstrictor** that increases systemic vascular resistance, leading to an **increase in blood pressure**. - The increased blood pressure activates **baroreceptors**, triggering a **reflex bradycardia** (decreased heart rate or pulse) to maintain cardiovascular homeostasis. *Blood pressure decreases; pulse decreases* - **Norepinephrine** is expected to *increase* blood pressure, not decrease it. - A decrease in both blood pressure and pulse in this context would suggest worsening shock or an adverse reaction, not a therapeutic effect. *Blood pressure increases; pulse increases* - While norepinephrine increases blood pressure, the direct stimulation of beta-1 receptors on the heart causing an increased heart rate is often *overridden* by the **baroreceptor reflex** that reduces heart rate due to the sharp rise in blood pressure. - An increase in both parameters is less typical with norepinephrine as the predominant effect on heart rate is usually reflex bradycardia. *Blood pressure decreases; pulse increases* - **Norepinephrine** is a powerful pressor agent and would not cause a *decrease* in blood pressure, especially in a hypotensive patient. - This combination of vital signs would indicate worsening **hypotension** and **tachycardia**, often seen in uncontrolled shock. *Blood pressure increases; pulse remains unchanged* - While **blood pressure increases** as expected with norepinephrine, it is very unlikely for the **pulse to remain unchanged** due to the robust **baroreceptor reflex** responding to the significant rise in blood pressure. - The reflex arc aims to normalize blood pressure by modulating heart rate, typically causing a decrease.

Question 182: A 56-year-old man with type 2 diabetes mellitus comes to the physician for a follow-up examination. He reports that he has been compliant with his current antidiabetic medication regimen. His hemoglobin A1c concentration is 8.5%. The physician prescribes a drug that reversibly inhibits a membrane-bound enzyme that hydrolyzes carbohydrate bonds. Which of the following drugs was most likely added to this patient's medication regimen?

• A. Canagliflozin
• B. Miglitol (Correct Answer)
• C. Linagliptin
• D. Pramlintide
• E. Rosiglitazone

Explanation: ***Miglitol*** - Miglitol is an **alpha-glucosidase inhibitor** that reversibly inhibits enzymes like sucrase and maltase in the brush border of the small intestine. - This action **delays carbohydrate digestion and absorption**, reducing postprandial glucose excursions, which fits the description of inhibiting a "membrane-bound enzyme that hydrolyzes carbohydrate bonds." *Canagliflozin* - Canagliflozin is a **sodium-glucose co-transporter 2 (SGLT2) inhibitor** that acts in the kidney to reduce glucose reabsorption, leading to increased glucose excretion in the urine. - It does not inhibit carbohydrate-hydrolyzing enzymes in the gastrointestinal tract. *Linagliptin* - Linagliptin is a **dipeptidyl peptidase-4 (DPP-4) inhibitor** that increases the levels of incretin hormones (GLP-1 and GIP), thereby enhancing glucose-dependent insulin secretion and suppressing glucagon secretion. - This mechanism is distinct from inhibiting carbohydrate hydrolysis. *Pramlintide* - Pramlintide is an **amylin analog** that slows gastric emptying, suppresses postprandial glucagon secretion, and promotes satiety. - It works by mimicking the action of amylin, not by inhibiting enzymes that break down carbohydrates. *Rosiglitazone* - Rosiglitazone is a **thiazolidinedione (TZD)** that acts as an agonist for peroxisome proliferator-activated receptor-gamma (PPAR-γ) to improve insulin sensitivity in peripheral tissues. - Its mechanism of action is related to gene transcription and insulin sensitization rather than direct inhibition of carbohydrate-hydrolyzing enzymes.

Question 183: A 72-year-old man with type 2 diabetes mellitus, hypertension, and systolic heart failure comes to the physician because of a 5-day history of progressively worsening shortness of breath at rest. Physical examination shows jugular venous distention, diffuse crackles over the lower lung fields, and bilateral lower extremity edema. As a part of treatment, he is given a derivative of a hormone that acts by altering guanylate cyclase activity. This drug has been found to reduce pulmonary capillary wedge pressure and causes systemic hypotension as an adverse effect. The drug is most likely a derivative of which of the following hormones?

• A. Prostacyclin
• B. Aldosterone
• C. Somatostatin
• D. Brain natriuretic peptide (Correct Answer)
• E. Angiotensin II

Explanation: ***Brain natriuretic peptide*** - **Brain natriuretic peptide (BNP)** derivatives, like nesiritide, activate **guanylate cyclase**, leading to increased cGMP, vasodilation, and reduced preload/afterload, alleviating heart failure symptoms. - The patient's symptoms (shortness of breath, jugular venous distention, crackles, edema) are classic for **acute decompensated heart failure**, making a BNP derivative an appropriate treatment. *Prostacyclin* - **Prostacyclin** analogs (e.g., epoprostenol) are primarily used for **pulmonary hypertension** due to their potent vasodilatory effects in the pulmonary circulation. - They activate **adenylyl cyclase** (increasing cAMP), not guanylate cyclase (which increases cGMP), representing a different mechanism of action. *Aldosterone* - **Aldosterone** is a mineralocorticoid that promotes **sodium and water retention** and potassium excretion, exacerbating heart failure symptoms. - Its antagonists (e.g., spironolactone) are used in chronic heart failure but do not directly act via guanylate cyclase for acute symptom relief. *Somatostatin* - **Somatostatin** is a peptide hormone that **inhibits the secretion of various hormones**, including growth hormone, insulin, and glucagon. - It is used in conditions like acromegaly or variceal bleeding and has no direct role in heart failure management via guanylate cyclase. *Angiotensin II* - **Angiotensin II** is a potent vasoconstrictor and a key component of the **renin-angiotensin-aldosterone system (RAAS)**, contributing to hypertension and heart failure progression. - Drugs targeting angiotensin II (ACE inhibitors, ARBs) reduce its effects but do not act by directly altering guanylate cyclase activity; instead, they block its receptors or synthesis.

Question 184: A 49-year-old man being treated for Helicobacter pylori infection presents to his primary care physician complaining of lower back pain. His physician determines that a non-steroidal anti-inflammatory drug (NSAID) would be the most appropriate initial treatment. Which of the following is the most appropriate NSAID for this patient?

• A. Aspirin
• B. Ibuprofen
• C. Celecoxib (Correct Answer)
• D. Naproxen
• E. Diclofenac

Explanation: **Celecoxib** - This patient is being treated for a *Helicobacter pylori* infection, indicating a potential risk for **gastrointestinal complications** like ulcers. **Celecoxib** is a selective **COX-2 inhibitor**, which has a lower risk of causing GI side effects compared to non-selective NSAIDs. - Its selective inhibition of COX-2 helps reduce pain and inflammation while largely sparing the **COX-1 enzyme**, which is responsible for maintaining the **gastric mucosal lining**. *Aspirin* - **Aspirin** is a non-selective NSAID that inhibits both **COX-1** and **COX-2** enzymes. - Inhibition of COX-1 can lead to a significant increase in the risk of **gastrointestinal bleeding** and **ulcer formation**, which is particularly concerning for a patient with an *H. pylori* infection. *Ibuprofen* - **Ibuprofen** is a non-selective NSAID that can cause **gastrointestinal irritation** and damage by inhibiting **COX-1**. - Its use would increase the risk of worsening the patient's existing **gastrointestinal vulnerability** due to the *H. pylori* infection. *Naproxen* - **Naproxen** is another non-selective NSAID with a relatively long half-life, making its **gastrointestinal side effects** potentially more prolonged and severe than some other non-selective NSAIDs. - It carries a **higher risk for GI bleeding** and ulcers compared to selective COX-2 inhibitors, especially in patients with pre-existing GI issues. *Diclofenac* - **Diclofenac** is a non-selective NSAID that carries a risk of **gastrointestinal adverse events**, although some studies suggest it might have a slightly better GI safety profile than other non-selective NSAIDs at lower doses. - However, in a patient with *H. pylori*, it still poses a significant risk for **ulcers** and bleeding compared to a COX-2 selective inhibitor.

Question 185: A 37-year-old man is brought to the emergency department following a motor vehicle collision. His temperature is 38.1°C (100.6°F), pulse is 39/min, respirations are 29/min, and blood pressure is 58/42 mm Hg. There is no improvement in his blood pressure despite adequate fluid resuscitation. A drug is administered that causes increased IP3 concentrations in arteriolar smooth muscle cells and increased cAMP concentrations in cardiac myocytes. This drug only has a negligible effect on cAMP concentration in bronchial smooth muscle cells. Which of the following sets of cardiovascular changes is most likely following administration of this drug?

• A. Heart Rate ↓ Blood Pressure ↓ Systemic Vascular Resistance ↑
• B. Heart Rate ↑ Blood Pressure ↑ Systemic Vascular Resistance ↓
• C. Heart Rate ↑ Blood Pressure ↑ Systemic Vascular Resistance ↑ (Correct Answer)
• D. Heart Rate ↑ Blood Pressure ↓ Systemic Vascular Resistance ↓
• E. Heart Rate No change Blood Pressure ↑ Systemic Vascular Resistance ↑

Explanation: ***Heart Rate ↑ Blood Pressure ↑ Systemic Vascular Resistance ↑*** - This drug profile describes **norepinephrine**, which has potent **α1 (increases IP3)** and **β1 (increases cAMP in heart)** agonist activity with minimal β2 effects. - The increase in **IP3 in arteriolar smooth muscle cells** leads to **vasoconstriction** via increased intracellular calcium, resulting in markedly **increased systemic vascular resistance (SVR)**. - The increase in **cAMP in cardiac myocytes** provides **positive inotropy (contractility) and chronotropy (heart rate)** through β1 receptor stimulation. - The combined effects of increased cardiac output and increased SVR result in a **significant increase in blood pressure**, making this the ideal vasopressor for distributive shock. - Note: While baroreceptor reflexes might blunt the heart rate increase in normal states, in severe shock with autonomic dysfunction, the direct β1 effect predominates. *Heart Rate ↓ Blood Pressure ↓ Systemic Vascular Resistance ↑* - An increase in **IP3 in arteriolar smooth muscle cells** would cause **vasoconstriction (increased SVR)**, which tends to increase blood pressure, not decrease it. - An increase in **cAMP in cardiac myocytes** would increase heart rate and contractility through β1 stimulation, not decrease them. *Heart Rate ↑ Blood Pressure ↑ Systemic Vascular Resistance ↓* - While heart rate and blood pressure would increase due to the drug's effects on cardiac myocytes, the increased IP3 in arteriolar smooth muscle cells would lead to **vasoconstriction** and thus an **increase in systemic vascular resistance**, not a decrease. - A decrease in systemic vascular resistance would typically lower blood pressure unless cardiac output increases significantly to compensate. *Heart Rate ↑ Blood Pressure ↓ Systemic Vascular Resistance ↓* - The drug's mechanism of action, particularly the increase in **IP3 leading to vasoconstriction**, is fundamentally inconsistent with a decrease in both blood pressure and systemic vascular resistance. - While heart rate would increase via β1 stimulation, decreased BP with decreased SVR contradicts the described α1-mediated vascular effects. *Heart Rate No change Blood Pressure ↑ Systemic Vascular Resistance ↑* - The increase in **cAMP in cardiac myocytes** directly stimulates **β1 adrenergic receptors**, leading to increased **heart rate**, not "no change." - While **blood pressure** and **systemic vascular resistance** would correctly increase, the absence of heart rate change is inconsistent with the drug's β1 agonist effects on the heart.

Question 186: A 64-year-old man presents to the emergency department with sudden onset of pleuritic chest pain and dyspnea on exertion. He has a history of lung cancer and is currently being treated with outpatient chemotherapy. His temperature is 98.9°F (37.2°C), blood pressure is 111/64 mmHg, pulse is 130/min, respirations are 25/min, and oxygen saturation is 90% on room air. Initial laboratory values in the emergency department are seen below. Hemoglobin: 8.2 g/dL Hematocrit: 26% Leukocyte count: 7,700/mm^3 with normal differential Platelet count: 157,000/mm^3 A CT angiogram demonstrates a blood clot in the pulmonary vasculature. The patient is started on heparin and he is admitted to the ICU. Laboratory values 6 days later are shown below. Hemoglobin: 8.0 g/dL Hematocrit: 25% Leukocyte count: 7,500/mm^3 with normal differential Platelet count: 22,000/mm^3 Which of the following is the most appropriate next step in management?

• A. Platelet transfusion
• B. No treatment changes needed
• C. Blood transfusion
• D. Stop heparin (Correct Answer)
• E. Start warfarin

Explanation: ***Stop heparin*** - The patient's **platelet count dropped significantly** from 157,000/mm³ to 22,000/mm³ after 6 days of heparin, strongly suggesting **heparin-induced thrombocytopenia (HIT)**. - In suspected HIT, **heparin must be immediately discontinued** and an alternative non-heparin anticoagulant initiated to prevent thrombotic complications. *Platelet transfusion* - **Platelet transfusions are generally contraindicated in HIT** unless there is severe, life-threatening bleeding, as they may worsen the prothrombotic state. - The primary concern in HIT is the **paradoxical thrombosis risk**, not simply the low platelet count itself. *No treatment changes needed* - The **precipitous drop in platelet count** to 22,000/mm³ in a patient on heparin is a critical finding requiring immediate action due to the high risk of paradoxical thrombosis. - Ignoring this significant laboratory change would lead to potential harm from **thrombotic events** associated with HIT. *Blood transfusion* - While the patient's hemoglobin is low (8.0 g/dL), a blood transfusion is not the most immediate or appropriate next step in managing a suspected case of **heparin-induced thrombocytopenia (HIT)**. - The primary and most urgent concern is the dangerously low and rapidly falling platelet count in the context of heparin use. *Start warfarin* - **Warfarin should not be initiated as monotherapy in HIT** until therapeutic anticoagulation is achieved with a non-heparin agent. - Starting warfarin in the acute phase before stopping heparin can lead to a rapid drop in protein C, increasing the risk of **venous limb gangrene**.

Question 187: An 8-year-old boy is brought to the emergency department by his parents 30 minutes after losing consciousness. He was at a water park with his family when he fell to the ground and started to have jerking movements of the arms and legs. On arrival, he continues to have generalized, violent muscle contractions and is unresponsive to verbal and painful stimuli. The emergency department physician administers lorazepam. The expected beneficial effect of this drug is most likely caused by which of the following mechanisms?

• A. Increased affinity of GABAA receptors for GABAB agonists
• B. Noncompetitive NMDA receptor antagonism
• C. Increased duration of chloride channel opening
• D. Allosteric activation of GABAA receptors (Correct Answer)
• E. Inhibition of GABA transaminase

Explanation: ***Allosteric activation of GABAA receptors*** - **Lorazepam** is a **benzodiazepine** that acts as a positive allosteric modulator of the **GABAA receptor**. - This binding enhances the effect of **GABA**, leading to increased frequency of **chloride channel opening** and neuronal hyperpolarization, which ultimately suppresses seizure activity. *Increased affinity of GABAA receptors for GABAB agonists* - This statement is incorrect because lorazepam acts on **GABAA receptors** and does not increase the affinity for **GABAB agonists**. - **GABAB agonists** like baclofen act on a different receptor subtype and have a distinct mechanism of action. *Noncompetitive NMDA receptor antagonism* - This mechanism describes drugs like **ketamine** or **phencyclidine (PCP)**, which block the **NMDA receptor** to produce anesthetic or dissociative effects. - Lorazepam's primary action is on the **GABAA receptor**, not the **NMDA receptor**. *Increased duration of chloride channel opening* - While benzodiazepines increase chloride influx, they primarily do so by increasing the **frequency** of **chloride channel opening**, not the duration. - **Barbiturates**, such as phenobarbital, are known to increase the **duration** of chloride channel opening. *Inhibition of GABA transaminase* - **GABA transaminase** is an enzyme responsible for GABA metabolism. Its inhibition would lead to increased GABA levels in the synapse. - **Valproic acid** is an example of an antiepileptic drug that inhibits **GABA transaminase**, but this is not the mechanism of action for lorazepam.

Question 188: A 71-year-old man is brought in by his wife with acute onset aphasia and weakness in his right arm and leg for the past 2 hours. The patient's wife says they were eating breakfast when he suddenly could not speak. His symptoms have not improved over the past 2 hours. The patient denies any similar symptoms in the past. His past medical history is significant for immune thrombocytopenic purpura, managed intermittently with oral prednisone, hypertension, managed with hydrochlorothiazide, and a previous myocardial infarction (MI) 6 months ago. The patient reports a 20-pack-year smoking history and moderate daily alcohol use. His family history is significant for his father who died of an MI at age 58 and his older brother who died of a stroke at age 59. The vital signs include: blood pressure 190/115 mm Hg, pulse 85/min, and respiratory rate 20/min. On physical examination, there is a noticeable weakness of the lower facial muscles on the right. The muscle strength in his upper and lower extremities is 4/5 on the right and 5/5 on the left. There is also a loss of sensation on the right. He has expressive aphasia. The laboratory findings are significant for the following: WBC 7,500/mm³ RBC 4.40 × 10⁶/mm³ Hematocrit 41.5% Hemoglobin 14.0 g/dL Platelet count 95,000/mm³ A noncontrast computed tomography (CT) scan of the head is unremarkable. Diffusion-weighted magnetic resonance imaging (MRI) and CT angiography (CTA) confirms a left middle cerebral artery (MCA) ischemic stroke. Which of the following aspects of this patient's history is a contraindication to intravenous (IV) tissue plasminogen activator (tPA)?

• A. Platelet count 95,000/mm3 (Correct Answer)
• B. 20-pack-year smoking history
• C. Age 71 years
• D. Myocardial infarction 6 months ago
• E. Blood pressure 190/115 mm Hg

Explanation: ***Platelet count 95,000/mm³*** - A **platelet count less than 100,000/mm³** is a **contraindication to IV tPA** due to an increased risk of hemorrhagic transformation. - This patient's history of **immune thrombocytopenic purpura (ITP)** explains the low platelet count, further increasing the bleeding risk. *20-pack-year smoking history* - A history of **smoking** is a significant **risk factor for stroke**, but it is **not a contraindication for tPA** administration. - While smoking contributes to atherosclerosis and increased stroke risk, it does not directly affect the immediate decision for thrombolysis. *Age 71 years* - Although older age is associated with increased risk of complications from tPA, **age itself is not an absolute contraindication** for intravenous tPA in eligible patients. - The decision to administer tPA in older adults is based on a comprehensive risk-benefit assessment, not solely on age. *Myocardial infarction 6 months ago* - A **prior myocardial infarction** is a risk factor for future strokes but is **not a contraindication to tPA** as long as it did not occur within the last 3 months (for specific types of MI with cardiac thrombus) or result in the placement of a cardiac device that would contraindicate tPA. - This event occurred 6 months ago, placing it outside of the acute concern for thrombolysis. *Blood pressure 190/115 mm Hg* - **Elevated blood pressure above 185/110 mm Hg** is a **contraindication to tPA**; however, it can often be **managed with antihypertensive medications** to bring it within the acceptable range prior to administration. - In this case, while the blood pressure is high, it can potentially be controlled to allow for tPA, unlike a low platelet count which is a more absolute contraindication.

Question 189: A steel welder presents to his family physician with a one-week history of intense abdominal cramping with nausea, vomiting, constipation, headaches, myalgias, and arthralgias. He claims that the symptoms started about two months after he began work on replacing the pipes in an early 20th century house. Blood was taken and he was found to have a microcytic, hypochromic anemia with basophilic stippling. Which of the following is the best treatment for his symptoms?

• A. Prussian blue
• B. Deferasirox
• C. EDTA (Correct Answer)
• D. N-acetylcysteine
• E. Deferoxamine

Explanation: ***EDTA*** - The patient's symptoms (abdominal cramping, nausea, vomiting, constipation, headaches, myalgias, arthralgias), occupation (steel welder working on old pipes), and lab findings (**microcytic, hypochromic anemia** with **basophilic stippling**) are highly suggestive of **lead poisoning**. - **EDTA (ethylenediaminetetraacetic acid)** is a chelating agent that binds to lead and promotes its excretion, making it the most appropriate treatment for severe lead poisoning. *Prussian blue* - This is an antidote for **thallium** and **radioactive cesium poisoning**, not lead. - It works by trapping these ions in the gut, preventing their absorption and increasing their fecal excretion. *Deferasirox* - This is an **oral iron chelator** used for treating **iron overload**, particularly in patients with thalassemia who receive frequent blood transfusions. - It is not indicated for lead poisoning. *N-acetylcysteine* - This agent is primarily used as an antidote for **acetaminophen overdose** by replenishing glutathione stores. - It also has applications in certain respiratory conditions as a mucolytic, but not in lead poisoning. *Deferoxamine* - This is another **iron chelator**, administered intravenously or subcutaneously, primarily used for acute iron intoxication or chronic iron overload (e.g., hemochromatosis). - Like deferasirox, it is specific for iron and not used for lead poisoning.

Question 190: A 14-year-old teenager is brought to the physician by her mother who seems extremely concerned that her daughter is unable to sleep at night and has become increasingly irritated and aggressive. She has been noticing changes in her daughter's behavior recently. She had no idea what was going on until she found pills hidden in her daughter's room a week ago. Her daughter confessed that she tried these drugs once with her friends and started using them since then. Her mother threw away all the pills and prevented her daughter from seeing her friends. This is when she started to notice her daughter tear often and sweat. She is seeking a quick and effective treatment for her daughter. Which drug was the teenager most likely using?

• A. Atomoxetine
• B. Naloxone
• C. Marijuana
• D. Oxycodone (Correct Answer)
• E. Cocaine

Explanation: ***Oxycodone*** - The patient's symptoms of **irritability**, **aggression**, inability to sleep, tearing, and sweating after the mother disposing of her pills are consistent with **opioid withdrawal**. - **Oxycodone** is a potent opioid analgesic that can lead to significant physical dependence and withdrawal symptoms upon cessation. *Atomoxetine* - **Atomoxetine** is a norepinephrine reuptake inhibitor used for **ADHD**; it does not typically cause these withdrawal symptoms. - Discontinuation of atomoxetine usually does not result in the severe physiological withdrawal syndrome described. *Naloxone* - **Naloxone** is an **opioid antagonist** used to reverse opioid overdose, not a drug of abuse that would cause these withdrawal symptoms. - Its mechanism of action involves blocking opioid receptors, which would precipitate withdrawal if given to an opioid-dependent individual but is not itself abused in this manner. *Marijuana* - **Marijuana withdrawal** can cause irritability and sleep disturbances, but typically does not involve physical symptoms like significant tearing and sweating. - Marijuana is an illicit drug, and withdrawal is generally less severe than opioid withdrawal. *Cocaine* - **Cocaine withdrawal** is primarily psychological, characterized by **dysphoria**, fatigue, and intense cravings, without the prominent physical symptoms like tearing and sweating seen here. - While cocaine abuse is strongly associated with aggression and irritability, the specific physical withdrawal symptoms point away from it.

Question 191: A 56-year-old man comes to the emergency department because of progressive swelling and pain in his left calf for 1 day. He does not have shortness of breath or chest pain. He has hypertension and chronic kidney disease. Current medications include enalapril, aspirin, simvastatin, and vitamin D. His temperature is 100.4°F (38°C), pulse is 84/min, and blood pressure is 135/92 mm Hg. Physical examination shows tenderness and swelling of the left lower extremity. A venous Doppler ultrasonography shows a thrombus in the left popliteal vein. Treatment with unfractionated heparin is begun. Two days later, physical examination shows improvement of symptoms. Laboratory studies at admission and 2 days after admission show: Admission Two days after admission Hemoglobin 11.2 g/dL 11.1 g/dL Leukocyte count 5,500/mm3 6,100/mm3 Platelet count 230,000/mm3 170,000/mm3 Serum Prothrombin time 12 seconds 13 seconds Partial thromboplastin time 30 seconds 55 seconds Estimated glomerular filtration rate 29 mL/min/1.73 m2 28 mL/min/1.73 m2 Which of the following is the most appropriate next step in management?

• A. Switch to warfarin
• B. Obtain serum immunoassay
• C. Switch to enoxaparin
• D. Discontinue heparin and initiate argatroban (Correct Answer)
• E. Continue unfractionated heparin

Explanation: ***Discontinue heparin and initiate argatroban*** - The **26% drop in platelet count** (from 230,000 to 170,000/mm³) occurring **2 days after starting unfractionated heparin (UFH)** raises high suspicion for **heparin-induced thrombocytopenia (HIT)**. - When HIT is suspected (intermediate to high probability by 4T score), the **most critical next step** is to **immediately discontinue all heparin products** and **start a non-heparin anticoagulant**. - **Argatroban** is the preferred alternative in this patient with **chronic kidney disease (eGFR 28 mL/min)** as it is hepatically metabolized and safe in renal impairment. - HIT antibody testing should be obtained concurrently, but **therapeutic anticoagulation must not be delayed** while awaiting results. *Obtain serum immunoassay* - While **HIT antibody testing** (heparin-PF4 immunoassay) should be obtained to confirm the diagnosis, it is **not the most appropriate next step**. - The priority is to **stop heparin exposure immediately** and provide alternative anticoagulation to prevent thrombotic complications. - Testing can and should be done concurrently with changing anticoagulation. *Switch to warfarin* - Initiating **warfarin alone** in suspected or confirmed HIT is **contraindicated** and can cause **venous limb gangrene** due to rapid depletion of protein C before clotting factors. - Warfarin should only be started after platelet count recovery (>150,000/mm³) and after at least 5 days of therapeutic non-heparin anticoagulation. *Switch to enoxaparin* - **Enoxaparin** (low-molecular-weight heparin) has **>90% cross-reactivity** with HIT antibodies. - Switching to LMWH in suspected HIT is **contraindicated** as it will perpetuate platelet activation and thrombosis. *Continue unfractionated heparin* - Continuing UFH with a significant **platelet drop** is dangerous and will worsen **HIT**, leading to life-threatening **arterial and venous thrombosis**. - Immediate discontinuation is imperative.

Question 192: A 35-year-old woman presents to the emergency department with severe nausea and diarrhea. One day prior to presentation, she went to a new seafood restaurant known for serving exotic fish. For the past day she experienced nausea, diarrhea, weakness, and a tingling sensation in her extremities. In the emergency department, her temperature is 100.3°F (37.9°C), blood pressure is 95/60 mmHg, pulse is 105/min, and respirations are 20/min. On physical examination, she appears fatigued and has 1+ Achilles and patellar reflexes. Which of the following is the mechanism of action of the compound most likely responsible for this patient's clinical presentation?

• A. Increases synthesis of histamine
• B. Promotes depolarization of Na+ channels (Correct Answer)
• C. Superantigen that activates T-cells
• D. Permanent Gs activation
• E. Prevents depolarization of Na+ channels

Explanation: ***Promotes depolarization of Na+ channels*** - The patient's symptoms, including **nausea**, **diarrhea**, **weakness**, **tingling extremities**, and consumption of **exotic fish**, are highly suggestive of **ciguatera poisoning**. - **Ciguatoxin**, the primary toxin responsible for ciguatera, acts by **binding to voltage-gated sodium channels and keeping them in an open state**, leading to **persistent depolarization** and sustained sodium influx. - This mechanism explains the **neurological symptoms** (paresthesias, weakness, hyporeflexia) and **gastrointestinal symptoms** characteristic of ciguatera poisoning. *Prevents depolarization of Na+ channels* - This mechanism describes **sodium channel BLOCKERS** such as **tetrodotoxin** (found in pufferfish). - Tetrodotoxin **blocks sodium channels**, preventing depolarization and causing paralysis, respiratory failure, and potentially death. - While tetrodotoxin poisoning can present with neurological symptoms, the clinical picture here (GI symptoms predominant, mild hypotension, consumption from "exotic fish restaurant") is more consistent with ciguatera, which has the **opposite mechanism** (promotes channel opening). *Increases synthesis of histamine* - This mechanism is associated with **scombroid poisoning**, which typically involves the consumption of improperly stored dark-meat fish like tuna or mackerel. - Bacterial histidine decarboxylase converts histidine to histamine in decomposing fish. - Scombroid poisoning presents as an **allergic-type reaction** (flushing, urticaria, headache, bronchospasm) rather than the neurological symptoms seen in this patient. *Superantigen that activates T-cells* - This mechanism is characteristic of toxins produced by bacteria such as *Staphylococcus aureus* or *Streptococcus pyogenes*, causing conditions like **toxic shock syndrome**. - Toxic shock syndrome presents with high fever, diffuse erythematous rash, hypotension, and multi-organ involvement. - Foodborne illness caused by superantigens typically involves severe gastrointestinal distress but not the specific neurological symptoms like paresthesias and hyporeflexia. *Permanent Gs activation* - **Gs protein** activation leads to increased **cAMP** levels, seen with **cholera toxin** (*Vibrio cholerae*) or **pertussis toxin** (*Bordetella pertussis*). - Cholera toxin causes massive secretory **watery diarrhea** ("rice-water stools") leading to severe dehydration. - This mechanism does not explain the neurological findings of tingling extremities, weakness, and hyporeflexia seen in this patient.

Question 193: A 19-year-old woman with a history of bipolar disorder and an unknown cardiac arrhythmia presents with palpitations and chest pain. She admits to taking lithium and procainamide regularly, but she ran out of medication 2 weeks ago and has not been able to get refills. Her family history is significant for bipolar disorder in her mother and maternal aunt. Her vital signs include blood pressure 130/90 mm Hg, pulse 110/min, respiratory rate 18/min. Physical examination is significant for a widely split first heart sound with a holosystolic murmur loudest over the left sternal border. Visible cyanosis is noted in the lips and nailbeds. An electrocardiogram is performed which shows intermittent supraventricular tachyarrhythmia with a right bundle branch block. Her cardiac enzymes are normal. An echocardiogram is performed, which shows evidence of a dilated right atria with portions of the tricuspid valve displaced towards the apex. Which of the following medications was this patient most likely exposed to prenatally?

• A. Insulin
• B. Antihypertensive
• C. Mood stabilizer (Correct Answer)
• D. Antidepressant
• E. Isotretinoin

Explanation: ***Mood stabilizer*** - The echocardiogram findings of a **dilated right atrium** and **apically displaced tricuspid valve leaflets** are classic for **Ebstein anomaly**. - **Lithium**, a mood stabilizer used for bipolar disorder, is a known teratogen associated with **Ebstein anomaly** when taken during the first trimester of pregnancy. *Insulin* - **Insulin** is the primary treatment for diabetes and is not directly associated with **Ebstein anomaly**. - While uncontrolled maternal diabetes can lead to various congenital anomalies, the specific cardiac defect described is not typically linked to insulin use itself. *Antihypertensive* - **Antihypertensive medications** are used to treat high blood pressure and are not known to cause **Ebstein anomaly**. - Certain antihypertensives might have other fetal effects, but this specific cardiac malformation is not a recognized side effect. *Antidepressant* - Studies have linked some **antidepressants** to various congenital anomalies, but **Ebstein anomaly** is not a common or direct association. - The clinical picture strongly points to a lithium-induced anomaly. *Isotretinoin* - **Isotretinoin** is a severe teratogen primarily known for causing **craniofacial, central nervous system, and cardiovascular defects**, including conotruncal abnormalities. - While it can cause congenital heart defects, **Ebstein anomaly** is not its most characteristic cardiac malformation, and the patient's history of bipolar disorder points more directly to lithium.

Question 194: A 62-year-old man comes to the physician because of gradual onset of bilateral ankle swelling over the past month. He also noticed reddish blotches of skin around his ankles. Five weeks ago, he came to the physician with difficulty walking and a resting tremor. He was diagnosed with Parkinson disease and started on medication. He has a history of hypertension and his antihypertensive medications were also adjusted. His temperature is 37.3°C (99.1°F), pulse is 64/min, respirations are 13/min, and blood pressure is 124/74 mm Hg. Physical examination shows bilateral 2+ edema in the ankles. There is purple-red discoloration on the lower legs in a reticular pattern. Neurologic examination shows resting tremor in both hands and bilateral cogwheel rigidity in the elbows. Which of the following pharmacotherapies is the most likely cause of this patient's edema?

• A. Lisinopril
• B. Hydrochlorothiazide
• C. Levodopa/carbidopa
• D. Amantadine (Correct Answer)
• E. Benztropine

Explanation: ***Amantadine*** - **Amantadine** is known to cause peripheral edema, particularly in the lower extremities, as a side effect. - The patient's history of **Parkinson disease** and recent initiation of medication makes amantadine a highly likely cause if it was part of his regimen. - **Key diagnostic clue:** The purple-red discoloration in a reticular pattern (livedo reticularis) combined with peripheral edema is a **classic and pathognomonic presentation** of amantadine side effects. *Lisinopril* - **Lisinopril** (an ACE inhibitor) can cause angioedema of the face, lips, or tongue but is not typically associated with bilateral ankle edema. - While it can be used for hypertension, it's not a common cause of this specific type of peripheral edema. *Hydrochlorothiazide* - **Hydrochlorothiazide** is a diuretic that helps to reduce fluid retention and treat edema, rather than cause it. - It works by increasing the excretion of sodium and water by the kidneys. *Levodopa/carbidopa* - While **levodopa/carbidopa** can cause various side effects in Parkinson's patients, peripheral edema is not a common or significant side effect. - Common side effects include nausea, dizziness, dyskinesia, and psychiatric disturbances. *Benztropine* - **Benztropine** is an anticholinergic medication used for Parkinson's disease, and its common side effects include dry mouth, constipation, and blurred vision. - It is not typically associated with causing peripheral edema.

Question 195: A 56-year-old woman presents with fatigue and joint pain in her fingers and wrists for the last 6 months. She says the pain is present in both hands, and her wrists are also swollen. Furthermore, she describes morning stiffness in her joints lasting about 2 hours, which improves with use. She has been taking acetaminophen, which provided minimal relief, but the swelling has gotten progressively worse. She also feels increasingly tired. Her past medical history reveals she has been successfully treated for Helicobacter pylori (H. pylori) related ulcers last year but still takes omeprazole for her mild gastroesophageal reflux. The patient denies any smoking history and stopped drinking when her gastric symptoms started. Which of the following analgesic drugs is the best choice to use in this patient?

• A. Indomethacin
• B. Naproxen
• C. Diclofenac
• D. Aspirin
• E. Celecoxib (Correct Answer)

Explanation: ***Celecoxib*** - This patient presents with symptoms highly suggestive of **rheumatoid arthritis**, characterized by **symmetric polyarticular joint pain**, swelling, and prolonged morning stiffness, along with fatigue. Given her history of **H. pylori-related ulcers** and current omeprazole use for GERD, she is at increased risk for **gastrointestinal complications** from traditional NSAIDs. - **Celecoxib** is a **selective COX-2 inhibitor**, which preferentially inhibits the COX-2 enzyme responsible for inflammation and pain, while sparing COX-1, which protects the gastric mucosa. This makes it a safer choice for patients with a **history of GI ulcers** or at high risk for ulcer development. *Indomethacin* - Indomethacin is a **non-selective NSAID** that inhibits both COX-1 and COX-2. Given the patient's history of H. pylori ulcers and current omeprazole use, it carries a **high risk of causing gastric irritation** and ulcer recurrence. - Its use would counteract the protective effects of omeprazole and potentially lead to further gastrointestinal complications. *Naproxen* - Naproxen is also a **non-selective NSAID** and thus carries a **significant risk of gastrointestinal adverse effects**, including gastric ulcers and bleeding, especially in a patient with a history of H. pylori ulcers. - Using naproxen would be inappropriate due to the increased risk of exacerbating her pre-existing gastric issues. *Diclofenac* - Diclofenac is another **non-selective NSAID** with a considerable risk of **gastrointestinal complications**, similar to indomethacin and naproxen. - Its use is not recommended given the patient's vulnerable gastric history, making it an unsafe option for long-term pain management in this case. *Aspirin* - **Regular-dose aspirin** is a **non-selective NSAID** and is particularly known for its strong inhibition of COX-1, leading to a high risk of **gastrointestinal bleeding** and ulcer formation. - While low-dose aspirin is used for cardiovascular protection, high-dose aspirin for pain and inflammation is contraindicated in patients with a history of ulcers.

Question 196: A 48-year-old man comes to the emergency department because of a 1-hour history of heavy nasal bleeding. He drinks half a bottle of sherry daily. His pulse is 112/min, and blood pressure is 92/54 mm Hg. Physical examination shows scattered ecchymoses across the extremities and oozing from a venipuncture site. Laboratory studies show a prothrombin time of 28 seconds and a partial thromboplastin time of 36 seconds. Impaired function of which of the following proteins is the most likely cause of this patient's hemorrhage?

• A. Von Willebrand factor
• B. Protein S
• C. Epoxide reductase
• D. Prolyl hydroxylase
• E. Gamma-glutamyl carboxylase (Correct Answer)

Explanation: ***Gamma-glutamyl carboxylase*** - This enzyme is crucial for the post-translational modification of vitamin K-dependent clotting factors (II, VII, IX, X, protein C, protein S) by adding a **gamma-carboxyglutamate** residue, which is essential for their function. - Chronic alcohol abuse, suggested by drinking half a bottle of sherry daily, often leads to **hepatic dysfunction** and **nutritional deficiencies**, including vitamin K deficiency. Vitamin K deficiency impairs gamma-glutamyl carboxylase activity by depriving it of its essential cofactor (reduced vitamin K), leading to dysfunctional clotting factors. The prolonged **PT (extrinsic and common pathways)** and slightly prolonged **aPTT (intrinsic and common pathways)**, along with bleeding signs (epistaxis, ecchymoses, oozing from venipuncture), are consistent with this. *Von Willebrand factor* - Deficiency or dysfunction of **von Willebrand factor** primarily causes defects in **primary hemostasis**, leading to mucosal bleeding (like epistaxis) and increased bleeding time. - However, it would typically not cause significant prolongation of both **PT** and **aPTT**, as it is not directly involved in the coagulation cascade measured by these tests. *Protein S* - **Protein S** is a natural anticoagulant and a cofactor for activated protein C, which inactivates factors Va and VIIIa. - A deficiency would lead to a **procoagulant state**, increasing the risk of thrombosis, not a bleeding disorder like the one described. *Epoxide reductase* - **Vitamin K epoxide reductase (VKOR)** is responsible for recycling oxidized vitamin K back to its reduced form, which serves as the cofactor for gamma-glutamyl carboxylase. - While VKOR dysfunction (e.g., by warfarin inhibition) would also lead to similar coagulation abnormalities, in the context of vitamin K deficiency from chronic alcoholism and malnutrition, the primary functional impairment occurs at the level of **gamma-glutamyl carboxylase**, which lacks its essential cofactor (reduced vitamin K) to perform the carboxylation reaction. This makes gamma-glutamyl carboxylase the most direct answer to the question of which protein's function is impaired. *Prolyl hydroxylase* - **Prolyl hydroxylase** is involved in the hydroxylation of proline residues, primarily in collagen synthesis. - A deficiency or impaired function would lead to disorders like **scurvy** (due to vitamin C deficiency), which can cause bleeding due to fragile blood vessels, but it would not typically cause the specific pattern of prolonged **PT** and **aPTT** seen in this patient, which points directly to a defect in the coagulation cascade.

Question 197: A 59-year-old woman is scheduled to undergo a right hip total arthroplasty for severe hip osteoarthritis that has failed conservative management. She has never had surgery before. She has a history of major depressive disorder and takes sertraline daily and ibuprofen occasionally for pain. Her mother died of breast cancer and her father died from a myocardial infarction. She has a brother who had an adverse reaction following anesthesia, but she does not know details of the event. In the operating room, the anesthesiologist administers isoflurane and succinylcholine. Two minutes later, the patient develops hypercarbia and hypertonicity of her bilateral upper and lower extremities. Her temperature is 103.7°F (39.8°C), blood pressure is 155/95 mmHg, pulse is 115/min, and respirations are 20/min. A medication with which of the following mechanisms of action is most strongly indicated for this patient?

• A. Muscarinic antagonist
• B. Antihistamine
• C. Ryanodine receptor antagonist (Correct Answer)
• D. Cholinesterase inhibitor
• E. Dopamine receptor agonist

Explanation: ***Ryanodine receptor antagonist*** - The patient's presentation with **hyperthermia**, **hypercarbia**, and **muscle rigidity** after exposure to isoflurane and succinylcholine is highly indicative of **malignant hyperthermia (MH)**. - **Dantrolene**, a **ryanodine receptor antagonist**, is the primary treatment for MH as it blocks the release of calcium from the sarcoplasmic reticulum, thereby reducing muscle contraction and heat production. *Muscarinic antagonist* - **Muscarinic antagonists** like atropine block the action of acetylcholine at muscarinic receptors and are used to treat **bradycardia** or reduce secretions. - They would not address the underlying pathophysiology of malignant hyperthermia, which involves uncontrolled calcium release from the sarcoplasmic reticulum. *Antihistamine* - **Antihistamines** block histamine receptors and are used to treat **allergic reactions** or reduce nausea and vomiting. - They have no role in the management of malignant hyperthermia, which is not an allergic response. *Cholinesterase inhibitor* - **Cholinesterase inhibitors** increase acetylcholine levels at the neuromuscular junction and are used to reverse **neuromuscular blockade** or treat **myasthenia gravis**. - Administering a cholinesterase inhibitor would likely intensify muscle contraction and rigidity, worsening the patient's condition in malignant hyperthermia. *Dopamine receptor agonist* - **Dopamine receptor agonists** are primarily used to treat **Parkinson's disease** or as **vasopressors** in critical care. - They have no direct therapeutic effect on the severe muscle rigidity and hypermetabolic state characteristic of malignant hyperthermia.

Question 198: A 70-year-old man comes to the physician for the evaluation of pain, cramps, and tingling in his lower extremities over the past 6 months. The patient reports that the symptoms worsen with walking more than two blocks and are completely relieved by rest. Over the past 3 months, his symptoms have not improved despite his participating in supervised exercise therapy. He has type 2 diabetes mellitus. He had smoked one pack of cigarettes daily for the past 50 years, but quit 3 months ago. He does not drink alcohol. His current medications include metformin, atorvastatin, and aspirin. Examination shows loss of hair and decreased skin temperature in the lower legs. Femoral pulses are palpable; pedal pulses are absent. Which of the following is the most appropriate treatment for this patient?

• A. Compression stockings
• B. Endarterectomy
• C. Bypass surgery
• D. Percutaneous transluminal angioplasty
• E. Administration of cilostazol (Correct Answer)

Explanation: ***Administration of cilostazol*** - The patient presents with classic symptoms of **peripheral artery disease (PAD)**, including **intermittent claudication** (pain with exertion, relieved by rest), **loss of hair**, **decreased skin temperature**, and **absent pedal pulses**. - **Cilostazol** is a phosphodiesterase inhibitor that improves walking distance and reduces symptoms of claudication by causing **vasodilation** and inhibiting **platelet aggregation**. *Compression stockings* - Compression stockings are primarily used for conditions like **venous insufficiency** or **lymphedema**, which involve problems with venous return or lymphatic drainage. - They are **contraindicated** in patients with significant PAD because they can further occlude already compromised arterial flow and worsen tissue ischemia. *Endarterectomy* - **Endarterectomy** is a surgical procedure to remove plaque from the inner lining of an artery. It is indicated for **localized, severe arterial stenosis** and is more invasive than other revascularization options. - While it can be considered for PAD, less invasive options are usually tried first, especially in a patient who has not yet received optimal medical therapy. *Bypass surgery* - **Bypass surgery** involves rerouting blood flow around a blocked artery using a graft (vein or synthetic material). It is a more invasive revascularization procedure for PAD with significant, extensive arterial occlusions. - It is typically reserved for **severe symptoms** refractory to medical management and less invasive procedures, or for critical limb ischemia. *Percutaneous transluminal angioplasty* - **Percutaneous transluminal angioplasty (PTA)** is a minimally invasive procedure that uses a balloon to widen a narrowed artery, often with stent placement. - It is an effective revascularization option for PAD but is generally considered after lifestyle modifications and pharmacotherapy (like cilostazol) have failed to improve symptoms sufficiently.

Question 199: A 4-year-old boy is brought to the emergency department with intense crying and pain in both hands after playing with ice cubes. His mother denies any preceding trauma. The temperature is 37.0°C (98.6°F), the blood pressure is 90/55 mm Hg, and the pulse is 100/min. The physical examination shows swollen dorsa of the hands and scleral icterus. The laboratory tests show hemoglobin of 10.1 g/dL and unconjugated hyperbilirubinemia. The cellulose acetate electrophoresis shows 60% HbS and absence of HbA. Which of the following can reduce the recurrence of the patient’s current condition?

• A. Vaccinations
• B. Avoidance of sulfa drugs
• C. Folic acid
• D. Hydroxyurea (Correct Answer)
• E. Allopurinol

Explanation: ***Hydroxyurea*** - This patient presents with **dactylitis** (pain and swelling in hands) due to **vaso-occlusive crisis** from **sickle cell anemia**, confirmed by **HbS 60%, absence of HbA** and **unconjugated hyperbilirubinemia**. - **Hydroxyurea** is the **primary disease-modifying therapy** that increases **fetal hemoglobin (HbF)** levels, which prevents HbS polymerization and reduces sickling. - It significantly reduces the frequency of **vaso-occlusive crises** (including dactylitis), acute chest syndrome, and need for transfusions in both children and adults with sickle cell disease. *Vaccinations* - While vaccinations like **pneumococcal** and **meningococcal vaccines** are crucial for sickle cell patients due to functional asplenia, they prevent infections, not directly reduce the recurrence of vaso-occlusive crises. - Infections can trigger crises, so vaccines are important supportive care but not the primary intervention for crisis recurrence. *Avoidance of sulfa drugs* - Sulfa drugs can cause **hemolysis** in patients with **glucose-6-phosphate dehydrogenase (G6PD) deficiency**, which is a separate condition. - They are not directly implicated in preventing vaso-occlusive crises in sickle cell disease unless the patient also has G6PD deficiency, which is not indicated here. *Folic acid* - **Folic acid** is a daily supplement for sickle cell patients to support increased **erythropoiesis** due to chronic hemolysis. - It helps prevent **megaloblastic anemia** but does not reduce the frequency or severity of sickling episodes or vaso-occlusive crises. *Allopurinol* - **Allopurinol** is used to prevent **uric acid nephropathy** and **gout** by reducing uric acid production, often given during chemotherapy or in conditions with high cell turnover. - It is not a treatment for sickle cell disease itself or for preventing vaso-occlusive crises.

Question 200: A 21-year-old woman was brought to the emergency department after her roommate found her unconscious at their apartment. On arrival, her GCS was 3/15, with bilateral mydriasis, fever of 39.4℃ (103.0℉), and ventricular tachycardia which was converted to sinus rhythm. She had one episode of a generalized tonic-clonic seizure on the way to the hospital which was managed with intravenous diazepam. Her hypertension was managed with nitroglycerin. After nasogastric tube insertion, gastric lavage and activated charcoal were given. Biochemistry result showed elevated creatine phosphokinase (CPK) of 268 U/L and low serum bicarbonate of 16.7 mmol/L. Her blood and urine samples will most likely show intoxication with which of the following drugs?

• A. Opioid
• B. PCP
• C. Marijuana
• D. MPTP
• E. Cocaine (Correct Answer)

Explanation: ***Cocaine*** - Cocaine intoxication presents with a classic "sympathomimetic toxidrome" including **mydriasis**, **tachycardia** (including ventricular tachycardia), **hypertension**, **hyperthermia**, and **seizures**. - **Elevated CPK** (due to rhabdomyolysis from seizures and hyperthermia) and **low serum bicarbonate** (due to lactic acidosis from hypoperfusion and increased metabolic demand) are characteristic findings. *Opioid* - Opioid overdose typically causes **miosis** (pinpoint pupils), **respiratory depression**, and **CNS depression**, which are directly opposite to the presented symptoms. - While opioids can cause CNS depression and unresponsiveness, the rest of the clinical picture, especially mydriasis, hyperthermia, and tachycardia, is inconsistent. *PCP* - Phencyclidine (PCP) intoxication can cause severe agitation, psychosis, nystagmus, hypertension, and tachycardia, but **bilateral mydriasis** is less typical, and it doesn't commonly lead to ventricular arrhythmias or the profound metabolic derangements seen. - While PCP can induce seizures and hyperthermia, the overall clinical constellation strongly points away from it. *Marijuana* - Marijuana (cannabis) intoxication typically causes conjunctival injection, tachycardia, and altered perception but not severe CNS depression, ventricular arrhythmias, hyperthermia, or seizures in this acute and severe manner. - The patient's critical condition with GCS 3, seizures, and severe cardiotoxicity is inconsistent with a primary marijuana overdose. *MPTP* - MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin that selectively destroys dopaminergic neurons in the substantia nigra, leading to **irreversible parkinsonism**. - It does not cause acute, severe sympathomimetic toxidrome, ventricular arrhythmias, or hyperthermia as presented in the case.

Question 201: A 66-year-old man presents to the emergency department for shortness of breath for the last 2 hours. Despite his diagnosis of heart failure 2 years ago, he has refused to make any diet changes. He takes aspirin and carvedilol but is poorly compliant. His vital signs are pulse of 135/min, respirations 30/min, and a blood pressure of 150/80 mm Hg. The patient is visibly distressed and unable to lie down. He is taking shallow breaths and auscultation reveals bilateral crackles in the chest. Jugular venous distension is seen. Pitting edema is present in the lower limbs. A chest X-ray shows prominent interstitial markings bilaterally with alveolar infiltrates. Which of the following is the mechanism of action of the drug that can relieve his ongoing symptoms?

• A. By holding water within the tubule, leading to osmotic diuresis
• B. Blocking the NaCl channels in the distal tubule of the nephron
• C. Blocking the angiotensin II receptors, leading to vasodilation
• D. Acting on the β-adrenergic receptors to increase cardiac contractility
• E. Blocking the Na+-K+-2Cl- cotransporter in the thick ascending limb of the loop of Henle (Correct Answer)

Explanation: ***Blocking the Na+-K+-2Cl- cotransporter in the thick ascending limb of the loop of Henle*** - This describes the mechanism of action of **loop diuretics** (e.g., furosemide), which are the most effective class of diuretics for rapid relief of **pulmonary edema** and **volume overload** in acute decompensated heart failure. - Blocking this cotransporter prevents the reabsorption of a large amount of sodium, potassium, and chloride, leading to significant diuresis and reduction of **preload**, thereby improving shortness of breath. *By holding water within the tubule, leading to osmotic diuresis* - This mechanism describes **osmotic diuretics** like mannitol, which are primarily used for reducing intracranial pressure or intraocular pressure and are not the drug of choice for acute pulmonary edema due to heart failure. - While they cause diuresis, their effect is less potent and rapid compared to loop diuretics for congestion in heart failure, and they can sometimes **expand intravascular volume** initially, potentially worsening pulmonary edema in some patients. *Blocking the NaCl channels in the distal tubule of the nephron* - This describes the mechanism of action of **thiazide diuretics**, which act on the **distal convoluted tubule**. - Thiazides are less potent than loop diuretics and are generally used for chronic management of hypertension or mild to moderate heart failure, not for the acute, severe volume overload seen in this patient. *Blocking the angiotensin II receptors, leading to vasodilation* - This describes the mechanism of **angiotensin receptor blockers (ARBs)**, which reduce blood pressure and afterload through vasodilation and are used in chronic heart failure management. - While ARBs have a role in heart failure, they do not provide the immediate relief of acute pulmonary edema and severe volume overload needed for this patient's acute symptoms. *Acting on the β-adrenergic receptors to increase cardiac contractility* - This describes the mechanism of **beta-agonists** (e.g., dobutamine) or **cardiac glycosides** (e.g., digoxin), which aim to improve cardiac output. - While these drugs can be used in some heart failure settings, they are not the primary treatment for the **acute pulmonary congestion** and **volume overload** presented, and beta-agonists can increase myocardial oxygen demand, potentially worsening ischemia.

Question 202: A 61-year-old man with longstanding diabetes and coronary artery disease presents to the ER with chest pain and dyspnea. The echocardiogram reveals moderate-to-severe mitral regurgitation and an ejection fraction of 27%. A chest X-ray shows bibasilar infiltrates. A new drug is added to his medication regimen, and the physician mentions urinary frequency, increased breast tissue development, and erectile dysfunction as possible side effects. What is the mechanism of action of this drug?

• A. Inhibits Na-Cl symporter on the distal convoluted tubule
• B. Inhibits epithelial Na-channels on the cortical collecting duct
• C. Inhibits mineralocorticoid receptor on the cortical collecting duct (Correct Answer)
• D. Inhibits Na-K-2Cl symporter on the ascending loop of Henle
• E. Inhibits beta-adrenergic receptors to decrease SA node automaticity

Explanation: ***Inhibits mineralocorticoid receptor on the cortical collecting duct*** - The patient's presentation of **heart failure** (chest pain, dyspnea, low ejection fraction, bibasilar infiltrates, mitral regurgitation) along with the side effects of **urinary frequency**, **gynecomastia**, and **erectile dysfunction** are characteristic of **spironolactone** or **eplerenone**. - These drugs are **aldosterone antagonists** that work by inhibiting the **mineralocorticoid receptor** in the cortical collecting duct, leading to diuresis and beneficial effects in heart failure. *Inhibits Na-Cl symporter on the distal convoluted tubule* - This describes the mechanism of action of **thiazide diuretics**, such as hydrochlorothiazide. - While thiazides cause urinary frequency, they are not typically associated with gynecomastia or erectile dysfunction. *Inhibits epithelial Na-channels on the cortical collecting duct* - This mechanism describes **potassium-sparing diuretics** like amiloride and triamterene (not aldosterone antagonists). - These drugs primarily prevent sodium reabsorption and potassium secretion, but they do not cause gynecomastia or erectile dysfunction as directly as spironolactone. *Inhibits Na-K-2Cl symporter on the ascending loop of Henle* - This is the mechanism of action for **loop diuretics**, such as furosemide or bumetanide. - Loop diuretics are potent diuretics and cause urinary frequency but are not known to cause gynecomastia or erectile dysfunction. *Inhibits beta-adrenergic receptors to decrease SA node automaticity* - This mechanism describes **beta-blockers**, such as metoprolol or carvedilol, which are often used in heart failure management. - While beta-blockers can cause erectile dysfunction, they do not cause urinary frequency or gynecomastia.

Question 203: A 32-year-old woman comes to the emergency department because of a 3-hour history of severe nausea, vomiting, tremor, and anxiety. She recently started a new medication but does not remember its name. She has a history of major depressive disorder treated with fluoxetine. Her temperature is 38.9 C (102.1 F), pulse is 132/min, respirations are 22/min, and blood pressure is 152/94 mm Hg. She is confused. Physical examination shows diaphoresis and an ataxic gait. Patellar reflexes are 4+ bilaterally. This patient's condition is most likely due to which of the following medications?

• A. Haloperidol
• B. Succinylcholine
• C. Sumatriptan (Correct Answer)
• D. Amiodarone
• E. Scopolamine

Explanation: ***Sumatriptan*** - The patient's symptoms (fever, tachycardia, hypertension, confusion, diaphoresis, hyperreflexia, tremor, nausea, vomiting) are characteristic of **serotonin syndrome**. - **Sumatriptan** is a 5-HT1B/1D receptor agonist and, when co-administered with an SSRI like **fluoxetine**, can precipitate serotonin syndrome due to excessive serotonergic activity. *Haloperidol* - This is a **D2 dopamine receptor antagonist** primarily used as an antipsychotic. - While it can cause extrapyramidal symptoms, it does not typically induce the constellation of symptoms seen here, especially **hyperthermia** and **hyperreflexia** associated with serotonin syndrome. *Succinylcholine* - A **depolarizing neuromuscular blocker** used primarily for rapid-sequence intubation. - Its effects are systemic muscle paralysis, not central nervous system hyperstimulation or serotonin syndrome signs. *Amiodarone* - An **antiarrhythmic drug** that can cause various adverse effects, including thyroid dysfunction, pulmonary fibrosis, and liver toxicity. - It does not directly affect serotonin levels or induce a **hyperadrenergic state** with hyperreflexia as seen in serotonin syndrome. *Scopolamine* - An **anticholinergic agent** used for motion sickness. - Overdose would present with anticholinergic toxidrome symptoms, such as dry mouth, blurred vision, urinary retention, and altered mental status, but typically **hyporeflexia** and **dry skin**, opposite to what is observed here.

Question 204: An 8-year-old girl is brought to the physician by her mother because of a 6-month history of an episodic dry cough, shortness of breath, and chest tightness. She has seasonal allergic rhinitis. Physical examination shows high-pitched expiratory wheezes throughout both lung fields. Pulmonary function testing shows an FEV1 of 70% (N ≥ 80%). Which of the following drugs would be most effective at reducing bronchial inflammation in this patient?

• A. Tiotropium
• B. Budesonide (Correct Answer)
• C. Salmeterol
• D. Montelukast
• E. Adenosine

Explanation: ***Budesonide*** - **Budesonide** is an **inhaled corticosteroid** (ICS) that is the most effective long-term control medication for persistent asthma by directly reducing **airway inflammation**. - Given the patient's symptoms (episodic cough, shortness of breath, chest tightness, wheezing, and reduced FEV1) and history of allergic rhinitis, **asthma** is likely, and an ICS is the cornerstone of treatment for managing chronic inflammation. *Tiotropium* - **Tiotropium** is a **long-acting anticholinergic** used primarily for **COPD** and, in some cases, severe asthma that is not well-controlled by ICS/LABA combinations. - While it helps with bronchodilation, it does not directly target the underlying **airway inflammation** as effectively as corticosteroids. *Salmeterol* - **Salmeterol** is a **long-acting beta-2 agonist (LABA)** that causes bronchodilation but does not address the underlying **bronchial inflammation**. - LABAs should never be used as monotherapy for asthma and must always be combined with an **inhaled corticosteroid** to prevent serious adverse events and improve asthma control. *Montelukast* - **Montelukast** is a **leukotriene receptor antagonist** that can help reduce inflammation and bronchoconstriction, particularly in **allergy-induced asthma** and **exercise-induced bronchoconstriction**. - While it has anti-inflammatory effects, it is generally less potent than **inhaled corticosteroids** in reducing overall bronchial inflammation in persistent asthma. *Adenosine* - **Adenosine** is a nucleoside used for the treatment of **supraventricular tachycardia** due to its ability to temporarily block the AV node. - It has no role in the management of **asthma** or the reduction of bronchial inflammation.

Question 205: A 55-year-old man comes to the physician because of a 4-month history of episodic, pressure-like chest pain. The chest pain occurs when he is walking up stairs and improves with rest. He has hypertension and type 2 diabetes mellitus. His father died from a myocardial infarction at the age of 50 years. Current medications include hydrochlorothiazide and metformin. His pulse is 85/min, respirations are 12/min, and blood pressure is 140/90 mm Hg. Cardiac examination shows normal heart sounds without any murmurs, rubs, or gallops. An ECG shows high amplitude of the S wave in lead V3. An exercise stress test is performed but stopped after 4 minutes because the patient experiences chest pain. An ECG obtained during the stress test shows sinus tachycardia and ST-segment depressions in leads V1–V4. Which of the following is the most appropriate long-term pharmacotherapy to reduce the frequency of symptoms in this patient?

• A. Metoprolol (Correct Answer)
• B. Clopidogrel
• C. Aspirin
• D. Nitroglycerin
• E. Isosorbide mononitrate

Explanation: ***Metoprolol*** - **Beta-blockers** like metoprolol are first-line agents for **symptom relief** in stable angina by reducing myocardial oxygen demand. - They decrease **heart rate**, **blood pressure**, and **myocardial contractility**, thereby reducing the frequency and severity of anginal episodes. *Clopidogrel* - **Clopidogrel** is an antiplatelet agent used primarily to prevent **thrombotic events** in patients with established cardiovascular disease or acute coronary syndromes. - It does not directly reduce the frequency of anginal symptoms, but rather prevents progression to **myocardial infarction** or **stroke**. *Aspirin* - **Aspirin** is an antiplatelet medication used for **secondary prevention** of cardiovascular events by inhibiting platelet aggregation. - While crucial for reducing cardiovascular risk, it does not directly alleviate the **frequency of anginal symptoms** themselves. *Nitroglycerin* - **Nitroglycerin** is a short-acting nitrate used to provide **immediate relief** of anginal pain during an acute episode. - It is not a long-term pharmacotherapy for reducing the *frequency* of symptoms. *Isosorbide mononitrate* - **Isosorbide mononitrate** is a long-acting nitrate used to *prevent* angina, but it is typically a **second-line agent** after beta-blockers due to potential for **tolerance** and side effects. - While it can reduce symptom frequency, beta-blockers are generally preferred as initial long-term therapy for symptom control.

Question 206: A 36-year-old woman complains of recurrent headaches. The pain is located on the right side of the head, is accompanied by nausea, worsens when lifting heavy objects, and typically lasts 2 days. She describes the pain as pulsatile and says that they are usually triggered by eating chocolates. Her headache is not associated with an aura. She sits in a dark room due to her increased discomfort. The patient has tried multiple over-the-counter medications without relief. Which of the following will most likely be the next treatment of choice for acute episodes?

• A. Beta-blocker
• B. GABA transaminase inhibitor
• C. 5-HT1B/D agonist (Correct Answer)
• D. Cyclooxygenase inhibitor
• E. D2 receptor blocker

Explanation: ***5-HT1B/D agonist*** - The patient's symptoms (unilateral, pulsatile headache, nausea, photophobia, aggravation by physical activity, chocolate trigger), are highly suggestive of a **migraine**. - **Triptans (5-HT1B/D agonists)** are the first-line treatment for acute moderate to severe migraine attacks, effectively aborting the headache when over-the-counter medications fail. *Beta-blocker* - **Beta-blockers** (e.g., propranolol) are primarily used for **migraine prophylaxis**, meaning they are taken regularly to *prevent* migraines, not to treat acute episodes. - While they can reduce the frequency and severity of migraines, they are not effective for pain relief once a headache has started. *GABA transaminase inhibitor* - A **GABA transaminase inhibitor** (e.g., vigabatrin) is an anti-epileptic drug that increases GABA levels in the brain. - These are typically used for **epilepsy treatment** and are not a standard treatment for acute migraines. *Cyclooxygenase inhibitor* - **Cyclooxygenase inhibitors (NSAIDs)**, such as ibuprofen or naproxen, are often tried for mild to moderate migraines. - In this case, the patient has already used **multiple over-the-counter medications without relief**, indicating that NSAIDs are likely insufficient for her severe migraine episodes. *D2 receptor blocker* - **D2 receptor blockers (antiemetics)** like metoclopramide or prochlorperazine are often used to treat the **nausea and vomiting** associated with migraines. - While helpful for symptomatic relief, they do not directly treat the headache pain itself and are typically used in conjunction with migraine-specific pain relievers or for intractable nausea.

Question 207: A 46-year-old woman presents with palpitations, tremors, and anxiety. She says these symptoms have been present ever since a recent change in her diabetic medication. The most recent time she felt these symptoms, her blood glucose level was 65 mg/dL, and she felt better after eating a cookie. Which of the following is the mechanism of action of the drug most likely to have caused this patient's symptoms?

• A. Inhibition of α-glucosidase
• B. Blocking of the ATP-sensitive K+ channels (Correct Answer)
• C. Block reabsorption of glucose in proximal convoluted tubule (PCT)
• D. Inhibitor of dipeptidyl peptidase (DPP-IV)
• E. Decreased hepatic gluconeogenesis

Explanation: ***Blocking of the ATP-sensitive K+ channels*** - The patient's symptoms of palpitations, tremors, anxiety, and a blood glucose level of 65 mg/dL, which improved after eating, are characteristic of **hypoglycemia**. - **Sulfonylureas**, such as glyburide or glipizide, cause hypoglycemia by **blocking ATP-sensitive K+ channels** on pancreatic beta cells, leading to insulin release independent of blood glucose levels. *Inhibition of α-glucosidase* - This mechanism, characteristic of drugs like **acarbose** and **miglitol**, delays carbohydrate absorption in the gut. - These drugs typically cause **gastrointestinal side effects** such as flatulence and diarrhea, not hypoglycemia or the associated adrenergic symptoms. *Block reabsorption of glucose in proximal convoluted tubule (PCT)* - This action describes **SGLT2 inhibitors** (e.g., canagliflozin, empagliflozin), which increase urinary glucose excretion. - While they can cause **genitourinary infections** and **polyuria**, they have a very low risk of hypoglycemia unless combined with insulin or sulfonylureas. *Inhibitor of dipeptidyl peptidase (DPP-IV)* - **DPP-IV inhibitors** (e.g., sitagliptin, saxagliptin) prevent the breakdown of incretins, thus enhancing glucose-dependent insulin secretion and suppressing glucagon. - These drugs typically have a **low risk of hypoglycemia** because their effects on insulin secretion are glucose-dependent. *Decreased hepatic gluconeogenesis* - This is the primary mechanism of **metformin**, which also increases insulin sensitivity in peripheral tissues. - Metformin is associated with **lactic acidosis** and **gastrointestinal upset**, but it does not typically cause hypoglycemia as a monotherapy because it does not stimulate insulin secretion.

Question 208: On the 3rd day post-anteroseptal myocardial infarction (MI), a 55-year-old man who was admitted to the intensive care unit is undergoing an examination by his physician. The patient complains of new-onset precordial pain which radiates to the trapezius ridge. The nurse informs the physician that his temperature was 37.7°C (99.9°F) 2 hours ago. On physical examination, the vital signs are stable, but the physician notes the presence of a triphasic pericardial friction rub on auscultation. A bedside electrocardiogram shows persistent positive T waves in leads V1–V3 and an ST segment: T wave ratio of 0.27 in lead V6. Which of the following is the drug of choice to treat the condition the patient has developed?

• A. Clarithromycin
• B. Aspirin (Correct Answer)
• C. Furosemide
• D. Colchicine
• E. Prednisolone

Explanation: **Aspirin** - The patient's symptoms (new-onset **precordial pain** radiating to the **trapezius ridge**, low-grade fever, and a **triphasic pericardial friction rub** after an **anteroseptal MI**) indicate **post-MI pericarditis** (early pericarditis). - **Aspirin** is the recommended first-line treatment for post-MI pericarditis, especially in patients who have recently had an MI, due to its anti-inflammatory properties and safety profile in this context. *Colchicine* - While **colchicine** is effective for pericarditis, it is typically used as an adjunct to NSAIDs or aspirin, or as a monotherapy for recurrent pericarditis. - It is not usually the primary drug of choice for acute post-MI pericarditis when aspirin can be used and the patient is stable. *Prednisolone* - **Glucocorticoids** like prednisolone should generally be avoided in post-MI pericarditis, as they can impair myocardial healing and potentially lead to ventricular remodeling and rupture. - They are reserved for refractory cases or when other therapies are contraindicated, and always used with caution due to their side effect profile. *Clarithromycin* - **Clarithromycin** is an antibiotic and is indicated for bacterial infections. - Pericarditis in this context is an inflammatory process, not an infection, so antibiotics would not be effective. *Furosemide* - **Furosemide** is a loop diuretic used to reduce fluid overload, often in conditions like heart failure or pulmonary edema. - It has no role in treating the inflammation associated with pericarditis and would not address the patient's symptoms or underlying condition.

Question 209: A 45-year-old woman with history of systemic sclerosis presents with new onset dyspnea, which is worsened with moderate exertion. She also complains of chest pain. An ECG was obtained, and showed right-axis deviation. Chest x-ray showed right ventricle hypertrophy. Given the patient's history and presentation, right heart catheterization was performed, which confirmed the suspected diagnosis of pulmonary artery hypertension. It is decided to start the patient on bosentan. Which of the following describes the method of action of bosentan?

• A. Endothelin receptor antagonist (Correct Answer)
• B. Endothelin receptor agonist
• C. Anticoagulant
• D. Phosphodiesterase type 5 inhibitor
• E. Calcium channel blocker

Explanation: ***Endothelin receptor antagonist*** - **Bosentan** is a **dual endothelin receptor antagonist** that blocks both ETA and ETB receptors. - By blocking these receptors, bosentan prevents the **vasoconstrictive** and **proliferative effects of endothelin-1**, a potent vasoconstrictor implicated in pulmonary hypertension. *Endothelin receptor agonist* - An **endothelin receptor agonist** would activate endothelin receptors, leading to **increased vasoconstriction** and worsening pulmonary hypertension. - This mechanism would **exacerbate** the patient's condition rather than alleviate it. *Anticoagulant* - **Anticoagulants** prevent **blood clot formation** and are used in some cases of pulmonary hypertension to reduce the risk of thrombosis. - However, they do not directly address the primary **vasoconstriction** and **vascular remodeling** found in pulmonary artery hypertension. *Phosphodiesterase type 5 inhibitor* - **Phosphodiesterase type 5 (PDE5) inhibitors** like sildenafil and tadalafil increase cyclic GMP levels, leading to **vasodilation** in the pulmonary vasculature. - While used in pulmonary hypertension, this is a **different mechanism of action** from bosentan. *Calcium channel blocker* - **Calcium channel blockers** are used in a small subset of pulmonary hypertension patients who are **vasoreactive** on acute vasodilator testing. - They primarily act by reducing calcium influx into vascular smooth muscle cells, leading to **vasodilation**, which is not the mechanism of bosentan.

Question 210: A 47-year-old man with gastroesophageal reflux disease comes to the physician because of severe burning chest pain and belching after meals. He has limited his caffeine intake and has been avoiding food close to bedtime. Esophagogastroduodenoscopy shows erythema and erosions in the distal esophagus. Which of the following is the mechanism of action of the most appropriate drug for this patient?

• A. Enhancement of the mucosal barrier
• B. Inhibition of ATPase (Correct Answer)
• C. Inhibition of H2 receptors
• D. Neutralization of gastric acid
• E. Inhibition of D2 receptors

Explanation: **Inhibition of ATPase** - The patient's symptoms (severe burning chest pain, belching after meals) and EGD findings (erythema and erosions in the distal esophagus) are classic for **Gastroesophageal Reflux Disease (GERD)**. - The most effective treatment for GERD involves **proton pump inhibitors (PPIs)**, which work by irreversibly inhibiting the **H+/K+-ATPase** (proton pump) in the gastric parietal cells, thereby reducing acid secretion. *Enhancement of the mucosal barrier* - Medications that enhance the mucosal barrier, like **sucralfate**, provide a protective layer and are primarily used for stress ulcers or as an adjunct therapy, not as first-line treatment for erosive esophagitis. - While beneficial, this mechanism does not directly address the *overproduction of acid* that is the primary cause of reflux and esophageal damage in GERD. *Inhibition of H2 receptors* - **H2-receptor blockers** (e.g., ranitidine, cimetidine) reduce acid secretion by blocking histamine's action on parietal cells, but they are generally less potent and effective than PPIs for healing erosive esophagitis. - They tend to lose effectiveness over time due to **tachyphylaxis** and are often used for milder GERD symptoms or as maintenance therapy. *Neutralization of gastric acid* - **Antacids** (e.g., calcium carbonate, aluminum hydroxide) provide rapid, but temporary, relief by directly neutralizing existing stomach acid. - They do not prevent acid production, making them unsuitable for managing persistent erosive esophagitis. *Inhibition of D2 receptors* - This mechanism is characteristic of **dopamine antagonists**, primarily used as antiemetics (e.g., metoclopramide) or antipsychotics (e.g., haloperidol). - While metoclopramide can increase esophageal sphincter tone and gastric emptying, it is not the primary mechanism of action for the most effective drug in treating erosive esophagitis.

Question 211: A 63-year-old man comes to the physician for a routine health maintenance examination. He feels well. He has a history of hypertension, atrial fibrillation, bipolar disorder, and osteoarthritis of the knees. Current medications include lisinopril, amiodarone, lamotrigine, and acetaminophen. He started amiodarone 6 months ago and switched from lithium to lamotrigine 4 months ago. The patient does not smoke. He drinks 1–4 beers per week. He does not use illicit drugs. Vital signs are within normal limits. Examination shows no abnormalities. Laboratory studies show: Serum Na+ 137 mEq/L K+ 4.2 mEq/L Cl- 105 mEq/L HCO3- 24 mEq/L Urea nitrogen 14 mg/dL Creatinine 0.9 mg/dL Alkaline phosphatase 82 U/L Aspartate aminotransferase (AST) 110 U/L Alanine aminotransferase (ALT) 115 U/L Which of the following is the most appropriate next step in management?

• A. Discontinue amiodarone (Correct Answer)
• B. Discontinue acetaminophen
• C. Follow-up laboratory results in 3 months
• D. Follow-up laboratory results in 6 months
• E. Decrease alcohol consumption

Explanation: ***Discontinue amiodarone*** * The patient has elevated **AST** and **ALT** levels, suggestive of **drug-induced liver injury**. Amiodarone is a known cause of **hepatotoxicity**, which can occur even with normal baseline liver function. * **Amiodarone-induced liver injury** can range from asymptomatic transaminase elevation to **fulminant hepatic failure**; therefore, discontinuing the drug is crucial to prevent further liver damage. *Discontinue acetaminophen* * Although **acetaminophen** can cause **hepatotoxicity** at high doses, the patient is likely taking it at therapeutic doses for osteoarthritis, as suggested by its use in routine care and the absence of overdose symptoms. * The chronic nature of amiodarone use (6 months) and its well-established risk of **liver injury** make it a more probable cause of the elevated transaminases than **therapeutic-dose acetaminophen**. *Follow-up laboratory results in 3 months* * The current **liver enzyme elevations** (AST 110 U/L, ALT 115 U/L) are significant and indicate acute liver injury. Waiting 3 months for follow-up without intervention significantly risks further liver damage. * Prompt identification and removal of the offending agent are necessary to prevent potentially irreversible **hepatic injury**. *Follow-up laboratory results in 6 months* * Delaying follow-up for 6 months is an inappropriate and potentially harmful approach given the current enzyme elevations. There is an immediate need to identify and address the cause of **liver injury**. * Such a delay could lead to progression of **liver damage**, especially if the causative agent (e.g., amiodarone) continues to be administered. *Decrease alcohol consumption* * While excessive alcohol consumption can cause **elevated liver enzymes**, the patient’s intake of 1–4 beers per week is considered light to moderate and is unlikely to be the sole cause of these significant elevations. * The presence of a known **hepatotoxic medication** (amiodarone) alongside the elevated enzymes makes the drug a much more probable cause than the patient's modest alcohol intake.

Question 212: A 45-year-old man has a history of smoking 1 pack per day and drinking a six-pack of beer daily over the last ten years. He is admitted to the medical floor after undergoing a cholecystectomy. One day after the surgery, the patient states that he feels anxious and that his hands are shaking. While being checked for a clean surgical site, the patient starts shaking vigorously and loses consciousness. The patient groans and falls to the floor. His arms and legs begin to jerk rapidly and rhythmically. This episode lasts for almost five minutes, and the patient's airway, breathing, and circulation are stabilized per seizure protocol. What is the best next step for this patient?

• A. Antibiotics
• B. Morphine
• C. Chest radiograph
• D. Urinalysis
• E. Lorazepam (Correct Answer)

Explanation: ***Lorazepam*** - The patient exhibits classic signs of **alcohol withdrawal syndrome**, including anxiety, tremors, and a generalized tonic-clonic seizure, which is a medical emergency. - **Benzodiazepines** like lorazepam are the first-line treatment for alcohol withdrawal seizures due to their ability to potentiate **GABA** (gamma-aminobutyric acid) and stabilize neuronal hyperactivity. *Antibiotics* - There is no clinical indication for infection in this patient's presentation; the symptoms are clearly related to **alcohol withdrawal**. - Administering antibiotics without evidence of infection contributes to **antibiotic resistance** and potential side effects. *Morphine* - **Opioids** like morphine can depress the respiratory system and do not address the underlying pathophysiology of alcohol withdrawal seizures. - Administering morphine could worsen the patient's condition by masking symptoms or increasing the risk of respiratory compromise. *Chest radiograph* - A chest radiograph is primarily used to evaluate **pulmonary pathology** like pneumonia or aspiration, which are not the immediate concerns given the seizure and alcohol history. - While aspiration is a risk during seizures, the immediate priority is to stop the ongoing seizure and address the underlying cause. *Urinalysis* - A urinalysis is used to detect urinary tract infections, kidney disease, or metabolic abnormalities, none of which are suggested by the patient's acute presentation of seizures and withdrawal symptoms. - While it may be part of a broader workup, it is not the most urgent next step for an ongoing or recent seizure due to alcohol withdrawal.

Question 213: 2 hours after being admitted to the hospital because of a fracture of the right ankle, a 75-year-old man continues to complain of pain despite treatment with acetaminophen and ibuprofen. He has a history of dementia and cannot recall his medical history. The presence of which of the following features would most likely be a reason to avoid treatment with morphine in this patient?

• A. Severe hypertension
• B. Persistent cough
• C. Biliary tract dysfunction
• D. Tachypnea (Correct Answer)
• E. Watery diarrhea

Explanation: ***Tachypnea*** - **Tachypnea** (increased respiratory rate) can indicate underlying **respiratory compromise**, making morphine use risky due to its potential for **respiratory depression**. - In a 75-year-old with a fracture and possible underlying health issues, exacerbating respiratory distress with opioids could be dangerous. *Severe hypertension* - While morphine can cause **hypotension** due to vasodilation, it is not typically contraindicated in severe hypertension. - In fact, the hypotensive effect of morphine can sometimes be beneficial in conditions like **acute pulmonary edema** associated with hypertension. *Persistent cough* - Morphine is known to have **antitussive effects**, meaning it can help suppress a cough. - Therefore, a persistent cough would more likely be a reason *to use* morphine, rather than avoid it, especially if the cough is non-productive and distressing. *Biliary tract dysfunction* - Morphine can cause **spasm of the sphincter of Oddi**, leading to increased pressure in the biliary tract and potentially exacerbating pain in patients with biliary dysfunction. - However, this is usually a concern for patients with pre-existing biliary colic or pancreatitis, and not a primary contraindication in acute pain management unless other safer alternatives are available. *Watery diarrhea* - Opioids like morphine are well-known to cause **constipation** by slowing gut motility, due to their action on mu-opioid receptors in the enteric nervous system. - Therefore, watery diarrhea would not be a reason to avoid morphine; in some cases, the constipating effect could even be considered beneficial.

Question 214: Four days after undergoing a total abdominal hysterectomy for atypical endometrial hyperplasia, a 59 year-old woman reports abdominal bloating and discomfort. She has also had nausea without vomiting. She has no appetite despite not having eaten since the surgery and drinking only sips of water. Her postoperative pain has been well controlled on a hydromorphone patient-controlled analgesia (PCA) pump. Her foley was removed on the second postoperative day and she is now voiding freely. Although she lays supine in bed for most of the day, she is able to walk around the hospital room with a physical therapist. Her temperature is 36.5°C (97.7°F), pulse is 84/min, respirations are 10/min, and blood pressure is 132/92 mm Hg. She is 175 cm (5 ft 9 in) tall and weighs 115 kg (253 lb); BMI is 37.55 kg/m2. Examination shows a mildly distended, tympanic abdomen; bowel sounds are absent. Laboratory studies are within normal limits. An x-ray of the abdomen shows uniform distribution of gas in the small bowel, colon, and rectum without air-fluid levels. Which of the following is the most appropriate next step in the management of this patient?

• A. Esophagogastroduodenoscopy
• B. Begin total parenteral nutrition
• C. Colonoscopy
• D. Gastrografin enema
• E. Reduce use of opioid therapy (Correct Answer)

Explanation: ***Reduce use of opioid therapy*** - The patient's symptoms (bloating, discomfort, nausea, absent bowel sounds, diffuse gas on X-ray) after abdominal surgery are consistent with a **postoperative ileus**, which is often exacerbated by **opioid use**. - Reducing opioids, if pain control allows, can help normalize gastrointestinal motility and resolve the ileus, as her vital signs are stable and there are no signs of obstruction or infection. *Esophagogastroduodenoscopy* - This procedure is primarily used to evaluate the **upper gastrointestinal tract** (esophagus, stomach, duodenum) for conditions like ulcers, inflammation, or obstruction. - While the patient has nausea, there is no evidence suggesting an upper GI pathology that would warrant an EGD, especially with diffuse gas distribution on X-ray. *Begin total parenteral nutrition* - **Total parenteral nutrition (TPN)** is indicated when a patient cannot meet their nutritional needs via the enteral route for an extended period, typically more than 7-10 days, or in severe malnutrition. - The patient has only been NPO for four days post-op, and addressing the underlying cause of her GI symptoms (likely ileus) is the priority before considering long-term nutritional support. *Colonoscopy* - **Colonoscopy** is used to visualize the large intestine for conditions such as polyps, cancer, or inflammatory bowel disease. - There are no symptoms or signs (e.g., lower GI bleeding, chronic diarrhea) to suggest a need for colonoscopy in this acute postoperative setting. *Gastrografin enema* - A **Gastrografin enema** is a diagnostic and sometimes therapeutic study used to evaluate the colon and identify conditions like anastomotic leaks or obstructions, particularly in the context of recent surgery. - The abdominal X-ray shows diffuse gas without air-fluid levels and the patient's symptoms are classic for an ileus, not a mechanical obstruction that would require a contrast study.

Question 215: A 53-year-old man presents to the office for a routine examination. The medical history is significant for diabetes mellitus, for which he is taking metformin. The medical records show blood pressure readings from three separate visits to fall in the 130–160 mm Hg range for systolic and 90–100 mm Hg range for diastolic. Prazosin is prescribed. Which of the following are effects of this drug?

• A. Vasodilation, decreased heart rate, bronchial constriction
• B. Vasodilation, increased peristalsis, bronchial dilation
• C. Vasoconstriction, bladder sphincter constriction, mydriasis
• D. Vasoconstriction, increase in AV conduction rate, bronchial dilation
• E. Vasodilation, bladder sphincter relaxation (Correct Answer)

Explanation: ***Vasodilation, bladder sphincter relaxation*** - **Prazosin** is an **alpha-1 adrenergic receptor antagonist**, which blocks the effects of norepinephrine on vascular smooth muscle, leading to **vasodilation** and decreased blood pressure. - Blocking alpha-1 receptors in the bladder neck and prostate causes **bladder sphincter relaxation**, which can improve urine flow and is also useful in benign prostatic hyperplasia (BPH). - These are the two primary clinically relevant effects of alpha-1 blockade with prazosin. *Vasodilation, decreased heart rate, bronchial constriction* - While prazosin causes **vasodilation**, it does not typically decrease heart rate directly; alpha-1 blockade can lead to **reflex tachycardia** due to decreased blood pressure. - Prazosin has no significant effect on bronchial smooth muscle and does not cause **bronchial constriction**; bronchial effects are primarily mediated by beta-2 receptors or muscarinic (M3) receptors. *Vasodilation, increased peristalsis, bronchial dilation* - Prazosin does cause **vasodilation** but does not directly cause **increased peristalsis**; gastrointestinal motility is mainly regulated by the autonomic nervous system via muscarinic receptors and the enteric nervous system. - Prazosin does not cause **bronchial dilation**; this effect is mediated by beta-2 adrenergic receptor stimulation. *Vasoconstriction, bladder sphincter constriction, mydriasis* - Prazosin is an alpha-1 antagonist, meaning it *blocks* **vasoconstriction** and instead causes vasodilation. - Similarly, it causes **bladder sphincter relaxation**, not constriction. - Prazosin has minimal effects on pupil size; mydriasis would be caused by alpha-1 agonists or muscarinic antagonists, not alpha-1 antagonists. *Vasoconstriction, increase in AV conduction rate, bronchial dilation* - Prazosin causes **vasodilation**, not vasoconstriction. - It does not significantly affect **AV conduction rate** or directly cause **bronchial dilation**.

Question 216: A 65-year-old woman arrives for her annual physical. She has no specific complaints. She has seasonal allergies and takes loratadine. She had a cholecystectomy 15 years ago. Her last menstrual period was 9 years ago. Both her mother and her maternal aunt had breast cancer. A physical examination is unremarkable. The patient is given the pneumococcal conjugate vaccine and the shingles vaccine. A dual-energy x-ray absorptiometry (DEXA) scan is obtained. Her T-score is -2.6. She is prescribed a new medication. The next month the patient returns to her primary care physician complaining of hot flashes. Which of the following is the most likely medication the patient was prescribed?

• A. Raloxifene (Correct Answer)
• B. Denosumab
• C. Teriparatide
• D. Zoledronic acid
• E. Alendronate

Explanation: ***Raloxifene*** - This patient has osteoporosis (T-score -2.6), increased **breast cancer risk** (family history), and postmenopausal status. **Raloxifene** is a **selective estrogen receptor modulator (SERM)** that treats osteoporosis and reduces breast cancer risk. - The medication's **estrogen-antagonist effect** in the hypothalamus can cause or worsen **hot flashes**, a known side effect that explains her new complaint. *Denosumab* - **Denosumab** is a **monoclonal antibody** that inhibits osteoclast function, effectively treating osteoporosis. - It works differently from SERMs and is **not associated with hot flashes** as a side effect. *Teriparatide* - **Teriparatide** is a **parathyroid hormone analog** that promotes bone formation, used for severe osteoporosis. - It is not a SERM and does **not cause hot flashes** as a typical side effect. *Zoledronic acid* - **Zoledronic acid** is a **bisphosphonate** that inhibits osteoclast activity, effectively treating osteoporosis. - While intravenous administration can cause flu-like symptoms, it is **not associated with hot flashes**. *Alendronate* - **Alendronate** is an **oral bisphosphonate** that reduces bone resorption in osteoporosis. - Its side effect profile mainly involves gastrointestinal issues and esophageal irritation, and it does **not cause hot flashes**.

Question 217: A 25-year-old man is scheduled for an orthopedic surgery. His routine preoperative laboratory tests are within normal limits. An urticarial reaction occurs when a non-depolarizing neuromuscular blocking agent is injected for muscle relaxation and mechanical ventilation. The patient’s lungs are manually ventilated with 100% O2 by bag and mask and then through an endotracheal tube. After a few minutes, edema of the face and neck rapidly ensues and giant hives appear over most of his body. Which of the following neuromuscular blocking agents was most likely used in this operation?

• A. Ketamine
• B. Succinylcholine
• C. Nitrous oxide
• D. Neostigmine
• E. D-tubocurarine (Correct Answer)

Explanation: ***D-tubocurarine*** - The rapid onset of widespread **urticaria**, facial and neck **edema**, and giant hives immediately after injection of a **non-depolarizing neuromuscular blocking agent** strongly points to an **anaphylactic reaction**. d-Tubocurarine is a historical non-depolarizing neuromuscular blocker that is known for its propensity to cause **histamine release**, leading to severe hypersensitivity reactions including anaphylaxis and therefore is rarely used today. - The symptoms described are classic signs of a severe allergic reaction, which is a known and significant side effect of d-tubocurarine due to its potent histamine-releasing properties. *Ketamine* - **Ketamine** is a dissociative anesthetic, not a neuromuscular blocking agent. It primarily affects the central nervous system, producing a trance-like state, pain relief, sedation, and amnesia. - While it can cause some cardiovascular stimulation, it does not typically induce **histamine release** leading to anaphylactic-like reactions as described with neuromuscular blockers. *Succinylcholine* - **Succinylcholine** is a depolarizing neuromuscular blocker that can cause adverse effects like **hyperkalemia**, malignant hyperthermia, and muscle pain. - Although it can rarely trigger an allergic reaction, it is not primarily known for causing widespread **histamine release** and anaphylaxis like d-tubocurarine. *Nitrous oxide* - **Nitrous oxide** is an inhalational anesthetic gas used for sedation and analgesia; it is not a neuromuscular blocking agent. - Its adverse effects are generally related to its anesthetic properties, such as nausea and vomiting, and it does not cause **allergic reactions** of this nature. *Neostigmine* - **Neostigmine** is an acetylcholinesterase inhibitor used to **reverse the effects of non-depolarizing neuromuscular blockers**, not as a blocking agent itself. - It increases acetylcholine levels at the neuromuscular junction; its side effects are typically cholinergic, such as bradycardia, salivation, and bronchospasm, and it does not cause anaphylaxis from histamine release.

Question 218: A 6-year-old boy is brought to the emergency department 12 hours after ingesting multiple pills. The patient complains of noise in both his ears for the past 10 hours. The patient’s vital signs are as follows: pulse rate, 136/min; respirations, 39/min; and blood pressure, 108/72 mm Hg. The physical examination reveals diaphoresis. The serum laboratory parameters are as follows: Na+ 136 mEq/L Cl- 99 mEq/L Arterial blood gas analysis under room air indicates the following results: pH 7.39 PaCO2 25 mm HG HCO3- 15 mEq/L Which of the following is the most appropriate first step in the management of this patient?

• A. Hemodialysis
• B. Supportive care
• C. Gastrointestinal decontamination
• D. Urine alkalinization (Correct Answer)
• E. Multiple-dose activated charcoal

Explanation: ***Urine alkalinization*** - This patient likely has **salicylate toxicity** (suggested by **tinnitus**, hyperpnea leading to **respiratory alkalosis** followed by **metabolic acidosis**, and diaphoresis), for which **urine alkalinization** is a primary treatment. - Making the urine alkaline helps to **ionize salicylates**, trapping them in the renal tubules and increasing their renal excretion. *Hemodialysis* - **Hemodialysis** is reserved for severe salicylate toxicity, such as refractory acidosis, severe central nervous system effects, renal failure, or very high salicylate levels, not as a first step. - While it can remove salicylates, less invasive and effective options like urine alkalinization should be attempted first. *Supportive care* - While essential, **supportive care** alone (e.g., maintaining hydration, monitoring vital signs) is not sufficient for active management of significant salicylate overdose. - It does not address the underlying toxicology, which requires specific interventions to enhance drug elimination. *Gastrointestinal decontamination* - **Single-dose activated charcoal** would be indicated if the ingestion was within 1-2 hours, but 12 hours have passed, making it less effective. - Other GI decontamination methods like **gastric lavage** are rarely indicated and generally not recommended beyond 1 hour post-ingestion due to risks versus benefits. *Multiple-dose activated charcoal* - **Multiple-dose activated charcoal (MDAC)** is used for drugs that undergo enterohepatic recirculation or have delayed absorption, but its efficacy in salicylate poisoning, especially 12 hours post-ingestion, is debated and not a first-line intervention. - Urine alkalinization is a more direct and effective method for accelerating salicylate elimination from the body.

Question 219: An investigator is studying a drug that acts on a G protein-coupled receptor in the pituitary gland. Binding of the drug to this receptor leads to increased production of inositol triphosphate (IP3) in the basophilic cells of the anterior pituitary. Administration of this drug every 90 minutes is most likely to be beneficial in the treatment of which of the following conditions?

• A. Prostate cancer
• B. Variceal bleeding
• C. Central diabetes insipidus
• D. Anovulatory infertility (Correct Answer)
• E. Hyperkalemia

Explanation: ***Anovulatory infertility*** - The drug's action on a G protein-coupled receptor leading to increased **IP3 production** in pituitary basophils suggests activation of the **gonadotropin-releasing hormone (GnRH) receptor**. - **Pulsatile administration** (e.g., every 90 minutes) of GnRH or its agonists is crucial for stimulating the release of **FSH and LH**, which can induce ovulation in women with anovulatory infertility due to hypothalamic-pituitary dysfunction. *Prostate cancer* - While GnRH agonists are used in prostate cancer, they are typically administered **continuously or in depot forms** to desensitize the GnRH receptor, thereby suppressing testosterone production. - **Pulsatile administration** would rather stimulate testosterone release, which is detrimental in prostate cancer. *Variceal bleeding* - **Variceal bleeding** is primarily managed with vasoconstrictors like **octreotide** (a somatostatin analog) or **vasopressin**, which are unrelated to GnRH receptor activation. - The mechanism of action described (increased IP3 in pituitary basophils) does not align with treatments for variceal bleeding. *Central diabetes insipidus* - **Central diabetes insipidus** is caused by a deficiency in **vasopressin (ADH)**, which regulates water balance in the kidneys. - Treatment involves synthetic ADH (**desmopressin**), not drugs acting on GnRH receptors and affecting pituitary basophils. *Hyperkalemia* - **Hyperkalemia** is an electrolyte imbalance characterized by high potassium levels and is managed with medications that shift potassium intracellularly (e.g., insulin, beta-agonists) or promote its excretion (e.g., diuretics, potassium binders). - The described drug action on pituitary GnRH receptors is unrelated to potassium homeostasis.

Question 220: A 14-year-old boy is brought to the emergency department because of a 4-hour history of vomiting, lethargy, and confusion. Three days ago, he was treated with an over-the-counter medication for fever and runny nose. He is oriented only to person. His blood pressure is 100/70 mm Hg. Examination shows bilateral optic disc swelling and hepatomegaly. His blood glucose concentration is 65 mg/dL. Toxicology screening for serum acetaminophen is negative. The over-the-counter medication that was most likely used by this patient has which of the following additional effects?

• A. Increased partial thromboplastin time
• B. Decreased uric acid elimination
• C. Decreased expression of glycoprotein IIb/IIIa
• D. Irreversible inhibition of ATP synthase
• E. Irreversible inhibition of cyclooxygenase-1 (Correct Answer)

Explanation: ***Irreversible inhibition of cyclooxygenase-1*** - The patient's presentation is classic for **Reye syndrome** (vomiting, lethargy, confusion, cerebral edema with optic disc swelling, hepatomegaly, hypoglycemia) following recent viral illness treated with OTC medication - **Aspirin** is strongly associated with Reye syndrome in children with viral infections and should be avoided in this population - The "additional effect" of aspirin is its mechanism of action: **irreversible acetylation and inhibition of COX-1 and COX-2** - This irreversible COX inhibition also explains aspirin's antiplatelet effects (via inhibition of thromboxane A2 synthesis) and anti-inflammatory properties *Increased partial thromboplastin time* - PTT measures the intrinsic and common coagulation pathways and is prolonged by **heparin** or clotting factor deficiencies - Aspirin affects **platelet function** (prolonging bleeding time), not the coagulation cascade measured by PTT - While Reye syndrome can cause coagulopathy from liver dysfunction, increased PTT is not a direct pharmacologic effect of aspirin *Decreased uric acid elimination* - **Low-dose aspirin** (<2 g/day) can decrease renal uric acid excretion and may precipitate gout - While this is true, it is not the primary or most clinically relevant "additional effect" in this context - High-dose aspirin actually increases uric acid excretion (uricosuric effect) *Decreased expression of glycoprotein IIb/IIIa* - This is the mechanism of **GP IIb/IIIa inhibitors** (abciximab, eptifibatide, tirofiban), not aspirin - Aspirin inhibits platelet aggregation by preventing thromboxane A2 synthesis, not by affecting GP IIb/IIIa expression - These are IV antiplatelet agents used in acute coronary syndromes, not OTC medications *Irreversible inhibition of ATP synthase* - This is not a mechanism of aspirin or other common OTC fever/cold medications - While Reye syndrome involves mitochondrial dysfunction, aspirin does not directly inhibit ATP synthase - The mitochondrial injury in Reye syndrome is likely multifactorial

Question 221: A 39-year-old woman is brought to the emergency department 30 minutes after her husband found her unconscious on the living room floor. She does not report having experienced light-headedness, nausea, sweating, or visual disturbance before losing consciousness. Three weeks ago, she was diagnosed with open-angle glaucoma and began treatment with an antiglaucoma drug in the form of eye drops. She last used the eye drops 1 hour ago. Examination shows pupils of normal size that are reactive to light. An ECG shows sinus bradycardia. This patient is most likely undergoing treatment with which of the following drugs?

• A. Brimonidine
• B. Dorzolamide
• C. Latanoprost
• D. Pilocarpine
• E. Timolol (Correct Answer)

Explanation: ***Timolol*** - **Timolol** is a **non-selective beta-blocker** used to treat open-angle glaucoma by reducing aqueous humor production - Can be **systemically absorbed** from eye drops, causing cardiac side effects including **bradycardia, hypotension, and syncope** - The patient's presentation of **sudden unconsciousness without prodromal symptoms** plus **sinus bradycardia** is classic for beta-blocker toxicity - Systemic absorption is enhanced with frequent dosing and can occur even with topical ophthalmic use *Brimonidine* - **Brimonidine** is an **alpha-2 adrenergic agonist** that reduces aqueous humor production and increases uveoscleral outflow - Systemic absorption can cause CNS depression, fatigue, and hypotension, but **bradycardia is not a prominent feature** - Would not typically present with syncope as the primary manifestation *Dorzolamide* - **Dorzolamide** is a **carbonic anhydrase inhibitor** that reduces aqueous humor production - Systemic side effects include metabolic acidosis and electrolyte disturbances with chronic use - **Not associated with significant bradycardia or acute syncope** *Latanoprost* - **Latanoprost** is a **prostaglandin F2-alpha analog** that increases uveoscleral outflow to lower intraocular pressure - Side effects are primarily local (iris pigmentation, eyelash growth, conjunctival hyperemia) - Has **minimal systemic absorption** and would not cause bradycardia or syncope *Pilocarpine* - **Pilocarpine** is a **muscarinic cholinergic agonist** that causes miosis and increases trabecular outflow - Can cause cholinergic side effects including bradycardia, but typically accompanied by **miosis, salivation, lacrimation, nausea, and sweating** - Patient has **normal-sized reactive pupils** and no cholinergic symptoms, ruling this out

Question 222: An 18-year-old boy is brought to the emergency department by his parents because he suddenly collapsed while playing football. His parents mention that he had complained of dizziness while playing before, but never fainted in the middle of a game. On physical examination, the blood pressure is 130/90 mm Hg, the respirations are 15/min, and the pulse is 110/min. The chest is clear, but a systolic ejection murmur is present. The remainder of the examination revealed no significant findings. An electrocardiogram is ordered, along with an echocardiogram. He is diagnosed with hypertrophic cardiomyopathy and the physician lists all the precautions he must follow. Which of the following drugs will be on the list of contraindicated substances?

• A. Βeta-blockers
• B. Dobutamine
• C. Nitrates (Correct Answer)
• D. Calcium channel blockers
• E. Potassium channel blockers

Explanation: ***Nitrates*** - **Nitrates** cause **vasodilation**, which decreases **preload** and worsens **left ventricular outflow tract obstruction (LVOTO)** in **hypertrophic cardiomyopathy (HCM)**, potentially leading to syncope or sudden death. - Reduced preload exacerbates the dynamic obstruction, causing a critical drop in cardiac output. - **Commonly encountered substances** patients must avoid include nitroglycerin, isosorbide, and **phosphodiesterase-5 inhibitors** (sildenafil, tadalafil) which potentiate nitrate effects. - This is a critical counseling point for HCM patients in everyday life. *Beta-blockers* - **Beta-blockers** are **first-line treatment** for **hypertrophic cardiomyopathy (HCM)** as they reduce heart rate, improve diastolic filling, and decrease contractility, thereby reducing **LVOTO**. - They alleviate symptoms and reduce the risk of sudden cardiac death in HCM. *Dobutamine* - **Dobutamine** is a **beta-1 adrenergic agonist** that increases contractility and heart rate, which would worsen **LVOTO** in HCM. - While also contraindicated in HCM, dobutamine is only used in **controlled hospital settings** for stress testing or hemodynamic support, not a substance patients encounter in daily life. - The question focuses on outpatient counseling about substances to avoid in everyday situations. *Calcium channel blockers* - **Non-dihydropyridine calcium channel blockers** (verapamil, diltiazem) are used in **HCM management**, particularly in patients who cannot tolerate beta-blockers. - They improve **diastolic function** and reduce **LVOTO** by decreasing contractility and heart rate. - **Caution:** Dihydropyridines (nifedipine, amlodipine) can worsen obstruction and should be avoided. *Potassium channel blockers* - **Antiarrhythmics** like **amiodarone** (potassium channel blocker) are used in **HCM** patients for atrial or ventricular arrhythmias. - Not contraindicated; therapeutically indicated for rhythm management.

Question 223: A 58-year-old man presents to the physician due to difficulty initiating and sustaining erections for the past year. According to the patient, he has a loving wife and he is still attracted to her sexually. While he still gets an occasional erection, he has not been able to maintain an erection throughout intercourse. He no longer gets morning erections. He is happy at work and generally feels well. His past medical history is significant for angina and he takes isosorbide dinitrate as needed for exacerbations. His pulse is 80/min, respirations are 14/min, and blood pressure is 130/90 mm Hg. The physical examination is unremarkable. Nocturnal penile tumescence testing reveals the absence of erections during the night. The patient expresses a desire to resume sexual intimacy with his spouse. Which of the following is the best next step to treat this patient?

• A. Stop isosorbide dinitrate
• B. Check prolactin levels (Correct Answer)
• C. Start captopril
• D. Refer to a psychiatrist
• E. Start sildenafil

Explanation: ***Check prolactin levels*** - The absence of **morning erections** and **nocturnal penile tumescence (NPT)** indicates **organic erectile dysfunction** rather than psychogenic causes. - When organic ED is suspected, **hormonal evaluation** is an essential component of the workup. - **Hyperprolactinemia** can cause ED by suppressing **gonadotropin-releasing hormone (GnRH)**, leading to decreased testosterone levels and impaired erectile function. - While testosterone levels are often checked first, **prolactin screening** is part of standard endocrine evaluation for organic ED, particularly when other common causes have been excluded by history and physical exam. - Among the given options, this represents appropriate diagnostic workup before considering treatment. *Stop isosorbide dinitrate* - While **nitrates** like isosorbide dinitrate are contraindicated with **PDE5 inhibitors**, stopping nitrate therapy without an alternative management plan for his **angina** would be dangerous. - Abrupt discontinuation could precipitate anginal episodes or acute coronary events. - This does not address the underlying organic cause of ED demonstrated by absent nocturnal erections. *Start captopril* - **Captopril** is an **ACE inhibitor** used for hypertension and heart failure, not for erectile dysfunction. - The patient's blood pressure (130/90 mm Hg) does not mandate immediate antihypertensive therapy. - This option does not address the patient's primary concern or the organic cause of his ED. *Refer to a psychiatrist* - The patient reports being happy at work, feeling well, and maintaining **sexual attraction** to his spouse, making primary psychogenic ED unlikely. - The **absent nocturnal erections on NPT testing** objectively demonstrates an **organic etiology** rather than psychological causes. - Psychogenic ED typically shows preserved nocturnal erections; their absence here indicates organic pathology requiring medical workup. *Start sildenafil* - **Sildenafil** is a **PDE5 inhibitor** that is **absolutely contraindicated** in patients taking **nitrates** like isosorbide dinitrate. - Concurrent use can cause severe, potentially life-threatening **hypotension** due to synergistic vasodilation. - Before considering PDE5 inhibitor therapy, the patient's angina management would need to be restructured, and diagnostic workup for reversible causes of ED should be completed.

Question 224: A 36-year-old man presents with increasing shortness of breath for a month, which is aggravated while walking and climbing up the stairs. He also complains of pain and stiffness in both wrists, and the distal interphalangeal and metacarpophalangeal joints of both hands. He was diagnosed with rheumatoid arthritis 6 months ago and was started on methotrexate with some improvement. He is a lifetime non-smoker and has no history of drug abuse. The family history is insignificant for any chronic disease. The blood pressure is 135/85 mm Hg, pulse rate is 90/min, temperature is 36.9°C (98.5°F), and the respiratory rate is 22/min. Physical examination reveals short rapid breathing with fine end-inspiratory rales. An echocardiogram is normal with an ejection fraction of 55%. A chest X-ray shows diffuse bilateral reticular markings with multiple pulmonary nodules. Which of the following is the most likely cause of this patient’s lung condition?

• A. Idiopathic pulmonary fibrosis
• B. Cardiogenic pulmonary edema
• C. Granulomatous lung disease
• D. Drug-induced pulmonary disease (Correct Answer)
• E. Radiation-induced pulmonary disease

Explanation: ***Drug-induced pulmonary disease*** - The patient's recent diagnosis of **rheumatoid arthritis** and initiation of **methotrexate** are key clues, as methotrexate is a common cause of drug-induced pneumonitis. - Symptoms like **shortness of breath**, **fine inspiratory rales**, and chest X-ray findings of **bilateral reticular markings** and **pulmonary nodules** are consistent with drug-induced lung injury. *Idiopathic pulmonary fibrosis* - This condition typically affects **older adults** (over 50) and progresses slowly, which is less consistent with the patient's age and the relatively rapid onset of symptoms. - While it causes **reticular markings**, the presence of multiple **pulmonary nodules** makes it less likely. *Cardiogenic pulmonary edema* - The **normal echocardiogram** with an ejection fraction of 55% rules out significant cardiac dysfunction as the cause of pulmonary edema. - This condition would also primarily show **interstitial and alveolar edema**, not nodules or prominent reticular markings without signs of heart failure. *Granulomatous lung disease* - This category includes conditions like **sarcoidosis** or **tuberculosis**, which can cause nodules and reticular changes. - However, there are no other clinical features (e.g., hilar lymphadenopathy, erythema nodosum, or signs of infection) to specifically suggest a granulomatous process in this context, and the history of recent drug initiation is a stronger lead. *Radiation-induced pulmonary disease* - The patient has no history of **radiation exposure** to the chest, which is a prerequisite for this diagnosis. - This condition typically occurs within 6 months of radiation therapy and presents with symptoms localized to the irradiated field.

Question 225: A 25-year-old man is brought to the emergency department by his girlfriend for a nosebleed. Pinching the nose for the past hour has not stopped the bleeding. For the past several months, he has had recurring nosebleeds that resolved with pressure. He has no history of hypertension or trauma. He has asthma that is well controlled with an albuterol inhaler. He has intermittent tension headaches for which he takes aspirin. His temperature is 37.9°C (100.2°F), pulse is 114/min, and blood pressure is 160/102 mm Hg. Physical examination shows active bleeding from both nostrils. Pupil size is 6 mm bilaterally in bright light. The lungs are clear to auscultation. The hemoglobin concentration is 13.5 g/dL, prothrombin time is 12 seconds, partial thromboplastin time is 35 seconds, and platelet count is 345,000/mm3. Which of the following is the most likely explanation for this patient's symptoms?

• A. Hypertension
• B. Adverse effect of medication
• C. Cocaine use (Correct Answer)
• D. Hereditary hemorrhagic telangiectasia
• E. Nasopharyngeal angiofibroma

Explanation: ***Cocaine use*** - Cocaine is a **vasoconstrictor** that causes localized **ischemia** and tissue necrosis, especially in the nasal septum, leading to frequent and severe epistaxis. - The patient's **dilated pupils (mydriasis)** and acute hypertension (BP 160/102 mm Hg) are also consistent with stimulant use, such as cocaine. *Hypertension* - While the patient's blood pressure is elevated, **hypertension** is more likely a contributing factor or a symptom of acute stress/substance use rather than the primary cause of recurrent, refractory nosebleeds in a young patient. - Recurrent epistaxis caused solely by hypertension typically occurs in older individuals with poorly controlled chronic hypertension, which is not the case here. *Adverse effect of medication* - The patient takes **aspirin** for headaches, which can inhibit **platelet aggregation** and worsen bleeding. However, this alone would not typically explain chronic, recurrent, and severe nosebleeds in the absence of other bleeding diatheses. - The patient's normal platelet count, PT, and PTT suggest that a general coagulation disorder or significant medication-induced coagulopathy is unlikely to be the primary cause. *Hereditary hemorrhagic telangiectasia* - This genetic disorder (also known as **Osler-Weber-Rendu disease**) causes **fragile blood vessels** (telangiectasias) often in the nasal mucosa, leading to recurrent epistaxis. It is often associated with family history. - While it can cause recurrent nosebleeds, the additional features like acute hypertension and mydriasis strongly point away from HHT as the primary cause in this acute presentation. *Nasopharyngeal angiofibroma* - This is a highly **vascular tumor** that typically presents in adolescent males with recurrent epistaxis, **nasal obstruction**, and potential for local invasion. - Though it causes severe nosebleeds, the acute signs of **mydriasis** and **hypertension** are not direct symptoms of an angiofibroma and are more indicative of stimulant use.

Question 226: A middle aged man is brought in by emergency medical services after being found unconscious, lying on the street next to an empty bottle of vodka. His past medical history is unknown. Upon evaluation, he opens his eyes spontaneously and is able to obey commands. After peripheral access is obtained, IV normal saline and glucose are administered. Suddenly, the patient becomes confused and agitated. Horizontal nystagmus is noted on exam. This acute presentation was likely caused by a deficiency in which of the following?

• A. Vitamin B6
• B. Vitamin B12
• C. Vitamin B1 (Correct Answer)
• D. Vitamin B9
• E. Vitamin A

Explanation: ***Vitamin B1*** - The patient exhibits classic signs of **Wernicke-Korsakoff syndrome**, caused by **thiamine (Vitamin B1) deficiency**, commonly seen in chronic alcoholics. - The sudden neurological deterioration (confusion, agitation, nystagmus) after intravenous **glucose administration** without prior thiamine repletion is characteristic, as glucose metabolism depletes remaining thiamine reserves. *Vitamin B6* - **Pyridoxine (Vitamin B6) deficiency** can cause peripheral neuropathy, sideroblastic anemia, and seizures, but typically not acute encephalopathy or nystagmus exacerbated by glucose. - It is less commonly associated with acute neurological decline in the context of chronic alcoholism compared to thiamine. *Vitamin B12* - **Cobalamin (Vitamin B12) deficiency** can lead to megaloblastic anemia and peripheral neuropathy, and in severe cases, subacute combined degeneration of the spinal cord. - However, it does not typically present with acute confusion, nystagmus, and agitation, especially not exacerbated by glucose administration. *Vitamin B9* - **Folate (Vitamin B9) deficiency** typically causes megaloblastic anemia and, in some cases, neurological symptoms due to high homocysteine levels, but not the acute constellation of symptoms described. - Like B12 deficiency, it is not acutely worsened by glucose administration. *Vitamin A* - **Vitamin A deficiency** can lead to night blindness, xerophthalmia, and immune dysfunction. - It does not cause acute neurological symptoms such as confusion, agitation, or nystagmus, and is unrelated to glucose metabolism in this context.

Question 227: A 32-year-old male patient presents to the emergency department after being found down on a sidewalk. He is able to be aroused but seems confused and confabulates extensively during history taking. Physical exam of the eye reveals nystagmus and the patient is unable to complete finger-to-nose or heel-to-shin testing. Chart review shows that the patient is well known for a long history of alcohol abuse. Which of the following substances should be administered prior to giving IV glucose to this patient?

• A. Vitamin B12
• B. Vitamin B1 (Correct Answer)
• C. Vitamin C
• D. Fomepizole
• E. Folate

Explanation: ***Vitamin B1*** - This patient presents with signs of **Wernicke-Korsakoff syndrome**, characterized by **nystagmus**, **ataxia** (difficulty with finger-to-nose and heel-to-shin), and **global confusion with confabulation**, in the setting of chronic **alcohol abuse**. - **Thiamine (Vitamin B1) deficiency** is the underlying cause, and administering IV glucose before thiamine can precipitate or worsen Wernicke encephalopathy by increasing glucose metabolism, which further depletes the already low thiamine stores. *Vitamin B12* - While **alcohol abuse** can lead to various nutritional deficiencies, **Vitamin B12 deficiency** is more commonly associated with macrocytic anemia and neurological symptoms like peripheral neuropathy or subacute combined degeneration, not the acute neurological picture described here. - There is no specific indication to administer B12 prior to glucose in this context. *Vitamin C* - **Vitamin C (ascorbic acid) deficiency** causes **scurvy**, presenting with bleeding gums, petechiae, and poor wound healing. - It is not indicated for the neurological symptoms observed in this patient. *Fomepizole* - **Fomepizole** is an antidote used for **methanol or ethylene glycol poisoning** by inhibiting alcohol dehydrogenase. - There is no information in the patient's presentation to suggest methanol or ethylene glycol toxicity. *Folate* - **Folate deficiency** is common in alcoholics and can cause **macrocytic anemia** and contribute to neurological issues like peripheral neuropathy. - However, it does not address the acute neurological syndrome described (Wernicke-Korsakoff) and its administration is not prioritized before glucose in this specific acute scenario.

Question 228: A 64-year-old female with a history of end-stage renal disease presents to her primary care physician complaining of weakness. She reports a six-month history of progressive weakness accompanied by occasional dull aching pain in her arms, legs, and lower back. She has also started to increase her fiber intake because of occasional strained bowel movements. Her past medical history is notable for poorly controlled diabetes, major depressive disorder, and obesity. She takes insulin and sertraline. She has a twenty pack-year smoking history and drinks alcohol socially. Her temperature is 98.5°F (36.9°C), blood pressure is 130/85 mmHg, pulse is 80/min, and respirations are 16/min. Laboratory findings are shown below: Serum: Na+: 138 mEq/L Cl-: 99 mEq/L K+: 3.9 mEq/L HCO3-: 26 mEq/L BUN: 20 mg/dL Glucose: 140 mg/dL Creatinine: 2.0 mg/dL Parathyroid hormone: 720 µU/mL Ca2+: 11.1 mg/dL Phosphorus (inorganic): 4.8 mg/dl A medication with which of the following mechanisms of action is most likely indicated to address this patient’s symptoms?

• A. Aldosterone receptor antagonist
• B. Carbonic anhydrase inhibitor
• C. Osteoprotegerin analog
• D. Calcimimetic agent (Correct Answer)
• E. Sodium chloride cotransporter antagonist

Explanation: ***Calcimimetic agent*** - The patient's presentation with **end-stage renal disease (ESRD)**, elevated **parathyroid hormone (PTH)**, and elevated **calcium** and **phosphate** indicates **secondary hyperparathyroidism** with associated **renal osteodystrophy**. - **Calcimimetic agents** like cinacalcet increase the sensitivity of the **calcium-sensing receptor** on the parathyroid gland, reducing PTH secretion and ultimately lowering calcium and phosphate levels. *Aldosterone receptor antagonist* - An **aldosterone receptor antagonist** (e.g., spironolactone) is primarily used to treat **heart failure**, **hypertension**, and **hyperaldosteronism**. - While the patient has elevated blood pressure, there is no direct indication for hyperaldosteronism, and this class of drug would not directly address her metabolic bone disease. *Carbonic anhydrase inhibitor* - A **carbonic anhydrase inhibitor** (e.g., acetazolamide) is used for conditions like **glaucoma**, **metabolic alkalosis**, or **high-altitude sickness**. - It works by inhibiting carbonic anhydrase, leading to bicarbonate diuresis and fluid/electrolyte changes, which is not relevant to this patient's primary issue of secondary hyperparathyroidism. *Osteoprotegerin analog* - An **osteoprotegerin (OPG) analog**, such as denosumab, is used to treat **osteoporosis** by inhibiting **osteoclast activity**. - While the patient has bone pain, an OPG analog would not address the underlying pathology of **secondary hyperparathyroidism** as effectively as a calcimimetic, which directly targets PTH overproduction. *Sodium chloride cotransporter antagonist* - A **sodium chloride cotransporter antagonist** (e.g., thiazide diuretics, loop diuretics) primarily targets hypertension and edema. - These agents alter kidney electrolyte handling, but they are not the primary treatment for **secondary hyperparathyroidism** or its associated metabolic bone disease in ESRD.

Question 229: A 30-year-old man with history of intravenous drug use and methamphetamine-associated chronic thromboembolic pulmonary hypertension (CTEPH) is brought to the emergency department by his girlfriend for worsening abdominal pain and fevers. The patient said the pain was initially around his umbilicus, but he is now experiencing intense tenderness near his groin. He was initially prescribed rivaroxaban, but due to insurance issues, he was switched to warfarin for management of CTEPH two weeks ago. His temperature is 102°F (38.9°C), blood pressure is 95/60 mmHg, pulse is 95/min, respirations are 22/min. He states that his blood pressure usually runs low. His physical exam is notable for an unremarkable cardiac exam, bibasilar crackles, and RLQ tenderness with rebound tenderness when the LLQ is palpated. Laboratory results are shown below: Hemoglobin: 11 g/dL Hematocrit: 35 % Leukocyte count: 16,000/mm^3 with normal differential Platelet count: 190,000/mm^3 Serum: Na+: 137 mEq/L Cl-: 100 mEq/L K+: 3.7 mEq/L HCO3-: 23 mEq/L BUN: 40 mg/dL Glucose: 110 mg/dL Creatinine: 0.8 mg/dL Ca2+: 9.1 mg/dL AST: 34 U/L ALT: 45 U/L International normalized ratio (INR): 6.2 Prothrombin time (PT): 40 seconds Partial thromboplastin time: 70 seconds Blood type: O Rhesus: Positive Antibody screen: Negative A clinical diagnosis is made and supported by the surgical consult team in lieu of imaging. The next operating room for an add-on procedure will not be available for another 5 hours. Appropriate medical therapy is initiated. What is the best next step for surgical optimization?

• A. Fresh frozen plasma
• B. Prothrombin complex concentrate (Correct Answer)
• C. Protamine
• D. Do nothing
• E. Phytonadione

Explanation: ***Prothrombin complex concentrate*** - The patient has **warfarin over-anticoagulation (INR 6.2)** and requires **emergency surgery** for suspected appendicitis with peritonitis, necessitating rapid reversal of anticoagulation. - **Prothrombin complex concentrate (4-factor PCC)** contains concentrated factors II, VII, IX, and X (and proteins C & S), providing **rapid and complete reversal** of warfarin's anticoagulant effects within minutes, which is crucial in emergency surgical situations. - PCC is **preferred over FFP** per current guidelines (ACCP, AHA) for urgent warfarin reversal due to faster administration, smaller volume, and more predictable INR correction. - **Vitamin K should be administered concurrently** to provide sustained reversal (takes 12-24 hours), but PCC is essential for immediate correction before surgery. *Fresh frozen plasma* - While FFP contains all coagulation factors and can reverse warfarin, it requires **larger volumes (4-6 units)**, takes longer to thaw and administer, and is **less effective** in rapidly correcting INR to normal range compared to PCC. - Administering large volumes of FFP can lead to **volume overload** (especially concerning in CTEPH patients) and **transfusion-related complications**. - PCC is superior for urgent reversal in patients requiring emergency surgery. *Protamine* - **Protamine** is used to reverse the anticoagulant effects of **unfractionated heparin** (and partially reverses low molecular weight heparin), not warfarin. - It would have **no effect** on the patient's elevated INR due to warfarin use. - Note: The elevated PTT (70s) in this case may suggest concurrent heparin bridging therapy or other factor deficiency, but the primary issue requiring reversal is the critical warfarin over-anticoagulation. *Do nothing* - This patient has **surgical peritonitis** (appendicitis with peritoneal signs) and requires emergency surgery with an INR of 6.2, creating **high risk of surgical bleeding**. - Proceeding to surgery without reversing anticoagulation would result in **life-threatening hemorrhage**. - Delaying treatment would likely result in further **clinical deterioration** with possible perforation and sepsis. *Phytonadione* - **Phytonadione (Vitamin K)** reverses warfarin's effects by restoring hepatic synthesis of vitamin K-dependent clotting factors, but its onset of action is **slow (12-24 hours for full effect)**, making it unsuitable as the sole agent for immediate reversal in patients requiring emergent surgery. - While **Vitamin K should be administered** alongside PCC to provide sustained reversal, it is **not sufficient alone** for rapid correction in surgical emergencies.

Question 230: A 74-year-old female with a history of lung adenocarcinoma status post lobectomy, chronic obstructive pulmonary disease, congestive heart failure, and diabetic nephropathy presents to clinic complaining of hearing loss. Over the last week, she has noticed that she has had difficulty hearing the telephone or the television. When sitting in a quiet room, she also has noticed a high-pitched ringing in her ears. She denies any vertigo or disequilibrium. Further review reveals ongoing dyspnea on exertion and worsening cough productive of whitish sputum for the last month. The patient was recently discharged from the hospital for a congestive heart failure exacerbation. She lives alone and keeps track of all her medications, but admits that sometimes she gets confused. She has a 20 pack-year tobacco history. Her home medications include aspirin, lisinopril, furosemide, short-acting insulin, and a long-acting ß-agonist inhaler. Two weeks ago she completed a course of salvage chemotherapy with docetaxel and cisplatin. Her tympanic membranes are clear and intact with no signs of trauma or impaction. Auditory testing reveals bilateral hearing impairment to a whispered voice. The Weber test is non-lateralizing. Rinne test is unrevealing. Hemoglobin: 11.8 g/dL Leukocyte count: 9,400/mm^3 Platelet count: 450,000/mm^3 Serum (Present visit): Na+: 134 mEq/L K+: 3.8 mEq/L Cl-: 95 mEq/L HCO3-: 30 mEq/L BUN: 45 mg/dL Creatinine: 2.1 mg/dL Serum (1 month ago): Na+: 135 mEq/L K+: 4.6 mEq/L Cl-: 102 mEq/L HCO3-: 24 mEq/L BUN: 22 mg/dL Creatinine: 1.2 mg/dL On follow up visit two weeks later, the patient's hearing has significantly improved. Which of the following is the most likely cause of her initial hearing loss?

• A. Cisplatin
• B. Furosemide (Correct Answer)
• C. Lisinopril
• D. Docetaxel
• E. Aspirin

Explanation: ***Furosemide*** - The patient's **renal function has worsened** significantly, indicated by the rise in **BUN and creatinine**, making her more susceptible to **ototoxicity** from furosemide due to reduced drug clearance. - Her recent discharge for **congestive heart failure exacerbation** suggests she was likely on higher doses or had increased exposure to furosemide during hospitalization. - The **significant improvement in hearing within two weeks** is the key diagnostic feature, as **furosemide-induced ototoxicity is reversible** when the drug is discontinued or the dose is reduced, unlike other ototoxic agents. - Loop diuretics like furosemide cause ototoxicity by disrupting the ionic balance in the endolymph of the inner ear, but this effect is typically **transient and reversible**. *Cisplatin* - **Cisplatin** is a known **ototoxic chemotherapy agent**, and its timing (two weeks post-treatment) fits with the onset of symptoms. - However, cisplatin-induced ototoxicity is typically **irreversible and permanent**, involving destruction of the **outer hair cells** of the cochlea. - The **rapid improvement in the patient's hearing** within two weeks makes cisplatin an unlikely cause, as its ototoxicity results in persistent, dose-dependent bilateral sensorineural hearing loss. *Lisinopril* - **Lisinopril**, an **ACE inhibitor**, is not associated with **ototoxicity** or hearing loss. - Its primary mechanisms of action are related to **blood pressure regulation** and **cardiovascular remodeling**, with no direct known impact on auditory function. *Docetaxel* - **Docetaxel** is a **taxane chemotherapy drug** that can cause neurological side effects, including **peripheral neuropathy**, but it is not commonly associated with **ototoxicity** or hearing loss. - The rapid resolution of hearing loss makes ototoxicity from docetaxel improbable. *Aspirin* - **Aspirin** can cause **reversible ototoxicity** (tinnitus and hearing loss), particularly at high doses (typically >3 g/day) in a condition called **salicylism**. - However, the patient's hearing loss is more directly attributable to **furosemide** given the context of recent CHF exacerbation requiring aggressive diuretic therapy and worsening renal function that would increase furosemide levels.

Question 231: A 23-year-old Caucasian male presents to the emergency department with a persistent penile erection for the last 6 hours. He recently began outpatient treatment for depression with associated insomnia. He traveled to Mexico 5 months ago. His medical history is otherwise unremarkable. Which of the following is the most likely precipitating factor for priapism in this patient?

• A. Depression treatment with venlafaxine
• B. Infection acquired in Mexico
• C. Depression treatment with trazodone (Correct Answer)
• D. Sickle cell disease
• E. Depression treatment with bupropion

Explanation: ***Depression treatment with trazodone*** - **Trazodone** is well-known to cause **priapism** as a rare but serious side effect (incidence ~1 in 6,000), particularly at higher doses. - The mechanism involves **α1-adrenergic blockade**, which impairs detumescence of the corpus cavernosum. - Trazodone is commonly prescribed for **depression with insomnia** due to its sedating properties, which directly aligns with this patient's presentation. - The patient's recent initiation of depression treatment, combined with the symptom of priapism, strongly points to this medication. *Depression treatment with venlafaxine* - While venlafaxine is an antidepressant, priapism is **not a commonly associated side effect** with this medication. - Serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine are rarely implicated in priapism. - Venlafaxine is less commonly used specifically for insomnia. *Infection acquired in Mexico* - Although travel can expose individuals to various infections, there is **no direct link between recent travel to Mexico and priapism** in an otherwise healthy individual. - Furthermore, priapism due to infection is less likely to be the sole initial symptom without other signs of systemic illness. *Sickle cell disease* - **Sickle cell disease** is a common cause of priapism, especially in young males, due to **vaso-occlusion** in the penile microvasculature. - However, the patient is **Caucasian** and his medical history is described as "otherwise unremarkable," making a severe underlying condition like sickle cell disease less likely without prior diagnosis or symptoms. - Sickle cell disease would typically be diagnosed in childhood with recurrent vaso-occlusive crises. *Depression treatment with bupropion* - **Bupropion** is an antidepressant that works via dopamine and norepinephrine reuptake inhibition, and priapism is **not a recognized side effect** of this drug. - It does not typically interfere with the penile erection mechanisms in a way that would cause priapism. - Bupropion is generally activating rather than sedating, making it less ideal for patients with insomnia.

Question 232: A 42-year-old woman presents to the emergency department with pain in her abdomen. She was eating dinner when her symptoms began. Upon presentation, her symptoms have resolved. She has a past medical history of type II diabetes mellitus, hypertension, heavy menses, morbid obesity, and constipation. Her current medications include atorvastatin, lisinopril, insulin, metformin, aspirin, ibuprofen, and oral contraceptive pills. She has presented to the ED for similar complaints in the past. Her temperature is 98.1°F (36.7°C), blood pressure is 160/97 mmHg, pulse is 84/min, respirations are 15/min, and oxygen saturation is 98% on room air. Physical exam and abdominal exam are unremarkable. The patient is notably obese and weighs 315 pounds. Cardiac and pulmonary exams are within normal limits. Which of the following is the best prophylactic measure for this patient?

• A. Ibuprofen
• B. Antibiotics, IV fluids, and NPO
• C. Gastric bypass surgery
• D. Ursodeoxycholic acid (Correct Answer)
• E. Strict diet and rapid weight loss in the next month

Explanation: ***Ursodeoxycholic acid*** - The patient's presentation with sporadic abdominal pain after eating, along with risk factors like **obesity**, **female sex**, and **oral contraceptive use**, is highly suggestive of **biliary colic** due to gallstones. Ursodeoxycholic acid can dissolve small cholesterol gallstones and prevent their formation, serving as a prophylactic measure. - This medication is particularly useful in patients who are not surgical candidates or for preventing gallstone formation during **rapid weight loss**, though its primary role here is to manage existing or recurrent symptoms without immediate surgical intervention. *Ibuprofen* - Ibuprofen is an **NSAID** used for symptomatic pain relief and inflammation, but it does not address the underlying cause of gallstone formation or associated pain. - Chronic use of NSAIDs like ibuprofen can have **gastrointestinal side effects**, such as gastritis or ulcers, which can mimic or exacerbate abdominal pain. *Antibiotics, IV fluids, and NPO* - This regimen is typically used for acute cholecystitis, cholangitis, or pancreatitis, which are more severe complications of gallstone disease, often presenting with fever, elevated inflammatory markers, and persistent pain. - The patient's symptoms **resolved spontaneously**, and she is afebrile with normal vital signs, indicating that such aggressive acute management is not currently needed. *Gastric bypass surgery* - While gastric bypass surgery can lead to significant weight loss and potentially improve some of the patient's comorbidities, rapid weight loss itself can **increase the risk of gallstone formation**. - Without addressing the gallstone risk specifically, gastric bypass alone would not be the best prophylactic measure for the gallbladder issues, and ursodeoxycholic acid might even be prescribed **pre- or post-operatively** to prevent gallstone complications. *Strict diet and rapid weight loss in the next month* - **Rapid weight loss**, particularly at a rate greater than 1-1.5 kg per week, is a well-known risk factor for the formation of gallstones and can precipitate biliary colic. - While weight loss is beneficial for her other comorbidities (diabetes, hypertension, morbid obesity), a **strict and rapid diet** without prophylactic measures like ursodeoxycholic acid could worsen or induce gallstone-related symptoms rather than prevent them.

Question 233: A 3-year-old boy presents with progressive lethargy and confusion over the last 5 days. He lives with his parents in a home that was built in the early 1900s. His parents report that "his tummy has been hurting" for the last 3 weeks and that he is constipated. He eats and drinks normally, but occasionally tries things that are not food. Abdominal exam shows no focal tenderness. Hemoglobin is 8 g/dL and hematocrit is 24%. Venous lead level is 55 ug/dL. Which therapy is most appropriate for this boy's condition?

• A. Succimer (Correct Answer)
• B. Psyllium
• C. Folic acid
• D. Docusate
• E. Deferoxamine

Explanation: ***Succimer*** - With a venous lead level of 55 ug/dL and neurological symptoms (lethargy, confusion), **chelation therapy** is indicated. - **Succimer** (**2,3-dimercaptosuccinic acid** or **DMSA**) is an oral chelating agent commonly used for lead poisoning in children with levels between 45-70 ug/dL, as it is effective and has fewer side effects than parenteral options. *Psyllium* - **Psyllium** is a **bulk-forming laxative** used to treat constipation, which is a symptom of lead poisoning in this patient. - However, addressing the lead toxicity with chelation is paramount; constipation is a secondary issue that would be managed after initial stabilization or concurrently with chelation if severe. *Folic acid* - **Folic acid** is used to treat **folate deficiency anemia**. While the patient has anemia, it is a microcytic anemia secondary to lead poisoning interfering with heme synthesis, not folate deficiency. - Supplementation with folic acid would not address the underlying **lead toxicity** or the anemia caused by it. *Docusate* - **Docusate** is a **stool softener** used to relieve constipation, a symptom this patient experiences due to lead poisoning. - Similar to psyllium, this treats a symptom rather than the root cause (**lead poisoning**), which requires specific chelation therapy due to the high lead levels and neurological involvement. *Deferoxamine* - **Deferoxamine** is a chelating agent primarily used for **iron overload** (e.g., in thalassemia, hemochromatosis). - It is **not indicated** for lead poisoning and would be ineffective and potentially harmful in this context.

Question 234: A 38-year-old man presents to the emergency department with chest pain and difficulty breathing for the last 3 hours. He denies cough, nasal discharge or congestion, sneezing, and palpitations. There is no history of recent surgery or hospitalization but he mentions that he was diagnosed with a psychiatric disorder 6 months ago and has been on medication, as prescribed by the psychiatrist. His past medical history is negative for any cardiac or respiratory conditions. His temperature is 38.1°C (100.5°F), pulse is 112/min, blood pressure is 128/84 mm Hg, and respiratory rate is 24/min. Auscultation of the chest reveals crackles and a decreased intensity of breath sounds over the right infrascapular region. The heart sounds are normal and there are no murmurs. His plasma D-dimer level is elevated. A contrast-enhanced computed tomography (CT) of the chest shows a filling defect in 2 segmental pulmonary arteries on the right side. Which of the following medications is most likely to cause the condition found in this man?

• A. Alprazolam
• B. Lithium
• C. Haloperidol
• D. Chlorpromazine (Correct Answer)
• E. Valproic acid

Explanation: ***Chlorpromazine*** - The patient presents with symptoms and CT findings consistent with **pulmonary embolism (PE)** (chest pain, dyspnea, crackles, decreased breath sounds, elevated D-dimer, and filling defects in pulmonary arteries). - **Chlorpromazine** is a **low-potency typical antipsychotic** that increases **venous thromboembolism (VTE)** risk through multiple mechanisms: marked **sedation** leading to immobility, **orthostatic hypotension**, **weight gain**, **hyperprolactinemia**, and direct prothrombotic effects. - Among typical antipsychotics, **low-potency agents like chlorpromazine** cause more sedation and immobility than high-potency agents, conferring higher VTE risk. *Alprazolam* - **Alprazolam** is a benzodiazepine used for anxiety and panic disorders. - It is **not associated** with increased risk of **venous thromboembolism** or pulmonary embolism. *Lithium* - **Lithium** is a mood stabilizer used for bipolar disorder. - While it has various side effects (tremor, polyuria, thyroid dysfunction), **VTE or PE is not a recognized adverse effect**. *Haloperidol* - **Haloperidol** is a **high-potency typical antipsychotic** that also carries some VTE risk. - However, high-potency antipsychotics cause **less sedation** and orthostatic hypotension compared to low-potency agents like chlorpromazine, resulting in **relatively lower VTE risk**. - The patient's medication is more likely to be **chlorpromazine** given the clinical context. *Valproic acid* - **Valproic acid** is an anticonvulsant and mood stabilizer. - Known side effects include **hepatotoxicity**, **pancreatitis**, and **thrombocytopenia**, but **not an increased risk of thromboembolism** or PE.

Question 235: A 35-year-old woman comes to the physician accompanied by her husband after he started noticing strange behavior. He first noticed her talking to herself 8 months ago. For the past 6 months, she has refused to eat any packaged foods out of fear that the government is trying to poison her. She has no significant past medical history. She smoked marijuana in college but has not smoked any since. She appears restless. Mental status examination shows a flat affect. Her speech is clear, but her thought process is disorganized with many loose associations. The patient is diagnosed with schizophrenia and started on olanzapine. This patient is most likely to experience which of the following adverse effects?

• A. Dyslipidemia (Correct Answer)
• B. Diabetes insipidus
• C. Agranulocytosis
• D. Myoglobinuria
• E. Seizures

Explanation: ***Dyslipidemia*** - **Olanzapine** is a **second-generation antipsychotic** commonly associated with significant **metabolic side effects**, including **weight gain**, **dyslipidemia**, and **insulin resistance**. - These metabolic disturbances increase the risk of cardiovascular disease. *Diabetes insipidus* - This is a rare side effect, not typically associated with **olanzapine** or other **second-generation antipsychotics**. - **Lithium** is an antimanic agent that can cause **nephrogenic diabetes insipidus**, but it is not relevant here. *Agranulocytosis* - While a serious side effect of some antipsychotics, **agranulocytosis** is most notably associated with **clozapine**, - **Olanzapine** has a much lower risk of causing **agranulocytosis** compared to clozapine. *Myoglobinuria* - **Myoglobinuria** is associated with conditions like significant muscle damage (e.g., rhabdomyolysis). - It is not a direct or common adverse effect of **olanzapine** therapy. *Seizures* - While some antipsychotics can lower the **seizure threshold**, **olanzapine** generally has a relatively low risk of inducing seizures. - The risk is higher with certain other antipsychotics, particularly at high doses, or in patients with pre-existing seizure disorders.

Question 236: A 58-year-old African-American man with a history of congestive heart failure presents to the emergency room with headache, frequent vomiting, diarrhea, anorexia, and heart palpitations. He is taking a drug that binds the sodium-potassium pump in myocytes. EKG reveals ventricular dysrhythmia. Which of the following is likely also present in the patient?

• A. Angioedema
• B. Changes in color vision (Correct Answer)
• C. Bronchoconstriction
• D. Cough
• E. Decreased PR interval

Explanation: ***Changes in color vision*** - The patient's symptoms (headache, vomiting, diarrhea, anorexia, heart palpitations, ventricular dysrhythmia) and the medication (**cardiac glycoside, like digoxin**) that binds the **sodium-potassium pump** are classic signs of **digoxin toxicity**. - **Yellow-green vision**, known as xanthopsia, is a highly characteristic and specific visual disturbance associated with digoxin toxicity, often described as seeing halos around lights. *Angioedema* - **Angioedema** is an adverse effect commonly associated with **ACE inhibitors** due to their impact on bradykinin metabolism, which is not the drug class described. - This symptom is unrelated to the mechanism of a sodium-potassium pump inhibitor or cardiac glycoside toxicity. *Bronchoconstriction* - **Bronchoconstriction** is a common side effect of **beta-blockers**, especially in patients with reactive airway disease, but not directly linked to cardiac glycosides. - There is no direct mechanism by which a drug binding the sodium-potassium pump would cause airway narrowing. *Cough* - A persistent, dry **cough** is a well-known side effect of **ACE inhibitors**, which increase bradykinin levels. - This symptom is not characteristic of digoxin toxicity or the action of a sodium-potassium pump inhibitor. *Decreased PR interval* - **Digoxin** typically works by **slowing AV nodal conduction**, which would lengthen, not decrease, the **PR interval** (if it were to change significantly due to toxicity, it would be prolongation or AV block). - A decreased PR interval can be seen in conditions like **Wolff-Parkinson-White syndrome**, or a rapid heart rate.

Question 237: A 38-year-old woman applies a PABA sunscreen to her skin before going to the beach. Which type(s) of ultraviolet light will it protect her against?

• A. UVA and UVB
• B. UVB and UVC
• C. UVB (Correct Answer)
• D. UVA
• E. UVC

Explanation: ***UVB*** - **Para-aminobenzoic acid (PABA)** and its derivatives primarily absorb **UVB radiation** (290-320 nm), which is responsible for sunburn and erythema. - PABA-containing sunscreens are effective at preventing the acute effects of sun exposure like sunburn caused by UVB. - Traditional PABA sunscreens are primarily effective against **UVB only**, not broad-spectrum. *UVA and UVB* - While some modern sunscreens offer broad-spectrum protection against both UVA and UVB, traditional PABA sunscreens are primarily effective against **UVB only**. - **UVA filters** (e.g., avobenzone, zinc oxide, titanium dioxide) are needed in addition to PABA to achieve protection against both types of radiation. *UVB and UVC* - PABA sunscreens protect against **UVB**, but **UVC radiation** (100-280 nm) is mostly blocked by the Earth's ozone layer and does not reach the Earth's surface. - Sunscreens are not typically formulated to protect against UVC, as it is not a clinical concern for typical sun exposure. *UVA* - PABA is **not effective** at significantly absorbing or blocking **UVA radiation** (320-400 nm), which is primarily associated with photoaging, deeper skin damage, and tanning. - Protection against UVA requires different chemical filters (avobenzone, ecamsule) or physical blockers (zinc oxide, titanium dioxide). *UVC* - **UVC radiation** does not reach the Earth's surface due to complete absorption by the ozone layer, making protection against it unnecessary for sunscreen formulations. - Sunscreens, including those containing PABA, are not designed to filter UVC as it poses no risk in normal outdoor settings.

Question 238: A 59-year-old male with history of hypertension presents to your clinic for achy, stiff joints for the last several months. He states that he feels stiff in the morning, particularly in his shoulders, neck, and hips. Occasionally, the aches travel to his elbows and knees. His review of systems is positive for low-grade fever, tiredness and decreased appetite. On physical exam, there is decreased active and passive movements of his shoulders and hips secondary to pain without any obvious deformities or joint swelling. His laboratory tests are notable for an ESR of 52 mm/hr (normal for males: 0-22 mm/hr). What is the best treatment in management?

• A. Corticosteroid (Correct Answer)
• B. Bisphosphonate
• C. Methotrexate
• D. Nonsteroidal antiinflammatory agent
• E. Hyaluronic acid

Explanation: ***Corticosteroid*** - The patient's symptoms (aching, stiff joints in shoulders, neck, and hips, morning stiffness, fever, fatigue, and elevated **ESR**) are highly suggestive of **polymyalgia rheumatica (PMR)**. - **Corticosteroids** are the first-line and most effective treatment for PMR, leading to rapid symptomatic relief. *Bisphosphonate* - **Bisphosphonates** are primarily used to treat and prevent **osteoporosis** by reducing bone resorption. - They have no direct role in the anti-inflammatory management of conditions like polymyalgia rheumatica. *Methotrexate* - **Methotrexate** is a **disease-modifying antirheumatic drug (DMARD)** often used in conditions like **rheumatoid arthritis** or as a corticosteroid-sparing agent in some autoimmune diseases. - It is not the initial treatment of choice for polymyalgia rheumatica, as corticosteroids provide faster and more definitive relief. *Nonsteroidal antiinflammatory agent* - **NSAIDs** can provide some symptomatic relief for mild musculoskeletal pain, but they are generally ineffective for the systemic inflammation seen in **polymyalgia rheumatica**. - They do not address the underlying inflammatory process and are not considered adequate treatment for PMR. *Hyaluronic acid* - **Hyaluronic acid injections** are used to treat **osteoarthritis**, primarily in the knee, to lubricate the joint and reduce pain. - This treatment is for joint degeneration and has no role in the systemic inflammatory condition of polymyalgia rheumatica.

Question 239: A 63-year-old man with a history of stage 4 chronic kidney disease (CKD) has started to develop refractory anemia. He denies any personal history of blood clots in his past, but he says that his mother has also had to be treated for deep venous thromboembolism in the past. His past medical history is significant for diabetes mellitus type 2, hypertension, non-seminomatous testicular cancer, and hypercholesterolemia. He currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and he currently denies any illicit drug use. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 87/min, and respiratory rate 17/min. On physical examination, the pulses are bounding, the complexion is pale, but breath sounds remain clear. Oxygen saturation was initially 91% on room air, with a new oxygen requirement of 2 L by nasal cannula. His primary care physician refers him to a hematologist, who is considering initiating the erythropoietin-stimulating agent (ESA), darbepoetin. Which of the following is true regarding the use of ESA?

• A. ESAs show efficacy with low iron levels
• B. ESAs can improve survival in patients with breast and cervical cancers
• C. ESAs are generally initiated when the hemoglobin level is < 10 g/dL (Correct Answer)
• D. The highest-tolerated dose should be used in patients with chronic kidney disease
• E. ESAs are utilized in patients receiving myelosuppressive chemotherapy with an anticipated curative outcome

Explanation: ***ESAs are generally initiated when the hemoglobin level is < 10 g/dL*** - Clinical guidelines recommend **considering** erythropoietin-stimulating agents (ESAs) when the hemoglobin level falls below **10 g/dL** to manage anemia in chronic kidney disease, balancing benefits and risks. - Using ESAs at higher hemoglobin targets (e.g., >11.5 g/dL) has been associated with increased risks of **cardiovascular events**, **stroke**, and **thrombosis**. - Treatment decisions should be individualized, considering symptoms, transfusion requirements, and patient preferences. *ESAs show efficacy with low iron levels* - **Iron deficiency** is a common cause of **ESA hyporesponsiveness**, meaning ESAs are less effective when iron stores are low. - Adequate **iron supplementation** is crucial before and during ESA therapy to maximize treatment efficacy and reduce the required ESA dose. *ESAs can improve survival in patients with breast and cervical cancers* - ESAs have shown **no survival benefit** and may even worsen outcomes in patients with certain cancers, including **breast** and **cervical cancers**. - Their use in cancer patients is generally restricted to managing **chemotherapy-induced anemia** to avoid transfusions, not to improve cancer-specific survival. *The highest-tolerated dose should be used in patients with chronic kidney disease* - The goal in CKD patients is to use the **lowest effective ESA dose** to achieve and maintain a hemoglobin level sufficient to avoid transfusions, typically between 10 and 11.5 g/dL. - Using the highest-tolerated dose is **not recommended** due to increased risks of cardiovascular events, stroke, and **thromboembolism**. *ESAs are utilized in patients receiving myelosuppressive chemotherapy with an anticipated curative outcome* - ESAs are generally **contraindicated** in patients receiving myelosuppressive chemotherapy with an anticipated curative outcome, especially in non-myeloid malignancies. - This is because ESAs may promote **tumor growth** and are linked to **inferior outcomes**, including reduced locoregional control and survival, in this specific population.

Question 240: A 19-year-old man is brought to the emergency department by the police. The officers indicate that he was acting violently and talking strangely. In the ED, he becomes increasingly more violent. On exam his vitals are: Temp 101.1 F, HR 119/min, BP 132/85 mmHg, and RR 18/min. Of note, he has vertical nystagmus on exam. What did this patient most likely ingest prior to presentation?

• A. Marijuana
• B. Dextromethorphan
• C. Ketamine
• D. Phencyclidine (Correct Answer)
• E. Mescaline

Explanation: ***Phencyclidine*** - **Phencyclidine (PCP)** intoxication is characterized by acute behavioral changes, violence, hyperthermia, tachycardia, and hypertension. - **Vertical nystagmus** is a classic and highly suggestive sign of PCP intoxication, due to its effect on cerebellar and vestibular pathways. *Marijuana* - Marijuana typically causes euphoria, relaxation, altered perception of time, and conjunctival injection, not aggression or vertical nystagmus. - While it can impair coordination, it rarely leads to the extreme violence and specific vital sign abnormalities seen here. *Dextromethorphan* - Dextromethorphan (DXM) abuse can cause dissociative effects, hallucinations, nystagmus (often horizontal), and tachycardia. - However, the severe violence and classic vertical nystagmus exhibited in this case are more characteristic of PCP. *Ketamine* - Ketamine, a dissociative anesthetic, can cause hallucinations, agitation, and nystagmus, similar to PCP. - While it shares some effects with PCP, **vertical nystagmus** is more specifically associated with PCP toxicity. *Mescaline* - Mescaline is a psychedelic hallucinogen that primarily causes visual hallucinations, altered thought processes, and euphoria. - It does not typically produce the severe violent behavior, hyperthermia, or characteristic vertical nystagmus seen with PCP.

Question 241: A researcher is investigating the behavior of two novel chemotherapeutic drugs that he believes will be effective against certain forms of lymphoma. In order to evaluate the safety of these drugs, this researcher measures the concentration and rate of elimination of each drug over time. A partial set of the results is provided below. Time 1: Concentration of Drug A: 4 mg/dl Concentration of Drug B: 3 mg/dl Elimination of Drug A: 1 mg/minute Elimination of Drug B: 4 mg/minute Time 2: Concentration of Drug A: 2 mg/dl Concentration of Drug B: 15 mg/dl Elimination of Drug A: 0.5 mg/minute Elimination of Drug B: 4 mg/minute Which of the following statements correctly identifies the most likely relationship between the half-life of these two drugs?

• A. The half-life of drug A is always longer than that of drug B
• B. The half-life of both drug A and drug B are constant
• C. The half-life of both drug A and drug B are variable
• D. The half-life of drug A is variable but that of drug B is constant
• E. The half-life of drug A is constant but that of drug B is variable (Correct Answer)

Explanation: ***The half-life of drug A is constant but that of drug B is variable*** - Drug A shows a **constant fraction** eliminated per unit time (1 mg/minute from 4 mg/dl, then 0.5 mg/minute from 2 mg/dl), indicating **first-order kinetics** and thus a constant half-life. - Drug B's elimination rate remains constant (4 mg/minute) despite varying concentrations (3 mg/dl then 15 mg/dl), which suggests **zero-order kinetics** and a variable half-life dependent on concentration. *The half-life of drug A is always longer than that of drug B* - This statement is incorrect because Drug B exhibits **zero-order kinetics**, meaning its **half-life changes** with concentration, making a constant comparison invalid. - At very high concentrations, Drug B's half-life could actually be longer than Drug A's if the elimination rate is slow relative to the large amount of drug. *The half-life of both drug A and drug B are constant* - This is incorrect because Drug B demonstrates **zero-order kinetics**, where the elimination rate is constant, but the **half-life is variable** and directly depends on the drug concentration. - For zero-order kinetics, a constant amount of drug is eliminated per unit time, not a constant fraction, which causes the half-life to change. *The half-life of both drug A and drug B are variable* - This is incorrect because Drug A exhibits **first-order kinetics**, where a **constant proportion** of the drug is eliminated per unit time, resulting in a **constant half-life**. - Its elimination rate is directly proportional to its concentration (1 mg/min from 4 mg/dl, 0.5 mg/min from 2 mg/dl), which defines first-order kinetics. *The half-life of drug A is variable but that of drug B is constant* - This statement is the opposite of what the data indicates for Drug A; Drug A's elimination is **proportional to its concentration**, signifying **first-order kinetics** and a constant half-life. - Drug B's elimination rate is constant regardless of concentration, which points to **zero-order kinetics** and thus a variable half-life.

Question 242: An 8-year-old boy is brought to the emergency department by his parents because of vomiting, abdominal pain, and blurry vision for the past hour. The parents report that the boy developed these symptoms after he accidentally ingested 2 tablets of his grandfather’s heart failure medication. On physical examination, the child is drowsy, and his pulse is 120/min and irregular. Digoxin toxicity is suspected. A blood sample is immediately sent for analysis and shows a serum digoxin level of 4 ng/mL (therapeutic range: 0.8–2 ng/mL). Which of the following electrolyte abnormalities is most likely to be present in the boy?

• A. Hypermagnesemia
• B. Hypokalemia
• C. Hypercalcemia
• D. Hyperkalemia (Correct Answer)
• E. Hypocalcemia

Explanation: ***Hyperkalemia*** - **Digoxin** inhibits the **Na+/K+-ATPase pump**, leading to an increase in intracellular sodium and a decrease in intracellular potassium. - The decreased function of the Na+/K+-ATPase pump results in reduced cellular uptake of potassium, causing **elevated extracellular potassium** levels. *Hypermagnesemia* - **Magnesium** is not directly affected by digoxin toxicity in a way that would lead to hypermagnesemia; in fact, hypomagnesemia can exacerbate digoxin toxicity. - High magnesium levels are typically associated with renal failure or excessive intake of magnesium-containing antacids or laxatives. *Hypokalemia* - While hypokalemia can **predispose to digoxin toxicity** (by increasing digoxin binding to the Na+/K+-ATPase pump), acute digoxin overdose, as described here, often leads to **hyperkalemia** due to the direct inhibition of the pump's ability to drive potassium into cells. - The classic association of hypokalemia with digoxin refers more to its role as a risk factor for toxicity, especially with diuretic use, rather than a direct consequence of acute overdose. *Hypercalcemia* - **Calcium** levels are not directly altered to hypercalcemia by digoxin toxicity. - Digoxin's mechanism involves increasing intracellular calcium by promoting calcium influx and inhibiting its efflux via the Na+/Ca2+ exchanger, but this typically does not manifest as measurable serum hypercalcemia. *Hypocalcemia* - Digoxin toxicity does not directly cause hypocalcemia. - Digoxin actually leads to **increased intracellular calcium**, which is responsible for its positive inotropic effect, but this change is primarily intracellular and does not result in systemic hypocalcemia.

Question 243: A 31-year-old woman presents to her primary care physician with a 2-week history of diarrhea. She says that she has also noticed that she is losing weight, which makes her feel anxious since she has relatives who have suffered from anorexia. Finally, she says that she is worried she has a fever because she feels warm and has been sweating profusely. On physical examination she is found to have proptosis, fine tremor of her hands, and symmetrical, non-tender thyroid enlargement. Which of the following types of enzymes is targeted by a treatment for this disease?

• A. Peroxidase (Correct Answer)
• B. Kinase
• C. Catalase
• D. Cyclooxygenase
• E. Phosphatase

Explanation: ***Peroxidase*** - The patient's symptoms (diarrhea, weight loss, anxiety, sweating, proptosis, fine tremor, and symmetrical thyroid enlargement) are classic for **Graves' disease**, a form of **hyperthyroidism**. - **Thionamides** (e.g., propylthiouracil, methimazole) are a primary treatment for Graves' disease, and they work by inhibiting **thyroid peroxidase (TPO)**, an enzyme crucial for thyroid hormone synthesis. *Kinase* - **Kinases** are enzymes that catalyze the transfer of phosphate groups, often involved in signaling pathways. While kinases are important drug targets, they are not directly involved in the primary treatment mechanism for Graves' disease. - Examples of kinase inhibitors include those used in cancer therapy, but not for hyperthyroidism's specific pathophysiology. *Catalase* - **Catalase** is an enzyme that catalyzes the decomposition of hydrogen peroxide into water and oxygen, protecting cells from oxidative damage. - It has no direct role in the synthesis of thyroid hormones or as a target for hyperthyroidism treatment. *Cyclooxygenase* - **Cyclooxygenase (COX)** enzymes are involved in the synthesis of prostaglandins and thromboxanes, key mediators of inflammation and pain. - COX inhibitors (like NSAIDs) are used for pain and inflammation, not for managing the hyperactive thyroid gland in Graves' disease. *Phosphatase* - **Phosphatases** are enzymes that remove phosphate groups from molecules. They play a role in various cellular processes but are not the primary target for drugs treating Graves' disease. - While important in metabolic regulation, they are not directly inhibited by thionamide drugs used in hyperthyroidism.

Question 244: A 36-year-old man comes to the clinic for follow-up of his general anxiety disorder. He was diagnosed a year ago for excessive worry and irritability and was subsequently started on paroxetine. He demonstrated great response to therapy but is now complaining of decreased libido, which is affecting his marriage and quality of life. He wishes to switch to a different medication at this time. Following a scheduled tapering of paroxetine, the patient is started on a different medication that is a partial agonist of the 5-HT1A receptor. Which of the following is the most likely drug that was prescribed?

• A. Diazepam
• B. Duloxetine
• C. Phenelzine
• D. Amitriptyline
• E. Buspirone (Correct Answer)

Explanation: ***Buspirone*** - **Buspirone** is a **5-HT1A receptor partial agonist** used for generalized anxiety disorder - Has a **lower incidence of sexual side effects** compared to SSRIs, making it an ideal alternative when patients experience SSRI-induced sexual dysfunction - Delayed onset of action (2-4 weeks) but effective for long-term anxiety management without dependence risk *Diazepam* - Benzodiazepine that enhances GABA-A receptor activity, not a 5-HT1A partial agonist - While effective for acute anxiety, carries risks of dependence, sedation, and tolerance - Not appropriate for long-term management or as a switch for SSRI-induced sexual dysfunction *Duloxetine* - Serotonin-norepinephrine reuptake inhibitor (SNRI), not a 5-HT1A partial agonist - Can also cause **sexual dysfunction** similar to SSRIs (decreased libido, anorgasmia) - Would not address the patient's primary complaint *Phenelzine* - Monoamine oxidase inhibitor (MAOI) affecting multiple neurotransmitters, not a 5-HT1A partial agonist - Requires strict dietary restrictions (tyramine-free diet) and has significant drug interactions - Reserved for treatment-resistant anxiety/depression, not first-line for SSRI side effect management *Amitriptyline* - Tricyclic antidepressant (TCA) that inhibits norepinephrine and serotonin reuptake - Not a 5-HT1A partial agonist - Can cause sexual dysfunction along with anticholinergic effects (dry mouth, constipation, urinary retention), sedation, and orthostatic hypotension

Question 245: A 28-year-old woman presents with weakness, fatigability, headache, and faintness. She began to develop these symptoms 4 months ago, and their intensity has been increasing since then. Her medical history is significant for epilepsy diagnosed 4 years ago. She was prescribed valproic acid, which, even at a maximum dose, did not control her seizures. She was prescribed phenytoin 6 months ago. Currently, she takes 300 mg of phenytoin sodium daily and is seizure-free. She also takes 40 mg of omeprazole daily for gastroesophageal disease, which was diagnosed 4 months ago. She became a vegan 2 months ago. She does not smoke and consumes alcohol occasionally. Her blood pressure is 105/80 mm Hg, heart rate is 98/min, respiratory rate is 14/min, and temperature is 36.8℃ (98.2℉). Her physical examination is significant only for paleness. Blood test shows the following findings: Erythrocytes 2.5 x 109/mm3 Hb 9.7 g/dL Hct 35% Mean corpuscular hemoglobin 49.9 pg/cell (3.1 fmol/cell) Mean corpuscular volume 136 µm3 (136 fL) Reticulocyte count 0.1% Total leukocyte count 3110/mm3 Neutrophils 52% Lymphocytes 37% Eosinophils 3% Monocytes 8% Basophils 0% Platelet count 203,000/mm3 Which of the following factors most likely caused this patient’s condition?

• A. Omeprazole intake
• B. Alcohol intake
• C. Epilepsy
• D. Phenytoin intake (Correct Answer)
• E. Vegan diet

Explanation: ***Phenytoin intake*** - The patient presents with **macrocytic anemia** (MCV 136 µm3) and **leukopenia** (WBC 3110/mm3), which are characteristic of **folate deficiency**. Phenytoin is a well-established cause of drug-induced folate deficiency, especially with long-term use (patient has been on phenytoin for 6 months). - Phenytoin causes folate deficiency primarily by **inhibiting intestinal folate absorption** and interfering with folate-dependent enzymatic reactions. This leads to impaired DNA synthesis, resulting in megaloblastic anemia and leukopenia. - The timeline fits perfectly: phenytoin started 6 months ago, symptoms began 4 months ago, allowing time for folate stores to deplete. *Incorrect: Omeprazole intake* - Omeprazole is a **proton pump inhibitor** that can impair the absorption of **vitamin B12** due to reduced gastric acid, which is needed to cleave B12 from dietary proteins. - While vitamin B12 deficiency can also cause macrocytic anemia, it typically takes **years** to develop after the onset of malabsorption (the patient has only been on omeprazole for 4 months). Additionally, B12 deficiency does not typically cause the degree of leukopenia seen here. *Incorrect: Alcohol intake* - **Chronic alcohol abuse** can cause macrocytic anemia through multiple mechanisms: direct bone marrow toxicity, folate deficiency (poor intake and absorption), and liver disease. - However, the patient reports only **occasional alcohol consumption**, making this an unlikely primary cause. Alcohol-related folate deficiency requires chronic heavy use. *Incorrect: Epilepsy* - Epilepsy itself is **not directly associated** with macrocytic anemia or leukopenia. - The hematologic abnormalities are due to the **antiepileptic medication** (phenytoin) rather than the neurological condition itself. *Incorrect: Vegan diet* - A **vegan diet** is a common cause of **vitamin B12 deficiency** since B12 is primarily found in animal products (meat, dairy, eggs). - However, the patient became vegan only **2 months ago**. The body has substantial B12 stores (in the liver) that typically last **3-5 years** before deficiency develops. This timeline is too short to explain the current presentation. Additionally, B12 deficiency alone does not typically cause significant leukopenia as seen here.

Question 246: A 40-year-old man presents with multiple episodes of sudden-onset severe pain in his right side of the face lasting for only a few seconds. He describes the pain as lancinating, giving the sensation of an electrical shock. He says the episodes are precipitated by chewing or touching the face. Which of the following side effects is characteristic of the drug recommended for treatment of this patient’s most likely condition?

• A. Syndrome of inappropriate ADH (Correct Answer)
• B. Hirsutism
• C. Pinpoint pupils
• D. Gingival hyperplasia
• E. Alopecia

Explanation: ***Syndrome of inappropriate ADH*** - The patient's symptoms (sudden-onset severe lancinating facial pain, precipitated by chewing/touching the face) are classic for **trigeminal neuralgia**. - The first-line treatment for trigeminal neuralgia is **carbamazepine**, which can cause a serious side effect of **Syndrome of Inappropriate Antidiuretic Hormone (SIADH)** leading to hyponatremia. *Hirsutism* - **Hirsutism** (excessive hair growth) is a common side effect associated with the anticonvulsant medication **phenytoin**, not carbamazepine. - Phenytoin is used for seizures and status epilepticus, not typically first-line for trigeminal neuralgia. *Pinpoint pupils* - **Pinpoint pupils** are characteristic of **opioid overdose** or organophosphate poisoning, and are not a typical side effect of carbamazepine. - Opioids are generally not effective for trigeminal neuralgia. *Gingival hyperplasia* - **Gingival hyperplasia** (overgrowth of gum tissue) is a well-known side effect of chronic **phenytoin** use. - This is not associated with carbamazepine. *Alopecia* - **Alopecia** (hair loss) can be a side effect of several medications, including some chemotherapy agents and anticonvulsants like **valproic acid**, but it is not a hallmark side effect of carbamazepine. - Valproic acid is primarily used for seizures and bipolar disorder.

Question 247: A 14-year-old boy comes to the physician for a follow-up after a blood test showed a serum triglyceride level of 821 mg/dL. Several of his family members have familial hypertriglyceridemia. The patient is prescribed a fibrate medication that increases his risk of gallstone disease. The expected beneficial effect of this drug is most likely due to which of the following actions?

• A. Increased PPAR-gamma activity
• B. Increased bile acid sequestration
• C. Increased lipoprotein lipase activity (Correct Answer)
• D. Decreased HMG-CoA reductase activity
• E. Decreased lipolysis in adipose tissue

Explanation: **Increased lipoprotein lipase activity** - Fibrates, such as **gemfibrozil** and **fenofibrate**, are agonists of **peroxisome proliferator-activated receptor alpha (PPAR-alpha)**, which upregulates the expression of **lipoprotein lipase (LPL)**. - Increased LPL activity leads to enhanced catabolism of **triglyceride-rich lipoproteins** (VLDL and chylomicrons), thereby lowering serum triglyceride levels. *Increased PPAR-gamma activity* - This is the primary mechanism of action for **thiazolidinediones (glitazones)**, used in the treatment of **type 2 diabetes mellitus**. - PPAR-gamma activation primarily improves **insulin sensitivity** and promotes **adipogenesis**, with a less direct effect on triglyceride clearance compared to PPAR-alpha activation. *Increased bile acid sequestration* - This is the mechanism of action for **bile acid resins** (e.g., cholestyramine, colestipol), which bind bile acids in the intestine, preventing their reabsorption. - This leads to increased synthesis of **new bile acids** from cholesterol in the liver, thereby lowering **LDL cholesterol** levels, but not directly targeting triglycerides. *Decreased HMG-CoA reductase activity* - This describes the mechanism of action of **statins** (e.g., atorvastatin, simvastatin), which are potent inhibitors of **HMG-CoA reductase**, the rate-limiting enzyme in **cholesterol biosynthesis**. - Statins primarily reduce **LDL cholesterol** levels, with a secondary, less pronounced effect on triglycerides. *Decreased lipolysis in adipose tissue* - **Niacin (vitamin B3)** primarily works by inhibiting **hormone-sensitive lipase** in adipose tissue, which reduces the release of **free fatty acids** into circulation. - This, in turn, decreases hepatic synthesis of **triglycerides** and **VLDL**, thus lowering triglyceride levels.

Question 248: A 29-year-old woman came to the emergency department due to severe symptoms of intoxication and unexplained convulsions. She is accompanied by her husband who reports that she takes disulfiram. There is no prior personal and family history of epilepsy. She shows signs of confusion, hyperirritability, and disorientation. On further evaluation, the patient is noted to have stomatitis, glossitis, and cheilosis. A chest X-ray is unremarkable. The deficiency of which of the vitamins below is likely to be the major cause of this patient’s symptoms?

• A. B12
• B. B6 (Correct Answer)
• C. B9
• D. B2
• E. B3

Explanation: ***B6*** - The patient's presentation of **seizures, confusion, and oral symptoms (stomatitis, glossitis, cheilosis)** in the context of **disulfiram use** strongly suggests **pyridoxine (vitamin B6) deficiency**. - **Disulfiram inhibits pyridoxine phosphokinase**, which converts pyridoxine to its active form (pyridoxal-5-phosphate), leading to functional B6 deficiency. - **Seizures are a hallmark of B6 deficiency** because pyridoxal-5-phosphate is a cofactor for glutamic acid decarboxylase, which synthesizes GABA; reduced GABA leads to increased neuronal excitability and seizures. - B6 deficiency also causes **peripheral neuropathy, cheilosis, glossitis, and stomatitis**. *B2* - Vitamin B2 (riboflavin) deficiency does cause **stomatitis, glossitis, and cheilosis**, along with seborrheic dermatitis and normocytic anemia. - However, **riboflavin deficiency does not typically cause seizures**, which is the most acute and concerning symptom in this case. - While disulfiram can affect multiple vitamin pathways, the seizure presentation points specifically to B6. *B12* - Vitamin B12 deficiency typically presents with **megaloblastic anemia** and **neurological symptoms** such as subacute combined degeneration (posterior column and corticospinal tract), peripheral neuropathy, and cognitive changes. - The acute seizures and oral mucosal symptoms are not characteristic of B12 deficiency. *B9* - Vitamin B9 (folate) deficiency primarily causes **megaloblastic anemia** with symptoms of fatigue and weakness. - While **glossitis** can occur, it's usually accompanied by anemia, and seizures are not a feature of folate deficiency. - The clinical picture does not fit folate deficiency. *B3* - Vitamin B3 (niacin) deficiency causes **pellagra**, characterized by the classic triad: **dermatitis, diarrhea, and dementia** (the "3 Ds"). - While glossitis can be present, the **absence of photosensitive dermatitis and diarrhea** makes pellagra unlikely. - Seizures are not a typical feature of pellagra.

Question 249: A 4-month-old girl with Down syndrome is brought into the pediatrician’s office by her father for her first well-child visit. The father states she was a home birth at 39 weeks gestation after an uneventful pregnancy without prenatal care. The child has not received any routine immunizations. The father states that sometimes when she is crying or nursing she "gets a little blue", but otherwise the patient is healthy. The patient is within the normal range of weight and height. Her blood pressure is 110/45 mm Hg, the pulse is 185/min, the respiratory rate is 25/min, and the temperature is 37.1°C (98.7°F). The physician notes an elevated heart rate, widened pulse pressure, and some difficulty breathing. On exam, the patient is playful and in no apparent distress. On lung exam, some faint crackles are heard at the lung bases without wheezing. Cardiac exam is significant for a harsh, machine-like murmur. An echocardiogram verifies the diagnosis. What is the next step in treatment of this patient?

• A. Antibiotics
• B. Heart transplant
• C. PGE2
• D. Emergent open heart surgery
• E. Indomethacin (Correct Answer)

Explanation: ***Indomethacin*** - The patient's history of Down syndrome, cyanosis during crying, elevated heart rate, widened pulse pressure, crackles, and a **harsh, machine-like murmur** are classic signs of a **patent ductus arteriosus (PDA)** with significant left-to-right shunting. - **Indomethacin** is a **prostaglandin inhibitor** that promotes closure of the PDA by blocking prostaglandin synthesis. While it is most effective in premature neonates, it can still be attempted in older infants with symptomatic PDA as **initial pharmacological management**. - Given this is a **Pharmacology** question and the patient shows signs of mild heart failure but is "playful and in no apparent distress," a trial of **indomethacin** is appropriate before considering invasive interventions. - If indomethacin fails, **elective surgical or transcatheter closure** would be the next step, but pharmacological closure should be attempted first in stable patients. *Antibiotics* - While **prophylactic antibiotics** might be considered in some cardiac conditions to prevent endocarditis, the primary issue here is a structural heart defect causing **hemodynamic changes**, not an infection. - Antibiotics would not address the underlying **patent ductus arteriosus** or the progressive symptoms of increased pulmonary blood flow. *Heart transplant* - A **heart transplant** is typically reserved for end-stage cardiac failure that is refractory to all other medical and surgical interventions. - The patient's condition is amenable to medical management or closure of the **patent ductus arteriosus**, which can significantly improve cardiac function without need for transplant. *PGE2* - **Prostaglandin E2 (PGE2)** is used to **maintain patency** of the ductus arteriosus in ductal-dependent congenital heart disease where blood flow through the ductus is critical for survival (e.g., severe coarctation of the aorta, transposition of great arteries, hypoplastic left heart syndrome). - In this case, the **patent ductus arteriosus** is causing symptoms of **pulmonary overcirculation** and mild heart failure, so maintaining its patency with PGE2 would worsen the patient's condition. *Emergent open heart surgery* - While **surgical closure** is definitive treatment for PDA, **emergent** surgery is not indicated in a stable patient who is "playful and in no apparent distress." - The standard approach is to attempt **medical management first** (indomethacin or other prostaglandin inhibitors), then consider **elective closure** (transcatheter or surgical) if pharmacological treatment fails. - Modern management typically favors **transcatheter closure** over open heart surgery when anatomically feasible, and the procedure is performed electively, not emergently, unless there is severe hemodynamic compromise.

Question 250: A 70-year-old man presents to an urgent care clinic with bilateral flank pain for the past 2 days. During the last week, he has been experiencing some difficulty with urination, which prevented him from leaving his home. Now, he has to go to the bathroom 4–5 times per hour and he wakes up multiple times during the night to urinate. He also complains of straining and difficulty initiating urination with a poor urinary stream. The temperature is 37.5°C (99.5°F), the blood pressure is 125/90 mm Hg, the pulse is 90/min, and the respiratory rate is 18/min. The physical examination showed bilateral flank tenderness and palpable kidneys bilaterally. A digital rectal exam revealed a smooth, severely enlarged prostate without nodules. A CT scan is obtained. He is prescribed a drug that will alleviate his symptoms by reducing the size of the prostate. Which of the following best describes the mechanism of action of this drug?

• A. 5-alpha reductase inhibitor (Correct Answer)
• B. Cholinergic agonist
• C. Anticholinergic
• D. Phosphodiesterase-5 inhibitors
• E. Alpha-1-adrenergic antagonists

Explanation: ***5-alpha reductase inhibitor*** - The patient's symptoms (difficulty urinating, frequent urination, straining, poor stream) and **enlarged prostate** on digital rectal exam are classic for **Benign Prostatic Hyperplasia (BPH)**. The question specifies a drug that *reduces prostate size*. - **5-alpha reductase inhibitors** (e.g., finasteride, dutasteride) block the conversion of testosterone to **dihydrotestosterone (DHT)**, which is responsible for prostate growth. This leads to a reduction in prostate size over several months. *Cholinergic agonist* - **Cholinergic agonists** increase parasympathetic tone, leading to bladder contraction. - While they might help with bladder emptying in hypotonic bladder, they would not reduce prostate size and could worsen symptoms if the obstruction is severe, potentially leading to increased bladder pressure or hydronephrosis. *Anticholinergic* - **Anticholinergic drugs** relax the bladder detrusor muscle, reducing bladder overactivity and symptoms of urgency and frequency. - They do not address the underlying prostatic hypertrophy or reduce prostate size and could exacerbate urinary retention in a patient with significant prostatic obstruction. *Phosphodiesterase-5 inhibitors* - **Phosphodiesterase-5 (PDE5) inhibitors** (e.g., sildenafil, tadalafil) are primarily used for erectile dysfunction, and tadalafil can also improve BPH symptoms by relaxing smooth muscle in the bladder neck and prostate. - However, they do not **reduce the size of the prostate**; their mechanism of action is related to smooth muscle relaxation, not inhibition of prostate growth. *Alpha-1-adrenergic antagonists* - **Alpha-1-adrenergic antagonists** (e.g., tamsulosin, doxazosin) relax the smooth muscle in the prostate and bladder neck, improving urinary flow by reducing dynamic obstruction. - While effective for BPH symptoms, they do not **reduce the size of the prostate**; they only alleviate symptoms by relaxing the existing tissue.

Question 251: A 23-year-old woman presents with flatulence and abdominal cramping after meals. For the last year, she has been feeling uneasy after meals and sometimes has severe pain after eating breakfast in the morning. She also experiences flatulence and, on rare occasions, diarrhea. She says she has either cereal or oats in the morning which she usually consumes with a glass of milk. The patient is afebrile and vital signs are within normal limits. Physical examination is unremarkable. Which of the following drugs should be avoided in this patient?

• A. Pantoprazole
• B. Cimetidine
• C. Sucralfate
• D. Loperamide
• E. Magnesium hydroxide (Correct Answer)

Explanation: ***Magnesium hydroxide*** - Magnesium hydroxide is an **osmotic laxative**, and its side effects include **diarrhea**, which the patient already experiences. - In a patient presenting with symptoms suggestive of **lactose intolerance** (abdominal cramping, flatulence, and occasional diarrhea after consuming milk with cereal), a laxative intensifying these symptoms should be avoided. *Pantoprazole* - **Pantoprazole** is a proton pump inhibitor primarily used to reduce stomach acid, which is not indicated for the patient's symptoms. - It would not worsen the patient's current symptoms of **flatulence** and **occasional diarrhea**. *Cimetidine* - **Cimetidine** is an H2 receptor antagonist used to decrease stomach acid, which is not relevant to the patient's symptoms of **lactose intolerance**. - Its side effects generally do not include significant changes in **bowel habits** that would exacerbate the patient's presentation. *Sucralfate* - **Sucralfate** is a cytoprotective agent that forms a protective barrier in the stomach, primarily used for ulcers. - It works locally in the gastrointestinal tract and is not known to cause symptoms like significant **flatulence** or **diarrhea**. *Loperamide* - **Loperamide** is an anti-diarrheal medication, which would be used to treat diarrhea, not avoided. - It would likely alleviate the patient's occasional diarrhea rather than exacerbate it.

Question 252: A 60-year-old man visits his primary care doctor after being discharged from the hospital 3 weeks ago. He presented to the hospital with chest pain and was found to have ST elevations in leads I, aVL, and V6. He underwent cardiac catheterization with balloon angioplasty and was discharged on appropriate medications. At this visit, he complains of feeling deconditioned over the past week. He states that he is not able to jog his usual 3 miles and feels exhausted after walking up stairs. He denies chest pain. His temperature is 98.6°F (37°C), blood pressure is 101/62 mmHg, pulse is 59/min, and respirations are 18/min. His cardiac exam is notable for a 2/6 early systolic murmur at the left upper sternal border. He describes mild discomfort with palpation of his epigastrium. The remainder of his exam is unremarkable. His laboratory workup is shown below: Hemoglobin: 8 g/dL Hematocrit: 25 % Leukocyte count: 11,000/mm^3 with normal differential Platelet count: 400,000/mm^3 Serum: Na+: 136 mEq/L Cl-: 103 mEq/L K+: 3.8 mEq/L HCO3-: 25 mEq/L BUN: 45 mg/dL Glucose: 89 mg/dL Creatinine: 1.1 mg/dL Which medication is most likely contributing to this patient's current presentation?

• A. Atorvastatin
• B. Carvedilol
• C. Furosemide
• D. Lisinopril
• E. Aspirin (Correct Answer)

Explanation: ***Aspirin*** - The patient's **epigastric discomfort**, **anemia** (hemoglobin 8 g/dL, hematocrit 25%), and the presence of a new **systolic murmur** (suggesting flow murmur due to anemia) are highly indicative of **upper gastrointestinal bleeding**. - **Aspirin**, an antiplatelet medication often prescribed after an MI, is a common cause of **gastric ulcers** and subsequent GI bleeding due to its inhibition of prostaglandin synthesis, which compromises the gastric mucosal barrier. *Atorvastatin* - While statins can cause **myalgias** and, rarely, **rhabdomyolysis**, they are not typically associated with GI bleeding or anemia. - The patient's deconditioning is more likely related to anemia than a direct statin effect, and there are no signs of muscle pain or elevated creatine kinase. *Carvedilol* - This **beta-blocker** is prescribed post-MI to reduce cardiac workload and improve survival, but it does not cause GI bleeding or anemia. - Its side effects include **bradycardia**, **hypotension**, and fatigue, which could contribute to deconditioning but not the primary findings of anemia and epigastric discomfort. *Furosemide* - Furosemide is a **loop diuretic** used to manage fluid overload, not typically prescribed routinely after an uncomplicated MI unless signs of heart failure are present. - While it can cause electrolyte imbalances or hypovolemia, it does not directly lead to GI bleeding or anemia. *Lisinopril* - **ACE inhibitors** like lisinopril are commonly prescribed post-MI to prevent ventricular remodeling and reduce mortality. - Known side effects include **cough** and **angioedema**, but they do not cause GI bleeding or anemia.

Question 253: A 56-year-old woman with rheumatoid arthritis comes to the physician for a follow-up examination. She has no other history of serious illness. Menopause occurred 1 year ago. Current medications include antirheumatic drugs and hormone replacement therapy. She exercises regularly. A DEXA scan shows a T-score of -1.80, indicating decreased bone density. Which of the following drugs is most likely involved in the pathogenesis of this finding?

• A. Naproxen
• B. Medroxyprogesterone acetate
• C. Adalimumab
• D. Prednisone (Correct Answer)
• E. Sulfasalazine

Explanation: ***Prednisone*** - **Glucocorticoids** like prednisone are a major cause of secondary osteoporosis due to their direct inhibitory effects on osteoblast function and promotion of osteoclast activity. - Long-term use of prednisone, common in managing rheumatoid arthritis, significantly increases the risk of decreased bone density, even with a history of regular exercise and hormone replacement therapy. *Naproxen* - **Naproxen** is a **nonsteroidal anti-inflammatory drug (NSAID)** used for pain and inflammation; it does not directly cause bone loss or osteoporosis. - While it may be used in rheumatoid arthritis, its mechanism of action does not involve bone metabolism. *Medroxyprogesterone acetate* - **Medroxyprogesterone acetate (MPA)** is a progestin that can cause **bone mineral density loss** with long-term use, particularly as a contraceptive injection (Depo-Provera). - However, the patient is on **hormone replacement therapy** (likely estrogen, which is bone-protective) and MPA's effect on bone is generally less significant than that of glucocorticoids in this context, and it's not a typical long-term RA medication. *Adalimumab* - **Adalimumab** is a **TNF-alpha inhibitor** used to treat rheumatoid arthritis; it has no known adverse effect on bone density. - By controlling the inflammatory process in RA, it may indirectly help preserve bone health by reducing inflammation-induced bone erosion. *Sulfasalazine* - **Sulfasalazine** is a **disease-modifying antirheumatic drug (DMARD)** used for rheumatoid arthritis and inflammatory bowel disease. - It does not have any direct adverse effects on bone density or metabolism.

Question 254: Serum studies show a troponin T concentration of 6.73 ng/mL (N < 0.01), and fingerstick blood glucose concentration of 145 mg/dL. The cardiac catheterization team is activated. Treatment with unfractionated heparin, aspirin, ticagrelor, and sublingual nitroglycerin is begun, and the patient's pain subsides. His temperature is 37.3°C (99.1°F), pulse is 65/min, respirations are 23/min, and blood pressure is 91/60 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 96%. Which of the following is the most appropriate additional pharmacotherapy?

• A. Intravenous morphine
• B. Intravenous furosemide
• C. Intravenous insulin
• D. Oral atorvastatin (Correct Answer)
• E. Intravenous nitroglycerin

Explanation: ***Oral atorvastatin*** - All patients with **acute coronary syndrome (ACS)** should receive high-intensity statin therapy, such as **atorvastatin 80 mg daily**, as early as possible. - Statins stabilize plaques, reduce inflammation, and improve endothelial function, which are crucial in the acute setting of a myocardial infarction. *Intravenous morphine* - Morphine can be used for persistent chest pain refractory to nitroglycerin, but its routine use is now questioned due to potential adverse effects like hypotension and delayed antiplatelet absorption. - The patient's pain has already subsided with initial treatment, and his blood pressure is already low (91/60 mm Hg), making morphine less appropriate. *Intravenous furosemide* - Furosemide is a loop diuretic primarily used for treating **fluid overload** and **pulmonary edema**, which are not indicated by the patient's current presentation (oxygen saturation 96%, no mention of crackles or dyspnea). - Its use in a patient with **borderline hypotension** could worsen hemodynamic stability. *Intravenous insulin* - While the patient has elevated fingerstick glucose (145 mg/dL), this level does not immediately require intravenous insulin unless there is evidence of **diabetic ketoacidosis** or **hyperosmolar hyperglycemic state**, or persistent severe hyperglycemia. - More moderate hyperglycemia can often be managed with subcutaneous insulin or diet in the acute phase, and focuses remain on cardiac stabilization. *Intravenous nitroglycerin* - Intravenous nitroglycerin is indicated for ongoing ischemic chest pain or uncontrolled hypertension in ACS, but the patient's pain has subsided and he is **hypotensive** (91/60 mm Hg). - Administering more nitroglycerin would likely worsen his hypotension and could compromise coronary perfusion.

Question 255: A 28-year-old female presents to her primary care provider for headache. The patient reports that every few weeks she has an episode of right-sided, throbbing headache. The episodes began several years ago and are accompanied by nausea and bright spots in her vision. The headache usually subsides if she lies still in a dark, quiet room for several hours. The patient denies any weakness, numbness, or tingling during these episodes. Her past medical history is significant for acne, hypothyroidism, obesity, and endometriosis. Her home medications include levothyroxine, oral contraceptive pills, and topical tretinoin. She has two glasses of wine with dinner several nights a week and has never smoked. She works as a receptionist at a marketing company. On physical exam, the patient has no focal neurologic deficits. A CT of the head is performed and shows no acute abnormalities. Which of the following is the most appropriate treatment for this patient during these episodes?

• A. Acetazolamide
• B. Topiramate
• C. Verapamil
• D. High-flow oxygen
• E. Sumatriptan (Correct Answer)

Explanation: ***Sumatriptan*** - The patient's presentation with **throbbing, unilateral headaches** accompanied by **nausea** and **visual aura** (bright spots), relieved by rest in a quiet room, is classic for **migraine with aura**. - **Triptans** like sumatriptan are first-line abortive treatments for moderate to severe migraines, effectively targeting serotonin receptors to reduce headache pain and associated symptoms. *Acetazolamide* - This medication is a **carbonic anhydrase inhibitor** primarily used for conditions like **glaucoma**, **altitude sickness**, and **idiopathic intracranial hypertension**, not acute migraine attacks. - It works by reducing cerebrospinal fluid production and is not indicated for the immediate relief of migraine symptoms. *Topiramate* - **Topiramate** is an **anti-epileptic drug** that is used for **migraine prophylaxis** (prevention), not for acute treatment of a migraine episode. - While it can reduce the frequency of migraines over time, it will not alleviate an ongoing headache. *Verapamil* - **Verapamil** is a **calcium channel blocker** and is primarily used for **cluster headache prophylaxis** or for conditions like hypertension and angina. - It is not an effective acute treatment for migraine, and its use is typically reserved for preventative measures in specific headache types. *High-flow oxygen* - **High-flow oxygen** is a highly effective acute treatment for **cluster headaches**, which present with very distinct symptoms like excruciating unilateral pain, often with autonomic features (e.g., lacrimation, rhinorrhea). - This patient's symptoms are consistent with migraine, not cluster headache, making oxygen an inappropriate treatment.

Question 256: A 55-year-old man with a history of congestive heart failure, hypertension, and hyperlipidemia presents to his primary care clinic. He admits he did not adhere to a low salt diet on a recent vacation. He now has progressive leg swelling and needs two pillows to sleep because he gets short of breath when lying flat. Current medications include aspirin, metoprolol, lisinopril, atorvastatin, and furosemide. His physician decides to increase the dosage and frequency of the patient’s furosemide. Which of the following electrolyte abnormalities is associated with loop diuretics?

• A. Hyperchloremia
• B. Hypocalcemia
• C. Hypermagnesemia
• D. Hypouricemia
• E. Hypokalemia (Correct Answer)

Explanation: ***Hypokalemia*** - **Loop diuretics** are most commonly associated with **hypokalemia**, which is one of their most clinically significant electrolyte disturbances. - Loop diuretics inhibit the **Na-K-2Cl cotransporter** in the thick ascending limb, increasing sodium delivery to the collecting duct. - This stimulates **aldosterone-mediated potassium secretion** via principal cells, leading to increased urinary potassium loss. - **Clinical significance**: Hypokalemia can cause muscle weakness, cardiac arrhythmias, and potentiates digoxin toxicity—particularly important in heart failure patients. *Hyperchloremia* - Loop diuretics cause **hypochloremia**, not hyperchloremia. - Chloride reabsorption is blocked in the thick ascending limb, leading to increased chloride excretion. *Hypocalcemia* - Loop diuretics increase **urinary calcium excretion** (hypercalciuria) by reducing the positive luminal charge needed for paracellular calcium reabsorption. - However, this typically does **not cause clinically significant hypocalcemia** in most patients. - In contrast, thiazide diuretics decrease calcium excretion. *Hypermagnesemia* - Loop diuretics cause **hypomagnesemia**, not hypermagnesemia. - They disrupt the positive lumen potential necessary for magnesium reabsorption in the thick ascending limb. *Hypouricemia* - Loop diuretics cause **hyperuricemia**, not hypouricemia. - They compete with uric acid for secretion in the proximal tubule, promoting uric acid reabsorption and decreasing its excretion.

Question 257: A 45-year-old woman comes to the emergency department with recurrent episodes of shaking, sweating, and palpitations. The patient is confused and complains of hunger. One week ago, she had similar symptoms that improved after eating. She has hypertension and a history of biliary pancreatitis. She underwent cholecystectomy 1 year ago. She works as a nurse aide in a nursing care facility. She does not smoke or drink alcohol. She does not exercise. Her temperature is 36.7°C (98°F), pulse is 104/min, respirations are 20/min, and blood pressure is 135/88 mm Hg. Examination shows tremors and diaphoresis. Laboratory studies show: Blood glucose 50 mg/dL Thyroid-stimulating hormone 1 mU/L C-peptide 0.50 ng/mL (N=0.8–3.1) Abdominal ultrasound reveals a 1-cm anechoic lesion in the head of the pancreas. Which of the following is the most likely cause of this patient's symptoms?

• A. Pancreatic neoplasm
• B. Pancreatic pseudocyst
• C. Graves' disease
• D. Surreptitious insulin use (Correct Answer)
• E. Type 1 diabetes mellitus

Explanation: ***Surreptitious insulin use*** - The patient's symptoms of **hypoglycemia** (shaking, sweating, palpitations, confusion, hunger) combined with a **low C-peptide level** (0.50 ng/mL) and a normal TSH strongly suggest **exogenous insulin administration**. - As a nurse aide, she has access to insulin, and the normal pancreatic ultrasound (1 cm anechoic lesion is non-specific and unlikely to cause these symptoms) rules out an **insulinoma**, which would present with high C-peptide. *Pancreatic neoplasm* - While a pancreatic neoplasm can cause various symptoms, an **insulinoma** (a type of pancreatic neuroendocrine tumor) would present with **hypoglycemia** but typically with **elevated C-peptide levels**, as it produces endogenous insulin. - The ultrasound finding of a 1-cm anechoic lesion is **non-specific** and not definitively indicative of an insulinoma or any other functional neoplasm causing these specific symptoms. *Pancreatic pseudocyst* - Pancreatic pseudocysts are collections of fluid that can occur after **pancreatitis** or trauma, and while this patient has a history of biliary pancreatitis, pseudocysts generally cause symptoms like **abdominal pain, distension, and early satiety**, not hypoglycemia. - They also do not explain the **low C-peptide** and recurrent episodes of neuroglycopenic symptoms. *Graves' disease* - Graves' disease is an **autoimmune hyperthyroid condition** that causes symptoms like palpitations, sweating, and tremors, but it is characterized by **low TSH** with elevated free T3/T4 due to negative feedback, not hypoglycemia or low C-peptide. - The patient's **normal TSH** (1 mU/L) rules out Graves' disease as the cause of her current symptoms. *Type 1 diabetes mellitus* - Type 1 diabetes is characterized by **insulin deficiency** due to autoimmune destruction of pancreatic beta cells, leading to **hyperglycemia**, not hypoglycemia. - While patients with type 1 diabetes may experience hypoglycemia if they administer too much insulin, the underlying disease itself causes high blood glucose, and the C-peptide would be very low or undetectable in a new diagnosis, but not as the cause of recurrent spontaneous hypoglycemia.

Question 258: A 76-year-old woman comes to the physician because of a sudden loss of vision in her right eye for 10 minutes that morning, which subsided spontaneously. Over the past 2 months, she has had multiple episodes of left-sided headaches and pain in her jaw while chewing. Examination shows conjunctival pallor. Range of motion of the shoulders and hips is slightly limited by pain. Her erythrocyte sedimentation rate is 69 mm/h. Treatment with the appropriate medication for this patient's condition is initiated. Which of the following sets of laboratory findings is most likely as a consequence of treatment? | Lymphocytes | Neutrophils | Eosinophils | Fibroblasts |

• A. ↓ ↑ ↓ ↓ (Correct Answer)
• B. ↓ ↓ ↓ ↓
• C. ↑ ↑ ↓ ↑
• D. ↓ ↓ ↑ ↓
• E. ↑ ↓ ↓ ↓

Explanation: ***↓ ↑ ↓ ↓*** - The patient's symptoms (sudden visual loss, headaches, jaw claudication, polymyalgia rheumatica-like symptoms, and elevated **ESR**) are highly suggestive of **giant cell arteritis (GCA)**. - The treatment for GCA is high-dose **corticosteroids**, which cause characteristic hematologic changes: **lymphopenia** (↓), **neutrophilia** (↑), **eosinopenia** (↓), and **decreased fibroblast proliferation** (↓). - Corticosteroids induce **lymphocyte apoptosis** and redistribution, cause **neutrophil demargination** from vessel walls and inhibit neutrophil apoptosis (leading to increased circulating neutrophils), sequester **eosinophils** in lymphoid tissue, and suppress **fibroblast activity**. *↓ ↓ ↓ ↓* - While lymphocytes, eosinophils, and fibroblasts decrease with corticosteroid use, **neutrophils** typically **increase**, not decrease, due to demargination from vascular walls and inhibited apoptosis. - This option incorrectly shows neutropenia when neutrophilia is expected. *↑ ↑ ↓ ↑* - Corticosteroids cause **lymphopenia** (↓), not lymphocytosis (↑). - **Fibroblasts** also decrease (↓), not increase (↑), as corticosteroids inhibit fibroblast proliferation and collagen synthesis. - This option incorrectly shows increases in both lymphocytes and fibroblasts. *↓ ↓ ↑ ↓* - Corticosteroids cause **eosinopenia** (↓), not eosinophilia (↑). - Eosinophils are sequestered in lymphoid tissues and undergo apoptosis with corticosteroid treatment. - This option also incorrectly shows neutropenia instead of the expected neutrophilia. *↑ ↓ ↓ ↓* - Corticosteroids cause **lymphopenia** (↓), not lymphocytosis (↑). - Lymphocytes undergo apoptosis and redistribute from circulation with corticosteroid therapy. - This option also incorrectly shows neutropenia instead of neutrophilia.

Question 259: A previously healthy 61-year-old man comes to the physician because of bilateral knee pain for the past year. The pain is worse with movement and is relieved with rest. Physical examination shows crepitus, pain, and decreased range of motion with complete flexion and extension of both knees. There is no warmth, redness, or swelling. X-rays of both knees show irregular joint space narrowing, osteophytes, and subchondral cysts. Which of the following is the most appropriate pharmacotherapy?

• A. Allopurinol
• B. Naproxen (Correct Answer)
• C. Celecoxib
• D. Infliximab
• E. Prednisone

Explanation: ***Naproxen*** - The patient's presentation with **bilateral knee pain worse with movement**, relief with rest, crepitus, and characteristic X-ray findings (joint space narrowing, osteophytes, subchondral cysts) is classic for **osteoarthritis (OA)** [3]. - **NSAIDs** like naproxen are **first-line pharmacotherapy** for managing pain and inflammation in osteoarthritis that is not adequately controlled by acetaminophen or topical agents [1]. - As a **non-selective NSAID**, naproxen is an appropriate initial choice for a patient without specified risk factors for GI complications or cardiovascular disease [2]. *Allopurinol* - **Allopurinol** is a xanthine oxidase inhibitor used to reduce **urate production in hyperuricemia** and prevent gout attacks. - The patient's symptoms are not consistent with gout, as there is **no acute inflammatory arthritis, redness, warmth, or swelling**. *Celecoxib* - **Celecoxib** is a **COX-2 selective NSAID** that can be used for osteoarthritis pain. - It is generally preferred in patients with **documented GI risk factors** (history of peptic ulcer, concurrent anticoagulation, or advanced age with other risk factors). - While this 61-year-old patient has age as a consideration, in the absence of other specified GI risk factors, either non-selective or COX-2 selective NSAIDs are reasonable; **naproxen is acceptable as initial therapy** and is more cost-effective. *Infliximab* - **Infliximab** is a **biologic disease-modifying antirheumatic drug (DMARD)**, specifically a TNF-alpha inhibitor, used to treat inflammatory arthritides like rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. - It is **not indicated for osteoarthritis**, which is a degenerative joint disease rather than an autoimmune inflammatory process. *Prednisone* - **Prednisone** is a corticosteroid used to **reduce inflammation** in various conditions, including inflammatory arthritides and acute pain flares. - While it can provide symptomatic relief, it is **not a first-line or long-term pharmacotherapy for osteoarthritis** due to significant **side effects** with chronic use (weight gain, hyperglycemia, osteoporosis, immunosuppression) [1].

Question 260: A 72-year-old man with congestive heart failure is brought to the emergency department because of chest pain, shortness of breath, dizziness, and palpitations for 30 minutes. An ECG shows a wide complex tachycardia with a P-wave rate of 105/min, an R-wave rate of 130/min, and no apparent relation between the two. Intravenous pharmacotherapy is initiated with a drug that prolongs the QRS and QT intervals. The patient was most likely treated with which of the following drugs?

• A. Carvedilol
• B. Verapamil
• C. Flecainide
• D. Quinidine (Correct Answer)
• E. Sotalol

Explanation: **Quinidine** - Quinidine is a **Class IA antiarrhythmic** that blocks fast sodium channels, prolonging both the **QRS complex** (due to slowed conduction) and the **QT interval** (due to prolonged repolarization). - The ECG findings of **wide-complex tachycardia** and **AV dissociation** (P-wave rate different from R-wave rate without apparent relation) are consistent with ventricular tachycardia, which Class IA drugs can treat. *Carvedilol* - Carvedilol is a **beta-blocker** (Class II antiarrhythmic) that primarily slows heart rate and AV nodal conduction, generally **shortening the QT interval** or having no effect, and would not widen the QRS complex. - Beta-blockers are typically contraindicated in **decompensated heart failure** and **wide-complex tachycardia** due to their negative inotropic effects and risk of worsening decompensation. *Verapamil* - Verapamil is a **non-dihydropyridine calcium channel blocker** (Class IV antiarrhythmic) that mainly slows AV nodal conduction. It would not cause QRS widening and can shorten the QT interval. - Verapamil is generally contraindicated in **wide-complex tachycardias** of unknown origin as it can precipitate cardiovascular collapse if the arrhythmia is ventricular. *Flecainide* - Flecainide is a **Class IC antiarrhythmic** that primarily blocks fast sodium channels, causing significant **QRS widening** but has **minimal effect on the QT interval**, which is contrary to the case description. - Class IC agents are also generally avoided in patients with **structural heart disease** like congestive heart failure due to increased mortality risk. *Sotalol* - Sotalol is a **Class III antiarrhythmic** (beta-blocker with potassium channel blockade) that primarily prolongs the **QT interval** by blocking potassium channels. While it prolongs the QT, it does **not significantly widen the QRS complex**. - Its beta-blocking effects could exacerbate **decompensated heart failure** in this patient, similar to carvedilol.

Question 261: You are a resident on an anesthesiology service and are considering using nitrous oxide to assist in placing a laryngeal mask airway (LMA) in your patient, who is about to undergo a minor surgical procedure. You remember that nitrous oxide has a very high minimal alveolar concentration (MAC) compared to other anesthetics. This means that nitrous oxide has:

• A. no effect on lipid solubility or potency
• B. decreased lipid solubility and decreased potency (Correct Answer)
• C. decreased lipid solubility and increased potency
• D. increased lipid solubility and increased potency
• E. increased lipid solubility and decreased potency

Explanation: ***Decreased lipid solubility and decreased potency*** - A **very high MAC** indicates that a large concentration of the anesthetic agent is required to produce immobility in 50% of patients, signifying **low potency**. - According to the **Meyer-Overton rule**, anesthetic potency is directly correlated with lipid solubility; therefore, low potency implies **decreased lipid solubility**. *No effect on lipid solubility or potency* - This statement is incorrect as MAC is a direct measure of potency, and potency is linked to lipid solubility by the **Meyer-Overton rule**. - A high MAC unequivocally indicates **low potency**, and indirectly, low lipid solubility. *Decreased lipid solubility and increased potency* - This is incorrect because **increased potency** would be associated with a **low MAC**. - Potency and lipid solubility are positively correlated, so decreased lipid solubility would lead to **decreased potency**. *Increased lipid solubility and increased potency* - This is incorrect; while **increased lipid solubility** is associated with **increased potency**, increased potency would manifest as a **low MAC**, not a high one. - The given information states a **very high MAC**, which signifies low potency. *Increased lipid solubility and decreased potency* - This statement contradicts the **Meyer-Overton rule**, which establishes a direct relationship between lipid solubility and anesthetic potency. - Therefore, **increased lipid solubility** should correspond to **increased potency**, not decreased potency.

Question 262: A 47-year-old patient returns to his primary care physician after starting aspirin two weeks ago for primary prevention of coronary artery disease. He complains that he wakes up short of breath in the middle of the night and has had coughing "attacks" three times. After discontinuing aspirin, what medication is most appropriate for prevention of similar symptoms in this patient?

• A. Prednisone
• B. Montelukast (Correct Answer)
• C. Albuterol
• D. Fluticasone
• E. Tiotropium

Explanation: ***Montelukast*** - The patient is experiencing symptoms consistent with **aspirin-exacerbated respiratory disease (AERD)**, characterized by asthma symptoms, nasal polyps, and aspirin sensitivity. - **Montelukast**, a **leukotriene receptor antagonist**, is effective in preventing these symptoms by blocking the inflammatory effects of leukotrienes, which are overproduced in AERD. *Prednisone* - While **oral corticosteroids** like prednisone can treat acute exacerbations of AERD, they are not suitable for long-term primary prevention due to significant side effects. - Long-term use of prednisone is associated with issues like **osteoporosis**, **diabetes**, and **hypertension**. *Albuterol* - **Albuterol** is a **short-acting beta-agonist (SABA)** used for rescue relief of acute asthma symptoms and bronchospasm, not for long-term prevention. - It does not address the underlying inflammatory pathway triggered by aspirin in AERD. *Fluticasone* - **Fluticasone** is an **inhaled corticosteroid (ICS)** primarily used for long-term control of asthma by reducing airway inflammation. - While it can help with some asthma symptoms, it does not specifically prevent the aspirin-induced bronchospasm seen in AERD as effectively as leukotriene modifiers. *Tiotropium* - **Tiotropium** is a **long-acting muscarinic antagonist (LAMA)** primarily used in the maintenance treatment of **COPD** and sometimes for severe asthma. - It works by bronchodilation but does not target the specific leukotriene pathway involved in AERD.

Question 263: A 31-year-old woman comes to the physician because of intermittent episodes of stabbing right lower jaw pain for 6 weeks. The pain is severe, sharp, and lasts for a few seconds. These episodes commonly occur when she washes her face, brushes her teeth, or eats a meal. She does not have visual disturbances, weakness of her facial muscles, or hearing loss. Five weeks ago, she had an episode of acute bacterial sinusitis, which was treated with antibiotics. Which of the following is the most appropriate initial treatment for this patient's condition?

• A. Doxepin
• B. Microvascular decompression
• C. Carbamazepine (Correct Answer)
• D. Valacyclovir
• E. Amoxicillin

Explanation: ***Carbamazepine*** - The patient's presentation with severe, sharp, short-lasting right lower jaw pain triggered by facial activities (washing, brushing, eating) is classic for **trigeminal neuralgia**. - **Carbamazepine** is the first-line and most effective initial treatment for trigeminal neuralgia due to its mechanism of stabilizing neuronal membranes and reducing abnormal firing. *Doxepin* - **Doxepin** is a tricyclic antidepressant that can be used for neuropathic pain but is typically not the first-line agent, especially in severe, classic trigeminal neuralgia. - Its primary use is often for chronic neuropathic pain or in conditions where mood disorders are comorbid, which is not indicated here as the primary concern. *Microvascular decompression* - **Microvascular decompression** is a surgical procedure considered for trigeminal neuralgia when medical management, particularly with carbamazepine, fails or is not tolerated. - It is an invasive procedure and not an appropriate initial treatment for a newly diagnosed case before trying pharmacotherapy. *Valacyclovir* - **Valacyclovir** is an antiviral medication used to treat herpes virus infections, such as shingles (herpes zoster). - While postherpetic neuralgia can cause facial pain, the described pain characteristics (brief, sharp, triggered) are more typical of trigeminal neuralgia, and there is no mention of a vesicular rash. *Amoxicillin* - **Amoxicillin** is an antibiotic used to treat bacterial infections. - While the patient had a recent episode of sinusitis, her current pain is distinct from typical sinus pain and strongly suggestive of a neuropathic condition, not an ongoing bacterial infection.

Question 264: A 25-year-old woman presents to an urgent care center following a bee sting while at a picnic with her friends. She immediately developed a skin rash and swelling over her arm and face. She endorses diffuse itching over her torso. Past medical history is significant for a mild allergy to pet dander and ragweed. She occasionally takes oral contraceptive pills and diphenhydramine for her allergies. Family history is noncontributory. Her blood pressure is 119/81 mm Hg, heart rate is 101/min, respiratory rate is 21/min, and temperature is 37°C (98.6°F). On physical examination, the patient has severe edema over her face and severe stridor with inspiration at the base of both lungs. Of the following options, this patient is likely experiencing which of the following hypersensitivity reactions?

• A. Type 2 - cytotoxic hypersensitivity reaction
• B. Type 1 - anaphylactic hypersensitivity reaction (Correct Answer)
• C. Both A & B
• D. Type 4 - cell mediated (delayed) hypersensitivity reaction
• E. Type 3 - immune complex mediated hypersensitivity reaction

Explanation: ***Type 1 - anaphylactic hypersensitivity reaction*** - The rapid onset of symptoms like **skin rash**, **swelling (angioedema)**, **diffuse itching (pruritus)**, and **stridor** immediately following a **bee sting** is characteristic of an immediate, IgE-mediated hypersensitivity reaction. - This type of reaction involves the release of **histamine** and other mediators from **mast cells** and **basophils**, leading to systemic symptoms, including potential airway obstruction. *Type 2 - cytotoxic hypersensitivity reaction* - Type 2 hypersensitivity involves **antibodies** (IgG or IgM) binding to antigens on the surface of **target cells**, leading to cell destruction. - Examples include **hemolytic anemia** or **transfusion reactions**, which do not match the presented symptoms of allergic rash and angioedema. *Both A & B* - This option is incorrect because the patient's symptoms are highly consistent with a **Type 1 reaction** and do not align with the mechanisms or clinical manifestations of a Type 2 reaction. - The immediate and widespread allergic response points specifically to IgE-mediated anaphylaxis. *Type 4 - cell mediated (delayed) hypersensitivity reaction* - Type 4 hypersensitivity is a **delayed reaction** mediated by **T cells**, typically appearing 24-72 hours after exposure. - Examples include **contact dermatitis** or the **tuberculin skin test**, which are much slower in onset and different in presentation than the immediate, severe reaction described. *Type 3 - immune complex mediated hypersensitivity reaction* - Type 3 hypersensitivity involves the formation of **immune complexes** (antigen-antibody complexes) that deposit in tissues, causing inflammation. - Conditions like **serum sickness** or **lupus nephritis** are examples and typically have a slower onset and different clinical presentation (e.g., vasculitis, glomerulonephritis) compared to acute anaphylaxis.

Question 265: A 23-year-old man comes to the emergency department because of a 2-day history of painful swelling of the right hand. There is no associated recent trauma. Physical examination shows a 3 × 3-cm area of induration that is fluctuant and warm to the touch, consistent with an abscess. The patient consents to incision and drainage of the abscess in the emergency department. Following evaluation of the patient's allergy status, a short-acting, local anesthetic drug is administered via subcutaneous infiltration. Which of the following local anesthetics would provide the shortest duration of analgesia?

• A. Etidocaine
• B. Ropivacaine
• C. Chloroprocaine (Correct Answer)
• D. Mepivacaine
• E. Lidocaine

Explanation: ***Chloroprocaine*** - **Chloroprocaine** is an **ester-type** local anesthetic, which are rapidly metabolized by plasma cholinesterases, resulting in a **short duration of action**. - Its rapid metabolism makes it suitable for procedures requiring **brief analgesia** and a quick return to normal sensation. *Etidocaine* - **Etidocaine** is an **amide-type** local anesthetic known for its **long duration of action** due to its high lipid solubility and protein binding. - It would provide analgesia for a significantly longer period than the brief procedure indicated. *Ropivacaine* - **Ropivacaine** is an **amide-type** local anesthetic with a **long duration of action**, commonly used for regional anesthesia and continuous infusions. - It has a slower onset but prolonged effect, making it unsuitable for the shortest duration requirement. *Mepivacaine* - **Mepivacaine** is an **amide-type** local anesthetic with a **moderate duration of action**, longer than chloroprocaine but shorter than ropivacaine or bupivacaine. - Its duration is not the shortest among the options provided, as ester-type anesthetics are generally shorter-acting. *Lidocaine* - **Lidocaine** is an **amide-type** local anesthetic with an **intermediate duration of action**, making it one of the most commonly used. - While relatively short-acting compared to other amides, it is still longer than chloroprocaine due to its different metabolism.

Question 266: A 49-year-old woman is brought to the emergency department for a severe, sudden-onset generalized headache that began while she was riding an exercise bike at home that morning. After quickly getting off the bike and lying down, she lost consciousness. She was unconscious for a period of one minute. When she regained consciousness, she had neck stiffness, nausea, and two episodes of vomiting. She has hypertension. She does not smoke or drink alcohol. Her current medications include chlorthalidone and a multivitamin. She is in severe distress. Her temperature is 37.3°C (99.1F°), pulse is 88/min, respirations are 18/min, and blood pressure is 169/102 mm Hg. A CT scan of the head without contrast shows hyperdense material between the arachnoid mater and the pia mater. The patient is taken to the operating room for surgical clipping and transferred to the intensive care unit. Five days later, she has new-onset focal weakness of her left lower extremity. Her temperature is 37.1°C (98.8°F), pulse is 70/min, respirations are 17/min, and blood pressure is 148/90 mm Hg. Strength is 3/5 in the left lower extremity and 5/5 in the right lower extremity. Which of the following would most likely have been able to prevent this patient's condition?

• A. Intravenous labetalol
• B. Oral aspirin and clopidogrel
• C. Intravenous sodium nitroprusside
• D. Intravenous fresh frozen plasma
• E. Oral nimodipine (Correct Answer)

Explanation: ***Oral nimodipine*** - This patient experienced **delayed cerebral ischemia** due to **vasospasm** following a **subarachnoid hemorrhage (SAH)**, indicated by her new-onset focal weakness five days after the initial event. - **Nimodipine**, a calcium channel blocker, is the only medication proven to improve outcomes in SAH by preventing or reversing **cerebral vasospasm**. *Intravenous labetalol* - **Labetalol** is an antihypertensive used to control blood pressure, which might be elevated in SAH due to stress, but it does not prevent vasospasm. - While blood pressure control is important, labetalol would not directly address the underlying mechanism of delayed cerebral ischemia. *Oral aspirin and clopidogrel* - **Aspirin** and **clopidogrel** are antiplatelet agents used to prevent arterial thrombotic events (e.g., stroke, myocardial infarction) and could worsen bleeding in the setting of SAH. - They have no role in preventing or treating **cerebral vasospasm** after SAH. *Intravenous sodium nitroprusside* - **Sodium nitroprusside** is a potent vasodilator used for rapid blood pressure reduction in hypertensive emergencies, but it does not specifically target or prevent SAH-induced vasospasm. - Its use might even cause a rapid drop in cerebral perfusion pressure, potentially worsening brain ischemia. *Intravenous fresh frozen plasma* - **Fresh frozen plasma (FFP)** is used to reverse coagulopathies or to replace clotting factors, which could be relevant if there was a coagulopathy contributing to bleeding or a need for rapid reversal of anticoagulation. - However, FFP does not prevent **cerebral vasospasm** or delayed cerebral ischemia post-SAH.

Question 267: A 72-year-old woman comes to the emergency department because of severe pain in her right lower leg for 3 hours. She has also had worsening tingling that started 3 hours before. She has never had such pain in her leg in the past. Over the last couple months, she has occasionally had episodes of palpitations. She has hypertension and type 2 diabetes mellitus. Current medications include hydrochlorothiazide and lisinopril. Her pulse is 88/min and her blood pressure is 135/80 mm Hg. Physical examination shows a cool and pale right leg with delayed capillary filling. Muscle strength and tone in the right calf and foot are reduced. Femoral pulse is present bilaterally. Pedal pulses are absent on the right. Inhibition of which of the following would have most likely prevented this patient's condition?

• A. Voltage-gated cardiac potassium channels
• B. Synthesis of vitamin K-dependent factors (Correct Answer)
• C. Receptors of sympathetic nervous system
• D. Receptors for platelet aggregation
• E. Voltage-gated cardiac sodium channels

Explanation: ***Synthesis of vitamin K-dependent factors*** - The patient's presentation with **sudden onset severe leg pain**, **cool and pale limb**, **absent pedal pulses**, and a history of **palpitations (suggesting atrial fibrillation)** points to acute limb ischemia due to an **embolus** likely originating from the heart. - Atrial fibrillation leads to blood stasis and clot formation in the atria. Inhibiting the synthesis of **vitamin K-dependent coagulation factors (II, VII, IX, X, proteins C and S)** with an agent like warfarin would prevent these clots. *Voltage-gated cardiac potassium channels* - Inhibiting these channels (e.g., with **amiodarone** or **sotalol**) primarily affects cardiac repolarization and action potential duration, used to treat or prevent arrhythmias. - While it may help manage the underlying atrial fibrillation, it does not directly prevent the formation of clots that have already developed or are forming, which is the immediate cause of the limb ischemia. *Receptors of sympathetic nervous system* - Blocking sympathetic receptors (e.g., **beta-blockers**) can help control heart rate and blood pressure, which might be used to manage atrial fibrillation or hypertension. - However, this intervention does not directly target the coagulation cascade responsible for forming the embolus that occluded the leg vessel. *Receptors for platelet aggregation* - Inhibiting platelet aggregation (e.g., with **aspirin** or **clopidogrel**) would prevent arterial thrombosis, which is often seen in coronary artery disease or peripheral artery disease. - The patient's sudden, severe symptoms and history of palpitations are more suggestive of an embolic event originating from the heart, where **anticoagulation (targeting fibrin formation)** is more effective than antiplatelet therapy alone. *Voltage-gated cardiac sodium channels* - Blocking these channels (e.g., with **flecainide** or **lidocaine**) is primarily used to treat or prevent certain cardiac arrhythmias by altering the depolarization phase of the action potential. - Similar to potassium channel inhibition, this addresses the arrhythmia but does not directly prevent the formation of existing or impending thrombi responsible for the limb ischemia.

Question 268: A 27-year-old homeless man presents to the emergency department with abdominal pain and vomiting. He has a known history of intravenous drug use and has been admitted to the hospital several times before. On physical examination his temperature is 99°F (37.2°C), blood pressure is 130/85 mmHg, pulse is 90/min, respirations are 19/min, and pulse oximetry is 99% on room air. The patient is in obvious discomfort. There is increased salivation and lacrimation. Pupils are reactive to light and 5 mm bilaterally. Cardiopulmonary exam is unremarkable. There is diffuse abdominal tenderness to palpation with no rebound or guarding. Which of the following interventions would have prevented this patient’s current condition?

• A. Naltrexone
• B. Buprenorphine (Correct Answer)
• C. Lorazepam
• D. Naloxone
• E. Bupropion

Explanation: ***Buprenorphine*** - This patient is presenting with symptoms consistent with **opioid withdrawal** (abdominal pain, vomiting, increased salivation, lacrimation). **Buprenorphine** is used for **opioid dependence treatment** as it's a **partial opioid agonist** that helps manage withdrawal symptoms and cravings, thus preventing acute withdrawal episodes. - By stabilizing opioid receptors, buprenorphine, often combined with naloxone (Suboxone), reduces the risk of relapse and prevents the cycle of **intravenous drug use** that leads to withdrawal. *Naltrexone* - **Naltrexone** is an **opioid antagonist** used to prevent relapse in individuals who have achieved abstinence from opioids. It blocks the effects of opioids. - However, administering naltrexone to someone actively using opioids or in withdrawal would precipitate or worsen withdrawal symptoms, making it unsuitable for preventing this acute presentation. *Lorazepam* - **Lorazepam** is a **benzodiazepine** primarily used to treat **anxiety**, **insomnia**, and **seizures**, and it is often used in **alcohol withdrawal**. - While it can help manage some anxiety associated with opioid withdrawal, it does not address the underlying opioid dependence or prevent the physical symptoms of withdrawal itself, nor does it prevent the underlying cause of withdrawal which is abstinence from opioids. *Naloxone* - **Naloxone** is a potent, short-acting **opioid antagonist** used to **reverse opioid overdose** by rapidly displacing opioids from receptors. - It would not prevent withdrawal; in fact, administering naloxone to an opioid-dependent individual would acutely precipitate severe withdrawal. *Bupropion* - **Bupropion** is an **antidepressant** that also aids in **smoking cessation**. It works by inhibiting the reuptake of norepinephrine and dopamine. - It has no role in the prevention or treatment of opioid withdrawal and would not have altered this patient's current condition.

Question 269: A 45-year-old man with a history of recurrent gouty arthritis comes to the physician for a follow-up examination. Four weeks ago, he was diagnosed with hyperuricemia and treatment with allopurinol was begun. Since then, he has had another acute gout attack, which resolved after treatment with ibuprofen. His temperature is 37.1°C (98.8°F). Physical examination shows painless, chalky nodules on the metatarsophalangeal joint of his right foot. Laboratory studies show: Serum Creatinine 1.0 mg/dL Uric acid 8.5 mg/dL Cholesterol 278 mg/dL Urine Uric acid 245 mg/24 h (N = 240-755) From a pharmacological mechanism perspective, based on the urine findings, this patient would theoretically benefit from treatment with which of the following drugs to prevent future gout attacks?

• A. Indomethacin
• B. Rasburicase
• C. Colchicine
• D. Prednisolone
• E. Probenecid (Correct Answer)

Explanation: ***Probenecid*** - This patient's 24-hour urine uric acid excretion is **245 mg/24h**, which is at the lower end of the normal range (240-755 mg/24h). In gout management, patients excreting **<600 mg/24h** are typically classified as **underexcretors**, meaning their hyperuricemia is primarily due to decreased renal excretion of uric acid rather than overproduction. - **Probenecid** is a **uricosuric agent** that works by inhibiting the URAT1 transporter in the proximal tubule, thereby blocking uric acid reabsorption and increasing renal excretion of uric acid. - Since this patient is an underexcretor and allopurinol alone has not adequately controlled his serum uric acid (still 8.5 mg/dL with continued gout attacks), adding probenecid would directly address the underlying mechanism of **impaired renal excretion** and help lower serum uric acid levels. *Indomethacin* - **Indomethacin** is an **NSAID** used to treat acute gout attacks by inhibiting cyclooxygenase and reducing inflammation and pain. - It does not lower serum uric acid levels and therefore does not prevent future gout attacks. It is used for symptomatic relief during acute flares, not for prophylaxis. *Rasburicase* - **Rasburicase** is a recombinant **urate oxidase** enzyme that converts uric acid to allantoin, a more water-soluble compound that is easily excreted. - It is reserved for **acute severe hyperuricemia**, particularly in **tumor lysis syndrome**, and is administered intravenously. It is not used for chronic gout management or prophylaxis in ambulatory patients. *Colchicine* - **Colchicine** inhibits **microtubule polymerization**, thereby preventing neutrophil migration and activation in response to uric acid crystals. - While it is effective for acute gout treatment and can be used for prophylaxis during initiation of urate-lowering therapy, it does not reduce serum uric acid levels. It only prevents the inflammatory response to existing crystals. *Prednisolone* - **Prednisolone** is a **corticosteroid** used to treat acute gout attacks by suppressing inflammation, particularly when NSAIDs are contraindicated (e.g., renal impairment, GI ulcers). - Like other anti-inflammatory agents, it does not address the underlying hyperuricemia or lower uric acid levels, so it cannot prevent future attacks.

Question 270: A group of investigators is studying a drug to treat refractory angina pectoris. This drug works by selectively inhibiting the late influx of sodium ions into cardiac myocytes. At high doses, the drug also partially inhibits the degradation of fatty acids. Which of the following is the most likely effect of this drug?

• A. Increased prolactin release
• B. Decreased uric acid excretion
• C. Decreased serum pH
• D. Increased oxygen efficiency (Correct Answer)
• E. Decreased insulin release

Explanation: ***Increased oxygen efficiency*** - Inhibiting the **late sodium current** reduces intracellular calcium overload, preventing diastolic dysfunction and improving myocardial relaxation. - Partial inhibition of **fatty acid degradation** shifts myocardial metabolism towards glucose utilization, which is more oxygen-efficient. *Increased prolactin release* - This drug does not act on **dopamine receptors**, which are typically involved in regulating prolactin release. - **Ranolazine**, the drug described, has no known effect on the endocrine system, specifically prolactin. *Decreased uric acid excretion* - **Uric acid excretion** is primarily affected by renal handling, often influenced by diuretics or drugs that compete for renal transporters, which is not a mechanism of this drug. - This drug does not interfere with the **organic anion transporters (OATs)** responsible for uric acid secretion. *Decreased serum pH* - Changes in **serum pH** are usually associated with severe metabolic or respiratory disturbances, which are not direct effects of a drug targeting cardiac ion channels and metabolism. - The drug's mechanism of action does not directly produce **acidic byproducts** or inhibit acid-base regulatory systems. *Decreased insulin release* - Insulin release is primarily stimulated by **glucose** and modulated by various endocrine pathways, none of which are directly targeted by a drug that inhibits cardiac sodium channels and fatty acid oxidation. - There is no evidence that this class of drugs affects **pancreatic beta-cell function**.

Question 271: A 35-year-old woman comes to the physician because of recurring episodes of headache for the past 5 months. During this period, she has had headaches for approximately 20 days per month. The episodes last for about 2 hours each. She describes the headaches as dull, pressing, and non-pulsating holocranial pain. The symptoms do not increase with exertion. She has no vomiting, nausea, phonophobia, or photophobia. She has two children and has had a great deal of stress lately due to frequent fights with her husband. She appears well. Vital signs are within normal limits. Physical examination shows no abnormalities. Which of the following is the most appropriate pharmacotherapy for this patient?

• A. Valproate therapy
• B. Propranolol therapy
• C. Amitriptyline therapy (Correct Answer)
• D. Ergotamine therapy
• E. Aspirin therapy

Explanation: ***Amitriptyline therapy*** - The patient's presentation with **dull, pressing, non-pulsating holocranial pain** that does not worsen with exertion, without nausea, vomiting, photophobia, or phonophobia, is highly suggestive of **tension-type headache (TTH)**. - Given the high frequency (20 days/month) and duration (5 months), this is likely a **chronic tension-type headache**, for which **tricyclic antidepressants (TCAs)** like amitriptyline are the first-line prophylactic treatment. *Valproate therapy* - **Valproate** is primarily used for **migraine prophylaxis** and seizure disorders. - The patient's headache characteristics (dull, pressing, non-pulsating, no photophobia/phonophobia) are not consistent with migraine. *Propranolol therapy* - **Propranolol** is a beta-blocker also used for **migraine prophylaxis**. - As with valproate, the patient's headache features do not align with migraine, making propranolol less appropriate here. *Ergotamine therapy* - **Ergotamine** is an acute abortive medication for **migraine attacks**, not a prophylactic treatment for chronic headaches. - Its use in frequent headaches carries a risk of **medication overuse headache**, and it is not suitable for tension-type headaches. *Aspirin therapy* - **Aspirin** is an **NSAID** used for acute pain relief in episodic headaches, including tension-type headaches. - It is not considered an appropriate prophylactic therapy for **chronic, frequent tension-type headaches** and would not address the underlying issue effectively.

Question 272: A 47-year-old female presents to her primary care physician complaining of diarrhea and fatigue. She reports an eight-month history of increasingly frequent diarrhea, fatigue, and muscle weakness. She currently has over 15 episodes of watery diarrhea per day despite fasting. Her past medical history is notable for diabetes that is well controlled with metformin. Her temperature is 98.6°F (37°C), blood pressure is 100/70 mmHg, pulse is 95/min, and respirations are 18/min. Physical examination is notable for mild diffuse abdominal pain and facial flushing. An upper endoscopy is performed and the stomach is found to be less acidic than normal. In addition to correcting this patient’s dehydration, which of the following medications is most appropriate in the management of this patient?

• A. Metoclopramide
• B. Octreotide (Correct Answer)
• C. Metronidazole
• D. Omeprazole
• E. Secretin

Explanation: ***Octreotide*** - This patient's symptoms (watery diarrhea, fatigue, muscle weakness, facial flushing, and achlorhydria) are highly suggestive of a **VIPoma** (vasoactive intestinal peptide-secreting tumor). **Octreotide** is a somatostatin analog that inhibits the release of VIP and is the most appropriate medication for symptomatic control. - It also helps reduce **fluid and electrolyte losses** associated with severe secretory diarrhea caused by VIPomas. *Metoclopramide* - **Metoclopramide** is a prokinetic agent and antiemetic, primarily used for nausea, vomiting, and gastroparesis. - It does not address the underlying pathology of a VIPoma or the severe secretory diarrhea seen in this patient. *Metronidazole* - **Metronidazole** is an antibiotic used to treat bacterial infections, particularly anaerobic infections and certain parasitic infections. - There is no indication of an infectious cause for the severe diarrhea in this case, and it would not be effective for VIPoma-related symptoms. *Omeprazole* - **Omeprazole** is a proton pump inhibitor, used to reduce stomach acid production in conditions like GERD or peptic ulcers. - While the patient has less acidic stomach, this is a symptom of a VIPoma (due to VIP's inhibitory effect on gastric acid secretion), not the primary issue, and omeprazole would further decrease acid, which is already low. *Secretin* - **Secretin** is a hormone involved in regulating gastric acid and pancreatic bicarbonate secretion, used diagnostically in some gastrointestinal disorders. - It is not a therapeutic agent for chronic diarrhea or VIPoma.

Question 273: A 56-year-old man is brought to the clinic by his wife for complaints of progressive weakness for the past 3 months. He reports difficulty eating, especially when chewing foods like steak. The wife complains that he has been “out of it lately and has been forgetting my birthday." His past medical history is significant for celiac disease, for which he eats a gluten-free diet. He reports that he stepped on a nail last week, but the nail did not seem rusty so he just washed his feet afterward. His wife reports that he has been up to date on his tetanus vaccinations. Physical examination demonstrates weakness and fasciculations of the left upper extremity along with spastic clonus of the left ankle. The patient denies gait disturbances, vision or hearing changes, headaches, nausea/vomiting, gastrointestinal disturbances, or incontinence. What is best next step in terms of management for this patient?

• A. Tetanus immunoglobulin and vaccine
• B. Riluzole (Correct Answer)
• C. Vitamin B12
• D. Levodopa
• E. Donepezil

Explanation: ***Riluzole*** - The patient's presentation with **progressive weakness**, **difficulty chewing**, **fasciculations**, and **spastic clonus** strongly suggests **amyotrophic lateral sclerosis (ALS)**, a motor neuron disease. - **Riluzole** is a neuroprotective drug approved for ALS that can modestly extend survival and delay the need for tracheostomy. *Tetanus immunoglobulin and vaccine* - Although the patient stepped on a nail, his extensive neurological symptoms are **not consistent with tetanus**, which typically causes muscle spasms and rigidity. - The patient's wife states he is **up to date on tetanus vaccinations**, making tetanus less likely, and the neurological signs point elsewhere. *Vitamin B12* - **Vitamin B12 deficiency** can cause neurological symptoms like peripheral neuropathy, cognitive changes, and gait disturbances, but it typically does **not present with fasciculations and spasticity** as seen here. - While celiac disease increases the risk of malabsorption, the constellation of symptoms is more indicative of ALS. *Levodopa* - **Levodopa** is a primary treatment for **Parkinson's disease**, which involves tremors, bradykinesia, rigidity, and postural instability. - The patient's symptoms of primarily upper motor neuron (spastic clonus) and lower motor neuron (fasciculations) signs, with absent gait disturbances, are **not typical for Parkinson's disease**. *Donepezil* - **Donepezil** is an acetylcholinesterase inhibitor used to treat **Alzheimer's disease** and other forms of dementia. - Although the patient has some "forgetting," his predominant symptoms are **motor neuron deficits** rather than cognitive decline, making donepezil an inappropriate first-line treatment for his primary condition.

Question 274: A researcher is studying the circulating factors that are released when immune cells are exposed to antigens. Specifically, she is studying a population of CD2+ cells that have been activated acutely. In order to determine which factors are secreted by these cells, she cultures the cells in media and collects the used media from these plates after several days. She then purifies a small factor from this media and uses it to stimulate various immune cell types. She finds that this factor primarily seems to increase the growth and prolong the survival of other CD2+ cells. Which of the following is most likely the factor that was purified by this researcher?

• A. Interleukin-2 (Correct Answer)
• B. Interleukin-3
• C. Interleukin-4
• D. Interleukin-5
• E. Interleukin-1

Explanation: ***Interleukin-2*** - **Interleukin-2 (IL-2)** is a crucial cytokine for the **growth**, **proliferation**, and **survival** of T lymphocytes, which are CD2+ cells. - Activated T cells, like the acute CD2+ cells in the scenario, are a primary source of IL-2, and IL-2 acts in an **autocrine** and **paracrine** fashion to stimulate other T cells. *Interleukin-3* - **Interleukin-3 (IL-3)** primarily stimulates the growth and differentiation of **hematopoietic stem cells** and progenitors, not specifically mature CD2+ cells. - It plays a role in the development of various myeloid cell lineages and mast cells, and its main effect is not confined to T cells. *Interleukin-4* - **Interleukin-4 (IL-4)** is critical for the differentiation of naive T helper cells into **Th2 cells** and is a key cytokine for **B cell proliferation** and **antibody class switching** to IgE. - While it has immunomodulatory effects on T cells, its primary role is not in promoting the generalized growth and survival of other CD2+ cells. *Interleukin-5* - **Interleukin-5 (IL-5)** is predominantly involved in the growth, differentiation, and activation of **eosinophils**. - It also plays a role in B cell growth and IgA production, but its effects are not primarily on universal CD2+ cell growth and survival. *Interleukin-1* - **Interleukin-1 (IL-1)** is a **pro-inflammatory cytokine** produced by macrophages, monocytes, and other immune cells in response to infection or injury. - It primarily mediates **acute phase responses**, fever, and activates endothelial cells, but its main function is not to promote the growth and survival of T lymphocytes.

Question 275: A 20-year-old man comes to the physician because of recurrent episodes of shortness of breath and a nonproductive cough for the past 4 months. He has two episodes per week, which resolve spontaneously with rest. Twice a month, he wakes up at night with shortness of breath. His pulse is 73/min, respirations are 13/min, and blood pressure is 122/70 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 98%. Physical examination shows no abnormalities. Spirometry shows an FVC of 95%, an FEV1:FVC ratio of 0.85, and an FEV1 of 81% of predicted. Which of the following is the most appropriate initial pharmacotherapy?

• A. Terbutaline inhaler
• B. Mometasone inhaler and oral zafirlukast
• C. Oral montelukast sodium
• D. Fluticasone inhaler (Correct Answer)
• E. Budesonide and formoterol inhaler

Explanation: **Fluticasone inhaler** - The patient presents with symptoms consistent with **persistent asthma** (symptoms >2 times/week and nighttime awakenings >2 times/month). - **Inhaled corticosteroids** like fluticasone are the preferred initial **controller therapy** for persistent asthma due to their potent **anti-inflammatory effects**. *Terbutaline inhaler* - Terbutaline is a **short-acting beta-agonist (SABA)**, primarily used as a **rescue medication** for acute asthma symptoms. - While it would relieve acute symptoms, it does not address the underlying inflammation in persistent asthma and is not appropriate for **monotherapy** as initial pharmacotherapy in this context. *Mometasone inhaler and oral zafirlukast* - This combination includes an **inhaled corticosteroid (mometasone)** and a **leukotriene receptor antagonist (zafirlukast)**. - While appropriate for more severe or uncontrolled asthma, starting with a **single inhaled corticosteroid** is the recommended initial step for **persistent asthma** before adding a second-line agent. *Oral montelukast sodium* - Montelukast is a **leukotriene receptor antagonist** used in asthma management, often as an **add-on therapy** or for patients who cannot tolerate inhaled corticosteroids. - It is generally **less effective than inhaled corticosteroids** as initial monotherapy for persistent asthma in controlling inflammation and preventing exacerbations. *Budesonide and formoterol inhaler* - This is a combination of an **inhaled corticosteroid (budesonide)** and a **long-acting beta-agonist (formoterol)**. - This combination is typically used for **moderate to severe persistent asthma** or as **maintenance and reliever therapy (MART)**, not as the initial monotherapy for mild persistent asthma.

Question 276: A 68-year-old woman comes to the physician for a follow-up examination. Three months ago, she underwent heart transplantation for restrictive cardiomyopathy and was started on transplant rejection prophylaxis. Her pulse is 76/min and blood pressure is 148/82 mm Hg. Physical examination shows enlargement of the gum tissue. There is a well-healed scar on her chest. Serum studies show hyperlipidemia. The physician recommends removing a drug that decreases T cell activation by inhibiting the transcription of interleukin-2 from the patient's treatment regimen and replacing it with a different medication. Which of the following drugs is the most likely cause of the adverse effects seen in this patient?

• A. Mycophenolate mofetil
• B. Azathioprine
• C. Tacrolimus
• D. Cyclosporine (Correct Answer)
• E. Prednisolone

Explanation: ***Cyclosporine*** - The patient's symptoms of **gingival hyperplasia**, **hypertension**, and **hyperlipidemia** are classic side effects associated with cyclosporine. - Cyclosporine is a calcineurin inhibitor that **decreases T-cell activation** by inhibiting IL-2 transcription, matching the drug description. *Mycophenolate mofetil* - Mycophenolate mofetil is an **antiproliferative agent** that inhibits purine synthesis, primarily affecting lymphocytes. - Its common side effects are mainly **hematologic** (leukopenia, anemia) and **gastrointestinal** (diarrhea, nausea), not gingival hyperplasia or hypertension. *Azathioprine* - Azathioprine is a **purine analog** that impairs DNA synthesis and inhibits lymphocyte proliferation. - Key side effects include **myelosuppression** (leukopenia, thrombocytopenia) and **hepatotoxicity**, which are not present here. *Tacrolimus* - Tacrolimus is also a **calcineurin inhibitor** that inhibits IL-2 transcription, similar to cyclosporine. - While it can cause **hypertension** and **hyperlipidemia**, it is less commonly associated with **gingival hyperplasia** than cyclosporine. *Prednisolone* - Prednisolone is a **corticosteroid** used for immunosuppression, acting broadly on the immune system. - Common side effects include **hyperglycemia**, **osteoporosis**, and **cataracts**, not specific gingival overgrowth.

Question 277: A 63-year-old African American man presents to the physician for a follow-up examination. He has a history of chronic hypertension and type 2 diabetes mellitus. He has no history of coronary artery disease. His medications include aspirin, hydrochlorothiazide, losartan, and metformin. He exercises every day and follows a healthy diet. He does not smoke. He consumes alcohol moderately. There is no history of chronic disease in the family. His blood pressure is 125/75 mm Hg, which is confirmed on a repeat measurement. His BMI is 23 kg/m2. The physical examination shows no abnormal findings. The laboratory test results show: Serum HbA1C 6.9% Total cholesterol 176 mg/dL Low-density lipoprotein (LDL-C) 105 mg/dL High-density lipoprotein (HDL-C) 35 mg/dL Triglycerides 175 mg/dL The patient's 10-year risk of cardiovascular disease (CVD) is 18.7%. Lifestyle modifications including diet and exercise have been instituted. Which of the following is the most appropriate next step in pharmacotherapy?

• A. Fenofibrate
• B. Atorvastatin (Correct Answer)
• C. Metoprolol
• D. Liraglutide
• E. Lisinopril

Explanation: ***Atorvastatin*** - This patient has **diabetes mellitus**, an **LDL-C of 105 mg/dL**, and an estimated **10-year CVD risk of 18.7%**. Current guidelines recommend **high-intensity statin therapy** for individuals with diabetes aged 40-75 with an LDL-C >= 70 mg/dL and a 10-year ASCVD risk of 7.5% or higher. - Atorvastatin is a **high-intensity statin** that can significantly lower LDL-C and reduce cardiovascular event risk. *Fenofibrate* - **Fenofibrate** is primarily used to reduce **elevated triglyceride levels** and can increase HDL-C, but it is **not the first-line therapy** for primary prevention of cardiovascular disease in a patient with diabetes and elevated LDL-C like this one. - Its role is usually considered in cases of **severe hypertriglyceridemia** (typically >500 mg/dL) to prevent pancreatitis, or as an adjunct to statins if triglycerides remain high, but the primary goal here is LDL reduction. *Metoprolol* - **Metoprolol** is a **beta-blocker** primarily used for blood pressure control, heart rate reduction, and in conditions like angina or heart failure. - The patient's **blood pressure is well-controlled** (125/75 mmHg) with his current regimen, and there is no indication for a beta-blocker in this context for primary CVD prevention. *Liraglutide* - **Liraglutide** is a **GLP-1 receptor agonist** used in the management of **type 2 diabetes mellitus** to improve glycemic control and has shown cardiovascular benefits. - However, the patient's **HbA1c of 6.9%** indicates relatively good glycemic control for a patient with diabetes, and the immediate priority for CVD prevention, given his lipid profile and risk, is LDL-C lowering with a statin. *Lisinopril* - **Lisinopril** is an **ACE inhibitor** commonly used for **hypertension**, heart failure, and renal protection in diabetes. - The patient is already on **losartan**, an angiotensin receptor blocker (ARB), which serves a similar purpose, and his **blood pressure is well-controlled**, so adding lisinopril would be redundant and unnecessary for immediate CVD primary prevention.

Question 278: A 60-year-old man comes to the physician for the evaluation of nausea over the past week. During this period, he has also had several episodes of non-bloody vomiting. Last month, he was diagnosed with stage II Hodgkin lymphoma and was started on adriamycin, bleomycin, vinblastine, and dacarbazine. His temperature is 37°C (98.6°F), pulse is 95/min, and blood pressure is 105/70 mm Hg. Physical examination shows cervical lymphadenopathy. The liver is palpated 1 to 2 cm below the right costal margin, and the spleen is palpated 2 to 3 cm below the left costal margin. The remainder of the examination shows no abnormalities. The patient is started on an appropriate medication. Two weeks later, he develops headaches and states that his last bowel movement was 4 days ago. The patient was most likely treated with which of the following medications?

• A. 5-HT3 antagonist (Correct Answer)
• B. Cannabinoid receptor agonist
• C. H1 antagonist
• D. Muscarinic antagonist
• E. D2 antagonist

Explanation: ***5-HT3 antagonist*** - The patient was likely treated with a **5-HT3 antagonist** due to symptoms of nausea and vomiting following chemotherapy. This class of antiemetics can cause dose-dependent **headache** and **constipation** as common side effects. - The subsequent development of headaches and constipation (no bowel movement for 4 days) points to the known side effect profile of 5-HT3 antagonists, such as **ondansetron**. *Cannabinoid receptor agonist* - **Cannabinoid receptor agonists** (e.g., dronabinol) are used for chemotherapy-induced nausea and vomiting but are associated with side effects like **drowsiness**, **dizziness**, and **mood changes**, not typically headache and constipation. - They also tend to have a slower onset of action compared to 5-HT3 antagonists. *H1 antagonist* - **H1 antagonists** (e.g., diphenhydramine) are used for motion sickness and mild nausea, often causing **sedation** and **anticholinergic effects** like dry mouth, blurred vision, and urinary retention. - While they can cause constipation due to anticholinergic effects, headache is not a prominent side effect, and their primary role is not for severe chemotherapy-induced nausea. *Muscarinic antagonist* - **Muscarinic antagonists** (e.g., scopolamine) have antiemetic properties, particularly for motion sickness, but are not first-line for chemotherapy-induced nausea and vomiting. - These anticholinergic drugs are associated with side effects such as **dry mouth**, **constipation**, **urinary retention**, and **blurred vision**, but they are not the most likely choice given the clinical scenario and the specific combination of headache and constipation. *D2 antagonist* - **D2 antagonists** (e.g., metoclopramide, prochlorperazine) are effective antiemetics but are primarily associated with **extrapyramidal symptoms** (e.g., dystonia, parkinsonism), sedation, and hyperprolactinemia. - Although constipation can occur, the combination of headache and constipation in this context is more characteristic of 5-HT3 antagonists, which are commonly prescribed first-line for chemotherapy-induced nausea.

Question 279: An 18-year-old woman presents to the emergency department with a complaint of severe abdominal pain for the past 6 hours. She is anorexic and nauseous and has vomited twice since last night. She also states that her pain initially began in the epigastric region, then migrated to the right iliac fossa. Her vital signs include a respiratory rate of 14/min, blood pressure of 130/90 mm Hg, pulse of 110/min, and temperature of 38.5°C (101.3°F). On abdominal examination, there is superficial tenderness in her right iliac fossa, rebound tenderness, rigidity, and abdominal guarding. A complete blood count shows neutrophilic leukocytosis and a shift to the left. Laparoscopic surgery is performed and the inflamed appendix, which is partly covered by a yellow exudate, is excised. Microscopic examination of the appendix demonstrates a neutrophil infiltrate of the mucosal and muscular layers with extension into the lumen. Which of the following chemical mediators is responsible for pain in this patient?

• A. IgG and complement C3b
• B. Bradykinin and prostaglandin (Correct Answer)
• C. 5- hydroperoxyeicosatetraenoic acid (5-HPETE) and leukotriene A4
• D. Serotonin and histamine
• E. Tumor necrosis factor and interleukin-1

Explanation: ***Bradykinin and prostaglandin*** - **Bradykinin** and **prostaglandins** are key inflammatory mediators that directly stimulate **nociceptors**, leading to the sensation of pain. Prostaglandins are also responsible for inducing fever. - The patient's symptoms, including **severe abdominal pain**, fever, and local tenderness, are consistent with acute inflammation (appendicitis), where these mediators play a central role. *IgG and complement C3b* - **IgG** is an antibody involved in the adaptive immune response, primarily responsible for pathogen neutralization and opsonization. - **Complement C3b** is a component of the complement system involved in opsonization and forming the membrane attack complex, but neither directly mediates pain. *5- hydroperoxyeicosatetraenoic acid (5-HPETE) and leukotriene A4* - **5-HPETE** is an unstable intermediate in the lipoxygenase pathway, leading to the formation of leukotrienes. - **Leukotriene A4** is a precursor to other leukotrienes (e.g., LTB4, LTC4, LTD4) that are potent **chemotactic agents** and **bronchoconstrictors**, but they are not primary pain mediators. *Serotonin and histamine* - **Serotonin** is primarily involved in smooth muscle contraction, vasoconstriction, and neurotransmission; while it can modulate pain, it is not a direct primary mediator in acute appendicitis. - **Histamine** is released by mast cells and basophils, causing vasodilation and increased vascular permeability (contributing to edema), but its role in direct pain mediation in this context is less significant than bradykinin or prostaglandins. *Tumor necrosis factor and interleukin-1* - **Tumor necrosis factor (TNF)** and **interleukin-1 (IL-1)** are **pro-inflammatory cytokines** that are crucial in initiating and amplifying the inflammatory response. - While they contribute to fever and systemic symptoms of inflammation, their primary role is in cell signaling and immune cell activation rather than direct pain sensation.

Question 280: A 72-year-old man presents to the emergency department with a 1 hour history of bruising and bleeding. He says that he fell and scraped his knee on the ground. Since then, he has been unable to stop the bleeding and has developed extensive bruising around the area. He has a history of gastroesophageal reflux disease, hypertension, and atrial fibrillation for which he is taking an oral medication. He says that he recently started taking omeprazole for reflux. Which of the following processes is most likely inhibited in this patient?

• A. Sulfation
• B. Oxidation (Correct Answer)
• C. Filtration
• D. Acetylation
• E. Glucuronidation

Explanation: ***Oxidation*** - The patient is taking **omeprazole**, a proton pump inhibitor, which is a known **CYP450 inhibitor**. - Since the patient is also on an **oral anticoagulant** for atrial fibrillation, inhibition of CYP450 enzymes can reduce the metabolism of the anticoagulant, leading to **increased anticoagulant effect** and subsequent bleeding and bruising. *Sulfation* - **Sulfation** is a phase II metabolic reaction that converts compounds into more polar and excretable forms, but omeprazole primarily affects phase I metabolism involving CYP450 enzymes. - While sulfation can be important for the metabolism of some drugs, it is not the primary process inhibited by omeprazole to cause increased bleeding with oral anticoagulants. *Filtration* - **Filtration** is a renal process and not a metabolic enzyme pathway affected by omeprazole. - Omeprazole's interaction with anticoagulants mainly occurs through hepatic metabolism, not renal filtration. *Acetylation* - **Acetylation** is a phase II metabolic reaction, primarily carried out by **N-acetyltransferases**. - Omeprazole is primarily known to interact with **CYP450 enzymes** (phase I metabolism) rather than N-acetyltransferases. *Glucuronidation* - **Glucuronidation** is a phase II metabolic reaction involving **UGT enzymes** that typically inactivates and increases the excretion of drugs. - While important for drug metabolism, omeprazole's primary drug interactions leading to increased anticoagulant effects are via **CYP450 inhibition** (phase I metabolism), not directly through glucuronidation.

Question 281: A 55-year-old man comes to the physician because of a 2-month history of gradually worsening pain and burning in his feet that is impairing his ability to sleep. He also has a non-healing, painless ulcer on the bottom of his right toe, which has been progressively increasing in size despite the application of bandages and antiseptic creams at home. He has a 7-year history of type II diabetes mellitus treated with oral metformin. He also has narrow-angle glaucoma treated with timolol eye drops and chronic back pain due to a motorcycle accident a few years ago, which is treated with tramadol. Vital signs are within normal limits. Physical examination shows a 3-cm, painless ulcer on the plantar surface of the right toe. The ulcer base is dry, with no associated erythema, edema, or purulent discharge. Neurological examination shows loss of touch, pinprick sensation, proprioception, and vibration sense of bilateral hands and feet. These sensations are preserved in the proximal portions of the limbs. Muscle strength is normal. Bilateral ankle reflexes are absent. A diabetic screening panel is done and shows a fasting blood sugar of 206 mg/dL. An ECG shows a left bundle branch block. Which of the following is the most appropriate next step in the management of this patient's pain?

• A. Oxycodone
• B. Pregabalin (Correct Answer)
• C. Injectable insulin
• D. Amitriptyline
• E. Ulcer debridement

Explanation: ***Pregabalin*** - This patient presents with symptoms highly suggestive of **diabetic peripheral neuropathy**, including burning pain in the feet, a painless neuropathic ulcer, and loss of sensation in a stocking-glove distribution with absent ankle reflexes. **Pregabalin** is a first-line agent for neuropathic pain. - It works by binding to the **α2δ subunit of voltage-gated calcium channels**, reducing the release of excitatory neurotransmitters. - Pregabalin is **preferred over amitriptyline** in this patient due to his cardiac conduction abnormality (LBBB) and age-related concerns with anticholinergic effects. *Oxycodone* - **Opioids like oxycodone** are generally not recommended as first-line treatment for chronic neuropathic pain due to concerns about tolerance, dependence, and side effects. - While it may provide some pain relief, the **risks often outweigh the benefits** for long-term management of diabetic neuropathy. *Injectable insulin* - Poorly controlled **diabetes mellitus** is the underlying cause for the patient's neuropathy and ulcer, and optimizing glycemic control (e.g., with insulin) is crucial for preventing progression and complications. - However, **injectable insulin** is not a direct treatment for the symptomatic **neuropathic pain or burning sensation** the patient is experiencing. - While important for long-term management, it does not address the immediate complaint of pain. *Amitriptyline* - **Amitriptyline**, a tricyclic antidepressant, is another first-line medication for **neuropathic pain**. - However, it is **relatively contraindicated** in this patient due to his **left bundle branch block (LBBB)**, as tricyclic antidepressants can worsen cardiac conduction abnormalities and increase the risk of arrhythmias. - Additionally, as an **anticholinergic** agent, it is generally less preferred in older patients due to potential side effects like urinary retention, constipation, dry mouth, dizziness, and confusion. *Ulcer debridement* - **Ulcer debridement** is an important step in the management of the non-healing ulcer to promote healing and prevent infection. - While crucial for ulcer management, it does not directly address the primary complaint of **burning neuropathic pain** in the feet.

Question 282: A 28-year-old woman presents with increased facial hair growth. She says she noticed a marked growth and darkening of hair on her face and feels embarrassed. Past medical history is significant for asthma, well-controlled by medication, and epilepsy diagnosed 6 months ago, managed with phenytoin. Her other medications are albuterol, beclomethasone, a daily multivitamin, and a garlic supplement. The patient denies any smoking history, alcohol or recreational drug use. Family history is significant for asthma in her father. Review of systems is positive for occasional diplopia. Her pulse is 75/min, respiratory rate is 15 /min, and blood pressure is 110/76 mm Hg. Her body mass index (BMI) is 24 kg/m2. On physical examination, she appears healthy in no apparent distress. There are excessive facial hair growth and enlarged gums. The remainder of the examination is unremarkable. Which of the following medications is most likely responsible for this patient's symptoms?

• A. Garlic supplement
• B. Phenytoin (Correct Answer)
• C. Albuterol
• D. Beclomethasone
• E. Multivitamin

Explanation: ***Phenytoin*** - Phenytoin is a known cause of **hirsutism** (excessive facial hair growth) and **gingival hyperplasia** (enlarged gums). - The patient's recent diagnosis of **epilepsy** and subsequent treatment with phenytoin directly link her symptoms to this medication. *Garlic supplement* - Garlic supplements are generally associated with beneficial effects such as cardiovascular health and immune support. - They are **not known** to cause hirsutism or gingival hyperplasia. *Albuterol* - Albuterol is a **beta-2 adrenergic agonist** used for asthma relief, primarily causing bronchodilation. - Its common side effects include tremor, tachycardia, and headaches, but **not hirsutism or gingival hyperplasia**. *Beclomethasone* - Beclomethasone is an **inhaled corticosteroid** used to manage asthma and reduce airway inflammation. - While systemic corticosteroids can have various side effects, inhaled forms have fewer systemic effects, and neither type causes **hirsutism** or **gingival hyperplasia**. *Multivitamin* - Multivitamins provide essential vitamins and minerals, and generally do not cause adverse effects unless consumed in excessive amounts. - They are **not associated** with hirsutism or gingival hyperplasia.

Question 283: A 34-year-old woman is brought to the emergency department by fire and rescue after an apparent suicide attempt. She reports ingesting several pills 6 hours prior to presentation but cannot recall what they were. No pills were found on the scene. She complains of severe malaise, ringing in her ears, and anxiety. Her past medical history is notable for bipolar disorder, generalized anxiety disorder, rheumatoid arthritis, obesity, and diabetes. She takes lithium, methotrexate, metformin, and glyburide. She has a reported history of benzodiazepine and prescription opioid abuse. Her temperature is 102.2°F (39°C), blood pressure is 135/85 mmHg, pulse is 110/min, and respirations are 26/min. On exam, she appears diaphoretic and pale. Results from an arterial blood gas are shown: pH: 7.48 PaCO2: 32 mmHg HCO3-: 23 mEq/L This patient should be treated with which of the following?

• A. Ammonium chloride
• B. Atropine
• C. Sodium bicarbonate (Correct Answer)
• D. Flumazenil
• E. Physostigmine

Explanation: ***Sodium bicarbonate*** - This patient presents with symptoms highly suggestive of **salicylate (aspirin) overdose**: tinnitus, tachypnea, hyperthermia, altered mental status, and **respiratory alkalosis** on ABG. - **Sodium bicarbonate** is the treatment of choice to **alkalinize the urine** (target pH 7.5-8.0), which increases renal excretion of salicylates by trapping the ionized form in the urine. - Salicylate toxicity initially causes **respiratory alkalosis** (direct stimulation of the respiratory center), and can progress to **metabolic acidosis** in severe cases due to uncoupling of oxidative phosphorylation. *Ammonium chloride* - **Ammonium chloride** is an acidifying agent and would be **contraindicated** in salicylate toxicity. - Acidifying the urine would increase reabsorption of salicylate and worsen toxicity. - It has limited use in toxicology for enhancing excretion of basic drugs, but not applicable here. *Atropine* - **Atropine** is an anticholinergic agent used to treat bradycardia or organophosphate/cholinergic poisoning. - It is not indicated for salicylate toxicity and would not address the patient's acid-base disturbance or enhance drug elimination. *Flumazenil* - **Flumazenil** is a benzodiazepine receptor antagonist used to reverse **benzodiazepine overdose**. - While the patient has a history of benzodiazepine abuse, her presentation (tinnitus, hyperthermia, tachypnea, respiratory alkalosis) is classic for **salicylate toxicity**, not benzodiazepine overdose. - Flumazenil also carries risk of precipitating seizures in patients with chronic benzodiazepine use. *Physostigmine* - **Physostigmine** is a cholinesterase inhibitor used to treat **anticholinergic toxicity** (e.g., from antihistamines, TCAs). - The patient's symptoms are inconsistent with anticholinergic poisoning (which would present with hyperthermia, dry skin, mydriasis, urinary retention, altered mental status). - This patient has diaphoresis and tachypnea, more consistent with salicylate toxicity.

Question 284: A 47-year-old woman presents to the emergency department with ongoing dyspnea and confusion for 2 hours. She has a history of psychosis and alcohol abuse. She has smoked 1 pack per day for 25 years. She is agitated and confused. Her blood pressure is 165/95 mm Hg; pulse 110/min; respirations 35/min; and temperature, 36.7°C (98.1°F). The pulmonary examination shows tachypnea and mild generalized wheezing. Auscultation of the heart shows no abnormal sounds. The remainder of the physical examination shows no abnormalities. Laboratory studies show: Serum Na+ 138 mEq/L CI- 100 mEq/L Arterial blood gas analysis on room air pH 7.37 pCO2 21 mm Hg pO2 88 mm Hg HCO3- 12 mEq/L Which of the following best explains these findings?

• A. Alcoholic ketoacidosis
• B. Hyperventilation syndrome
• C. Severe chronic obstructive pulmonary disease
• D. Salicylate intoxication (Correct Answer)
• E. Vomiting

Explanation: ***Salicylate intoxication*** - The patient's presentation with **agitation, confusion, tachypnea, and wheezing** is consistent with acute salicylate poisoning. - The **ABG shows a mixed acid-base disturbance**, with a primary respiratory alkalosis (low pCO2 due to hyperventilation) and a partially compensated metabolic acidosis (low HCO3- and a normal pH, suggesting an underlying acidosis). The calculated anion gap in this case is 138 - (100 + 12) = 26, indicating a **high anion gap metabolic acidosis**, which is characteristic of salicylate toxicity. *Alcoholic ketoacidosis* - While alcoholic ketoacidosis presents with a **high anion gap metabolic acidosis**, it typically does not cause the prominent **respiratory alkalosis** seen here. - Patients are usually **hypoglycemic** or euglycemic and may have a history of recent heavy alcohol intake followed by decreased oral intake, but the respiratory symptoms are not as pronounced. *Hyperventilation syndrome* - This condition presents with **respiratory alkalosis** (low pCO2 and elevated pH), but it does not cause a **high anion gap metabolic acidosis** with a low bicarbonate. - Symptoms like agitation and dyspnea can be present, but the **ABG findings are inconsistent** with pure hyperventilation syndrome. *Severe chronic obstructive pulmonary disease* - Patients with severe COPD typically have **chronic respiratory acidosis** (elevated pCO2 and low pH), which is the opposite of the ventilatory pattern seen in this patient. - While they can present with dyspnea and wheezing, the **ABG results rule out** an acute exacerbation of COPD as the primary cause of this presentation. *Vomiting* - Chronic or severe vomiting typically leads to **metabolic alkalosis** (elevated pH and high bicarbonate) due to loss of gastric acid, often accompanied by hypokalemia. - The patient's **low bicarbonate and metabolic acidosis are inconsistent** with vomiting as the primary cause of her acid-base disturbance.

Question 285: A 7-year-old girl is brought to the physician because of a 1-month history of worsening fatigue, loss of appetite, and decreased energy. More recently, she has also had intermittent abdominal pain and nausea. She is at the 50th percentile for height and 15th percentile for weight. Her pulse is 119/min and blood pressure is 85/46 mm Hg. Physical examination shows darkened skin and bluish-black gums. The abdomen is soft and nontender. Serum studies show: Sodium 133 mEq/L Potassium 5.3 mEq/L Bicarbonate 20 mEq/L Urea nitrogen 16 mg/dL Creatinine 0.8 mg/dL Glucose 72 mg/dL Which of the following is the most appropriate pharmacotherapy?

• A. Succimer
• B. Deferoxamine
• C. Norepinephrine
• D. Isoniazid + rifampin + pyrazinamide + ethambutol
• E. Glucocorticoids (Correct Answer)

Explanation: ***Glucocorticoids*** - The patient's symptoms (fatigue, anorexia, abdominal pain, hypotension, hyperkalemia, hyponatremia) combined with **darkened skin** and **bluish-black gums** are highly suggestive of **adrenal insufficiency (Addison's disease)**. The blackened gums are due to increased **melanin deposition**. - **Glucocorticoid replacement therapy** (e.g., hydrocortisone) is the mainstay treatment for adrenal insufficiency to replace deficient hormones. *Succimer* - This is a **chelating agent** used for **lead poisoning**, which presents with symptoms like abdominal pain, fatigue, and neurological issues, but not typically darkened skin or characteristic electrolyte imbalances and gum findings seen here. - While lead poisoning can cause **encephalopathy** and developmental delays, it doesn't cause the distinct presentation of Addison's crisis. *Deferoxamine* - This is a **chelating agent** primarily used for **iron overload** (hemochromatosis or acute iron poisoning), which can cause fatigue and abdominal pain, but not the specific skin pigmentation, hypotension, and electrolyte disturbances of adrenal insufficiency. - Iron overload can damage organs like the liver and heart but does not typically cause adrenal crisis. *Norepinephrine* - While the patient is hypotensive, **norepinephrine** is a **vasopressor** used to acutely manage severe hypotension, typically in shock states. - It would not address the underlying **hormone deficiency** in adrenal insufficiency, which requires glucocorticoid replacement. *Isoniazid + rifampin + pyrazinamide + ethambutol* - This is the standard 4-drug regimen for treating **active tuberculosis**. - Although tuberculosis can rarely lead to adrenal insufficiency (Addison's disease) as a secondary complication, the primary treatment for the adrenal crisis itself is **glucocorticoid replacement**, not anti-tuberculosis drugs in the acute setting unless active TB is confirmed and directly causing the insufficiency.

Question 286: A 28-year-old woman comes to the physician because of an 8-hour history of painful leg cramping, a runny nose, and chills. She has also had diarrhea and abdominal pain. She appears irritable and yawns frequently. Her pulse is 115/min. Examination shows cool, damp skin with piloerection. The pupils are 7 mm in diameter and equal in size. Bowel sounds are hyperactive. Deep tendon reflexes are 3+ bilaterally. Withdrawal from which of the following substances is most likely the cause of this patient's symptoms?

• A. Barbiturate
• B. Heroin (Correct Answer)
• C. Gamma-hydroxybutyric acid
• D. Cocaine
• E. Alcohol

Explanation: ***Heroin*** - The constellation of symptoms including **painful muscle cramps**, **runny nose**, **chills**, **diarrhea**, **abdominal pain**, **irritability**, **frequent yawning**, **tachycardia**, **cool and damp skin with piloerection** ("goosebumps"), **dilated pupils**, **hyperactive bowel sounds**, and **hyperreflexia** is highly characteristic of **opioid withdrawal**. - **Heroin** is a potent opioid, and its withdrawal syndrome presents with these classic signs of autonomic hyperactivity and generalized discomfort. *Barbiturate* - **Barbiturate withdrawal** can cause anxiety, seizures, and delirium, but it typically presents with **CNS hyperexcitability** (tremors, seizures, hallucinations) rather than the pronounced autonomic symptoms and pain described. - While some symptoms like anxiety and tachycardia might overlap, the specific combination of **piloerection**, **dilated pupils**, and **hyperactive bowels** points away from barbiturate withdrawal. *Gamma-hydroxybutyric acid* - **GHB withdrawal** can manifest as anxiety, insomnia, tremors, and psychosis, but it does not typically cause the prominent **gastrointestinal distress**, **piloerection**, and **rhinorrhoea** seen in this patient. - It’s more associated with **seizures** and **delirium tremens-like symptoms** in severe cases. *Cocaine* - **Cocaine withdrawal** is often characterized by **dysphoria**, fatigue, increased appetite, and psychomotor retardation, reflecting a **"crash"** after stimulant use. - It does not typically involve the autonomic hyperactivity signs like **rhinorrhoea**, **piloerection**, or **dilated pupils** described, and the prominent physical symptoms (cramping, diarrhea) are absent. *Alcohol* - **Alcohol withdrawal** can cause tremors, anxiety, tachycardia, and seizures, and in severe cases, delirium tremens; however, **piloerection**, **dilated pupils**, and pronounced **gastrointestinal symptoms** (diarrhea, abdominal pain) as the primary presentation are less typical. - The time course and specific cluster of symptoms strongly favor opioid withdrawal over alcohol withdrawal.

Question 287: A crying 4-year-old child is brought to the emergency department with a red, swollen knee. He was in his usual state of health until yesterday, when he sustained a fall in the sandbox at the local park. His mother saw it happen; she says he was walking through the sandbox, fell gently onto his right knee, did not cry or seem alarmed, and returned to playing without a problem. However, later that night, his knee became red and swollen. It is now painful and difficult to move. The child’s medical history is notable for frequent bruising and prolonged bleeding after circumcision. On physical exam, his knee is erythematous, tender, and swollen, with a limited range of motion. Arthrocentesis aspirates frank blood from the joint. Which of the following single tests is most likely to be abnormal in this patient?

• A. Prothrombin time (PT)
• B. Bleeding time
• C. Complete blood count
• D. Platelet aggregation studies
• E. Partial thromboplastin time (PTT) (Correct Answer)

Explanation: ***Partial thromboplastin time (PTT)*** - This patient's presentation with **hemarthrosis** (frank blood in the joint after minor trauma), easy bruising, and prolonged bleeding after circumcision suggests a **coagulation factor deficiency**, most commonly hemophilia. - The **PTT** measures the integrity of the **intrinsic** and common coagulation pathways; deficiencies in factors VIII, IX, XI, or XII, which cause hemophilia A or B, prolong the PTT. *Prothrombin time (PT)* - The **PT** primarily assesses the **extrinsic** and common coagulation pathways, which involve factors VII, X, V, II, and fibrinogen. - In hemophilia A or B, the extrinsic pathway is typically unaffected, so the PT would remain **normal**. *Bleeding time* - **Bleeding time** assesses **platelet function** and **vascular integrity**, which would be abnormal in conditions like thrombocytopenia or von Willebrand disease. - This patient's symptoms are more consistent with a coagulation factor deficiency rather than a primary platelet disorder. *Complete blood count* - A **CBC** evaluates cell counts (red blood cells, white blood cells, platelets) and hemoglobin/hematocrit. - While it might show **anemia** if there has been significant blood loss, it would not directly identify a specific coagulation factor deficiency or be the most likely test to be abnormal in a clotting disorder of this nature. *Platelet aggregation studies* - **Platelet aggregation studies** are used to diagnose disorders of **platelet function**, such as Glanzmann thrombasthenia or Bernard-Soulier syndrome. - The clinical picture strongly points to a **factor deficiency** (e.g., hemophilia) causing severe bleeding into the joint, rather than a primary platelet aggregation defect.

Question 288: A 26-year-old man with a history of alcoholism presents to the emergency department with nausea, vomiting, and right upper quadrant pain. Serum studies show AST and ALT levels >5000 U/L. A suicide note is found in the patient's pocket. The most appropriate initial treatment for this patient has which of the following mechanisms of action?

• A. Glutathione substitute (Correct Answer)
• B. Competitive inhibitor of alcohol dehydrogenase
• C. Opioid receptor antagonist
• D. GABA receptor competitive antagonist
• E. Heavy metal chelator

Explanation: ***Glutathione substitute*** - This patient's presentation with **elevated AST/ALT** levels and a **suicide note** strongly suggests **acetaminophen overdose**, which depletes hepatic glutathione stores. - **N-acetylcysteine (NAC)**, the antidote for acetaminophen overdose, acts as a **glutathione substitute** and precursor, replenishing hepatic glutathione and aiding in the detoxification pathway of acetaminophen's toxic metabolite. *Competitive inhibitor of alcohol dehydrogenase* - This describes **fomepizole**, used to treat **methanol** or **ethylene glycol poisoning**, not acetaminophen overdose. - While the patient has a history of alcoholism, the extremely high transaminase levels point away from typical alcohol-induced liver injury and towards a different toxin. *Opioid receptor antagonist* - This describes **naloxone** or **naltrexone**, which are used to reverse **opioid overdose** or block opioid effects. - The symptoms described (nausea, vomiting, RUQ pain, high transaminases) are not typical of opioid overdose. *GABA receptor competitive antagonist* - This describes **flumazenil**, the antidote for **benzodiazepine overdose**. - While benzodiazepines can be used in suicide attempts, the clinical picture, specifically the profound liver injury, is not characteristic of benzodiazepine toxicity. *Heavy metal chelator* - This category includes drugs like **dimercaprol** or **EDTA**, used to treat poisoning by **heavy metals** such as lead, mercury, or arsenic. - There is no clinical indication for heavy metal poisoning in this scenario; the symptoms and lab findings are inconsistent with such exposures.

Question 289: A 42-year-old man presents with palpitations, 2 episodes of vomiting, and difficulty breathing for the past hour. He says he consumed multiple shots of vodka at a party 3 hours ago but denies any recent drug use. The patient denies any similar symptoms in the past. Past medical history is significant for type 2 diabetes mellitus diagnosed 2 months ago, managed with a single drug that has precipitated some hypoglycemic episodes, and hypothyroidism diagnosed 2 years ago, well-controlled medically. The patient is a software engineer by profession. He reports a 25-pack-year smoking history and currently smokes 1 pack a day. He drinks alcohol occasionally but denies any drug use. His blood pressure is 100/60 mm Hg, pulse is 110/min, and respiratory rate is 25/min. On physical examination, the patient appears flushed and diaphoretic. An ECG shows sinus tachycardia. Which of the following medications is this patient most likely taking to explain his symptoms?

• A. Pioglitazone
• B. Tolbutamide (Correct Answer)
• C. Levothyroxine
• D. Sitagliptin
• E. Metformin

Explanation: ***Tolbutamide*** - **Tolbutamide** is a first-generation sulfonylurea, which can cause a **disulfiram-like reaction** when consumed with alcohol, though this is more classically associated with chlorpropamide. - Symptoms like palpitations, flushing, vomiting, and dyspnea are consistent with a disulfiram-like reaction due to the accumulation of **acetaldehyde**. - The history of **hypoglycemic episodes** supports the use of a sulfonylurea, as these drugs stimulate insulin release and commonly cause hypoglycemia. *Pioglitazone* - **Pioglitazone** is a thiazolidinedione that improves insulin sensitivity but is not known to interact with alcohol to cause acute, severe symptoms like those described. - Its main side effects include **fluid retention**, weight gain, and an increased risk of heart failure, which are not present here. - It rarely causes hypoglycemia as monotherapy. *Levothyroxine* - **Levothyroxine** is a synthetic thyroid hormone used for hypothyroidism and does not interact with alcohol to produce a disulfiram-like reaction. - Overdosing could cause symptoms of **hyperthyroidism**, but this interaction with alcohol is highly specific to certain diabetes medications. *Sitagliptin* - **Sitagliptin** is a DPP-4 inhibitor that helps lower blood glucose but does not cause a disulfiram-like reaction with alcohol. - Side effects typically include **nasopharyngitis** and headache, unrelated to the patient's acute presentation. - It has a low risk of hypoglycemia as monotherapy. *Metformin* - **Metformin** is a biguanide that reduces hepatic glucose production and increases insulin sensitivity. While alcohol consumption with metformin can increase the risk of **lactic acidosis**, it does not typically cause the flushing, palpitations, and vomiting seen here. - The patient's symptoms are more characteristic of acetaldehyde accumulation. - Metformin rarely causes hypoglycemia as monotherapy.

Question 290: A 45-year-old man presents to the emergency department for worsening shortness of breath with exertion, mild chest pain, and lower extremity swelling. The patient reports increasing his alcohol intake and has been consuming a diet rich in salt over the past few days. Physical examination is significant for bilateral crackles in the lung bases, jugular venous distension, and pitting edema up to the knees. An electrocardiogram is unremarkable. He is admitted to the cardiac step-down unit. In the unit, he is started on his home anti-hypertensive medications, intravenous furosemide every 6 hours, and prophylactic enoxaparin. His initial labs on the day of admission are remarkable for the following: Hemoglobin: 12 g/dL Hematocrit: 37% Leukocyte count: 8,500 /mm^3 with normal differential Platelet count: 150,000 /mm^3 Serum: Na+: 138 mEq/L Cl-: 102 mEq/L K+: 4.1 mEq/L HCO3-: 25 mEq/L On hospital day 5, routine laboratory testing is demonstrated below: Hemoglobin: 12.5 g/dL Hematocrit: 38% Leukocyte count: 8,550 /mm^3 with normal differential Platelet count: 60,000 /mm^3 Serum: Na+: 140 mEq/L Cl-: 100 mEq/L K+: 3.9 mEq/L HCO3-: 24 mEq/L Physical examination is unremarkable for any bleeding and the patient denies any lower extremity pain. There is an erythematous and necrotic skin lesion in the left abdomen. Which of the following best explains this patient’s current presentation?

• A. ADAMTS13 protease deficiency
• B. Antibodies to heparin-platelet factor 4 complex (Correct Answer)
• C. Vitamin K epoxide reductase inhibitor
• D. Non-immune platelet aggregation
• E. Protein C deficiency

Explanation: ***Antibodies to heparin-platelet factor 4 complex*** - This patient's presentation with **thrombocytopenia** (platelet count dropping from 150,000 to 60,000 /mm^3) and a **necrotic skin lesion** after receiving enoxaparin (a low molecular weight heparin) is highly suggestive of **heparin-induced thrombocytopenia (HIT)**. - HIT is an immune-mediated adverse drug reaction where antibodies form against the **heparin-platelet factor 4 (PF4) complex**, leading to platelet activation, aggregation, and thrombosis, which can manifest as skin necrosis at injection sites. *ADAMTS13 protease deficiency* - **ADAMTS13 protease deficiency** causes **thrombotic thrombocytopenic purpura (TTP)**, which presents with the classic pentad of fever, neurological symptoms, renal dysfunction, thrombocytopenia, and microangiopathic hemolytic anemia. - While **thrombocytopenia** is present, other key features of TTP such as **microangiopathic hemolytic anemia** (indicated by schistocytes, increased LDH, decreased haptoglobin, and elevated indirect bilirubin) are not mentioned, and the skin lesion is more characteristic of HIT. *Vitamin K epoxide reductase inhibitor* - A **vitamin K epoxide reductase inhibitor** (e.g., warfarin) would interfere with the synthesis of vitamin K-dependent clotting factors, leading to an **increased INR/PT** and a **bleeding risk**, not typically thrombocytopenia or thrombotic skin lesions in the acute setting following heparin exposure. - While skin necrosis can rarely occur with warfarin (especially in Protein C deficiency), it's not the primary mechanism of thrombocytopenia seen here, and warfarin was not initiated in this patient. *Non-immune platelet aggregation* - **Non-immune platelet aggregation** is a broad term that could apply to various conditions, but it doesn't specifically explain the *combination* of **thrombocytopenia** and **thrombotic complications** (like skin necrosis) in the context of recent heparin exposure. - Conditions like **disseminated intravascular coagulation (DIC)** involve significant non-immune platelet aggregation, but DIC also presents with widespread bleeding and abnormal coagulation tests, which are not described. *Protein C deficiency* - **Protein C deficiency** is a **hereditary hypercoagulable state** that increases the risk of venous and arterial thrombosis. - While it can manifest as thrombotic events, especially **warfarin-induced skin necrosis**, it does not typically cause **thrombocytopenia** directly, nor would it explain the timing of the thrombocytopenia after heparin initiation.

Question 291: A 65-year old man comes to the emergency department because of altered mental status for 1 day. He has had headaches, severe nausea, vomiting, and diarrhea for 2 days. He has a history of hypertension, insomnia, and bipolar disorder. His medications include lisinopril, fluoxetine, atorvastatin, lithium, olanzapine, and alprazolam. His temperature is 37.2 °C (99.0 °F), pulse is 90/min, respirations are 22/min, and blood pressure is 102/68 mm Hg. He is somnolent and confused. His mucous membranes are dry. Neurological examination shows dysarthria, decreased muscle strength throughout, and a coarse tremor of the hands bilaterally. The remainder of the examination shows no abnormalities. In addition to IV hydration and electrolyte supplementation, which of the following is the next best step in management?

• A. Bowel irrigation
• B. Intravenous diazepam
• C. Oral cyproheptadine
• D. Intravenous dantrolene
• E. Hemodialysis (Correct Answer)

Explanation: ***Hemodialysis*** - This patient presents with symptoms consistent with **severe lithium toxicity** (altered mental status, somnolence, confusion, dysarthria, decreased muscle strength, coarse tremor) likely exacerbated by dehydration due to nausea, vomiting, and diarrhea. - **Hemodialysis** is indicated for severe lithium toxicity, especially when plasma lithium levels are very high (>4.0 mEq/L), there are signs of cerebellar toxicity or seizures, or if renal impairment prevents adequate lithium excretion. *Bowel irrigation* - **Whole-bowel irrigation** is primarily used for large ingestions of sustained-release or enteric-coated medications, or substances not adsorbed by activated charcoal. - It is generally *not* effective for removing lithium, as lithium is rapidly and completely absorbed from the gastrointestinal tract. *Intravenous diazepam* - **Benzodiazepines** like diazepam are useful for managing seizures or severe agitation associated with drug toxicities but do not address the underlying cause of lithium toxicity by removing the drug from the body. - While agitation and seizures might occur in severe lithium toxicity, the primary initial step in severe cases is to remove the excess lithium. *Oral cyproheptadine* - **Cyproheptadine** is an antihistamine with antiserotonergic properties, used in the treatment of **serotonin syndrome**. - This patient's clinical presentation is classic for **lithium toxicity**, not serotonin syndrome, although fluoxetine can contribute to serotonin syndrome, the tremor and neurological picture coupled with lithium use points to lithium toxicity. *Intravenous dantrolene* - **Dantrolene** is a muscle relaxant primarily used for conditions like **neuroleptic malignant syndrome** (NMS) or malignant hyperthermia due to its direct action on skeletal muscle. - It is not indicated for treating the central nervous system effects or removal of lithium in lithium toxicity.

Question 292: A 44-year-old woman comes to the physician because of a 6-month history of fatigue, constipation, and a 7-kg (15.4-lb) weight gain. Menses occur irregularly in intervals of 40–50 days. Her pulse is 51/min, and blood pressure is 145/86 mm Hg. Examination shows conjunctival pallor and cool, dry skin. There is mild, nonpitting periorbital edema. Serum thyroid-stimulating hormone concentration is 8.1 μU/mL. Treatment with the appropriate pharmacotherapy is initiated. After several weeks of therapy with this drug, which of the following hormonal changes is expected?

• A. Increased TRH
• B. Increased T3
• C. Decreased T4
• D. Increased T4
• E. Decreased TSH (Correct Answer)

Explanation: ***Decreased TSH*** - The patient has **primary hypothyroidism** (elevated TSH 8.1 μU/mL, symptoms of fatigue, constipation, bradycardia, weight gain, cool dry skin) and is treated with **levothyroxine (synthetic T4)**. - The phrase **"after several weeks of therapy"** is key: while T4 levels rise within days of starting levothyroxine, **TSH takes 6-8 weeks to normalize** due to the negative feedback loop. - As circulating thyroid hormone levels are restored, the **hypothalamic-pituitary-thyroid axis** re-establishes negative feedback, leading to **decreased TSH secretion** from the pituitary. - **Decreased TSH is the primary clinical marker** used to assess adequacy of thyroid hormone replacement after several weeks of therapy. *Increased T4* - While T4 levels do increase with levothyroxine therapy, this occurs **rapidly (within days)**, not over "several weeks." - The question's timeframe of "several weeks" directs attention to the **delayed TSH response**, which is what clinicians monitor at 6-8 weeks to adjust dosing. - T4 elevation is immediate; TSH normalization takes weeks and is the endpoint being tested. *Increased T3* - T3 levels will increase as **T4 is peripherally converted to the active form T3**, but this is not the primary hormonal change being monitored after several weeks. - The question asks about expected hormonal changes in the context of treatment monitoring, where **TSH is the gold standard**. *Increased TRH* - **Thyrotropin-releasing hormone (TRH)** from the hypothalamus stimulates TSH release. In primary hypothyroidism, both TRH and TSH are elevated. - With thyroid hormone replacement, negative feedback would lead to **decreased TRH**, not increased. *Decreased T4* - This is the opposite of what occurs with levothyroxine therapy. - The goal of treatment is to **increase** deficient T4 levels to the physiological range.

Question 293: A 50-year-old woman presents to the clinic with joint pain that has persisted for the last 2 months. She reports having intermittently swollen, painful hands bilaterally. She adds that when she wakes up in the morning, her hands are stiff and do not loosen up until an hour later. The pain tends to improve with movement. Physical examination is significant for warm, swollen, tender proximal interphalangeal joints, metacarpophalangeal joints, and wrists bilaterally. Laboratory results are positive for rheumatoid factor (4-fold greater than the upper limit of normal (ULN)) and anti-cyclic citrullinated peptide (anti-CCP) antibodies (3-fold greater than ULN). CRP and ESR are elevated. Plain X-rays of the hand joints show periarticular osteopenia and bony erosions. She was started on the first-line drug for her condition which inhibits dihydrofolate reductase. Which medication was this patient started on?

• A. Hydroxyurea
• B. Allopurinol
• C. Methotrexate (Correct Answer)
• D. 5-fluorouracil
• E. Leflunomide

Explanation: ***Methotrexate*** - The patient's clinical presentation (symmetrical polyarthritis, morning stiffness, elevated inflammatory markers, positive **rheumatoid factor**, and **anti-CCP antibodies**) is classic for **rheumatoid arthritis (RA)**. - **Methotrexate** is the **first-line disease-modifying anti-rheumatic drug (DMARD)** for RA and acts by inhibiting **dihydrofolate reductase**, thereby interfering with purine and pyrimidine synthesis. *Hydroxyurea* - **Hydroxyurea** is an antineoplastic agent that works by inhibiting **ribonucleotide reductase**, not dihydrofolate reductase. - It is primarily used in conditions like **myeloproliferative disorders** (e.g., chronic myeloid leukemia, polycythemia vera, essential thrombocythemia) and **sickle cell disease**, not rheumatoid arthritis. *Allopurinol* - **Allopurinol** is a **xanthine oxidase inhibitor** used to reduce **uric acid production** in conditions like **gout and tumor lysis syndrome**. - It is not indicated for the treatment of rheumatoid arthritis, nor does it inhibit dihydrofolate reductase. *5-fluorouracil* - **5-fluorouracil** is a **pyrimidine analog** that inhibits **thymidylate synthase** (after being metabolized to 5-FdUMP), primarily used in **chemotherapy for various cancers**, especially gastrointestinal malignancies. - It does not inhibit dihydrofolate reductase and is not used to treat rheumatoid arthritis. *Leflunomide* - **Leflunomide** is another DMARD used for rheumatoid arthritis, but it inhibits **dihydroorotate dehydrogenase**, an enzyme involved in *de novo pyrimidine synthesis*, not dihydrofolate reductase. - While it is a treatment for RA, it is not the medication that acts specifically by inhibiting dihydrofolate reductase.

Question 294: A 78-year-old woman presents to the orthopedic department for an elective total left knee arthroplasty. She has had essential hypertension for 25 years and type 2 diabetes mellitus for 35 years. She has smoked 20–30 cigarettes per day for the past 40 years. The operation was uncomplicated. On day 3 post-surgery, she complains of left leg pain and swelling. On examination, her left leg appears red and edematous, and there are dilated superficial veins on the left foot. Using Wells’ criteria, the patient is diagnosed with a provoked deep venous thrombosis. Which of the following is the best initial therapy for this patient?

• A. Oral apixaban monotherapy (Correct Answer)
• B. Inferior vena cava (IVC) filter
• C. Oral dabigatran monotherapy
• D. Complete bed rest
• E. Long-term aspirin

Explanation: ***Oral apixaban monotherapy*** - **Apixaban** is a **direct oral anticoagulant** (DOAC) that offers effective and convenient treatment for DVT, particularly in postoperative settings. - Its fixed-dose regimen, favorable safety profile (especially regarding bleeding risk), and lack of need for routine monitoring make it a preferred initial therapy for most patients with DVT. *Inferior vena cava (IVC) filter* - **IVC filters** are generally reserved for patients with contraindications to anticoagulation or those who experience recurrent PEs despite adequate anticoagulation. - They do not treat the DVT itself but rather aim to prevent pulmonary emboli, and their use is associated with potential complications. *Oral dabigatran monotherapy* - **Dabigatran** is another direct oral anticoagulant, but its initial DVT treatment typically involves a 5-10 day bridging period with a parenteral anticoagulant (e.g., LMWH) before starting oral therapy. - Unlike apixaban, it is not recommended as monotherapy for initial DVT treatment. *Complete bed rest* - **Complete bed rest** is not recommended for DVT as it can contribute to **venous stasis** and potentially worsen outcomes. - Early ambulation, once anticoagulation is initiated, is encouraged to reduce pain and swelling and promote recovery. *Long-term aspirin* - **Aspirin** has a role in secondary prevention of recurrent DVT/PE in some patients after initial anticoagulant therapy. - It is not sufficient as a primary or initial treatment for an acute DVT, as its antithrombotic effects are much weaker compared to DOACs or other anticoagulants.

Question 295: A previously healthy 46-year-old woman comes to the physician because of a 3-month history of fatigue and progressive shortness of breath. She does not take any medications. Her pulse is 93/min and blood pressure is 112/80 mm Hg. Examination shows no abnormalities. Her hemoglobin concentration is 8 g/dL, leukocyte count is 22,000/mm3, and platelet count is 80,000/mm3. A peripheral blood smear shows increased numbers of circulating myeloblasts. Bone marrow biopsy confirms the diagnosis of acute myeloid leukemia. ECG, x-ray of the chest, and echocardiogram show no abnormalities. The patient is scheduled to start induction chemotherapy with cytarabine and daunorubicin. This patient is at increased risk for which of the following long-term complications?

• A. Left ventricular dysfunction (Correct Answer)
• B. Gross hematuria
• C. Bilateral tinnitus
• D. Endometrial hyperplasia
• E. Decreased diffusing capacity of the lung for carbon monoxide

Explanation: ***Left ventricular dysfunction*** - **Daunorubicin** is an **anthracycline antibiotic** frequently used in AML chemotherapy; it is known to cause **dose-dependent cardiotoxicity**, leading to **left ventricular dysfunction** and congestive heart failure. - The risk of cardiotoxicity is cumulative and can manifest years after treatment, making it a significant long-term complication. *Gross hematuria* - **Gross hematuria** is typically associated with hemorrhagic cystitis, a common side effect of **cyclophosphamide** or **ifosfamide** due to their metabolite **acrolein**. - These agents are not part of the standard induction regimen mentioned (cytarabine and daunorubicin) for AML, thus making this complication less likely in this specific context. *Bilateral tinnitus* - **Bilateral tinnitus** is a common adverse effect of **cisplatin** and other **platinum-based chemotherapy agents**, which cause ototoxicity. - These drugs are not part of the standard induction chemotherapy for AML described in the scenario. *Endometrial hyperplasia* - **Endometrial hyperplasia** is primarily associated with **unopposed estrogen stimulation** and is not a direct long-term complication of cytarabine and daunorubicin chemotherapy. - While some chemotherapy can induce premature menopause, endometrial hyperplasia is not a specific or common drug-related long-term complication of this AML regimen. *Decreased diffusing capacity of the lung for carbon dioxide* - A **decreased diffusing capacity of the lung for carbon monoxide (DLCO)** is typically associated with **bleomycin-induced pulmonary fibrosis** or other interstitial lung diseases. - **Bleomycin** is not used in the standard AML induction regimen of cytarabine and daunorubicin, making this an unlikely long-term complication in this patient.

Question 296: A 23-year-old man presents with fatigue and increased daytime somnolence. He says his symptoms began gradually 6 months ago and have progressively worsened and have begun to interfere with his job as a computer programmer. He is also bothered by episodes of paralysis upon waking from naps and reports visual hallucinations when falling asleep at night. He has been under the care of another physician for the past several months, who prescribed him the standard pharmacotherapy for his most likely diagnosis. However, he has continued to experience an incomplete remission of symptoms and has been advised against increasing the dose of his current medication because of an increased risk of adverse effects. Which of the following side effects is most closely associated with the standard drug treatment for this patient’s most likely diagnosis?

• A. Weight gain and metabolic syndrome
• B. Nephrogenic diabetes insipidus
• C. Parkinsonism and tardive dyskinesia
• D. Loss of concentration, memory impairment
• E. Cardiac irregularities, nervousness, hallucinations (Correct Answer)

Explanation: ***Cardiac irregularities, nervousness, hallucinations*** - The patient's symptoms (fatigue, excessive daytime somnolence, sleep paralysis, and hypnagogic hallucinations) are classic for **narcolepsy**. - The standard pharmacotherapy for narcolepsy often includes **stimulants** (e.g., modafinil, armodafinil, methylphenidate, amphetamines), which can cause side effects like **cardiac irregularities** (tachycardia, arrhythmias), **nervousness/anxiety**, and in some cases, exacerbation of **hallucinations** or psychosis. *Weight gain and metabolic syndrome* - This side effect is primarily associated with **second-generation antipsychotics**, which are not the first-line treatment for narcolepsy. - While some medications can cause weight changes, it is not the most typical or limiting side effect for narcolepsy stimulants as implied by the clinical context. *Nephrogenic diabetes insipidus* - This is a well-known side effect of **lithium**, a mood stabilizer used in bipolar disorder, which is not indicated for narcolepsy. - There is no direct link between narcolepsy treatment and nephrogenic diabetes insipidus. *Parkinsonism and tardive dyskinesia* - These are **extrapyramidal side effects** primarily associated with **first-generation antipsychotics** and, less commonly, some second-generation antipsychotics or antiemetics. - These are not typical side effects of the stimulant medications used to treat narcolepsy. *Loss of concentration, memory impairment* - While some conditions can cause cognitive side effects, the **stimulants** used for narcolepsy are generally intended to **improve concentration and alertness**, not impair them. - If these side effects were to occur, they would be atypical or paradoxical reactions to standard treatment.

Question 297: A pharmaceutical company is studying a new drug that inhibits the glucose transporter used by intestinal enterocytes to absorb glucose into the body. The drug was designed such that it would act upon the glucose transporter similarly to how cyanide acts upon cytochrome proteins. During pre-clinical studies, the behavior of this drug on the activity of the glucose transporter is examined. Specifically, enterocyte cells are treated with the drug and then glucose is added to the solution at a concentration that saturates the activity of the transporter. The transport velocity and affinity of the transporters under these conditions are then measured. Compared to the untreated state, which of the following changes would most likely be seen in these transporters after treatment?

• A. Unchanged Km and decreased Vmax (Correct Answer)
• B. Unchanged Km and unchanged Vmax
• C. Increased Km and unchanged Vmax
• D. Increased Km and decreased Vmax
• E. Decreased Km and decreased Vmax

Explanation: ***Unchanged Km and decreased Vmax*** - The drug functions similarly to **cyanide**, which works as a **noncompetitive inhibitor** by binding irreversibly to a site other than the active site - **Noncompetitive inhibition** results in a **decreased Vmax** (maximum transport velocity) because fewer active transporters are available, but the **Km (substrate affinity) remains unchanged** as the binding affinity of the remaining active transporters is unaffected - This is the expected pattern when glucose is added at saturating concentrations in the presence of an irreversible noncompetitive inhibitor *Unchanged Km and unchanged Vmax* - This would imply no significant effect of the drug on the glucose transporter, which contradicts the drug's design as an inhibitor - An unaffected Vmax suggests that the maximum transport rate is maintained, and an unchanged Km indicates unaltered affinity—neither of which aligns with the action of a noncompetitive inhibitor *Increased Km and unchanged Vmax* - An **increased Km** signifies a **decreased affinity** of the transporter for glucose, which is characteristic of **competitive inhibition** - An **unchanged Vmax** means the maximum transport rate is still achievable at high substrate concentrations, as competitive inhibitors can be overcome by saturating substrate concentrations - This pattern does not match the cyanide-like irreversible noncompetitive inhibitor described *Increased Km and decreased Vmax* - This pattern suggests **mixed inhibition** or **uncompetitive inhibition**, where both Km and Vmax are affected - While Vmax is appropriately decreased, the increase in Km indicates reduced affinity, which is not the primary mechanism for a cyanide-like noncompetitive inhibitor that binds irreversibly to a separate site *Decreased Km and decreased Vmax* - A **decreased Km** would imply an **increased affinity** of the transporter for glucose, which is not expected from an inhibitor designed to reduce overall transport - Although Vmax is appropriately decreased, the change in Km does not fit the typical profile of a noncompetitive inhibitor acting in a cyanide-like manner

Question 298: A 65-year-old man is brought to the emergency department from his home. He is unresponsive. His son requested a wellness check because he had not heard from his father in 2 weeks. He reports that his father was sounding depressed during a telephone call. The paramedics found a suicide note and a half-empty bottle of antifreeze near the patient. The medical history includes hypertension and hyperlipidemia. The vital signs include: blood pressure 120/80 mm Hg, respiratory rate 25/min, heart rate 95/min, and temperature 37.0°C (98.5°F). He is admitted to the hospital. What do you expect the blood gas analysis to show?

• A. Non-anion gap metabolic acidosis
• B. Metabolic alkalosis
• C. Respiratory acidosis
• D. Anion gap metabolic acidosis (Correct Answer)
• E. Mixed acid-base disorder

Explanation: ***Anion gap metabolic acidosis*** - The patient's history of **antifreeze ingestion** indicates likely exposure to **ethylene glycol**, which is metabolized into toxic acids (glycolic and oxalic acid). - These accumulating acids lead to an **increased anion gap metabolic acidosis**. *Non-anion gap metabolic acidosis* - This type of acidosis typically results from **bicarbonate loss** (e.g., severe diarrhea) or **excessive chloride intake**, which is not indicated by the antifreeze ingestion. - It involves a normal anion gap because other unmeasured anions do not accumulate. *Metabolic alkalosis* - This imbalance is characterized by an **increase in bicarbonate** or a significant loss of acid, often due to vomiting or diuretic use. - Antifreeze poisoning directly leads to acid accumulation, precisely the opposite of metabolic alkalosis. *Respiratory acidosis* - This occurs due to **hypoventilation** and subsequent buildup of CO2, leading to increased carbonic acid. - While respiratory rate is elevated, the primary problem here is metabolic due to toxin ingestion, not respiratory CO2 retention. *Mixed acid-base disorder* - While a mixed disorder is possible in complex cases, the presentation with antifreeze poisoning is classically dominated by a **severe anion gap metabolic acidosis**. - There is no clear indication of a separate primary respiratory or alkalotic disorder at onset to warrant a "mixed" label as the primary anticipated finding.

Question 299: A 24-year-old man presents to the postoperative unit after undergoing an appendectomy following 2 episodes of acute appendicitis. He complains of nausea and vomiting. On physical examination, his temperature is 36.9°C (98.4ºF), pulse rate is 96/minute, blood pressure is 122/80 mm Hg, and respiratory rate is 14/minute. His abdomen is soft on palpation, and bowel sounds are normoactive. Intravenous ondansetron is administered, and the patient reports relief from his symptoms. Which of the following best explains the mechanism of action of this drug?

• A. Inhibition of serotonin receptors on the vagal and spinal afferent nerves from the intestines (Correct Answer)
• B. Inhibition of dopamine receptors on chemoreceptor trigger zone (CTZ)
• C. Inhibition of gastroesophageal motility
• D. Stimulation of 5-HT3 receptors on the nucleus of the tractus solitarius
• E. Stimulation of intestinal and colonic motility

Explanation: ***Inhibition of serotonin receptors on the vagal and spinal afferent nerves from the intestines*** - **Ondansetron** is a **5-HT3 receptor antagonist** that primarily acts by blocking serotonin receptors located on the **vagal and spinal afferent nerves** in the gastrointestinal tract. - By blocking these receptors, it prevents the transmission of **emetic signals** from the gut to the brainstem's vomiting center, effectively reducing nausea and vomiting. *Inhibition of dopamine receptors on chemoreceptor trigger zone (CTZ)* - This is the mechanism of action for **dopamine antagonists**, such as **metoclopramide** or **prochlorperazine**, which are also antiemetics but work differently from ondansetron. - The CTZ is located outside the blood-brain barrier and is sensitive to blood-borne toxins and drugs, but its primary pathway for signaling to the vomiting center is blocked by dopamine antagonists. *Inhibition of gastroesophageal motility* - This mechanism is not typically associated with antiemetics like ondansetron, which generally do not significantly affect gastroesophageal motility. - Inhibiting motility can sometimes worsen symptoms of nausea or lead to delayed gastric emptying, which is not the therapeutic goal of ondansetron. *Stimulation of 5-HT3 receptors on the nucleus of the tractus solitarius* - Ondansetron is an **antagonist** (inhibitor), not a stimulator, of 5-HT3 receptors. - Stimulation of 5-HT3 receptors on the nucleus of the tractus solitarius would likely *promote* nausea and vomiting, the opposite of ondansetron's effect. *Stimulation of intestinal and colonic motility* - Drugs that stimulate intestinal and colonic motility are typically **prokinetics**, like **metoclopramide** (which also has antiemetic properties via dopamine receptor antagonism), but this is not the primary mechanism of ondansetron. - Ondansetron's action is focused on blocking serotonin receptors to prevent nausea and vomiting, not directly on stimulating gut motility.

Question 300: A 57-year-old man presents for a regular check-up. He does not have any complaints at the time of presentation. He has a history of several episodes of acute non-necrotizing pancreatitis with the last episode being 2 years ago. Also, he was diagnosed with hypertension 5 years ago. Currently, he takes aspirin, atorvastatin, enalapril, and indapamide. He plays tennis twice a week, does low impact cardio workouts 3 times a week, and follows a low-fat diet. He smokes half a pack of cigarettes per day and refuses to quit smoking. The patient’s blood pressure is 140/85 mm Hg, heart rate is 88/min, respiratory rate is 14/min, and temperature is 36.6°C (97.9°F). His height is 181 cm (5 ft 11 in), weight is 99 kg (218 lb), and BMI is 30.8 kg/m2. Physical examination reveals multiple xanthomas on the patient’s trunk, elbows, and knees. Heart sounds are diminished with fixed splitting of S2 and an increased aortic component. The rest of the examination is unremarkable. The patient’s lipid profile shows the following results: Total serum cholesterol 235.9 mg/dL HDL 46.4 mg/dL LDL 166.3 mg/dL Triglycerides 600 mg/dL Glucose 99 mg/dL Which of the following modifications should be made to the patient’s therapy?

• A. Add aprotinin
• B. Add simvastatin
• C. Add metformin
• D. Add fenofibrate (Correct Answer)
• E. Increase atorvastatin dosage

Explanation: ***Add fenofibrate*** - The patient presents with significantly elevated **triglycerides (600 mg/dL)**, multiple episodes of **acute non-necrotizing pancreatitis**, and **eruptive xanthomas**, which are all indicative of severe hypertriglyceridemia. - **Fibrates, such as fenofibrate**, are the most effective class of drugs for lowering very high triglyceride levels and reducing the risk of pancreatitis. *Add aprotinin* - **Aprotinin** is an antifibrinolytic agent that is no longer used due to safety concerns and is not indicated for the management of hypertriglyceridemia or pancreatitis prevention. - Its primary use was in reducing blood loss during complex surgeries, specifically cardiac surgery. *Add simvastatin* - **Simvastatin** is a statin, and while statins are effective in reducing LDL cholesterol, they have a limited effect on significantly elevated triglycerides. - The patient is already on atorvastatin, and adding a second statin would not be the primary approach for managing severe hypertriglyceridemia, nor would it provide substantial additional triglyceride-lowering effects compared to a fibrate. *Add metformin* - **Metformin** is an oral antihyperglycemic agent used to treat type 2 diabetes by improving insulin sensitivity and reducing hepatic glucose production. - The patient's **glucose level is normal (99 mg/dL)**, and there is no indication of diabetes or pre-diabetes, making metformin inappropriate. *Increase atorvastatin dosage* - While atorvastatin can lower triglycerides to some extent, it is primarily used for LDL-C reduction. Increasing the dosage would not be as effective as a fibrate in addressing the severe **hypertriglyceridemia (600 mg/dL)** and the associated risk of pancreatitis. - The most significant concern for this patient is the high triglyceride level and the history of pancreatitis, which requires a more targeted therapy beyond increased statin dosage.

Question 301: A 7-year-old boy is brought to the physician by his mother because his teachers have noticed him staring blankly on multiple occasions over the past month. These episodes last for several seconds and occasionally his eyelids flutter. He was born at term and has no history of serious illness. He has met all his developmental milestones. He appears healthy. Neurologic examination shows no focal findings. Hyperventilation for 30 seconds precipitates an episode of unresponsiveness and eyelid fluttering that lasts for 7 seconds. He regains consciousness immediately afterward. An electroencephalogram shows 3-Hz spikes and waves. Which of the following is the most appropriate pharmacotherapy for this patient?

• A. Phenytoin
• B. Clonazepam
• C. Levetiracetam
• D. Carbamazepine
• E. Ethosuximide (Correct Answer)

Explanation: ***Ethosuximide*** - This patient presents with classic features of **absence seizures**, including brief staring spells with eyelid fluttering, precipitation by hyperventilation, and a characteristic **3-Hz spike-and-wave pattern on EEG**. **Ethosuximide** is the first-line pharmacotherapy for typical absence seizures due to its high efficacy and favorable side effect profile. - It works by blocking **T-type calcium channels** in the thalamic neurons, which are crucial in generating the 3-Hz spike-and-wave discharges characteristic of absence seizures. *Phenytoin* - **Phenytoin** is a broad-spectrum anticonvulsant primarily used for **tonic-clonic seizures** and **focal seizures**. - It is generally **ineffective** and can sometimes exacerbate absence seizures, making it an inappropriate choice for this patient. *Clonazepam* - **Clonazepam** is a benzodiazepine that can be used as an adjunct in some epilepsy syndromes, particularly for myoclonic or atypical absence seizures. - While it has broad anti-seizure properties, it is not the **first-line drug of choice** for typical absence seizures, and its use is often limited by sedative side effects and the potential for tolerance and dependence. *Levetiracetam* - **Levetiracetam** is a broad-spectrum antiepileptic drug effective for focal, generalized tonic-clonic, and myoclonic seizures. - While it can be used for absence seizures, **ethosuximide** or valproic acid are generally considered more effective as monotherapy options for typical absence seizures due to their specific mechanism of action. *Carbamazepine* - **Carbamazepine** is primarily used for **focal seizures** and **tonic-clonic seizures**. - Like phenytoin, **carbamazepine** is known to **exacerbate absence seizures**, making it an unsuitable and potentially harmful treatment choice for this patient.

Question 302: A 30-year-old woman presents to a medical clinic for a routine check-up. She gained about 5 kg (11 lb) since the last time she weighed herself 3 months ago. She also complains of constipation and sensitivity to cold. She also noticed her hair appears to be thinning. The patient started to use combined oral contraceptives a few months ago and she is compliant. On physical examination, the temperature is 37.0°C (98.6°F), the blood pressure is 110/70 mm Hg, the pulse is 65/min, and the respiratory rate is 14/min. The laboratory results are as follows: Thyroxine (T4), total 25 ug/dL Thyroxine (T4), free 0.8 ng/dL TSH 0.2 mU/L Which of the following is the main mechanism of action of the drug that caused her signs and symptoms?

• A. Inhibition of an enzyme in the thyroid gland
• B. Inducing endometrial atrophy
• C. Increase the thickness of cervical mucus secretions
• D. Inhibition of hormones in the pituitary gland (Correct Answer)
• E. Inhibition of hormones in hypothalamus

Explanation: ***Inhibition of hormones in the pituitary gland*** - The patient's symptoms (weight gain, constipation, cold sensitivity, hair thinning) combined with laboratory results showing **low TSH** and **low free T4** are indicative of **central hypothyroidism**. - **Combined oral contraceptives** contain estrogen, which increases **thyroxine-binding globulin (TBG)** levels. This leads to increased total T4 but a decrease in free T4. The body compensates by increasing TSH to maintain euthyroidism. However, if the patient has central hypothyroidism (pituitary suppression), the TSH will not increase appropriately. Thus, the main mechanism of oral contraceptives relates to its interaction with the **hypothalamic-pituitary-thyroid (HPT) axis**, where the estrogen component of COCs can suppress pituitary TSH secretion over time, leading to central hypothyroidism in susceptible individuals. The primary action of combined oral contraceptives (COCs) in preventing pregnancy is the **inhibition of gonadotropins (FSH and LH) from the pituitary gland**, thereby preventing ovulation. While this is the main contraceptive mechanism, the estrogen component of COCs is known to affect thyroid hormone binding and metabolism, which can unmask or exacerbate underlying thyroid dysregulation, leading to the observed picture of central hypothyroidism with suppressed TSH and low free T4. *Inhibition of an enzyme in the thyroid gland* - This mechanism of action is associated with **antithyroid drugs** like methimazole or propylthiouracil, used to treat **hyperthyroidism**, not hypothyroidism. - These drugs block thyroid hormone synthesis, leading to high TSH and low thyroid hormones, a picture of primary hypothyroidism, which is not what's observed here (TSH is low). *Inducing endometrial atrophy* - While combined oral contraceptives can cause **endometrial thinning**, this is a direct effect on the uterus and not the primary mechanism responsible for the systemic symptoms or the thyroid abnormalities described. - Endometrial atrophy is also seen in conditions like menopause or progestin-only contraception, but it does not explain the thyroid dysfunction. *Increase the thickness of cervical mucus secretions* - This is a primary contraceptive mechanism of **progestin-only contraceptives**, designed to impede sperm passage, but it is not the main mechanism of combined oral contraceptives leading to the observed systemic symptoms. - While combined oral contraceptives also affect cervical mucus, it's not the critical factor explaining the thyroid profile and symptoms in this case. *Inhibition of hormones in hypothalamus* - While oral contraceptives do influence the **hypothalamus-pituitary-ovarian axis**, the direct cause of the thyroid dysfunction in this scenario is due to direct effects on the liver (TBG) and the pituitary (TSH suppression), rather than primarily inhibiting hypothalamic hormones. - The direct and primary site of action for inducing the thyroid hormone changes due to COCs is more downstream at the pituitary and liver levels not the hypothalamus.

Question 303: A 54-year-old female presents to her primary care physician with recurrent episodes of flushing. At first she attributed these symptoms to hormonal changes. However, lately she has also been experiencing episodes of explosive, watery diarrhea. She has also noticed the onset of heart palpitations. Her vital signs are within normal limits. Her physical exam is notable for an elevated jugular venous pressure (JVP). Echocardiography shows tricuspid insufficiency. Urine 5-HIAA is elevated. Which of the following is the most appropriate next step in management?

• A. Levothyroxine
• B. Promethazine
• C. Octreotide (Correct Answer)
• D. Metoclopramide
• E. Ondansetron

Explanation: ***Octreotide*** - The patient's symptoms (flushing, watery diarrhea, palpitations, elevated JVP, tricuspid insufficiency) along with elevated urine **5-HIAA** are highly suggestive of **carcinoid syndrome**. - **Octreotide**, a somatostatin analog, is the most appropriate next step as it reduces the secretion of vasoactive substances (like serotonin) from carcinoid tumors, alleviating symptoms and often inhibiting tumor growth. *Levothyroxine* - **Levothyroxine** is used to treat **hypothyroidism** and is not indicated for the symptoms presented. - The patient's symptoms are not consistent with thyroid dysfunction. *Promethazine* - **Promethazine** is an antihistamine with antiemetic and sedative properties, used for nausea, vomiting, and allergies. - It does not address the underlying pathology or symptoms of carcinoid syndrome. *Metoclopramide* - **Metoclopramide** is a **dopamine antagonist** and prokinetic agent used to treat nausea, vomiting, and gastroparesis. - It would not be effective in managing the systemic effects of carcinoid syndrome. *Ondansetron* - **Ondansetron** is a **5-HT3 receptor antagonist** primarily used as an antiemetic, particularly for chemotherapy-induced nausea and vomiting. - While it targets serotonin receptors, it is not the primary treatment for the broad range of symptoms in carcinoid syndrome and would not effectively reduce the production of vasoactive mediators.

Question 304: A 35-year-old woman comes to the physician for evaluation of a 6-month history of persistent rhinorrhea and nasal congestion. She works in retail and notices her symptoms worsen anytime she is exposed to strong perfumes. Her symptoms have worsened since winter began 2 months ago. She has not had fever, nausea, wheezing, itching, or rash. She has no history of serious illness or allergies. She takes no medications. Her vital signs are within normal limits. Examination shows congested nasal mucosa, enlarged tonsils, and pharyngeal postnasal discharge. The remainder of the examination shows no abnormalities. Which of the following is the most appropriate next step in management?

• A. Oral phenylephrine
• B. Radioallergosorbent testing
• C. Percutaneous allergy testing
• D. Intranasal azelastine (Correct Answer)
• E. Oral diphenhydramine

Explanation: ***Intranasal azelastine*** - The patient's symptoms (rhinorrhea and nasal congestion) worsen with **irritants** (perfumes) and **cold weather**. The absence of itching, rash, or wheezing makes **allergic rhinitis** less likely. This presentation is highly suggestive of **vasomotor rhinitis**, for which intranasal antihistamines like azelastine are a highly effective treatment. - **Azelastine** is an antihistamine that, when administered intranasally, has local anti-inflammatory effects and can significantly reduce symptoms associated with non-allergic rhinitis, including **rhinorrhea** and **congestion**. *Oral phenylephrine* - **Oral phenylephrine** is a decongestant that primarily works by causing vasoconstriction to reduce nasal congestion. It does not address the underlying **vasomotor dysregulation** or rhinorrhea as effectively as an intranasal antihistamine. - Furthermore, **oral decongestants** can have systemic side effects such as elevated blood pressure, palpitations, and insomnia, which are generally avoided if local treatments are effective. *Radioallergosorbent testing* - **Radioallergosorbent testing (RAST)** measures **IgE antibodies** to specific allergens in the blood. This test is primarily used to diagnose **allergic rhinitis**. - Given the patient's symptoms are exacerbated by irritants (perfumes) and cold rather than specific allergens, and she lacks typical allergic symptoms like itching, **allergic rhinitis** is less probable, making RAST testing an unnecessary initial step. *Percutaneous allergy testing* - **Percutaneous allergy testing** (skin prick testing) is used to identify specific environmental allergens that trigger IgE-mediated allergic reactions. - As with RAST testing, the clinical picture does not strongly suggest an **allergic etiology**. The absence of typical allergic symptoms (itching, wheezing, rash) and the worsening with irritants point away from **allergic rhinitis**. *Oral diphenhydramine* - **Oral diphenhydramine** is a first-generation antihistamine that can reduce rhinorrhea and sneezing but often causes significant **sedation** and anticholinergic side effects. - It is generally not the preferred long-term treatment for chronic rhinitis due to its side effect profile, especially when effective topical agents are available.

Question 305: An 18-year-old girl comes to the clinic because she is concerned about her weight. She states that she is on her school’s cheerleading team and is upset because she feels she is the “fattest” girl on the team despite her healthy diet. She says that in the last 2 weeks since practice began, she has lost 2 lbs. The patient has bipolar disorder I. Her medications include lithium and a combined oral contraceptive that was recently started by her gynecologist, because “everyone is on it." Her mother has hypothyroidism and is treated with levothyroxine. The patient’s BMI is 23.2 kg/m2. Thyroid function labs are drawn and shown below: Thyroid-stimulating hormone (TSH): 4.0 mIU/L Serum thyroxine (T4): 18 ug/dL Free thyroxine (Free T4): 1.4 ng/dl (normal range: 0.7-1.9 ng/dL) Serum triiodothyronine (T3): 210 ng/dL Free triiodothyronine (T3): 6.0 pg/mL (normal range: 3.0-7.0 pg/mL) Which of the following is the most likely cause of the patient’s abnormal lab values?

• A. Familial hyperthyroidism
• B. Hypocholesterolemia
• C. Lithium
• D. Oral contraception-induced (Correct Answer)
• E. Surreptitious use of levothyroxine

Explanation: ***Oral contraception-induced*** - The patient's **total T4 and T3 are elevated**, while **free T4 and T3** are within normal limits, indicating an increase in thyroid-binding globulin (TBG). - Oral contraceptives, specifically **estrogen**, increase the synthesis of TBG in the liver, leading to higher total thyroid hormone levels as more hormone is bound. *Familial hyperthyroidism* - Familial hyperthyroidism would present with genuinely **elevated free T4 and T3** levels, alongside suppressed TSH, indicating true hyperthyroidism. - The patient's **normal free T4 and T3** and slightly elevated TSH rule out true hyperthyroidism. *Hypocholesterolemia* - While thyroid hormones can affect lipid metabolism, **hypocholesterolemia is not a direct cause** of altered thyroid lab values. - It is also not a common side effect of oral contraceptives, nor is it related to the specific pattern of elevated total T4/T3 with normal free hormones. *Lithium* - Lithium is known to **cause hypothyroidism** (elevated TSH, low T4/T3) or, less commonly, hyperthyroidism, but not isolated elevated total T4/T3 with normal free hormones due to increased TBG. - The patient's normal free thyroid hormones and only slightly elevated TSH are not consistent with significant lithium-induced thyroid dysfunction. *Surreptitious use of levothyroxine* - Surreptitious use of exogenous **levothyroxine** would typically result in suppressed TSH and elevated free T4, as the gland would be overstimulated or shut down. - The patient's normal free T4 and elevated total T4/T3 are not indicative of levothyroxine abuse.

Question 306: A 45-year-old woman comes to the physician because of early satiety and intermittent nausea for 3 months. During this period she has also felt uncomfortably full after meals and has vomited occasionally. She has not had retrosternal or epigastric pain. She has longstanding type 1 diabetes mellitus, diabetic nephropathy, and generalized anxiety disorder. Current medications include insulin, ramipril, and escitalopram. Vital signs are within normal limits. Examination shows dry mucous membranes and mild epigastric tenderness. Her hemoglobin A1C concentration was 12.2% 3 weeks ago. Which of the following drugs is most appropriate to treat this patient's current condition?

• A. Ondansetron
• B. Clarithromycin
• C. Calcium carbonate
• D. Metoclopramide (Correct Answer)
• E. Omeprazole

Explanation: ***Metoclopramide*** - This patient presents with symptoms of **gastroparesis**, including early satiety, nausea, vomiting, and postprandial fullness, in the setting of **longstanding type 1 diabetes mellitus** and a very high HbA1c (12.2%), indicative of poor glycemic control. - **Metoclopramide** is a prokinetic agent that acts as a **dopamine D2 receptor antagonist**. It increases gastric motility and emptying, which is the primary pathology in diabetic gastroparesis, making it the most appropriate treatment. *Ondansetron* - Ondansetron is a **serotonin 5-HT3 receptor antagonist** and primarily acts as an antiemetic, reducing nausea and vomiting. - While it could alleviate some symptoms, it does not address the underlying problem of **delayed gastric emptying** in gastroparesis. *Clarithromycin* - Clarithromycin is a **macrolide antibiotic** that can exhibit prokinetic effects due to its action on motilin receptors, but it is typically reserved for cases where metoclopramide is contraindicated or ineffective due to concerns regarding **antibiotic resistance** and potential side effects with prolonged use. - It is not a first-line treatment for diabetic gastroparesis. *Calcium carbonate* - Calcium carbonate is an **antacid** used to neutralize stomach acid, providing relief from heartburn and indigestion. - It would not be effective in treating the symptoms of gastroparesis, which are related to **impaired gastric motility**, not acid production. *Omeprazole* - Omeprazole is a **proton pump inhibitor (PPI)** that reduces stomach acid production by irreversibly binding to the H+/K+-ATPase pump. - It is used to treat conditions like GERD, peptic ulcers, and esophagitis, which are not suggested by the patient's primary symptoms of **early satiety and nausea without retrosternal pain**.

Question 307: A 58-year-old woman with New York Heart Association Class III heart failure, atrial fibrillation, and bipolar disorder presents to the urgent care center with nausea, vomiting, abdominal pain, double vision, and describes seeing green/yellow outlines around objects. Her current medications include ramipril, bisoprolol, spironolactone, digoxin, amiodarone, and lithium. Of the following, which medication is most likely responsible for her symptoms?

• A. Lithium
• B. Amiodarone
• C. Digoxin (Correct Answer)
• D. Bisoprolol
• E. Spironolactone

Explanation: ***Digoxin*** - The patient's symptoms, including **nausea**, **vomiting**, **abdominal pain**, **double vision**, and seeing **green/yellow outlines** around objects, are classic signs of **digoxin toxicity**. - This is particularly concerning given her Class III heart failure and atrial fibrillation for which digoxin is often prescribed, and the presence of other medications like amiodarone, which can increase digoxin levels. *Lithium* - **Lithium toxicity** typically presents with neurological symptoms such as **tremor**, **sedation**, **ataxia**, and seizures, as well as gastrointestinal upset. - While gastrointestinal symptoms can occur, the **visual disturbances** (double vision, green/yellow outlines) are not characteristic of lithium toxicity. *Amiodarone* - **Amiodarone side effects** can include **pulmonary fibrosis**, **thyroid dysfunction**, **corneal deposits** (halo vision), and liver toxicity. - Although visual halos can occur, the specific description of green/yellow outlines and generalized GI distress points away from amiodarone as the primary cause here. *Bisoprolol* - **Bisoprolol**, a beta-blocker, can cause **bradycardia**, **hypotension**, **fatigue**, and **dizziness**. - It does not typically cause the severe gastrointestinal symptoms or the specific visual disturbances described by the patient. *Spironolactone* - **Spironolactone**, an aldosterone antagonist, can cause **hyperkalemia**, **gynecomastia**, and gastrointestinal upset such as nausea. - However, it does not cause the specific visual changes or the constellation of symptoms prominent in this case.

Question 308: A 70-year-old man comes to the physician because of a 2-month history of progressive shortness of breath and a dry cough. He has also noticed gradual development of facial discoloration. He has not had fevers. He has coronary artery disease, hypertension, and atrial fibrillation. He does not smoke or drink alcohol. He does not remember which medications he takes. His temperature is 37°C (98.6°F), pulse is 90/min, respirations are 18/min, and blood pressure is 150/85 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 95%. Examination shows blue-gray discoloration of the face and both hands. Diffuse inspiratory crackles are heard. Laboratory studies show: Prothrombin time 12 seconds (INR=1.0) Serum Na+ 142 mEq/L Cl- 105 mEq/L K+ 3.6 mEq/L HCO3- 25 mg/dL Urea Nitrogen 20 Creatinine 1.2 mg/dL Alkaline phosphatase 70 U/L Aspartate aminotransferase (AST, GOT) 120 U/L Alanine aminotransferase (ALT, GPT) 110 U/L An x-ray of the chest shows reticular opacities around the lung periphery and particularly around the lung bases. The most likely cause of this patient's findings is an adverse effect to which of the following medications?

• A. Amiodarone (Correct Answer)
• B. Procainamide
• C. Metoprolol
• D. Lisinopril
• E. Warfarin

Explanation: ***Amiodarone*** - The patient's **progressive shortness of breath**, **dry cough**, and **diffuse inspiratory crackles** are consistent with **pulmonary fibrosis**, a known serious adverse effect of amiodarone. - The **blue-gray facial and hand discoloration** (smurfism/argyria-like effect) is a classic dermatologic side effect of long-term amiodarone use due to **iodine accumulation** in the skin. - The **elevated transaminases** (AST 120, ALT 110) suggest **hepatotoxicity**, another well-known adverse effect of amiodarone. - The patient's underlying atrial fibrillation and coronary artery disease make amiodarone a plausible medication for his history. *Procainamide* - This antiarrhythmic can cause a **lupus-like syndrome** (arthralgias, fever, rash) and agranulocytosis, but generally not interstitial lung disease or skin discoloration as described. - While it could be used for atrial fibrillation, its side effect profile does not match the patient's symptoms. *Metoprolol* - Metoprolol is a **beta-blocker** used for hypertension, coronary artery disease, and rate control in atrial fibrillation. - Its common side effects include **bronchospasm** (especially in asthmatics), bradycardia, and fatigue, but not interstitial lung disease or blue-gray skin discoloration. *Lisinopril* - Lisinopril is an **ACE inhibitor** used for hypertension and coronary artery disease. - Its common side effects include **dry cough** (due to bradykinin accumulation) and angioedema, but not interstitial lung disease or skin discoloration. The cough from Lisinopril is typically **non-productive and persistent**, and would not be associated with crackles or progressive shortness of breath from lung disease. *Warfarin* - Warfarin is an **anticoagulant** prescribed for atrial fibrillation to prevent stroke. - Its main side effects are **bleeding** and skin necrosis, but it does not cause pulmonary fibrosis or skin discoloration.

Question 309: A 66-year-old woman presents to the emergency department complaining of palpitations. She says that she has been experiencing palpitations and lightheadedness for the past 6 months, but before this morning the episodes usually resolved on their own. The patient's medical history is significant for a transient ischemia attack 2 months ago, hypertension, and diabetes. She takes aspirin, metformin, and lisinopril. She states her grandfather died of a stroke, and her mom has a "blood disorder." An electrocardiogram is obtained that shows an irregularly irregular rhythm with rapid ventricular response, consistent with atrial fibrillation. She is given intravenous metoprolol, which resolves her symptoms. In addition to starting a beta-blocker for long-term management, the patient meets criteria for anticoagulation. Both unfractionated heparin and warfarin are started. Five days later, the patient begins complaining of pain and swelling of her left lower extremity. A Doppler ultrasound reveals thrombosis in her left popliteal and tibial veins. A complete blood count is obtained that shows a decrease in platelet count from 245,000/mm^3 to 90,000/mm^3. Coagulation studies are shown below: Prothrombin time (PT): 15 seconds Partial thromboplastin time (PTT): 37 seconds Bleeding time: 14 minutes Which of the following is the most likely diagnosis?

• A. Thrombotic thrombocytopenic purpura
• B. Type I heparin-induced thrombocytopenia
• C. Warfarin toxicity
• D. Idiopathic thrombocytopenia purpura
• E. Type II heparin-induced thrombocytopenia (Correct Answer)

Explanation: ***Type II heparin-induced thrombocytopenia*** - This diagnosis is strongly supported by the patient's **recent heparin exposure**, a significant **drop in platelet count** (from 245,000 to 90,000/mm^3, a >50% reduction), and new onset **thrombosis** (popliteal and tibial vein thrombosis). - Type II HIT involves antibody formation against **heparin-platelet factor 4 (PF4) complexes**, leading to platelet activation, aggregation, and paradoxical thrombosis, often occurring 5-10 days after heparin initiation. *Thrombotic thrombocytopenic purpura* - While TTP involves microangiopathic hemolytic anemia, thrombocytopenia, and organ damage including neurological symptoms, the prompt onset of thrombosis after heparin strongly points away from TTP and towards **heparin-related complications**. - This patient’s symptoms are primarily thrombotic, and typical TTP findings like **schistocytes on blood smear** and **severe ADAMTS13 deficiency** are not mentioned. *Type I heparin-induced thrombocytopenia* - Type I HIT is characterized by a **mild, non-immune-mediated platelet drop** (usually not below 100,000/mm^3) that occurs within the first 2 days of heparin therapy. - It is **rarely associated with thrombosis**, which makes it an unlikely diagnosis given the severe platelet drop and new thromboses. *Warfarin toxicity* - Warfarin toxicity typically causes **bleeding complications** due to over-anticoagulation, rather than thrombosis, and is characterized by a **prolonged PT/INR**. - Although the patient's bleeding time is prolonged, the thrombotic events and significant platelet drop point away from warfarin toxicity as the primary diagnosis. *Idiopathic thrombocytopenia purpura* - ITP is an autoimmune disorder causing **isolated thrombocytopenia** (often severe) and **bleeding**, but it is generally *not* associated with paradoxical thrombosis. - The temporal relationship with heparin exposure and the thrombotic events are inconsistent with a primary diagnosis of unprovoked ITP.

Question 310: A 52-year-old man presents to the emergency room after a syncopal episode. The patient is awake, alert, and oriented; however, he becomes lightheaded whenever he tries to sit up. The medical history is significant for coronary artery disease and stable angina, which are controlled with simvastatin and isosorbide dinitrate, respectively. The blood pressure is 70/45 mm Hg and the heart rate is 110/min; all other vital signs are stable. IV fluids are started as he is taken for CT imaging of the head. En route to the imaging suite, the patient mentions that he took a new medication for erectile dysfunction just before he began to feel ill. What is the metabolic cause of this patient’s symptoms?

• A. Increased O2 consumption
• B. Increased PDE-5
• C. Increased cGMP (Correct Answer)
• D. Increased NO
• E. Nitric oxide synthase inhibition

Explanation: ***Increased cGMP*** - The patient likely took a **PDE-5 inhibitor** for erectile dysfunction, which prevents the breakdown of **cGMP**. - Elevated **cGMP** leads to increased **vasodilation** and a subsequent drop in blood pressure, explaining his syncopal episode and orthostatic hypotension. - This represents the **final metabolic mediator** of vasodilation in this drug interaction. *Increased O2 consumption* - While increased **O2 consumption** can exacerbate angina, it does not directly cause the profound **hypotension** and **syncope** seen in this patient. - The patient's controlled angina and the timing with a new ED medication point away from primary cardiac oxygen demand issues as the direct cause of the current symptoms. *Increased PDE-5* - **PDE-5 inhibitors** work by *decreasing* the breakdown of cGMP by inhibiting **phosphodiesterase-5 (PDE-5)**, not by increasing PDE-5 itself. - An increase in **PDE-5** would lead to *decreased* cGMP and vasoconstriction, which is the opposite of the patient's presentation. *Increased NO* - While **nitric oxide (NO)** from **isosorbide dinitrate** (a nitrate/NO donor) is indeed increased and contributes to the interaction, NO acts *upstream* by stimulating guanylate cyclase to produce cGMP. - The question asks for the **metabolic cause**, and **cGMP** is the direct effector molecule causing vasodilation, making it the more precise answer. - The dangerous interaction occurs because the PDE-5 inhibitor prevents cGMP breakdown while the nitrate increases cGMP production—**increased cGMP** is the final common pathway. *Nitric oxide synthase inhibition* - **Nitric oxide synthase (NOS) inhibition** would *decrease* **nitric oxide** production, leading to **vasoconstriction** and potentially *increased* blood pressure. - This mechanism is contrary to the patient's presentation of severe **hypotension** and syncopal episode.

Question 311: A 47-year-old man with bipolar I disorder and hypertension comes to the physician because of a 2-week history of increased thirst, urinary frequency, and sleep disturbance. He says that he now drinks up to 30 cups of water daily. He has smoked 2 packs of cigarettes daily for the past 20 years. Examination shows decreased skin turgor. Serum studies show a sodium concentration of 149 mEq/L, a potassium concentration of 4.1 mEq/L, and an elevated antidiuretic hormone concentration. His urine osmolality is 121 mOsm/kg H2O. Which of the following is the most likely explanation for these findings?

• A. Tumor in the adrenal cortex
• B. Adverse effect of a medication (Correct Answer)
• C. Paraneoplastic production of a hormone
• D. Polydipsia caused by acute psychosis
• E. Tumor of the pituitary gland

Explanation: ***Adverse effect of a medication*** - The patient's presentation of **polyuria**, **polydipsia**, **hypernatremia**, and **elevated ADH** with **low urine osmolality** is consistent with **nephrogenic diabetes insipidus**. - **Lithium**, a common treatment for bipolar I disorder, is a well-known cause of **nephrogenic diabetes insipidus** by interfering with the renal collecting duct's response to ADH. *Tumor in the adrenal cortex* - An adrenal cortical tumor would typically lead to conditions like **Cushing's syndrome** ( excess cortisol) or **Conn's syndrome** (excess aldosterone), causing **hypokalemia** and **hypertension**, but not primarily hypernatremia with low urine osmolality. - While it can affect fluid balance, it does not directly cause the classic presentation of **diabetes insipidus** with elevated ADH and low urine osmolality. *Paraneoplastic production of a hormone* - Paraneoplastic syndromes can cause various endocrine abnormalities, but paraneoplastic production of a hormone leading to **nephrogenic diabetes insipidus** with high ADH and low urine osmolality is highly unlikely. - More common paraneoplastic syndromes affecting water balance involve inappropriate ADH secretion (SIADH), leading to **hyponatremia**, not hypernatremia. *Polydipsia caused by acute psychosis* - Primary polydipsia typically results in **hyponatremia** due to excessive water intake diluting serum sodium, especially if renal concentrating mechanisms are intact. The patient has **hypernatremia**. - While patients with psychiatric conditions can exhibit **primary polydipsia**, the body usually compensates by suppressing ADH and excreting dilute urine; an **elevated ADH** makes this diagnosis less likely. *Tumor of the pituitary gland* - A pituitary tumor could cause **central diabetes insipidus** if it interfered with ADH production or release, but this would lead to a *low* or *inappropriately normal* ADH level, not an **elevated ADH** level. - An elevated ADH with nephrogenic diabetes insipidus indicates the kidneys are not responding to ADH, rather than a problem with ADH production.

Question 312: A newborn infant comes to the attention of the neonatal care unit because he started having heavy and rapid breathing. In addition, he was found to be very irritable with pale skin and profuse sweating. Finally, he was found to have cold feet with diminished lower extremity pulses. Cardiac auscultation reveals a harsh systolic murmur along the left sternal border. Notably, the patient is not observed to have cyanosis. Which of the following treatments would most likely be effective for this patient's condition?

• A. Prostaglandin I2
• B. Leukotriene E4
• C. Prostaglandin E2
• D. Prostaglandin E1 (Correct Answer)
• E. Thromboxane A2

Explanation: ***Prostaglandin E1*** - The newborn's presentation with **respiratory distress, irritability, pale skin, profuse sweating, cold feet, diminished lower extremity pulses**, and a **harsh systolic murmur** without cyanosis is highly suggestive of **coarctation of the aorta**. - **Prostaglandin E1 (PGE1)** is critical in maintaining the **patency of the ductus arteriosus**, which allows for blood flow to the lower body when there is severe obstruction like coarctation. *Prostaglandin I2* - **Prostaglandin I2 (PGI2)**, or **prostacyclin**, is a potent **vasodilator** and **platelet aggregation inhibitor**. - While it has vascular effects, it is not the primary prostaglandin used to maintain ductal patency in newborns with critical congenital heart disease. *Leukotriene E4* - **Leukotrienes** are mediators of inflammation and allergic reactions, primarily involved in bronchoconstriction and vascular permeability. - They do not play a significant role in the management of congenital heart defects requiring ductal patency. *Prostaglandin E2* - While **prostaglandin E2 (PGE2)** also contributes to maintaining ductal patency, **PGE1** is the preferred and more commonly used agent for this purpose in clinical practice. - Both PGE1 and PGE2 are members of the E-series prostaglandins, but PGE1 is the standard pharmaceutical intervention. *Thromboxane A2* - **Thromboxane A2 (TXA2)** is a potent **vasoconstrictor** and promotes **platelet aggregation**. - Its effects are opposite to what is desired in this patient, where maintained vessel patency (ductus arteriosus) is crucial.

Question 313: A 20-year-old man presents to your office with dyspnea, reporting nocturnal cough. You note expiratory wheezing on auscultation. Chest x-ray reveals increased anteroposterior diameter. Past medical history is significant for multiple episodes of "bronchitis" as a child. Which of the following drugs would be most effective for long-term treatment of this patient?

• A. Ipratropium
• B. Albuterol
• C. Fluticasone (Correct Answer)
• D. Theophylline
• E. Zileuton

Explanation: ***Fluticasone*** - This patient's symptoms (dyspnea, nocturnal cough, expiratory wheezing, history of "bronchitis," and increased AP diameter on CXR) are consistent with **asthma**, a chronic inflammatory airway disease. - **Inhaled corticosteroids** like fluticasone are the most effective long-term controllers for asthma, targeting the underlying inflammation. *Ipratropium* - **Ipratropium** is a **short-acting anticholinergic** used as a bronchodilator, primarily for relief of acute bronchospasm or in COPD, but it is not a first-line long-term controller for asthma. - It works by blocking muscarinic receptors to cause bronchodilation, but it does not address the underlying **airway inflammation** in asthma. *Albuterol* - **Albuterol** is a **short-acting beta-2 agonist (SABA)** used for quick relief of asthma symptoms by causing rapid bronchodilation. - It is a **rescue medication**, not a long-term controller, as it does not treat the chronic airway inflammation. *Theophylline* - **Theophylline** is a methylxanthine that causes bronchodilation and has some anti-inflammatory effects, but it has a **narrow therapeutic window** and potential for significant side effects. - It is generally considered a **third-line or add-on therapy** for asthma management, not a first-line long-term treatment. *Zileuton* - **Zileuton** is a **leukotriene pathway inhibitor** that works by inhibiting 5-lipoxygenase, reducing the production of inflammatory leukotrienes. - It may be used as an **add-on therapy** for asthma, particularly for aspirin-exacerbated respiratory disease, but it is less potent than inhaled corticosteroids for primary long-term control.

Question 314: Forty minutes after undergoing nasal polypectomy for refractory rhinitis, a 48-year-old woman develops chest tightness and shortness of breath. The surgical course was uncomplicated and the patient was successfully extubated. She received ketorolac for postoperative pain. She has a history of asthma, hypertension, and aspirin allergy. Her daily medications include metoprolol and lisinopril. Examination shows a flushed face. Chest auscultation reveals wheezes and decreased breath sounds in both lung fields. An ECG shows no abnormalities. Which of the following is the most likely underlying cause of this patient's symptoms?

• A. Prinzmetal angina
• B. Bradykinin-induced bronchial irritation
• C. Type 1 hypersensitivity reaction
• D. Excessive beta-adrenergic blockade
• E. Pseudoallergic reaction (Correct Answer)

Explanation: ***Pseudoallergic reaction*** - The patient has a history of **aspirin allergy** and **asthma**, which, combined with the administration of **ketorolac (an NSAID)** post-surgery, strongly suggests a pseudoallergic reaction (specifically **aspirin-exacerbated respiratory disease** or AERD). - Her symptoms of **chest tightness**, **shortness of breath**, **flushed face**, and **wheezing** are consistent with this reaction, which is mediated by **leukotriene overproduction** due to COX-1 inhibition. *Prinzmetal angina* - This condition is characterized by **coronary artery spasm**, leading to chest pain, often at rest, but less commonly associated with diffuse wheezing and shortness of breath unless a severe cardio-pulmonary interaction is present. - While it causes chest tightness, it would not typically explain the prominent **respiratory symptoms** such as wheezing and decreased breath sounds in both lung fields, especially in the context of recent NSAID use and aspirin allergy. *Bradykinin-induced bronchial irritation* - Bradykinin-induced reactions are more commonly associated with **ACE inhibitor use**, which this patient is taking (lisinopril), and can cause angioedema or a dry cough. - While it can induce bronchoconstriction in some individuals, it is less likely to cause such an acute and severe asthmatic response with flushing compared to a pseudoallergic reaction in a patient with a known aspirin allergy and NSAID exposure. *Type 1 hypersensitivity reaction* - A Type 1 hypersensitivity reaction (anaphylaxis) involves an IgE-mediated response to an allergen, leading to mast cell degranulation and histamine release. - While anaphylaxis can present with similar respiratory and dermatological symptoms, the key differentiator here is the patient's specific history of **aspirin allergy** and the specific trigger (ketorolac, an NSAID), which points to a non-IgE mediated pseudoallergic reaction due to altered arachidonic acid metabolism. *Excessive beta-adrenergic blockade* - The patient is on **metoprolol**, a beta-blocker, which can potentially worsen asthma by blocking bronchodilatory beta-2 receptors. - However, the sudden and severe onset of symptoms including flushing and the magnitude of airway narrowing strongly indicates a direct bronchoconstrictive trigger rather than just an exacerbation due to baseline beta-blockade, especially given the NSAID exposure.

Question 315: A 34-year-old male with a previous diagnosis of Grave's disease presents for a check-up. Since his diagnosis 4 months ago, the patient's symptoms have been relatively well-controlled with medications since starting them 3 weeks ago after an initial unsuccessful course of radioiodine ablation. The patient's complete blood count reveals decreased absolute neutrophils at 450/mL and a slightly decreased hematocrit of 39%. Which of the following is the most likely cause of this patient's abnormal laboratory results?

• A. Levothyroxine
• B. Atenolol
• C. Methimazole (Correct Answer)
• D. Perchlorate
• E. Complication from radioiodine ablation

Explanation: ***Methimazole*** - **Methimazole** is an antithyroid drug that can cause **agranulocytosis** (severe neutropenia) as a serious side effect, which aligns with the patient's decreased absolute neutrophils. - The onset of this adverse effect can occur within the first few weeks or months of starting the medication, consistent with the patient having started medication 3 weeks prior. *Levothyroxine* - **Levothyroxine** is a synthetic thyroid hormone used for hypothyroidism, not hyperthyroidism (Graves' disease). - It does not cause neutropenia or anemia as typical side effects. *Atenolol* - **Atenolol** is a beta-blocker used to manage symptomatic hyperthyroidism, but it does not treat the underlying cause. - It does not typically cause neutropenia or bone marrow suppression. *Perchlorate* - **Perchlorate** is an anion occasionally used to block iodide uptake in resistant cases of hyperthyroidism, but it is not a first-line treatment. - While it can cause **aplastic anemia** in rare cases, methimazole-induced agranulocytosis is far more common with standard hyperthyroid treatment. *Complication from radioiodine ablation* - **Radioiodine ablation** can lead to hypothyroidism but typically does not cause acute bone marrow suppression or neutropenia in this timeframe. - While theoretical concerns about radiation exposure exist, hematological complications like severe neutropenia are not a common or immediate consequence of therapeutic doses.

Question 316: A 60-year-old male presents to the emergency room with shortness of breath after waking up in the middle of the night with a "choking" sensation. The patient has a history of hypertension and MI. Physical examination reveals bibasilar inspiratory crackles and an S3 heart sound. Which of the following drugs should be administered for rapid, significant relief of this patient's symptoms?

• A. A drug that acts on the Na/K/Cl symporter in the thick ascending limb of the loop of Henle (Correct Answer)
• B. A drug that competes for mineralocorticoid receptors in the collecting duct
• C. A drug that acts on the Na/Cl cotransporter in the distal convoluted tubule
• D. A drug that inhibits angiotensin converting enzyme
• E. A drug that inhibits carbonic anhydrase

Explanation: **A drug that acts on the Na/K/Cl symporter in the thick ascending limb of the loop of Henle** - The patient's symptoms (shortness of breath, "choking" sensation, bibasilar crackles, S3 heart sound) are highly suggestive of **acute decompensated heart failure** with **pulmonary edema**. - **Loop diuretics** (e.g., furosemide), which inhibit the **Na/K/Cl symporter** in the thick ascending limb, are the most effective class of diuretics for rapid and significant fluid removal in such cases, leading to symptomatic relief. *A drug that competes for mineralocorticoid receptors in the collecting duct* - This describes **aldosterone antagonists** (e.g., spironolactone, eplerenone), which are typically used for their long-term beneficial effects in **chronic heart failure** by reducing mortality and morbidity. - They have a **slow onset of action** and are **not effective for rapid fluid removal** in acute settings, making them unsuitable for immediate symptom relief in acute pulmonary edema. *A drug that acts on the Na/Cl cotransporter in the distal convoluted tubule* - This describes **thiazide diuretics** (e.g., hydrochlorothiazide), which are primarily used for **hypertension** and mild edema due to their moderate diuretic efficacy. - Thiazides have a **limited diuretic effect** compared to loop diuretics and are generally **ineffective in acute pulmonary edema**, especially when renal function is impaired. *A drug that inhibits angiotensin converting enzyme* - This describes **ACE inhibitors** (e.g., enalapril, lisinopril), which are cornerstone medications for **chronic heart failure** and hypertension due to their effects on **vasodilation** and **remodeling**. - While beneficial long-term, they are **not first-line for rapid symptom relief** in acute pulmonary edema and can sometimes worsen hypotension or renal function in acute settings. *A drug that inhibits carbonic anhydrase* - This describes **carbonic anhydrase inhibitors** (e.g., acetazolamide), which are primarily used for **glaucoma**, **altitude sickness**, and metabolic alkalosis. - They have a **weak diuretic effect** and are **not indicated** for the treatment of acute pulmonary edema or severe fluid overload.

Question 317: A 31-year-old woman makes an appointment with a fertility specialist because she has not been able to conceive despite trying for over a year with her husband. She is concerned because her husband has 2 children from a previous marriage whereas she has no children. After obtaining a detailed history as well as lab tests, the specialist prescribes a certain drug. Interestingly, this drug is able to stimulate receptors in the presence of low hormone levels and inhibit the same receptors in the presence of high hormone levels. The drug that is most likely being prescribed in this case is associated with which of the following adverse events?

• A. Hirsutism
• B. Deep venous thrombosis
• C. Thrombophilia
• D. Osteoporosis
• E. Visual disturbances (Correct Answer)

Explanation: ***Visual disturbances*** - The description of the drug activating receptors in low hormone states and inhibiting them in high hormone states, coupled with its use for infertility, strongly suggests **clomiphene citrate**, a selective estrogen receptor modulator (SERM). - **Visual disturbances** such as blurred vision, scotomas, or photopsia are a relatively common adverse effect of clomiphene due to its effect on estrogen receptors in the retina. *Hirsutism* - **Hirsutism** (excessive hair growth) is typically associated with conditions causing androgen excess, like **polycystic ovary syndrome (PCOS)**, and is not a direct common adverse effect of clomiphene. - While clomiphene aims to induce ovulation, it does not directly cause an increase in androgens leading to hirsutism. *Deep venous thrombosis* - Although some hormonal treatments can increase the risk of **DVT**, clomiphene's association with DVT is **not as primary or common** as other adverse effects, and it's less direct compared to estrogen-containing medications. - The mechanism of action of clomiphene as a SERM modulating estrogen receptors does not typically lead to a significant procoagulant state comparable to exogenous estrogen. *Thrombophilia* - **Thrombophilia** refers to an increased tendency to form blood clots; while some hormonal medications can exacerbate thrombophilia, clomiphene is **not generally recognized** for causing thrombophilia or significantly increasing its risk. - Its mechanism of action primarily involves stimulating gonadotropin release rather than directly altering coagulation factors to induce thrombophilia. *Osteoporosis* - While **estrogen deficiency** can lead to osteoporosis, clomiphene's role is to modulate estrogen receptors; it can cause some anti-estrogenic effects, but **osteoporosis is not a common acute or direct adverse event** of its short-term use for fertility. - Long-term use of anti-estrogenic drugs like tamoxifen can increase osteoporosis risk, but clomiphene is typically used for a limited duration, making osteoporosis less relevant as an immediate adverse event.

Question 318: An 82-year-old male with congestive heart failure experiences rapid decompensation of his condition, manifesting as worsening dyspnea, edema, and increased fatigue. Labs reveal an increase in his serum creatinine from baseline. As part of the management of this acute change, the patient is given IV dobutamine to alleviate his symptoms. Which of the following effects occur as a result of this therapy?

• A. Decreased cardiac contractility
• B. Decreased heart rate
• C. Increased myocardial oxygen consumption (Correct Answer)
• D. Increased systemic vascular resistance due to systemic vasoconstriction
• E. Slowed atrioventricular conduction velocities

Explanation: ***Increased myocardial oxygen consumption*** - Dobutamine is a **beta-1 adrenergic agonist** that increases **myocardial contractility** and **heart rate**. - This enhanced cardiac workload directly leads to an **increased demand for oxygen** by the heart muscle. *Decreased cardiac contractility* - Dobutamine is primarily used in heart failure to **increase cardiac contractility** (positive inotropic effect), thus improving cardiac output. - Decreased contractility would worsen the patient's condition, which is contrary to the therapeutic goal of dobutamine. *Decreased heart rate* - Dobutamine, through its beta-1 agonism, typically causes an **increase in heart rate**, not a decrease. - A decreased heart rate would further compromise cardiac output in a decompensated heart failure patient. *Increased systemic vascular resistance due to systemic vasoconstriction* - Dobutamine has a relatively weak effect on alpha-1 adrenergic receptors, and its primary action is to cause **vasodilation**, which tends to **decrease systemic vascular resistance**. - While other inotropes like norepinephrine can cause vasoconstriction, dobutamine's effect on SVR is generally minimal or mildly vasodilatory, which helps to reduce afterload. *Slowed atrioventricular conduction velocities* - Beta-1 agonists like dobutamine generally tend to **increase atrioventricular (AV) conduction velocity** and can even precipitate arrhythmias. - Slowed AV conduction is characteristic of drugs like beta-blockers or calcium channel blockers, which would be contraindicated in this setting.

Question 319: A 52-year-old man comes to the physician because of a 3-day history of intermittent chest tightness that worsens with exercise. He has chronic atrial fibrillation treated with a drug that prolongs the QT interval. During cardiac stress testing, an ECG shows progressive shortening of the QT interval as the heart rate increases. Which of the following drugs is this patient most likely taking?

• A. Lidocaine
• B. Flecainide
• C. Carvedilol
• D. Dofetilide (Correct Answer)
• E. Diltiazem

Explanation: ***Dofetilide*** - **Dofetilide** is a **Class III antiarrhythmic** that blocks potassium channels (IKr) and **prolongs the QT interval**, making it the drug described in the stem. - It is **FDA-approved for conversion and maintenance of sinus rhythm in atrial fibrillation**, matching this patient's treatment history. - The QT shortening observed during stress testing is **normal physiologic behavior** seen with all drugs—the QT interval naturally decreases as heart rate increases (the corrected QT, or QTc, accounts for this). - Dofetilide carries a significant **risk of torsades de pointes**, especially with QT prolongation, which is why the stem emphasizes QT monitoring. *Lidocaine* - **Lidocaine** is a **Class IB antiarrhythmic** that primarily shortens or has minimal effect on the QT interval. - It is used for **ventricular arrhythmias** (especially in acute MI), **not for atrial fibrillation**. - Does not match the described QT-prolonging treatment. *Flecainide* - **Flecainide** is a **Class IC antiarrhythmic** that primarily slows conduction by blocking sodium channels. - It **does not significantly prolong the QT interval**—it may widen the QRS complex but doesn't affect ventricular repolarization substantially. - While it can be used for atrial fibrillation, it doesn't match the QT-prolonging drug described. *Carvedilol* - **Carvedilol** is a **non-selective beta-blocker** with alpha-1 blocking properties used for rate control in atrial fibrillation and heart failure. - Beta-blockers **do not prolong the QT interval**; they may slightly shorten it or have no effect. - Does not match the stem description. *Diltiazem* - **Diltiazem** is a **non-dihydropyridine calcium channel blocker** used for rate control in atrial fibrillation. - It **does not prolong the QT interval**—calcium channel blockers affect AV nodal conduction but not ventricular repolarization. - Does not match the drug described in the stem.

Question 320: A 23-year-old woman presents to her primary care physician for poor sleep. Her symptoms began approximately 1 week ago, when she started waking up multiple times throughout the night to urinate. She also reports an increase in her water intake for the past few days prior to presentation, as well as larger urine volumes than normal. Medical history is significant for asthma. Family history is significant for type 2 diabetes mellitus. She denies alcohol, illicit drug, or cigarette use. Her temperature is 98.6°F (37°C), blood pressure is 108/65 mmHg, pulse is 103/min, and respirations are 18/min. On physical exam, she has mildly dry mucous membranes and has no focal neurological deficits. Laboratory testing demonstrates the following: Serum: Na+: 145 mEq/L Cl-: 102 mEq/L K+: 4.2 mEq/L HCO3-: 28 mEq/L BUN: 15 mg/dL Glucose: 98 mg/dL Creatinine: 0.92 mg/dL Urine: Urine osmolality: 250 mOsm/kg The patient undergoes a water deprivation test, and her labs demonstrate the following: Na+: 147 mEq/L Cl-: 103 mEq/L K+: 4.4 mEq/L HCO3-: 22 mEq/L BUN: 16 mg/dL Glucose: 101 mg/dL Creatinine: 0.94 mg/dL Urine osmolality: 252 mOsm/kg Which of the following is the best next step in management?

• A. Counsel to decrease excess water intake
• B. Intravenous fluids
• C. Desmopressin (Correct Answer)
• D. Dietary modification
• E. Metformin

Explanation: ***Desmopressin*** - The patient exhibits symptoms of **polyuria** and **polydipsia**, with a persistently **low urine osmolality** (250-252 mOsm/kg) that **fails to concentrate after water deprivation test**. This indicates **diabetes insipidus (DI)**. - The **best next step** is a **desmopressin challenge test** to differentiate between **central DI** and **nephrogenic DI**. - In **central DI**, administration of desmopressin (synthetic ADH) will cause urine osmolality to **increase significantly** (>50% or >600 mOsm/kg), confirming the diagnosis. - In **nephrogenic DI**, the kidneys cannot respond to ADH, so urine osmolality **remains low** despite desmopressin administration. - This diagnostic step is essential before initiating long-term treatment, as central and nephrogenic DI have different management strategies. *Counsel to decrease excess water intake* - The increased water intake is a **compensatory response** to the excessive urine output caused by diabetes insipidus, not the primary cause. - Restricting water intake without addressing the underlying inability to concentrate urine could lead to severe **dehydration** and **hypernatremia**. - This would be dangerous and does not address the pathophysiology. *Intravenous fluids* - While the patient has **mild dehydration** (dry mucous membranes, Na+ 147 mEq/L after water deprivation), she is hemodynamically stable and not in hypovolemic shock. - IV fluids may provide temporary relief but **do not diagnose or treat the underlying disorder** (inability to concentrate urine). - The primary issue requires hormonal diagnosis and management, not just volume replacement. *Dietary modification* - The patient's **normal glucose** (98-101 mg/dL) rules out diabetes mellitus, so dietary changes for glycemic control are not indicated. - **Diabetes insipidus** is a disorder of **water balance due to ADH deficiency or resistance**, not a metabolic or dietary condition. - Dietary modification would not address the hormonal deficit. *Metformin* - **Metformin** is used to treat **type 2 diabetes mellitus**, which involves insulin resistance and hyperglycemia. - The patient has **normal blood glucose** and symptoms consistent with **diabetes insipidus** (a disorder of water metabolism), not diabetes mellitus (a disorder of glucose metabolism). - The name similarity is a distractor, but these are completely different conditions.

Question 321: A 53-year-old woman presents to her primary care physician due to her "feet feeling painful." She reports initially having decreased sensation on both of her feet and recently her hands. She now experiences paresthesias, numbness, and a "burning pain." She is recovering from a recent myocardial infarction. Approximately 1.5 weeks ago, she experienced mild watery diarrhea and an atypical pneumonia. For the past 3 weeks, she has been experiencing fatigue, trouble with concentration, and mild weight gain. Beyond this she has no other acute concerns. Her past medical history is significant for type II diabetes mellitus, hypertension, and coronary artery disease. She is currently taking metformin, aspirin, atorvastatin, metoprolol, and lisinopril. Her temperature is 99°F (37.2°C), blood pressure is 155/98 mmHg, pulse is 85/min, and respirations are 14/min. On physical exam, there is a loss of vibratory sensation and altered proprioception in the bilateral feet. She has impaired pain, light touch, and temperature sensation starting from her feet to mid-calf and hands. She has normal strength and muscle tone throughout her upper and lower extremities, as well as absent bilateral ankle reflexes. Which of the following is the best next step in management?

• A. Amitriptyline
• B. Lidocaine patch
• C. Gabapentin (Correct Answer)
• D. Venlafaxine
• E. Intravenous immunoglobulin

Explanation: ***Gabapentin*** - The patient's symptoms (paresthesias, numbness, burning pain, loss of vibratory sensation, impaired pain/light touch/temperature, absent ankle reflexes) are highly suggestive of **neuropathic pain**, likely from a **peripheral neuropathy**. - **Gabapentin** is a first-line agent for the treatment of neuropathic pain, working by modulating voltage-gated calcium channels to reduce neurotransmitter release, effectively alleviating symptoms like burning and tingling. *Amitriptyline* - **Amitriptyline** is a tricyclic antidepressant (TCA) that can be used for neuropathic pain. However, it is generally considered a second-line agent due to its significant **anticholinergic side effects** (e.g., dry mouth, constipation, sedation) as well as cardiac side effects, which might be problematic for a patient with a history of coronary artery disease and recent MI. *Lidocaine patch* - **Lidocaine patches** provide topical analgesia and are primarily used for **localized neuropathic pain**, such as postherpetic neuralgia or localized diabetic neuropathy. The patient's symptoms are described as bilateral and diffuse, affecting both feet and hands, making a topical treatment less suitable as a sole initial therapeutic approach. *Venlafaxine* - **Venlafaxine** is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is also used for neuropathic pain. While it is an effective option, especially when co-occurring depression is present, current guidelines often favor gabapentin or pregabalin as first-line agents due to a generally more favorable side effect profile and ease of titration, particularly in a patient with cardiovascular history. *Intravenous immunoglobulin* - **Intravenous immunoglobulin (IVIG)** is a treatment reserved for serious autoimmune neuropathies such as **Guillain-Barré Syndrome** or severe chronic inflammatory demyelinating polyneuropathy (CIDP). While the patient's symptoms could suggest an underlying neuropathy, there is no evidence of rapid progression or severe motor weakness that would indicate an acute inflammatory demyelinating process warranting IVIG.

Question 322: A 22-year-old female presents to her PCP after having unprotected sex with her boyfriend 2 days ago. She has been monogamous with her boyfriend but is very concerned about pregnancy. The patient requests emergency contraception to decrease her likelihood of getting pregnant. A blood hCG test returns negative. The PCP prescribes the patient ethinyl estradiol 100 mcg and levonorgestrel 0.5 mg to be taken 12 hours apart. What is the most likely mechanism of action for this combined prescription?

• A. Inhibition or delayed ovulation (Correct Answer)
• B. Interference of corpus luteum function
• C. Thickening of cervical mucus with sperm trapping
• D. Tubal constriction inhibiting sperm transportation
• E. Alteration of the endometrium impairing implantation of the fertilized egg

Explanation: ***Inhibition or delayed ovulation*** - The high doses of **estrogen** and **progestin** in the combined emergency contraception pill primarily act by suppressing the **luteinizing hormone (LH) surge**, which is essential for ovulation. - By inhibiting or delaying ovulation, the pill prevents the release of an egg, thus preventing fertilization since sperm cannot meet an egg. *Interference of corpus luteum function* - While hormonal contraceptives can affect the **corpus luteum**, high-dose emergency contraception primarily acts *before* the formation of a mature corpus luteum by preventing ovulation itself. - Once the corpus luteum is formed, its function is usually maintained if pregnancy occurs, and emergency contraception given *after* implantation is generally ineffective at terminating a pregnancy. *Thickening of cervical mucus with sperm trapping* - This is a well-known mechanism of action for *continuous* hormonal contraception (e.g., daily birth control pills), where lower, consistent doses of progestin make cervical mucus impenetrable to sperm. - While it might play a *minor* role, it is not the primary mechanism of action for high-dose emergency contraception administered acutely, which mainly targets ovulation. *Tubal constriction inhibiting sperm transportation* - There is no strong evidence to suggest that combined emergency contraception pills cause **tubal constriction** to significantly impair sperm or egg transport. - The main sites of action are the **hypothalamic-pituitary-ovarian axis** (for ovulation) and possibly the endometrium (for implantation), not direct tubal motility. *Alteration of the endometrium impairing implantation of the fertilized egg* - While hormonal contraceptives can alter the **endometrium** making it less receptive to implantation, this is considered a *secondary* or less significant mechanism for combined emergency contraception. - The primary goal and most effective action of these pills is to prevent fertilization by inhibiting ovulation, especially when taken shortly after unprotected intercourse and before implantation.

Question 323: A 49-year-old woman presents to her primary care physician with fatigue. She reports that she has recently been sleeping more than usual and says her “arms and legs feel like lead” for most of the day. She has gained 10 pounds over the past 3 months which she attributes to eating out at restaurants frequently, particularly French cuisine. Her past medical history is notable for social anxiety disorder. She took paroxetine and escitalopram in the past but had severe nausea and headache while taking both. She has a 10 pack-year smoking history and has several glasses of wine per day. Her temperature is 98.6°F (37°C), blood pressure is 130/65 mmHg, pulse is 78/min, and respirations are 16/min. Physical examination reveals an obese woman with a dysphoric affect. She states that her mood is sad but she does experience moments of happiness when she is with her children. The physician starts the patient on a medication to help with her symptoms. Three weeks after the initiation of the medication, the patient presents to the emergency room with a severe headache and agitation. Her temperature is 102.1°F (38.9°C), blood pressure is 180/115 mmHg, pulse is 115/min, and respirations are 24/min. Which of the following is the mechanism of action of the medication that is most likely responsible for this patient’s symptoms?

• A. Inhibition of serotonin and norepinephrine reuptake
• B. Inhibition of the adrenergic alpha-2 receptor and serotonin-2 and -3 receptors
• C. Inhibition of serotonin reuptake
• D. Partial agonism of serotonin-1A receptor
• E. Inhibition of amine degradation (Correct Answer)

Explanation: **Inhibition of amine degradation** - This mechanism of action describes **monoamine oxidase inhibitors (MAOIs)**. Given the patient's symptoms of **hypertensive crisis** (headache, agitation, hypertension, tachycardia, fever) after starting a new medication and her history of **eating French cuisine** (which could include tyramine-rich foods like aged cheeses and wines), an MAOI is the most likely culprit. - MAOIs prevent the breakdown of **monoamine neurotransmitters** (serotonin, norepinephrine, dopamine, tyramine), leading to their accumulation. In the presence of **tyramine-rich foods**, this can precipitate a **hypertensive crisis** due to excessive norepinephrine release. *Inhibition of serotonin and norepinephrine reuptake* - This describes **SNRIs (serotonin-norepinephrine reuptake inhibitors)** or **TCAs (tricyclic antidepressants)**. While these can cause side effects, a sudden and severe **hypertensive crisis** as described, especially without a clear dietary trigger interaction, is less characteristic than with MAOIs. - The patient's prior negative experiences with paroxetine and escitalopram (SSRIs) might make a physician choose a different class, but the dramatic symptoms point away from typical SNRI/TCA side effects for this presentation. *Inhibition of the adrenergic alpha-2 receptor and serotonin-2 and -3 receptors* - This mechanism is characteristic of **mirtazapine**. While mirtazapine can cause sedation and weight gain (presenting symptoms), it does not typically lead to a **hypertensive crisis** of this severity three weeks after initiation, nor does it have severe food interactions like MAOIs. - Mirtazapine's primary side effects often include sedation, increased appetite, and weight gain, but not the acute constellation observed here. *Inhibition of serotonin reuptake* - This describes **SSRIs (selective serotonin reuptake inhibitors)**. The patient had severe nausea and headache with paroxetine and escitalopram, which are SSRIs. While SSRIs can contribute to **serotonin syndrome** (which shares some features like agitation and hyperthermia), the profound **hypertension** and context of food interaction strongly favor an MAOI-induced hypertensive crisis. - SSRIs are less likely to cause such a severe **hypertensive crisis** acutely, and the patient's history suggests a physician would likely avoid this class due to past adverse reactions. *Partial agonism of serotonin-1A receptor* - This is the mechanism of action for **buspirone**, an anxiolytic. Buspirone is generally well-tolerated and does not cause the severe side effects seen in this patient, particularly **hypertensive crisis** or food interactions. - Buspirone is often used for generalized anxiety disorder, and while the patient has social anxiety, the described adverse event does not align with buspirone's known side effect profile.

Question 324: A 3-year-old boy is brought to the emergency department by his mother. His mother reports that she found him playing under the sink yesterday. She was concerned because she keeps some poisons for pest control under the sink but did not believe that he came in contact with the poisons. However, this morning the boy awoke with abdominal pain and epistaxis, causing her to rush him to the emergency department. You obtain stat lab-work with the following results: WBC: 6,000/microliter; Hgb: 11.2 g/dL; Platelets: 200,000/microliter; PTT: 35 seconds; INR: 6.5; Na: 140 mEq/L; K: 4 mEq/L; Cr: 0.7 mg/dL. Which of the following is likely to be the most appropriate treatment?

• A. Protamine sulfate
• B. Dimercaptosuccinic acid (DMSA)
• C. Packed red blood cells transfusion
• D. Vitamin K and fresh frozen plasma (Correct Answer)
• E. Penicillamine

Explanation: ***Vitamin K and fresh frozen plasma*** - The patient presents with **epistaxis** and a significantly **elevated INR (6.5)**, indicating a severe coagulopathy most likely due to **long-acting anticoagulant rodenticide poisoning** (superwarfarins like brodifacoum or bromadiolone found in pest control products). Vitamin K is the antidote, restoring normal clotting factor synthesis, while fresh frozen plasma provides immediate replacement of depleted clotting factors. - The combination of vitamin K and fresh frozen plasma directly addresses the **bleeding risk** and coagulation defect, which is critical in acute warfarin toxicity. Note that superwarfarin poisoning requires **prolonged vitamin K therapy** (weeks to months) due to the long half-life of these rodenticides. *Protamine sulfate* - This is an antidote for **heparin overdose**, which directly inhibits thrombin and Factor Xa. The patient's elevated INR is indicative of warfarin-type poisoning, not heparin. - Heparin toxicity is characterized by a prolonged **aPTT**, not primarily an elevated INR. *Dimercaptosuccinic acid (DMSA)* - DMSA is a **chelating agent** used to treat **heavy metal poisoning**, particularly **lead** and **mercury**. The patient's symptoms and lab results (elevated INR) are not consistent with heavy metal toxicity. - There is no indication of heavy metal exposure or symptoms like neurological deficits or gastrointestinal distress typical of lead or mercury poisoning. *Packed red blood cells transfusion* - While the patient has epistaxis, the **hemoglobin level (11.2 g/dL)** is still within a relatively normal range, indicating no acute, severe blood loss requiring immediate packed red blood cell transfusion. - Transfusing red blood cells would address anemia but would not correct the underlying **coagulopathy** or reverse the effects of the poison. *Penicillamine* - Penicillamine is a **chelating agent** used for **copper poisoning (Wilson's disease)**, **lead poisoning**, and sometimes **rheumatoid arthritis**. It is not indicated for coagulopathy from warfarin toxicity. - The clinical picture and lab findings do not suggest heavy metal or copper toxicity, which would present with different symptoms and lab abnormalities.

Question 325: A 66-year-old female presents to the emergency room with left hip pain after a fall. She is unable to move her hip due to pain. On exam, her left leg appears shortened and internally rotated. Hip radiographs reveal a fracture of the left femoral neck. She has a history of a distal radius fracture two years prior. Review of her medical record reveals a DEXA scan from two years ago that demonstrated a T-score of -3.0. Following acute management of her fracture, she is started on a medication that is known to induce osteoclast apoptosis. Which of the following complications is most closely associated with the medication prescribed in this case?

• A. Gingival hyperplasia
• B. Vertebral compression fracture
• C. Interstitial nephritis
• D. Osteonecrosis of the jaw (Correct Answer)
• E. Agranulocytosis

Explanation: ***Osteonecrosis of the jaw*** - The patient's history of a femoral neck fracture and a **DEXA T-score of -3.0** indicates **osteoporosis**, for which a medication inducing osteoclast apoptosis (e.g., **bisphosphonates** or **denosumab**) would be prescribed. - **Osteonecrosis of the jaw (ONJ)** is a recognized, although rare, severe complication particularly associated with bisphosphonate and denosumab use, often following dental procedures. *Gingival hyperplasia* - This complication is most commonly associated with **calcium channel blockers** (like nifedipine), **cyclosporine**, and **phenytoin**. - It is not a known side effect of medications that induce osteoclast apoptosis, such as bisphosphonates or denosumab. *Vertebral compression fracture* - While this patient is at high risk for osteoporotic fractures, medication that *treats* osteoporosis by inducing osteoclast apoptosis **reduces** the risk of new fractures, including vertebral compression fractures. - A new vertebral compression fracture would indicate treatment failure or an underlying progression of osteoporosis, not a direct complication of the medication if it is working effectively. *Interstitial nephritis* - **Interstitial nephritis** is an inflammatory kidney condition often associated with drugs like **NSAIDs**, **antibiotics (e.g., penicillins, sulfonamides)**, and **diuretics**. - It is not a characteristic side effect of bisphosphonates or other anti-resorptive agents used for osteoporosis. *Agranulocytosis* - Agranulocytosis is a severe reduction in **granulocytes (a type of white blood cell)**, typically associated with drugs like **propylthiouracil**, **methimazole**, **clozapine**, and certain **NSAIDs**. - Medications that induce osteoclast apoptosis for osteoporosis do not commonly cause agranulocytosis.

Question 326: A 43-year-old man comes to the physician because of anxiety, difficulty focusing on tasks, and a 4.6-kg (10-lb) weight loss over the past 4 weeks. He is diaphoretic. His pulse is 100/min, respirations are 18/min, and blood pressure is 150/78 mm Hg. Physical examination shows warm, moist skin, goiter, and a resting tremor of both hands. Laboratory studies show a thyroxine (T4) concentration of 30 μg/dL and a thyroid-stimulating hormone concentration of 0.1 μU/mL. The patient is started on methimazole and atenolol. The latter agent predominantly affects which of the following?

• A. Atrioventricular node activity (Correct Answer)
• B. His-Purkinje conduction
• C. Vagal tone
• D. Phase 0 depolarization slope of the cardiac action potential
• E. Effective refractory period of the cardiac action potential

Explanation: ***Atrioventricular node activity*** - Atenolol is a **beta-1 selective adrenergic blocker** used to manage hyperthyroidism symptoms. - It primarily acts on the **AV node** to slow conduction and decrease heart rate, effectively controlling tachycardia and palpitations. *His-Purkinje conduction* - Conduction through the **His-Purkinje system** is not significantly affected by beta-blockers like atenolol. - This system primarily dictates the rapid spread of electrical impulses through the ventricles. *Vagal tone* - Atenolol works by **blocking adrenergic receptors**, not by directly influencing the parasympathetic nervous system or vagal tone. - Increased vagal tone would slow heart rate, but this is a separate mechanism. *Phase 0 depolarization slope of the cardiac action potential* - This phase is mediated by **fast sodium channels** in ventricular myocytes and Purkinje fibers. - Beta-blockers primarily affect the **calcium-dependent action potentials** in the SA and AV nodes, not the fast sodium channels in ventricular tissue. *Effective refractory period of the cardiac action potential* - While beta-blockers can indirectly influence refractory periods by slowing heart rate, their primary direct effect is not on the **effective refractory period**. - Medications that block potassium channels or sodium channels more directly impact the effective refractory period.

Question 327: A 53-year-old woman comes to the physician because of increasing shortness of breath on exertion for 5 months. She reports that she can not climb more than 2 flights of stairs and she is no longer able to run her errands as usual. One year ago, she was diagnosed with triple-negative breast cancer. She underwent a right-sided modified radical mastectomy and adjuvant chemotherapy. Cardiac examination shows a laterally displaced point of maximal impulse. Coarse inspiratory crackles are heard in both lower lung fields. Echocardiography shows a left ventricular ejection fraction of 30%. The physician informs the patient that her symptoms are most likely due to an adverse effect of her chemotherapy. The drug most likely responsible for the patient's current symptoms belongs to which of the following groups of agents?

• A. Antimetabolites
• B. Monoclonal antibodies
• C. Alkylating agents
• D. Topoisomerase I inhibitors
• E. Anthracyclines (Correct Answer)

Explanation: ***Anthracyclines*** - The patient's presentation of **dilated cardiomyopathy** (shortness of breath, laterally displaced PMI, coarse crackles, reduced ejection fraction) following chemotherapy for breast cancer is characteristic of **anthracycline-induced cardiotoxicity**. - **Anthracyclines** such as doxorubicin and epirubicin are known to cause **dose-dependent cardiotoxicity**, leading to irreversible myocardial damage and heart failure. *Antimetabolites* - **Antimetabolites** (e.g., methotrexate, 5-fluorouracil) primarily interfere with DNA synthesis and repair. - While they can have side effects like myelosuppression and mucositis, **significant cardiotoxicity** leading to dilated cardiomyopathy is not their primary or most common adverse effect. *Monoclonal antibodies* - Some **monoclonal antibodies**, particularly trastuzumab (Herceptin), used in HER2-positive breast cancer, can cause cardiotoxicity, but it is typically **reversible** and not seen with triple-negative breast cancer unless used in combination with anthracyclines. - The type of cardiomyopathy with trastuzumab is usually **reversible cardiac dysfunction** rather than irreversible dilated cardiomyopathy. *Alkylating agents* - **Alkylating agents** (e.g., cyclophosphamide, cisplatin) primarily damage DNA, leading to cell death. - While they can cause various side effects, **dilated cardiomyopathy** is not a hallmark or common cardiotoxic effect, unlike anthracyclines, though high-dose cyclophosphamide can cause acute pericarditis or myocarditis. *Topoisomerase I inhibitors* - **Topoisomerase I inhibitors** (e.g., irinotecan, topotecan) typically cause gastrointestinal side effects (diarrhea), myelosuppression, and fatigue. - **Cardiotoxicity** leading to dilated cardiomyopathy is not a prominent or common side effect associated with this class of drugs.

Question 328: A 68-year-old man with type 2 diabetes mellitus comes to the physician because of a 5-month history of episodic palpitations, dizziness, and fatigue. His pulse is 134/min and irregularly irregular, and his blood pressure is 165/92 mm Hg. An ECG shows a narrow complex tachycardia with absent P waves. He is prescribed a drug that decreases the long-term risk of thromboembolic complications by inhibiting the extrinsic pathway of the coagulation cascade. The expected beneficial effect of this drug is most likely due to which of the following actions?

• A. Inhibit the reduction of vitamin K (Correct Answer)
• B. Activate gamma-glutamyl carboxylase
• C. Inhibit the phosphorylation of glutamate on the factor II precursor
• D. Activate factor VII calcium-binding sites
• E. Inhibit the absorption of vitamin K

Explanation: ***Inhibit the reduction of vitamin K*** - The patient's symptoms and ECG findings (irregularly irregular pulse, absent P waves, narrow complex tachycardia) are consistent with **atrial fibrillation**, which carries a high risk of **thromboembolic complications**. - The drug described, acting on the **extrinsic pathway** and reducing thromboembolic risk, is most likely **warfarin**, a **vitamin K antagonist** that inhibits the reduction (regeneration) of vitamin K, thus impairing the synthesis of coagulation factors II, VII, IX, and X. *Activate gamma-glutamyl carboxylase* - **Gamma-glutamyl carboxylase** is an enzyme that requires reduced vitamin K as a cofactor. - Warfarin's action is to **inhibit** the enzyme that *reduces* vitamin K, thereby *reducing* the activity of gamma-glutamyl carboxylase, not activating it. *Inhibit the phosphorylation of glutamate on the factor II precursor* - The modification of glutamate residues on coagulation factors is through **gamma-carboxylation**, not phosphorylation. - Warfarin inhibits the **gamma-carboxylation** of factors II, VII, IX, and X, not their phosphorylation. *Activate factor VII calcium-binding sites* - Factor VII, like other vitamin K-dependent factors, requires **gamma-carboxylation** for calcium binding, which is essential for its activation and function. - Warfarin **inhibits** this carboxylation, thereby impairing calcium binding and the activation of these factors, rather than activating their calcium-binding sites. *Inhibit the absorption of vitamin K* - While vitamin K absorption can be affected by certain conditions or drugs (e.g., malabsorption syndromes, broad-spectrum antibiotics), warfarin's primary mechanism of action is **post-absorption**, targeting the **epoxide reductase enzyme** involved in vitamin K recycling, not its intestinal absorption.

Question 329: An 11-year-old boy is brought to the physician by his mother because of a pruritic generalized rash for 2 days. He returned from a 3-day outdoor summer camp 1 week ago. During his time there, one child was sent home after being diagnosed with measles. The patient was diagnosed with a seizure disorder 6 weeks ago and he has asthma. Current medications include carbamazepine and an albuterol inhaler. His immunization records are unavailable. His temperature is 38.4°C (101.1°F), pulse is 88/min, and blood pressure is 102/60 mm Hg. Examination shows facial edema and a diffuse rash over the face, trunk, and extremities. There is cervical and inguinal lymphadenopathy. The remainder of the examination shows no abnormalities. Which of the following is the most appropriate next step in management?

• A. Perform rapid plasma reagin test
• B. Heterophile antibody test
• C. Discontinue carbamazepine (Correct Answer)
• D. Perform measles serology
• E. Administer penicillin therapy

Explanation: ***Discontinue carbamazepine*** - The patient's symptoms (pruritic generalized rash, facial edema, fever, and lymphadenopathy) developing after starting carbamazepine are highly suggestive of **drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome**, a severe adverse drug reaction. - The first and most critical step in managing **DRESS syndrome** is to immediately **discontinue the offending medication**, which in this case is carbamazepine. *Perform rapid plasma reagin test* - A **rapid plasma reagin (RPR) test** is used to screen for **syphilis**, which typically presents with a different rash morphology (e.g., maculopapular rash on palms and soles in secondary syphilis) and is less likely given the clear temporal association with a new medication. - The patient's symptoms are not consistent with the typical presentation of syphilis, and the priority should be addressing the suspected drug reaction. *Heterophile antibody test* - A **heterophile antibody test** is used to diagnose **infectious mononucleosis**, which can cause fever, rash, and lymphadenopathy. However, the facial edema is less typical, and the clear link to a new medication makes DRESS syndrome a more probable diagnosis. - While infectious mononucleosis can trigger rash, the combination of **facial edema** and the temporal relationship with carbamazepine initiation points more strongly to a drug-induced reaction rather than a primary infection. *Perform measles serology* - Although there was a measles case at the summer camp, the rash associated with **measles** is typically maculopapular, starts on the face, and spreads downward, often accompanied by **Koplik spots** and cough/coryza/conjunctivitis (**the 3 Cs**). - The presence of **facial edema** and the timing relative to carbamazepine initiation make measles less likely as the primary diagnosis requiring immediate action. *Administer penicillin therapy* - **Penicillin therapy** is indicated for bacterial infections, particularly streptococcal infections or syphilis (as mentioned with RPR). - The patient's presentation is more consistent with a **drug-induced hypersensitivity reaction** rather than a bacterial infection, making empirical antibiotic therapy inappropriate as the initial management step.

Question 330: A 35-year-old woman is admitted to the medical unit for worsening renal failure. Prior to admission, she was seen by her rheumatologist for a follow-up visit and was found to have significant proteinuria and hematuria on urinalysis and an elevated serum creatinine. She reports feeling ill and has noticed blood in her urine. She was diagnosed with systemic lupus erythematosus at the age of 22, and she is currently being treated with ibuprofen for joint pain and prednisone for acute flare-ups. Her blood pressure is 165/105 mmHg. Laboratory testing is remarkable for hypocomplementemia and an elevated anti-DNA antibody. A renal biopsy is performed, which demonstrates 65% glomerular involvement along with the affected glomeruli demonstrating endocapillary and extracapillary glomerulonephritis. In addition to glucocorticoid therapy, the medical team will add mycophenolate mofetil to her treatment regimen. Which of the following is the mechanism of action of mycophenolate mofetil?

• A. Interleukin-2 receptor complex inhibitor
• B. Inosine monophosphate dehydrogenase inhibitor (Correct Answer)
• C. mTOR inhibitor via FKBP binding
• D. Calcineurin inhibitor via cyclophilin binding
• E. T-cell proliferation inhibitor

Explanation: ***Inosine monophosphate dehydrogenase inhibitor*** - **Mycophenolate mofetil** (MMF) is a prodrug that inhibits **inosine monophosphate dehydrogenase (IMPDH)**, an enzyme essential for *de novo* purine synthesis. - This inhibition selectively blocks the proliferation of **T and B lymphocytes**, which are highly dependent on the *de novo* pathway for purine synthesis, thus suppressing the immune response in conditions like lupus nephritis. *Interleukin-2 receptor complex inhibitor* - This mechanism describes drugs like **basiliximab** and **daclizumab**, which are monoclonal antibodies that block the **IL-2 receptor** on T cells, preventing their activation and proliferation. - These agents are primarily used in **transplantation** to prevent acute rejection, not typically for lupus nephritis. *mTOR inhibitor via FKBP binding* - This mechanism belongs to drugs like **sirolimus** (rapamycin) and everolimus, which bind to **FK-binding protein (FKBP)** and then inhibit **mammalian target of rapamycin (mTOR)**. - While these drugs have immunosuppressive properties and are used in transplantation, they are not the primary mechanism of action for mycophenolate mofetil. *Calcineurin inhibitor via cyclophilin binding* - This mechanism describes drugs like **cyclosporine**, which binds to **cyclophilin** and then inhibits **calcineurin**, preventing the dephosphorylation of NFAT (nuclear factor of activated T-cells) and subsequent IL-2 transcription. - **Tacrolimus** also acts as a calcineurin inhibitor but binds to FKBP. These drugs are used in transplantation and some autoimmune diseases but are not how MMF works. *T-cell proliferation inhibitor* - While MMF *does* inhibit T-cell proliferation, this description is a general outcome of many immunosuppressants and not its specific molecular mechanism of action. - Many drugs can inhibit T-cell proliferation through different pathways, so a more precise description of MMF's action is its inhibition of **IMPDH**.

Question 331: A 36-year-old man is brought to the emergency department by his neighbor because of altered mental status. He was found 6 hours ago stumbling through his neighbor's bushes and yelling obscenities. The neighbor helped him home but found him again 1 hour ago slumped over on his driveway in a puddle of vomit. He is oriented to self but not to place or time. His temperature is 36.9°C (98.5°F), pulse is 82/min, respirations are 28/min, and blood pressure is 122/80 mm Hg. Cardiopulmonary exam shows no abnormalities. He is unable to cooperate for a neurological examination. Muscle spasms are seen in his arms and jaw. Serum laboratory studies show: Na+ 140 mEq/L K+ 5.5 mEq/L Cl- 101 mEq/L HCO3- 9 mEq/L Urea nitrogen 28 mg/dL Creatinine 2.3 mg/dL Glucose 75 mg/dL Calcium 7.2 mg/dL Osmolality 320 mOsm/kg Calculated serum osmolality is 294 mOsm/kg. Arterial blood gas shows a pH of 7.25 and lactate level of 3.2 mmol/L (N=< 1 mmol/L). Examination of the urine shows oxalate crystals and no ketones. This patient is most likely experiencing toxicity from which of the following substances?

• A. Methanol
• B. Ethanol
• C. Ethylene glycol (Correct Answer)
• D. Isopropyl alcohol
• E. Toluene

Explanation: ***Ethylene glycol*** - The presence of **calcium oxalate crystals** in the urine, a **high anion gap metabolic acidosis** (HCO3- 9 mEq/L, lactate 3.2 mmol/L), and an **elevated osmolal gap** (320 - 294 = 26 mOsm/kg) are classic indicators of ethylene glycol poisoning. - **Ethylene glycol** is metabolized into toxic compounds like oxalic acid and glycolic acid, which cause kidney damage, metabolic acidosis, and neurological symptoms such as altered mental status and muscle spasms. *Methanol* - While methanol poisoning also causes a **high anion gap metabolic acidosis** and an **elevated osmolal gap**, it typically leads to **visual disturbances** (e.g., "snowstorm" vision, blindness) which are not mentioned here. - The key differentiating factor here is the presence of **oxalate crystals** in the urine, which are characteristic of ethylene glycol, not methanol. *Ethanol* - Ethanol intoxication can cause altered mental status but usually does not lead to a **high anion gap metabolic acidosis** unless there is severe co-ingestion or underlying conditions. - It would not typically cause **oxalate crystals in the urine** or significant **renal failure (creatinine 2.3 mg/dL)** in this acute setting. *Isopropyl alcohol* - Isopropyl alcohol causes an **elevated osmolal gap** but typically results in **ketosis without acidosis** (due to its metabolism to acetone). - It does not produce **oxalate crystals** in the urine or a **high anion gap metabolic acidosis**. *Toluene* - Toluene poisoning is associated with a **non-anion gap metabolic acidosis** (renal tubular acidosis) and hypokalemia, which is in contrast to the high anion gap acidosis and hyperkalemia (K+ 5.5 mEq/L) seen in this patient. - It would not cause **oxalate crystals in the urine** or a significant **osmolal gap**.

Question 332: A 65-year-old woman is transferred to the intensive care unit after she underwent coronary stenting for a posterior-inferior STEMI. She is known to have allergies to amiodarone and captopril. A few hours after the transfer, she suddenly loses consciousness. The monitor shows ventricular fibrillation. CPR is initiated. After 3 consecutive shocks with a defibrillator, the monitor shows ventricular fibrillation. Which of the following medications should be administered next?

• A. Adrenaline and lidocaine (Correct Answer)
• B. Lidocaine and sotalol
• C. Adrenaline and verapamil
• D. Adrenaline and amiodarone
• E. Amiodarone and lidocaine

Explanation: ***Adrenaline and lidocaine*** - **Adrenaline (epinephrine)** is the standard vasopressor in ACLS for cardiac arrest, given at 1 mg IV/IO every 3-5 minutes to increase coronary and cerebral perfusion pressures, improving the chances of return of spontaneous circulation (ROSC). - **Lidocaine** is the recommended alternative antiarrhythmic for refractory ventricular fibrillation when **amiodarone is contraindicated** (as in this patient with documented amiodarone allergy). - Per **ACLS guidelines**, after failed defibrillation attempts, continue CPR, administer epinephrine, and give an antiarrhythmic agent (lidocaine 1-1.5 mg/kg when amiodarone cannot be used). *Lidocaine and sotalol* - **Lidocaine** is appropriate as an antiarrhythmic in refractory VF when amiodarone is contraindicated. - However, this option omits **epinephrine (adrenaline)**, which is a critical vasopressor required during cardiac arrest per ACLS protocols. - **Sotalol** is a beta-blocker with Class III antiarrhythmic properties, but it is not recommended for acute management of refractory VF in cardiac arrest. *Adrenaline and verapamil* - **Adrenaline** is indicated as the vasopressor for cardiac arrest. - **Verapamil** is a calcium channel blocker used for supraventricular arrhythmias; it is **contraindicated in ventricular fibrillation** due to negative inotropic effects and peripheral vasodilation that can worsen hemodynamic collapse during cardiac arrest. *Adrenaline and amiodarone* - While **adrenaline** is indicated and **amiodarone** would typically be the preferred antiarrhythmic for refractory VF, this patient has a **documented allergy to amiodarone**, making it contraindicated. - Lidocaine must be used as the alternative antiarrhythmic agent. *Amiodarone and lidocaine* - **Lidocaine** is appropriate in this scenario. - However, **amiodarone is contraindicated** due to the patient's known allergy. - This combination would be dangerous and violates basic principles of avoiding known allergens.

Question 333: A 62-year-old man presents to his geriatrician due to waking several times during the night and also rising too early in the morning. He says this has worsened over the past 7 months. In the morning, he feels unrefreshed and tired. His medical history is positive for hypertension and benign prostatic hyperplasia. He has never been a smoker. He denies drinking alcohol or caffeine prior to bedtime. Vital signs reveal a temperature of 36.6°C (97.8°F), blood pressure of 130/80 mm Hg, and heart rate of 77/min. Physical examination is unremarkable. After discussing good sleep hygiene with the patient, which of the following is the best next step in the management of this patient’s condition?

• A. Cognitive behavioral therapy for insomnia (CBT-I) (Correct Answer)
• B. Melatonin supplementation
• C. Referral to sleep medicine specialist
• D. Polysomnography
• E. Zolpidem

Explanation: ***Cognitive behavioral therapy for insomnia (CBT-I)*** - CBT-I is the **first-line treatment** for chronic insomnia according to the American Academy of Sleep Medicine and American College of Physicians guidelines - After addressing sleep hygiene (already done), CBT-I is the recommended next step before considering pharmacotherapy - CBT-I has **durable benefits** without the risks of medications, particularly important in elderly patients - Components include sleep restriction, stimulus control, cognitive restructuring, and relaxation techniques - In elderly patients, CBT-I avoids medication-related risks such as **falls, cognitive impairment, and dependence** *Zolpidem* - While hypnotics like zolpidem may provide short-term symptom relief, they are **not first-line therapy** for chronic insomnia - The American Geriatrics Society **Beers Criteria** lists benzodiazepines and Z-drugs (including zolpidem) as potentially inappropriate medications in older adults due to increased risk of **falls, fractures, cognitive impairment, and delirium** - Hypnotics should be reserved for situations where CBT-I is unavailable, ineffective, or when used as a short-term adjunct while implementing behavioral therapy - If used, they should be prescribed at the **lowest effective dose for the shortest duration** *Melatonin supplementation* - Melatonin is most helpful for **circadian rhythm disorders** (e.g., delayed sleep phase syndrome) or **jet lag** - Limited evidence supports its effectiveness for chronic insomnia with sleep maintenance problems (frequent awakenings and early morning awakening) in elderly patients - May have a role in patients with documented melatonin deficiency or specific circadian disorders *Referral to sleep medicine specialist* - Appropriate if initial interventions (sleep hygiene, CBT-I, limited pharmacotherapy trial) fail - Indicated when suspecting **primary sleep disorders** such as obstructive sleep apnea, restless legs syndrome, or periodic limb movement disorder - Not the immediate next step for straightforward chronic insomnia presentation after sleep hygiene counseling *Polysomnography* - Polysomnography (sleep study) is indicated when there is clinical suspicion of **sleep-disordered breathing** (sleep apnea), **narcolepsy**, **REM sleep behavior disorder**, or **periodic limb movement disorder** - This patient's presentation (sleep maintenance insomnia with frequent awakenings and early morning awakening) is most consistent with **primary insomnia**, not a parasomnia or sleep-disordered breathing - Red flags for sleep apnea (witnessed apneas, loud snoring, gasping, excessive daytime sleepiness, obesity) are absent - Polysomnography is **not routinely indicated** for the diagnosis of chronic insomnia

Question 334: An ECG from an 8-year-old male with neurosensory deafness and a family history of sudden cardiac arrest demonstrates QT-interval prolongation. Which of the following is this patient most at risk of developing?

• A. Hypertrophic cardiac myopathy
• B. Cardiac tamponade
• C. Essential hypertension
• D. Torsades de pointes (Correct Answer)
• E. First degree atrioventricular block

Explanation: ***Torsades de pointes*** - The combination of **neurosensory deafness**, **QT-interval prolongation**, and a family history of **sudden cardiac arrest** is highly suggestive of **Jervell and Lange-Nielsen syndrome**, a form of **long QT syndrome**. - Patients with long QT syndrome are at significant risk for developing **polymorphic ventricular tachycardia** known as **Torsades de pointes**, which can degenerate into **ventricular fibrillation** and cause sudden cardiac death. *Hypertrophic cardiac myopathy* - This condition involves thickening of the **ventricular walls** and is associated with outflow tract obstruction, not primarily with QT prolongation. - While it can cause sudden cardiac arrest, it typically presents with symptoms like **dyspnea, chest pain**, or syncope during exertion, and its ECG findings usually include **left ventricular hypertrophy** and **deep Q waves**. *Cardiac tamponade* - **Cardiac tamponade** results from the accumulation of fluid in the **pericardial sac**, compressing the heart and impairing its filling. - This condition is not related to **QT prolongation** or **sensorineural deafness** and would present with signs of **hemodynamic instability**, such as **pulsus paradoxus** and muffled heart sounds. *Essential hypertension* - **Essential hypertension** is chronic high blood pressure with no identifiable secondary cause, commonly affecting adults. - It is not associated with **congenital neurosensory deafness** or significant **QT-interval prolongation** in childhood. *First degree atrioventricular block* - **First-degree AV block** is characterized by a prolonged **PR interval** on ECG, indicating delayed conduction through the AV node. - While it's an electrical abnormality, it is distinct from **QT prolongation** and is not typically associated with **neurosensory deafness** or the same risk of sudden cardiac arrest as long QT syndrome.

Question 335: A 72-year-old man is brought to the emergency department from hospice. The patient has been complaining of worsening pain over the past few days and states that it is no longer bearable. The patient has a past medical history of pancreatic cancer which is being managed in hospice. The patient desires no "heroic measures" to be made with regards to treatment and resuscitation. His temperature is 98.8°F (37.1°C), blood pressure is 107/68 mmHg, pulse is 102/min, respirations are 22/min, and oxygen saturation is 99% on room air. Physical exam reveals an uncomfortable elderly man who experiences severe pain upon abdominal palpation. Laboratory values reveal signs of renal failure, liver failure, and anemia. Which of the following is the best next step in management?

• A. Ketorolac and fentanyl
• B. Ketorolac
• C. Morphine (Correct Answer)
• D. No intervention warranted
• E. Morphine and fentanyl patch

Explanation: ***Morphine*** - This patient is in **hospice** with **acute, unbearable pain** requiring **immediate relief** in the emergency department. **Intravenous or subcutaneous morphine** is the **best next step** as it provides **rapid onset of analgesia** (within 5-10 minutes for IV, 15-30 minutes for SC). - In the **ED setting**, the priority is to achieve **immediate pain control** for this acute exacerbation. Once stabilized, a comprehensive long-acting regimen can be coordinated with hospice, but the question asks for the **best next step**, which is immediate-acting opioid administration. - Morphine is appropriate despite renal failure in end-of-life care where **comfort is the primary goal**. Doses may need adjustment, but pain relief takes precedence in hospice patients. *Ketorolac and fentanyl* - **Ketorolac (NSAID)** is **contraindicated** in patients with **renal failure** and carries risk of **gastrointestinal bleeding**, especially concerning in advanced cancer with anemia. - While fentanyl is appropriate for pain management, a **fentanyl patch** takes **12-24 hours** to reach therapeutic levels and is unsuitable for **acute pain** requiring immediate relief. *Ketorolac* - **Ketorolac (NSAID)** is contraindicated due to **renal failure** and would be insufficient for severe cancer-related pain. - NSAIDs are generally avoided in hospice patients with multi-organ dysfunction and do not provide adequate analgesia for unbearable pain. *Morphine and fentanyl patch* - While this represents a comprehensive pain management approach, it is **not the best next step** in the **emergency department** for **acute pain**. - **Fentanyl patches** have a **delayed onset** (12-24 hours to reach steady state) and are designed for **chronic, stable pain management**, not acute exacerbations. - The immediate priority is rapid pain relief with short-acting opioids; long-acting formulations should be coordinated with hospice after acute stabilization. *No intervention warranted* - This is **unethical and inappropriate** given the patient's explicit complaint of unbearable pain. - **Comfort and symptom management** are the primary objectives of hospice care, making pain relief an absolute necessity.

Question 336: A 58-year-old woman comes to the physician for evaluation of vaginal dryness and pain during sexual intercourse with her husband. Four months ago, she was diagnosed with metastatic breast cancer and is currently undergoing chemotherapy. She has smoked one pack of cigarettes daily for 15 years but quit when she was diagnosed with breast cancer. Physical examination shows thinning of the vaginal mucosa. A dual-energy x-ray absorptiometry (DXA) study of her hip shows a T-score of -2.6. Six months ago, her T-score was -1.6. Which of the following drugs is most likely exacerbating this patient's symptoms?

• A. Paclitaxel
• B. Exemestane (Correct Answer)
• C. Tamoxifen
• D. Palbociclib
• E. Raloxifene

Explanation: **Exemestane** - This patient's symptoms of **vaginal dryness**, **dyspareunia**, and **accelerated bone loss (T-score decrease from -1.6 to -2.6)** are consistent with **estrogen deficiency**. Exemestane is an **aromatase inhibitor** that potently blocks peripheral estrogen synthesis, leading to profound estrogen deprivation and exacerbating these symptoms. - As a **postmenopausal woman** with **estrogen receptor-positive breast cancer**, aromatase inhibitors like exemestane are commonly used as adjuvant therapy. *Paclitaxel* - **Paclitaxel** is a **microtubule inhibitor** used in chemotherapy, but it primarily causes side effects such as **neuropathy**, **myelosuppression**, and **alopecia**, not direct exacerbation of estrogen-deficiency symptoms. - While chemotherapy can induce ovarian suppression in premenopausal women, this patient is likely postmenopausal given her age and presentation, and paclitaxel itself does not directly mediate estrogen deprivation to this extent. *Tamoxifen* - **Tamoxifen** is a **selective estrogen receptor modulator (SERM)**. In postmenopausal women, it acts as an **estrogen antagonist** in breast tissue but can be an **estrogen agonist in the bone and endometrium**, providing some protective effects against bone loss. - While it can cause some vaginal dryness, it is **less likely to cause significant bone density loss** compared to aromatase inhibitors, and often even has beneficial effects on BMD. *Palbociclib* - **Palbociclib** is a **CDK4/6 inhibitor** used in combination with endocrine therapy for advanced breast cancer. Its primary side effects include **myelosuppression (neutropenia)** and fatigue. - It does not directly impact estrogen levels or bone metabolism to cause vaginal atrophy and accelerated bone loss. *Raloxifene* - **Raloxifene** is also a **SERM** that acts as an **estrogen antagonist in breast tissue** and an **estrogen agonist in bone**, meaning it would typically improve or stabilize bone mineral density, not cause accelerated bone loss. - It is often used for the prevention and treatment of **osteoporosis in postmenopausal women** and for the reduction of invasive breast cancer risk.

Question 337: A 7-year-old boy is rushed to the urgent care department from a friend’s birthday party with breathing trouble. He is immediately placed on supplemental oxygen therapy. The patient’s father explains that peanut butter treats were served at the event, but he reported not having witnessed his son actually eat one. During the party, the patient approached his father with facial flushing, difficulty breathing, and itching of his face and neck. The patient was born at 40 weeks gestation via spontaneous vaginal delivery. He has met all age-related developmental milestones and is fully vaccinated. His past medical history is significant for peanut allergy and asthma. He carries an emergency inhaler. Family history is noncontributory. The patient’s vitals signs include a blood pressure of 110/85 mm Hg, a heart rate of 110/min, a respiratory rate of 25/min, and a temperature of 37.2°C (99.0°F). Physical examination reveals severe facial edema and severe audible stridor in both lungs. Which of the following types of hypersensitivity reaction is the most likely in this patient?

• A. Type 4–cell-mediated (delayed) hypersensitivity reaction
• B. Type 3–immune complex-mediated hypersensitivity reaction
• C. Mixed anaphylactic and cytotoxic hypersensitivity reaction
• D. Type 2–cytotoxic hypersensitivity reaction
• E. Type 1–anaphylactic hypersensitivity reaction (Correct Answer)

Explanation: ***Type 1–anaphylactic hypersensitivity reaction*** - This patient's symptoms (facial flushing, difficulty breathing, itching, facial edema, stridor) occurring rapidly after suspected **peanut exposure** are classic for a **Type 1 hypersensitivity reaction**, also known as **anaphylaxis**. - Type 1 reactions are **IgE-mediated**, leading to mast cell and basophil degranulation and the release of mediators like **histamine**, causing immediate allergic symptoms. *Type 4–cell-mediated (delayed) hypersensitivity reaction* - **Type 4 reactions** are **delayed**, typically manifesting 24-72 hours after exposure, and are mediated by **T-cells**, not antibodies. - Examples include contact dermatitis (e.g., poison ivy) or the tuberculin skin test, which do not fit the acute, severe presentation described. *Type 3–immune complex-mediated hypersensitivity reaction* - **Type 3 reactions** involve the formation of **immune complexes** (antigen-antibody complexes) that deposit in tissues, leading to inflammation. - These reactions can cause conditions like serum sickness or lupus nephritis and typically have a slower onset and different symptom profile than acute anaphylaxis. *Mixed anaphylactic and cytotoxic hypersensitivity reaction* - While a patient can experience multiple types of responses over time, a **mixed reaction** implies a simultaneous presentation of distinct **Type 1** and **Type 2** features. The primary and overwhelming presentation here is clearly Type 1 anaphylaxis. - There is no specific evidence presented to suggest a significant **cytotoxic (Type 2)** component in this acute presentation. *Type 2–cytotoxic hypersensitivity reaction* - **Type 2 reactions** involve **antibodies** (IgG or IgM) binding to antigens on cell surfaces, leading to cell destruction via complement activation or antibody-dependent cellular cytotoxicity. - Examples include hemolytic transfusion reactions or autoimmune hemolytic anemia, which do not align with the patient's acute allergic symptoms and stridor.

Question 338: A 26-year-old G1P0 presents to her first obstetric visit after having a positive urine pregnancy test at home. Her last menstrual period was 9 weeks ago. She has no past medical history, but her mother has rheumatoid arthritis. The patient states that for several weeks, she has felt especially warm, even when her co-workers do not, and had muscle weakness. She also complains of mood swings and fatigue. At this visit, her temperature is 99.0°F (37.2°C), blood pressure is 140/81 mmHg, pulse is 106/min, and respirations are 17/min. Physical exam is notable for 3+ deep tendon reflexes bilaterally and 4/5 strength in both hips and shoulders. Ultrasound confirms the presence of a heart beat and shows a crown rump length that is consistent with a gestational age of 9 weeks and 3 days. Which of the following is the best therapy for this patient?

• A. Methimazole
• B. Prednisone
• C. Propylthiouracil (Correct Answer)
• D. Intravenous immunoglobulin
• E. Radioactive thyroid ablation (I-131)

Explanation: ***Propylthiouracil*** - This patient presents with symptoms of **hyperthyroidism** (warmth, muscle weakness, mood swings, fatigue, tachycardia, hypertension, and hyperreflexia) exacerbated by pregnancy. **Propylthiouracil (PTU)** is the preferred treatment for hyperthyroidism in the **first trimester** of pregnancy due to a lower risk of teratogenicity compared to methimazole. - PTU works by **inhibiting thyroid hormone synthesis** and also blocks the peripheral conversion of T4 to T3. *Methimazole* - While an effective antithyroid drug, methimazole is generally **avoided in the first trimester** of pregnancy due to its association with rare but severe birth defects, such as **aplasia cutis** and choanal atresia. - It becomes the preferred treatment in the second and third trimesters if antithyroid medication is still required, due to a lower risk of liver toxicity compared to PTU. *Prednisone* - **Prednisone** is a corticosteroid used to manage inflammatory conditions and suppress the immune system; it is **not a primary treatment for hyperthyroidism**. - While it can be used in severe cases of thyroid storm to reduce peripheral conversion of T4 to T3, it is not the initial therapy for uncomplicated gestational hyperthyroidism. *Intravenous immunoglobulin* - **Intravenous immunoglobulin (IVIG)** is an immune modulator used in various autoimmune conditions but has **no direct role in the treatment of hyperthyroidism**. - It works by providing antibodies and modulating the immune response, which is not the primary mechanism needed to control excessive thyroid hormone production. *Radioactive thyroid ablation (I-131)* - **Radioactive iodine ablation** is absolutely **contraindicated in pregnancy** as it can cross the placenta and destroy the fetal thyroid gland, leading to **fetal hypothyroidism**. - This treatment is reserved for non-pregnant individuals with hyperthyroidism who fail antithyroid medications or have recurrent disease.

Question 339: A 69-year-old man is brought to the emergency room by his daughter due to confusion. She reports that her father did not remember who she was yesterday, and his refrigerator was completely empty when she tried to make him lunch. She states that he was acting like himself when she visited him last week. She also notes that he has struggled with alcoholism for many years and has not seen a doctor in over two decades. She is unsure if he has any other chronic medical conditions. In the emergency room, the patient’s temperature is 101.2°F (38.4°C), pulse is 103/min, respirations are 22/min, and O2 saturation is 92% on room air. His BMI is 17.1 kg/m^2. Physical exam reveals an extremely thin and frail man who is not oriented to person, place, or time. As he is being examined, he becomes unresponsive and desaturates to 84%. He is intubated and admitted to the intensive care unit for what is found to be pneumonia, and the patient is started on total parental nutrition as he is sedated and has a history of aspiration from a prior hospitalization. Two days later, physical exam is notable for new peripheral edema. Laboratory tests at that time reveal the following: Serum: Na+: 133 mEq/L Cl-: 101 mEq/L K+: 2.4 mEq/L HCO3-: 24 mEq/L BUN: 22 mg/dL Glucose: 124 mg/dL Creatinine: 1.1 mg/dL Phosphate: 1.1 mg/dL Mg2+: 1.0 mg/dL Which of the following could have prevented the complication seen in this patient?

• A. Initiation of furosemide
• B. Use of low-sugar TPN
• C. Use of enteral nutrition
• D. Initiation of intermittent dialysis
• E. Slow initiation of total parenteral nutrition (TPN) (Correct Answer)

Explanation: ***Slow initiation of total parenteral nutrition (TPN)*** - This patient likely developed **refeeding syndrome**, which is characterized by severe electrolyte shifts (especially **hypophosphatemia**, **hypokalemia**, and **hypomagnesemia**) and fluid retention (peripheral edema) upon rapid reintroduction of nutrition to severely malnourished individuals. - A **slow and gradual introduction of TPN** would have allowed the body to adapt to the increased metabolic demands, preventing the sudden intracellular shift of electrolytes and subsequent depletion in the serum. *Initiation of furosemide* - Furosemide is a **loop diuretic** primarily used to treat fluid overload and edema by increasing renal excretion of water and electrolytes. - While it could address the peripheral edema, it would not correct the underlying electrolyte imbalances of refeeding syndrome and could potentially worsen them (e.g., contributing to **hypokalemia**). *Use of low-sugar TPN* - Refeeding syndrome is triggered by the shift from fat metabolism to carbohydrate metabolism, leading to increased insulin secretion and subsequent intracellular movement of electrolytes. - While a lower glucose load might slightly mitigate the insulin response, it does not address the core issue of rapid nutrient repletion in a severely malnourished state, and the absolute amount of carbohydrates would still be significant in TPN. *Use of enteral nutrition* - **Enteral nutrition** (feeding via the gastrointestinal tract) is generally preferred over TPN when feasible, as it helps maintain gut integrity and has a lower risk of certain complications. - However, if initiated too rapidly in a severely malnourished patient, enteral nutrition can also precipitate refeeding syndrome, as the metabolic shifts are triggered by carbohydrate repletion regardless of the delivery route. *Initiation of intermittent dialysis* - **Intermittent dialysis** is a renal replacement therapy used for acute or chronic kidney failure to remove waste products and excess fluid. - This patient's creatinine and BUN are only mildly elevated for someone with pneumonia and dehydration, indicating **no clear indication for dialysis**; phosphorus and magnesium could be corrected with supplementation.

Question 340: A 60-year-old patient is at his physician’s office for a routine health maintenance exam. The patient has a past medical history of osteoarthritis in his right knee and GERD that is well-controlled with over the counter medication. On a fasting lipid profile, he is found to have high cholesterol. The patient is started on daily atorvastatin to reduce his risk of cardiovascular disease. What is the major apolipoprotein found on the lipoprotein most directly affected by his statin medication?

• A. Apolipoprotein C-II
• B. Apolipoprotein B-100 (Correct Answer)
• C. Apolipoprotein A-I
• D. Apolipoprotein B-48
• E. Apolipoprotein E

Explanation: ***Apolipoprotein B-100*** - Statins primarily reduce **LDL-C** levels by inhibiting **HMG-CoA reductase**, leading to increased LDL receptor expression and clearance of LDL particles from the blood. - **Apolipoprotein B-100** is the main apolipoprotein found on **LDL** and is crucial for its binding to the LDL receptor. *Apolipoprotein C-II* - This apolipoprotein activates **lipoprotein lipase**, which is involved in the hydrolysis of triglycerides in **chylomicrons** and **VLDL**, not directly targeted by statins. - While statins can indirectly affect VLDL, ApoC-II is not the major apolipoprotein of the lipoprotein most directly affected by statins. *Apolipoprotein A-I* - **Apolipoprotein A-I** is the primary apolipoprotein found on **HDL**, which is involved in **reverse cholesterol transport**. - While statins can have a modest effect on increasing HDL, their primary action is on reducing LDL. *Apolipoprotein B-48* - **Apolipoprotein B-48** is found exclusively on **chylomicrons**, which are responsible for the transport of exogenous dietary fats from the intestines. - Chylomicrons are not the primary target of statin therapy, which focuses on endogenous cholesterol metabolism. *Apolipoprotein E* - **Apolipoprotein E** is found on chylomicrons, VLDL, and HDL and plays a role in receptor binding for their clearance from circulation. - While important for lipoprotein metabolism, it is not the *major* apolipoprotein of the lipoprotein most *directly* affected by statins (LDL).

Question 341: A new drug X is being tested for its effect on renal function. During the experiments, the researchers found that in patients taking substance X, the urinary concentration of sodium decreases while urine potassium concentration increase. Which of the following affects the kidneys in the same way as does substance X?

• A. Aldosterone (Correct Answer)
• B. Furosemide
• C. Spironolactone
• D. Atrial natriuretic peptide
• E. Hydrochlorothiazide

Explanation: ***Aldosterone*** - **Aldosterone** acts on the **principal cells** of the **collecting duct** to increase sodium reabsorption and potassium secretion. - This action leads to a decrease in urinary sodium concentration and an increase in urinary potassium concentration, matching the effects of drug X. *Furosemide* - **Furosemide** is a **loop diuretic** that inhibits the **Na-K-2Cl cotransporter** in the **thick ascending limb** of the loop of Henle. - This inhibition leads to increased excretion of sodium, potassium, and water, resulting in higher urinary sodium concentration. *Spironolactone* - **Spironolactone** is an **aldosterone antagonist** that blocks aldosterone's effects on the collecting duct. - This leads to increased sodium excretion and decreased potassium excretion (potassium-sparing effect), which is the opposite of drug X. *Atrial natriuretic peptide* - **Atrial natriuretic peptide (ANP)** is released in response to atrial stretch and causes **natriuresis** (increased sodium excretion) and **diuresis**. - It works by dilating afferent arterioles and constricting efferent arterioles, increasing GFR, and inhibiting sodium reabsorption, thus increasing urinary sodium concentration. *Hydrochlorothiazide* - **Hydrochlorothiazide** is a **thiazide diuretic** that inhibits the **Na-Cl cotransporter** in the **distal convoluted tubule**. - This leads to increased sodium and chloride excretion but typically causes potassium wasting (hypokalemia), which differs from the increased urinary potassium concentration seen with drug X.

Question 342: A 7-year-old girl presents with a low-grade fever, lethargy, and fatigue for the past week. The patient’s mother says she also complains of leg pain for the past couple of weeks. No significant past medical history. The patient was born at term via spontaneous transvaginal delivery with no complications. On physical examination, the patient shows generalized pallor. Cervical lymphadenopathy is present. A bone marrow biopsy is performed which confirms the diagnosis of acute lymphoblastic leukemia (ALL). The patient is started on a chemotherapy regimen consisting of vincristine, daunorubicin, L-asparaginase, and prednisolone for induction, followed by intrathecal methotrexate for maintenance. Following the 4th cycle of chemotherapy, she develops bilateral ptosis. Physical examination shows a normal pupillary reflex and eye movements. She is started on pyridoxine and pyridostigmine, and, in 7 days, she has complete resolution of the ptosis. Which of the following drugs is most likely associated with this patient’s adverse reaction?

• A. Methotrexate
• B. Daunorubicin
• C. Prednisolone
• D. Pyridoxine
• E. Vincristine (Correct Answer)

Explanation: ***Vincristine*** - Vincristine is an **antimicrotubule agent** known for causing **peripheral neuropathy**, which can manifest as **cranial nerve palsies**, including ptosis from CN III involvement. - Vincristine can cause **neuromuscular junction dysfunction** similar to myasthenia gravis, leading to muscle weakness including extraocular muscles. - The response to **pyridostigmine** (an acetylcholinesterase inhibitor) confirms this mechanism, as it increases acetylcholine at the neuromuscular junction. - **Pyridoxine** (vitamin B6) is used for both prevention and treatment of vincristine-induced neuropathy. *Methotrexate* - Methotrexate is an **antifolate** that primarily causes **myelosuppression**, **mucositis**, and **hepatotoxicity**. - While intrathecal methotrexate can cause neurotoxicity, it typically presents as **meningeal irritation**, **seizures**, or **leukoencephalopathy**, not isolated ptosis. *Daunorubicin* - Daunorubicin is an **anthracycline** antibiotic primarily known for **cardiotoxicity** and **myelosuppression**. - It does not commonly cause **neurological side effects** like ptosis. *Prednisolone* - Prednisolone is a **corticosteroid** with side effects including **immunosuppression**, **hyperglycemia**, **osteoporosis**, and **mood changes**. - It is not directly associated with **neuromuscular side effects** such as isolated ptosis. *Pyridoxine* - Pyridoxine (vitamin B6) is used for the **treatment** and **prevention** of vincristine-induced neuropathy, not its causation. - The patient was started on pyridoxine to *resolve* the ptosis, indicating it is therapeutic for the vincristine-induced neurotoxicity.

Question 343: A 23-year-old woman is brought to the emergency department by her friend because of a 1-hour episode of confusion. Earlier that night, they were at a dance club, and the patient was very energetic and euphoric. Thirty minutes after arriving, she became agitated and nauseous. She no longer seemed to know where she was or how she got there, and she began talking to herself. She has no major medical illness. She is an undergraduate student at a local college. She does not smoke but drinks 10–14 mixed drinks each week. Her temperature is 38.3°C (100.9°F), pulse is 115/min and regular, respirations are 16/min, and blood pressure is 138/84 mm Hg. She oriented to self but not to time or place. Throughout the examination, she grinds her teeth. Her pupils are 7 mm in diameter and minimally reactive. Her skin is diffusely flushed and diaphoretic. Cardiopulmonary examination shows no abnormalities. Serum studies show: Na+ 129 mEq/L K+ 3.7 mEq/L HCO3- 22 mEq/L Creatinine 1.2 mg/dL Glucose 81 mg/dL Which of the following substances is the most likely cause of this patient's presentation?

• A. Ecstasy (Correct Answer)
• B. Cocaine
• C. Acetaminophen
• D. Diphenhydramine
• E. Codeine

Explanation: **Ecstasy** - The patient's **euphoria, confusion, agitation, teeth grinding (bruxism), mydriasis (7 mm pupils), hyperthermia, tachycardia, hypertension, and hyponatremia** are all characteristic of **MDMA (Ecstasy)** intoxication. These symptoms are consistent with its stimulant and serotonergic effects. - **Hyponatremia** can occur due to increased antidiuretic hormone (ADH) secretion induced by MDMA, combined with excessive fluid intake (often water) by users trying to combat hyperthermia and dehydration. *Cocaine* - While cocaine intoxication can cause **euphoria, agitation, tachycardia, hypertension, and mydriasis**, it typically does not cause the prominent **hyponatremia** seen in this patient. - **Bruxism** and the specific progression to **confusion and talking to herself** are more suggestive of MDMA's serotonergic effects rather than pure dopaminergic stimulation from cocaine. *Acetaminophen* - **Acetaminophen overdose** primarily causes **hepatic toxicity**, which would manifest as elevated liver enzymes, nausea, vomiting, and later jaundice. - It does not induce the **acute neurological symptoms** (euphoria, agitation, confusion, teeth grinding) or the distinctive **vital sign derangements** (hyperthermia, tachycardia, hypertension) observed in this patient. *Diphenhydramine* - **Diphenhydramine overdose** (an antihistamine with anticholinergic properties) would typically present with **anticholinergic toxidrome** symptoms, including dry mouth, blurred vision, urinary retention, dilated pupils, fever, and altered mental status (delirium, hallucinations). - While it can cause confusion and dilated pupils, the prominent **diaphoresis**, **tachycardia**, and **hyponatremia** are less characteristic of isolated diphenhydramine toxicity. *Codeine* - **Codeine** is an opioid, and overdose would cause symptoms of **opioid toxidrome**, such as **respiratory depression, miosis (pinpoint pupils)**, central nervous system depression (sedation, coma), and hypotension. - The patient's symptoms of alertness, agitation, dilated pupils, hypertension, and tachycardia are directly opposite to what would be expected from codeine intoxication.

Question 344: A 30-year-old woman presents complaining of shortness of breath, chest pain, and fatigue. The patient complains of dyspnea upon exertion, generalized fatigue, lethargy, and chest pain associated with strenuous activities. Her history is notable for an atrial septal defect at birth. Her temperature is 99.5°F (37.5°C), blood pressure is 147/98 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. On exam, she has a wide, fixed splitting of S2. Which of the following medications most directly treats the underlying pathophysiology causing this patient's presentation?

• A. Epoprostenol
• B. Metoprolol
• C. Lisinopril
• D. Nifedipine
• E. Bosentan (Correct Answer)

Explanation: ***Bosentan*** - Bosentan is an **endothelin receptor antagonist** that **vasodilates** the pulmonary vasculature, reducing **pulmonary hypertension**. This directly addresses the increased pulmonary artery pressures and subsequent right heart strain caused by long-standing left-to-right shunting from the **atrial septal defect (ASD)**. - The patient's symptoms (dyspnea, chest pain, fatigue) and signs (elevated pulmonary artery pressure evidenced by a wide, fixed splitting of S2 and systemic hypertension) are consistent with **pulmonary arterial hypertension (PAH)**, likely due to an uncorrected or late-presentation ASD leading to Eisenmenger syndrome. *Epoprostenol* - Epoprostenol is a **prostacyclin analog** that causes **vasodilation** and inhibits platelet aggregation, used in severe pulmonary hypertension. While it treats PAH, it is typically reserved for more advanced or rapidly progressive cases, often administered intravenously. - While it improves symptoms and survival in PAH, **endothelin receptor antagonists** like bosentan are often preferred as first-line oral therapy due to their specific mechanism targeting endothelin's role in PAH pathophysiology and easier administration. *Metoprolol* - Metoprolol is a **beta-blocker** used to treat hypertension, angina, and arrhythmias by reducing heart rate and contractility. It would not directly treat PAH. - In patients with right heart failure secondary to PAH, beta-blockers can sometimes be detrimental by reducing cardiac output, though their use in specific PAH subsets is being investigated. *Lisinopril* - Lisinopril is an **ACE inhibitor** that reduces blood pressure by blocking the renin-angiotensin-aldosterone system. It is primarily used for systemic hypertension and heart failure but does not specifically target pulmonary vascular remodeling or vasodilation. - While it might help with systemic hypertension, it offers no direct benefit for the primary pathophysiology of pulmonary arterial hypertension. *Nifedipine* - Nifedipine is a **calcium channel blocker** that causes systemic and, to some extent, pulmonary vasodilation, used for hypertension and angina. However, its use in PAH is typically reserved for a small subset of patients who are **vasoreactive** during acute vasodilator testing. - For the majority of PAH patients, and especially those with structural heart defects leading to PAH, other vasodilators like endothelin receptor antagonists or prostacyclins are more effective and safer.

Question 345: Please refer to the summary above to answer this question Which of the following is the most appropriate pharmacotherapy? Patient Information Age: 30 years Gender: F, self-identified Ethnicity: unspecified Site of Care: office History Reason for Visit/Chief Concern: "I'm so anxious about work." History of Present Illness: 7-month history of sensation that her heart is racing whenever she gives oral presentations at work she has also had moderate axillary sweating during these presentations and feels more anxious and embarrassed when this happens feels otherwise fine when she is interacting with her colleagues more casually around the workplace Past Medical History: alcohol use disorder, now abstinent for the past 2 years acute appendicitis, treated with appendectomy 5 years ago verrucae planae Medications: disulfiram, folic acid, topical salicylic acid Allergies: no known drug allergies Psychosocial History: does not smoke, drink alcohol, or use illicit drugs Physical Examination Temp Pulse Resp BP O2 Sat Ht Wt BMI 36.7°C (98°F) 82/min 18/min 115/72 mm Hg – 171 cm (5 ft 7 in) 58 kg (128 lb) 20 kg/m2 Appearance: no acute distress Pulmonary: clear to auscultation Cardiac: regular rate and rhythm; normal S1 and S2; no murmurs Abdominal: has well-healed laparotomy port scars; no tenderness, guarding, masses, bruits, or hepatosplenomegaly Extremities: no tenderness to palpation, stiffness, or swelling of the joints; no edema Skin: warm and dry; there are several skin-colored, flat-topped papules on the dorsal bilateral hands Neurologic: alert and oriented; cranial nerves grossly intact; no focal neurologic deficits Psychiatric: describes her mood as "okay"; speech has a rapid rate but normal rhythm; thought process is organized

• A. Clonazepam
• B. Olanzapine
• C. Sertraline
• D. Venlafaxine
• E. Propranolol (Correct Answer)

Explanation: ***Propranolol*** - This patient presents with symptoms consistent with **performance anxiety** (situational anxiety triggered by public speaking) characterized by a racing heart and sweating. **Propranolol**, a non-selective beta-blocker, is effective in reducing the peripheral physical symptoms of anxiety by blocking adrenergic receptors. - It works by blunting the **physical manifestations of sympathetic nervous system** activation (e.g., palpitations, tremors, sweating), which can be particularly distressing during performance situations. *Clonazepam* - **Clonazepam** is a long-acting benzodiazepine that can be used for anxiety but carries a significant risk of **dependence, tolerance, and withdrawal symptoms**, especially given the patient's history of alcohol use disorder. - While effective for acute anxiety, its use in performance anxiety should be cautious due to side effects like **sedation** and potential for abuse, making it less appropriate as a first-line treatment in this specific context. *Olanzapine* - **Olanzapine** is an atypical antipsychotic primarily used for **schizophrenia** and **bipolar disorder**, or as an augmentation strategy for severe, refractory mood or anxiety disorders. - Its side effect profile, which includes **metabolic issues** and sedation, makes it an inappropriate choice for treating isolated performance anxiety. *Sertraline* - **Sertraline** is an **SSRI** (selective serotonin reuptake inhibitor) often used for generalized anxiety disorder, panic disorder, or social anxiety disorder when symptoms are pervasive and persistent. - However, for **situational performance anxiety**, which is intermittent and triggered by specific events, SSRIs typically require several weeks to achieve therapeutic effects and are not ideal for immediate symptom relief. *Venlafaxine* - **Venlafaxine** is an **SNRI** (serotonin-norepinephrine reuptake inhibitor) indicated for various anxiety disorders, including generalized anxiety disorder and social anxiety disorder. - Similar to SSRIs, SNRIs take time to become effective and are generally reserved for more **chronic and widespread anxiety**, rather than acute, situational symptoms that can be effectively managed by a beta-blocker.

Question 346: A 70-year-old man is brought to the emergency department unconscious after a fall. He appears pale and is pulseless. A 12-lead EKG reveals wide, monomorphic sawtooth-like QRS complexes. He undergoes synchronized cardioversion three times at increasing voltage with no effect. Epinephrine is administered with minimal effect. Which drug will minimize his risk of developing multifocal ventricular tachycardia?

• A. Amiodarone (Correct Answer)
• B. Ibutilide
• C. Sotalol
• D. Dofetilide
• E. Procainamide

Explanation: ***Amiodarone*** - **Amiodarone** is a Class III antiarrhythmic, but it has properties of all four Vaughn-Williams classes, making it effective for a wide range of arrhythmias. It is often a first-line agent for both **ventricular tachycardia** and **ventricular fibrillation**. - Its broad spectrum of action helps to stabilize the myocardial electrical activity and reduce the likelihood of developing additional, polymorphic ventricular arrhythmias like **multifocal ventricular tachycardia**. *Ibutilide* - **Ibutilide** is a Class III antiarrhythmic primarily used for the rapid conversion of **atrial fibrillation** and **atrial flutter** to sinus rhythm by selectively prolonging the action potential duration. - While it prolongs repolarization, it is associated with a risk of **Torsades de Pointes**, a polymorphic ventricular tachycardia, and would not minimize the risk of multifocal ventricular tachycardia, but rather could induce it. *Sotalol* - **Sotalol** is a beta-blocker with Class III antiarrhythmic properties, used for both atrial and ventricular arrhythmias. - Like ibutilide, it also carries a risk of inducing **Torsades de Pointes** due to its action potential prolonging effects, making it unsuitable for minimizing the risk of multifocal ventricular tachycardia in this context. *Dofetilide* - **Dofetilide** is a pure Class III antiarrhythmic agent specifically used for the maintenance of sinus rhythm in patients with **atrial fibrillation** or **atrial flutter**. - It works by blocking the delayed rectifier potassium current, but similar to ibutilide and sotalol, it has a significant risk of **QT prolongation** and **Torsades de Pointes**, thus increasing the risk of polymorphic ventricular tachycardia. *Procainamide* - **Procainamide** is a Class IA antiarrhythmic drug that slows conduction and prolongs refractoriness in the atria, ventricles, and accessory pathways. It is used for both supraventricular and ventricular arrhythmias. - While it can be effective for some ventricular arrhythmias, it is also associated with a risk of **prolonging the QT interval** and inducing **Torsades de Pointes**, especially in patients with structural heart disease or electrolyte imbalances, making it less ideal for minimizing the risk of multifocal ventricular tachycardia compared to amiodarone.

Question 347: A 27-year-old P1G1 who has had minimal prenatal care delivers a newborn female infant. Exam reveals a dusky child who appears to be in distress. Her neck veins are distended and you note an enlarged v wave. She has a holosystolic murmur. Following echocardiogram, immediate surgery is recommended. For which of the following conditions was the mother likely receiving treatment during pregnancy?

• A. Bipolar disorder (Correct Answer)
• B. Hypothyroidism
• C. Depression
• D. Hypertension
• E. Diabetes

Explanation: ***Bipolar disorder*** - The newborn's symptoms, including a **holosystolic murmur**, **distended neck veins** with an **enlarged v wave**, and cyanosis, are highly suggestive of **Ebstein's anomaly**. - **Ebstein's anomaly** is a congenital heart defect strongly associated with maternal **lithium use** during pregnancy, a common treatment for bipolar disorder. *Hypothyroidism* - Maternal hypothyroidism is associated with an increased risk of miscarriage, stillbirth, and neurodevelopmental problems in the child, but not specifically with Ebstein's anomaly. - Treatment for hypothyroidism primarily involves thyroid hormone replacement, which is not linked to this specific cardiac defect. *Depression* - While various antidepressant medications can be taken during pregnancy, none are specifically linked to Ebstein's anomaly. - Maternal depression itself can impact fetal development due to stress, but not typically through this specific congenital heart defect. *Hypertension* - Maternal hypertension is associated with conditions like **pre-eclampsia**, fetal growth restriction, and preterm birth, but not specifically with Ebstein's anomaly. - Antihypertensive medications generally do not cause this specific congenital heart defect. *Diabetes* - Maternal diabetes can lead to **macrosomia**, **hypoglycemia**, and an increased risk of various congenital anomalies, including **ventricular septal defects** and **transposition of the great arteries**. - However, it is not specifically linked to Ebstein's anomaly, which is more characteristic of lithium exposure.

Question 348: A 50-year-old woman presents to the ED 6 hours after ingesting three bottles of baby aspirin. She complains of nausea, vomiting, dizziness, and tinnitus. Her blood pressure is 135/80 mmHg, pulse is 110/min, respirations are 32/min, temperature is 100.1 deg F (37.8 deg C), and oxygen saturation is 99% on room air. Arterial blood gas at room air shows, PCO2 11 mmHg, and PO2 129 mmHg. Blood salicylate level is 55 mg/dL. Management should involve which of the following acid-base principles?

• A. Serum neutralization, urine alkalization
• B. Serum alkalization, urine alkalization (Correct Answer)
• C. Serum neutralization, urine acidification
• D. Serum acidification, urine acidification
• E. Serum acidification, urine alkalization

Explanation: ***Serum alkalization, urine alkalization*** - Managing **aspirin overdose** involves **aggressive serum alkalization** to promote the shift of salicylic acid from the cells into the bloodstream, where it remains ionized and cannot freely diffuse into the CNS. This also reduces its toxicity by increasing the proportion of the ionized form. - Subsequently, **urine alkalization** with **sodium bicarbonate** is used to trap the ionized salicylate in the renal tubules, preventing reabsorption and enhancing its excretion. *Serum neutralization, urine alkalization* - This option is flawed because the goal is not to "neutralize" the serum pH to a neutral 7.0 but rather to raise it above normal towards an alkaline state (typically pH 7.45-7.55) to enhance salicylate elimination. - While urine alkalization is correct, the idea of serum neutralization is incorrect and could lead to inadequate treatment. *Serum neutralization, urine acidification* - This approach is entirely incorrect for **salicylate toxicity** as **acidifying the urine** would promote the reabsorption of salicylic acid from the renal tubules, worsening toxicity. - Serum neutralization, as mentioned, is not the correct term or goal for managing **aspirin overdose**. *Serum acidification, urine acidification* - This strategy would be **dangerous** in the context of **salicylate overdose** as it would significantly increase the proportion of **non-ionized salicylic acid**, allowing it to more readily cross cell membranes, including the blood-brain barrier, thereby increasing systemic and central nervous system toxicity. - It would also drastically reduce elimination. *Serum acidification, urine alkalization* - **Serum acidification** is contraindicated in **salicylate poisoning** as it drives salicylate into the tissues, exacerbating its toxicity, particularly in the central nervous system. - While urine alkalization is correct for enhancing elimination, combining it with serum acidification would counteract its benefits and worsen patient outcomes.

Question 349: A 72-year-old man of Asian descent seeks evaluation at your medical office and is frustrated about the frequency he wakes up at night to urinate. He comments that he has stopped drinking liquids at night, but the symptoms have progressively worsened. The physical examination is unremarkable, except for an enlarged, symmetric prostate free of nodules. Which of the following should you prescribe based on the main factor that contributes to the underlying pathogenesis?

• A. Prazosin
• B. Tamsulosin
• C. Leuprolide
• D. Phenylephrine
• E. Finasteride (Correct Answer)

Explanation: ***Finasteride*** - This medication is a **5-alpha reductase inhibitor** that reduces the size of the prostate by decreasing the conversion of testosterone to **dihydrotestosterone (DHT)**, the primary androgen responsible for prostate growth. - Given the patient's enlarged prostate and symptoms of **nocturia** that have progressively worsened despite behavioral changes, addressing the underlying stromal and epithelial proliferation of **benign prostatic hyperplasia (BPH)** is key. *Prazosin* - **Prazosin** is an **alpha-1 adrenergic antagonist** that works by relaxing the smooth muscle in the prostate and bladder neck, which can improve urine flow but does not address the underlying prostatic hypertrophy. - While it can alleviate symptoms of BPH, it does not treat the **main pathogenic factor** (prostate enlargement due to DHT) that contributes to the worsening condition. *Tamsulosin* - **Tamsulosin** is a selective **alpha-1A adrenergic blocker** that primarily relaxes smooth muscle in the prostate and bladder neck, improving urinary flow with fewer cardiovascular side effects compared to non-selective alpha blockers. - Like prazosin, it helps with symptom relief but does not target the **hormone-driven growth** of the prostate, which is the underlying cause of the worsening condition. *Leuprolide* - **Leuprolide** is a **GnRH agonist** mainly used in advanced prostate cancer or endometriosis; it suppresses gonadotropin release and, consequently, testosterone production. - It is not indicated for the management of **benign prostatic hyperplasia (BPH)**, which is the more likely diagnosis given the patient's presentation and symmetrical, non-nodular prostate. *Phenylephrine* - **Phenylephrine** is an **alpha-1 adrenergic agonist** that causes vasoconstriction and can contract the smooth muscle of the bladder neck, leading to increased outflow resistance. - This would **worsen rather than improve** the patient's symptoms of urinary obstruction and is contraindicated in BPH.

Question 350: An endocrinologist is working with a pharmaceutical research company on a new drug for diabetes mellitus type 2 (DM2). In their experimental studies, they isolated a component from Gila monster saliva, which was found to have > 50% homology with glucagon-like peptide-1 (GLP1). During the animal studies, the experimental drug was found to have no GLP1 agonist effect. Instead, it irreversibly binds DPP-IV with a higher affinity than GLP1. Which of the following drugs has a similar mechanism of action to this new experimental drug?

• A. Metformin
• B. Sitagliptin (Correct Answer)
• C. Canagliflozin
• D. Pramlintide
• E. Exenatide

Explanation: ***Sitagliptin*** - This drug is a **dipeptidyl peptidase-4 (DPP-4) inhibitor**, which works by preventing the breakdown of **endogenous GLP-1** and other incretin hormones. - By inhibiting DPP-4, sitagliptin increases the availability of GLP-1, leading to **glucose-dependent insulin secretion** and reduced glucagon secretion. - **Note:** While sitagliptin is a **reversible** DPP-4 inhibitor and the experimental drug is described as irreversible, sitagliptin shares the same **target enzyme (DPP-4)** and overall therapeutic mechanism, making it the closest match among the options provided. *Metformin* - Metformin is a **biguanide** that primarily reduces **hepatic glucose production** and improves insulin sensitivity in peripheral tissues. - Its mechanism does not involve direct interaction with DPP-4 or GLP-1 pathways, unlike the experimental drug. *Canagliflozin* - Canagliflozin is a **sodium-glucose co-transporter 2 (SGLT2) inhibitor** that blocks glucose reabsorption in the kidneys, leading to **increased urinary glucose excretion**. - Its action is independent of insulin and does not involve the incretin system or DPP-4 inhibition. *Pramlintide* - Pramlintide is an **amylin analog** that works by slowing gastric emptying, suppressing glucagon secretion, and promoting satiety. - It is administered via injection and acts synergistically with insulin, but does not affect DPP-4 enzyme activity. *Exenatide* - Exenatide is a **glucagon-like peptide-1 (GLP-1) receptor agonist** that directly mimics the action of GLP-1, stimulating insulin release and suppressing glucagon. - Notably, exenatide is also derived from Gila monster saliva (similar to the experimental drug's origin), but it acts as a GLP-1 agonist rather than a DPP-4 inhibitor, which is the opposite mechanism described for the experimental drug.

Question 351: A 34-year-old woman presents with acute onset loss of vision and visual disturbances. She says that, several hours ago, her vision began to get dim, and she sees halos around light sources. This was immediately followed by a severe frontal headache. Past medical history is significant for epilepsy. The patient says her anticonvulsant medication was changed recently but she doesn’t remember the name. Slit-lamp examination reveals mild chemosis, injection, and ciliary flush with diffuse stromal haze, along with very shallow peripheral anterior chambers with areas of iridocorneal touch in both eyes. Gonioscopy showed closed angles bilaterally. Which of the following antiepileptic drugs is most likely responsible for this patient’s condition?

• A. Tiagabine
• B. Zonisamide
• C. Lamotrigine
• D. Gabapentin
• E. Topiramate (Correct Answer)

Explanation: ***Topiramate*** - **Topiramate** is strongly associated with acute angle-closure glaucoma, often presenting with **myopic shift** and **ciliary body edema**, leading to closure of the anterior chamber angle. - The patient's symptoms of **acute vision loss**, **halos around lights**, **severe frontal headache**, and findings of **shallow anterior chambers** with **closed angles bilaterally** are classic for topiramate-induced angle closure. - Topiramate is a **sulfonamide derivative** that causes ciliochoroidal effusion, leading to anterior rotation of the ciliary body and forward displacement of the lens-iris diaphragm. *Tiagabine* - **Tiagabine** is associated with central nervous system side effects such as dizziness, somnolence, and confusion. - It is not typically linked to ophthalmological side effects involving acute angle-closure glaucoma. *Zonisamide* - **Zonisamide** is also a **sulfonamide derivative** and can rarely cause acute angle-closure glaucoma through a similar mechanism to topiramate. - However, **topiramate** is more commonly and strongly associated with this adverse effect. - Zonisamide is also known for other side effects like kidney stones and metabolic acidosis. *Lamotrigine* - **Lamotrigine** is primarily known for skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. - Ocular side effects are generally mild and do not include acute angle-closure glaucoma. *Gabapentin* - **Gabapentin** common side effects include drowsiness, dizziness, and peripheral edema. - It is not associated with acute angle-closure glaucoma or the specific constellation of ocular symptoms described.

Question 352: An 85-year-old man presents with the reappearance of his Parkinson’s disease (PD) symptoms over the last few months. He says he has been treated with various drugs over the last 20 years, but that currently his symptoms worsen as he nears the time for his next dose of medication. His movements have been slower lately and it’s difficult to initiate voluntary movements. His past medical history is significant for hypertension. He was diagnosed 10 years ago and was well-managed on medication. His current medications are levodopa/carbidopa, rasagiline, aspirin, and captopril. The vital signs include: pulse 70/min, respiratory rate 15/min, blood pressure 130/76 mm Hg, and temperature 36.7°C (98.1°F). Physical examination reveals the expected ‘pill-rolling’ resting tremor, which is alleviated by movement. Increased tone of arm muscles and resistance to passive movement at the joints is noted. When asked to walk across the room, he has difficulty taking the 1st step and has a stooped posture and takes short, shuffling, rapid steps. Laboratory studies show: Serum glucose (fasting) 97 mg/dL Sodium 141 mEq/L Potassium 4.0 mEq/L Chloride 100 mEq/L Cholesterol (total) 190 mg/dL HDL-cholesterol 42 mg/dL LDL-cholesterol 70 mg/dL Triglycerides 184 mg/dL The patient is started on a drug that increases the efficacy of his current anti-PD medication. Which of the following is most likely the drug that was added to this patient’s current regimen?

• A. Entacapone (Correct Answer)
• B. Atorvastatin
• C. Benztropine
• D. Selegiline
• E. Bromocriptine

Explanation: ***Entacapone*** - The patient is experiencing motor fluctuations, specifically "wearing-off" phenomena, where symptoms worsen before the next dose of **levodopa/carbidopa** is due. Entacapone, a **COMT inhibitor**, prolongs the half-life of levodopa, increasing its availability to the brain. - This drug acts by inhibiting the peripheral breakdown of levodopa by **catechol-O-methyltransferase (COMT)**, thereby increasing the amount of levodopa that crosses the blood-brain barrier. *Atorvastatin* - Atorvastatin is a **statin medication** used to lower cholesterol levels and is not indicated for the management of Parkinson's disease symptoms. - While the patient's lipids show high triglycerides and low HDL, the question specifically asks for a drug to improve Parkinson's symptoms. *Benztropine* - Benztropine is an **anticholinergic medication** used to treat tremors and rigidity in Parkinson's disease. - However, it is generally avoided in elderly patients due to its potential to cause cognitive side effects and is not primarily used to address "wearing-off" phenomena. *Selegiline* - Selegiline is a **monoamine oxidase-B (MAO-B) inhibitor** that prevents the breakdown of dopamine in the brain, and it is already part of the patient's current regimen (rasagiline is also an MAO-B inhibitor). - While it helps with PD symptoms, adding another MAO-B inhibitor or increasing its dose would not directly address the "wearing-off" phenomenon as effectively as a COMT inhibitor. *Bromocriptine* - Bromocriptine is a **dopamine agonist** that directly stimulates dopamine receptors in the brain. - While dopamine agonists can be used in Parkinson's disease, they are typically considered for early-stage disease or as an adjunct, and are not the first-line choice for levodopa "wearing-off" in an elderly patient.

Question 353: A 26-year-old G1P0 woman at 40 weeks estimated gestational age presents after experiencing labor pains. Pregnancy has been uncomplicated so far. Rupture of membranes occurs, and a transvaginal delivery is performed under epidural anesthesia, and the baby is delivered alive and healthy. The patient voids a few hours after the delivery and complains of mild irritation at the injection site on her back. On the second day, she complains of a severe headache over the back of her head. The headache is associated with pain and stiffness in the neck. Her headache is aggravated by sitting up or standing and relieved by lying down. The pain is relieved slightly by acetaminophen and ibuprofen. The patient is afebrile. Her vital signs include: pulse 100/min, respiratory rate 18/min, and blood pressure 128/84 mm Hg. Which of the following statements is the most accurate regarding this patient’s condition?

• A. A blockage of CSF is the cause of this patient’s headache
• B. An infection is present at the epidural injection site
• C. This patient’s condition can resolve on its own (Correct Answer)
• D. Excessive bed rest will worsen this patient’s condition
• E. Immediate intervention is required

Explanation: ***This patient’s condition can resolve on its own*** - The symptoms describe a **post-dural puncture headache (PDPH)**, a common complication of epidural anesthesia, which is often **self-limiting** within days to weeks. - Initial management involves conservative measures like bed rest, hydration, and analgesics, as many cases resolve without specific interventions. *A blockage of CSF is the cause of this patient’s headache* - PDPH is caused by a **leakage of cerebrospinal fluid (CSF)** through the dura mater, leading to **intracranial hypotension**, not a blockage of CSF flow. - The leakage reduces CSF pressure, causing the brain to sag when upright, stretching pain-sensitive structures like meninges and blood vessels. *An infection is present at the site of epidural injection site* - While localized irritation is mentioned, there are no signs of infection such as **fever**, **erythema**, or **purulent discharge** at the injection site, making infection less likely. - The headache characteristics (positional, severe, neck stiffness) are classic for PDPH, not typically seen in local epidural infections, which would also present with systemic signs. *Excessive bed rest will worsen this patient’s condition* - **Bed rest** typically **improves** the symptoms of PDPH by reducing the gravitational pull on the intracranial structures, thereby alleviating the headache. - Prolonged bed rest is generally recommended in the acute phase, often combined with hydration and caffeine, to help manage symptoms, not worsen them. *Immediate intervention is required* - While severe PDPH can be debilitating, immediate invasive intervention (like an **epidural blood patch**) is usually reserved for cases that are **severe and refractory to conservative management** after 24-48 hours. - Many patients experience spontaneous resolution or significant improvement with conservative measures, making immediate invasive intervention typically unnecessary.

Question 354: A 25-year-old man is admitted to the intensive care unit with confusion and severe dyspnea at rest which started 3 hours ago. The symptoms worsen when the patient lies down and improve in the sitting position. The patient has a history of cocaine abuse. The patient's blood pressure is 75/50 mm Hg, the heart rate is 95/min, the respiratory rate is 22/min, the temperature is 36.5℃ (97.7℉), and the SpO2 is 89% on room air. On physical examination, there is peripheral cyanosis with pallor, coldness of the extremities, diaphoresis, and marked peripheral veins distension. Lung auscultation reveals bilateral absence of the lung sounds over the lower lobes and widespread rales over the other lung fields. On cardiac auscultation, there is a protodiastolic gallop and S2 accentuation best heard in the second intercostal space at the left sternal border. Abdominal palpation shows signs of intraperitoneal fluid accumulation and hepatomegaly. Considering the low cardiac output, milrinone is administered as an inotropic agent. What is the most likely side effect which can result from administration of milrinone?

• A. Asystole
• B. Third grade AV-blockade
• C. Ventricular arrhythmias (Correct Answer)
• D. Supraventricular arrhythmia
• E. QT-prolongation

Explanation: ***Ventricular arrhythmias*** - **Milrinone** is a positive inotropic agent and vasodilator used in severe heart failure; it **increases cardiac contractility** and **reduces afterload**. - Its mechanism of action, phosphodiesterase (PDE-3) inhibition, can increase intracellular cAMP in cardiomyocytes, raising the risk of **ventricular arrhythmias**, particularly in patients with pre-existing heart conditions or electrolyte imbalances. *Asystole* - While milrinone can have significant cardiovascular effects, **asystole** (complete cessation of electrical and mechanical activity of the heart) is not a common or direct side effect. - Asystole is typically associated with conditions like severe myocardial ischemia, advanced conduction system disease, or terminal stages of shock. *Third grade AV-blockade* - **Third-degree AV block** involves complete dissociation between atrial and ventricular electrical activity. - Milrinone's primary action is to increase contractility and vasodilation; it does not directly interfere with the **AV node conduction** in a way that would commonly cause complete heart block. *Supraventricular arrhythmia* - While milrinone can cause various rhythm disturbances due to increased **cAMP levels** and myocardial excitability, **supraventricular arrhythmias** (like atrial fibrillation or flutter) are less commonly reported as a primary side effect compared to ventricular arrhythmias. - The direct effect on ventricular excitability is more pronounced. *QT-prolongation* - **QT prolongation** can lead to torsades de pointes and other ventricular arrhythmias, but milrinone itself is not typically listed as a drug that directly causes significant QT prolongation. - Medications that block **potassium channels** are more commonly associated with this side effect.

Question 355: A 61-year-old woman presents to the emergency room with left leg pain and swelling. She recently returned to the United States from a trip to India. Her past medical history is notable for osteoarthritis in both hips, lumbar spinal stenosis, and hypertension. She takes lisinopril. Her temperature is 99°F (37.2°C), blood pressure is 140/85 mmHg, pulse is 110/min, and respirations are 24/min. On examination, her left calf is larger than her right calf. A lower extremity ultrasound demonstrates a deep venous thrombosis in the left femoral vein. Results from a complete blood count are within normal limits. She is admitted and started on unfractionated heparin. Seven days later, she presents with a dark erythematous skin lesion on her left thigh and worsening left leg swelling. A lower extremity ultrasound demonstrates a persistent deep venous thrombosis in the left femoral vein as well as a new deep venous thrombosis in the left popliteal vein. Results of a complete blood count are shown below: Hemoglobin: 13.1 g/dL Hematocrit: 38% Leukocyte count: 9,600/mm^3 with normal differential Platelet count: 74,000/mm^3 A medication with which of the following mechanisms of action is most appropriate to initiate in this patient after stopping the heparin?

• A. Cyclooxygenase inhibitor
• B. Direct thrombin inhibitor (Correct Answer)
• C. Anti-thrombin III activator
• D. Adenosine-diphosphate (ADP) receptor antagonist
• E. Vitamin K epoxide reductase inhibitor

Explanation: **Direct thrombin inhibitor** - The patient's presentation with a new thrombus, despite being on heparin, and a significantly **decreased platelet count (74,000/mm^3)**, points toward **heparin-induced thrombocytopenia (HIT)**. - In HIT, heparin must be stopped immediately, and a **non-heparin anticoagulant** like a **direct thrombin inhibitor (e.g., argatroban, bivalirudin)** is the appropriate next step to prevent further thrombosis while avoiding platelet activation. *Cyclooxygenase inhibitor* - **Cyclooxygenase inhibitors (e.g., NSAIDs, aspirin)** primarily inhibit platelet aggregation and inflammation but are not the primary treatment for active thrombosis or HIT. - While effective in preventing arterial clots, they are **insufficient for treating established venous thrombosis**, especially in the context of HIT where platelet activation is a key pathological feature. *Anti-thrombin III activator* - **Heparin** itself works by activating antithrombin III, which is precisely the drug that caused the HIT in this patient. - Administering another antithrombin III activator (e.g., antithrombin III concentrate) would not address the underlying **pathogenesis of HIT**, which involves heparin-dependent antibodies causing platelet activation and thrombosis. *Adenosine-diphosphate (ADP) receptor antagonist* - **ADP receptor antagonists (e.g., clopidogrel, ticagrelor)** inhibit platelet aggregation and are used in arterial thrombotic conditions like acute coronary syndrome or stroke prevention. - While they inhibit platelets, they are **not the first-line treatment for HIT** and its associated venous thrombosis, which requires direct anticoagulation rather than solely antiplatelet therapy. *Vitamin K epoxide reductase inhibitor* - **Vitamin K epoxide reductase inhibitors (e.g., warfarin)** are effective oral anticoagulants that inhibit the synthesis of vitamin K-dependent clotting factors. - However, starting warfarin in acute HIT is **contraindicated** initially because it can lead to a paradoxical prothrombotic state due to a rapid decrease in protein C levels, especially if started before the platelet count has recovered or without overlap with a rapidly acting anticoagulant.

Question 356: A 26-year-old woman is brought to the emergency department after a motor vehicle accident. She was driving on the highway when she was struck by a van. At the hospital she was conscious but was bleeding heavily from an open wound in her left leg. Pulse is 120/min and blood pressure is 96/68 mm Hg. She receives 3 L of intravenous saline and her pulse slowed to 80/min and blood pressure elevated to 116/70 mm Hg. The next morning she is found to have a hemoglobin of 6.2 g/dL. Her team decides to transfuse 1 unit of packed RBCs. Twenty minutes into the transfusion she develops a diffuse urticarial rash, wheezing, fever, and hypotension. The transfusion is immediately stopped and intramuscular epinephrine is administered. Which of the following scenarios is most consistent with this patient's reaction to the blood transfusion?

• A. A patient history of cardiovascular disease
• B. Unsanitary blood product storage practices in the hospital
• C. A patient history of frequent sinopulmonary infections (Correct Answer)
• D. Facial twitching when the patient's cheek is tapped
• E. Prior transfusion reactions caused by the same donor

Explanation: ***A patient history of frequent sinopulmonary infections*** - The diffuse **urticarial rash, wheezing, fever, and hypotension** after a blood transfusion are classic signs of a **severe allergic reaction (anaphylaxis)**. - Patients with a history of frequent sinopulmonary infections often have **IgA deficiency**, which can lead to the formation of anti-IgA antibodies. If transfused with blood containing IgA, these antibodies can trigger a severe anaphylactic reaction. *A patient history of cardiovascular disease* - While cardiovascular disease can influence how a patient tolerates a transfusion, it does not directly cause the specific constellation of symptoms like **urticaria, wheezing, and fever** that point to an allergic reaction. - Cardiovascular issues might exacerbate circulatory collapse but wouldn't be the primary cause of an immediate, systemic allergic response. *Unsanitary blood product storage practices in the hospital* - Unsanitary storage practices are typically associated with **bacterial contamination** of blood products, leading to a **febrile non-hemolytic transfusion reaction** or **septic shock**, often with severe rigors and high fever. - This scenario would not commonly present with prominent **urticaria and wheezing** as primary symptoms of an acute reaction. *Facial twitching when the patient's cheek is tapped* - Facial twitching when the cheek is tapped is known as **Chvostek's sign**, which is indicative of **hypocalcemia**. - While rapid transfusion of large volumes of blood can sometimes lead to hypocalcemia due to citrate binding, the primary symptoms described (urticaria, wheezing, fever, hypotension) are not typical of hypocalcemia and point more strongly to an allergic reaction. *Prior transfusion reactions caused by the same donor* - While prior reactions to blood from the same donor could occur, it is highly unlikely in this scenario as blood components are typically sourced from various donors. - The focus is on the patient's intrinsic predisposition (like IgA deficiency) rather than a specific donor incompatibility, especially since this is likely her first transfusion given the trauma.

Question 357: A 60-year-old woman presents to the emergency room with chest pain that started 20 minutes ago while watching television at home. The pain is substernal and squeezing in nature. She rates the pain as 6/10 and admits to having similar pain in the past with exertion. Her past medical history is significant for diabetes mellitus that is controlled with metformin. The physical examination is unremarkable. An electrocardiogram (ECG) shows ST-segment depression in the lateral leads. She is started on aspirin, nitroglycerin, metoprolol, unfractionated heparin, and insulin. She is asked not to take metformin while at the hospital. Three sets of cardiac enzymes are negative. Lab results are given below: Serum glucose 88 mg/dL Sodium 142 mEq/L Potassium 3.9 mEq/L Chloride 101 mEq/L Serum creatinine 1.2 mg/dL Blood urea nitrogen 22 mg/dL Cholesterol, total 170 mg/dL HDL-cholesterol 40 mg/dL LDL-cholesterol 80 mg/dL Triglycerides 170 mg/dL Hematocrit 38% Hemoglobin 13 g/dL Leucocyte count 7,500/mm3 Platelet count 185,000 /mm3 Activated partial thromboplastin time (aPTT) 30 seconds Prothrombin time (PT) 12 seconds Urinalysis Glucose negative Ketones negative Leucocytes negative Nitrites negative Red blood cells (RBC) negative Casts negative An echocardiogram reveals left ventricular wall motion abnormalities. With the pain subsiding, she was admitted and the medications were continued. A coronary angiography is planned in 4 days. In addition to regular blood glucose testing, which of the following should be closely monitored in this patient?

• A. Activated partial thromboplastin time (aPTT) alone
• B. Prothrombin time alone
• C. aPTT and platelet count (Correct Answer)
• D. Platelet count alone
• E. Prothrombin time and platelet count

Explanation: ***aPTT and platelet count*** - The patient is receiving **unfractionated heparin**, which requires monitoring of **aPTT** to ensure therapeutic anticoagulation and prevent bleeding complications. - Heparin can also induce **heparin-induced thrombocytopenia (HIT)**, necessitating close monitoring of the **platelet count**. *Activated partial thromboplastin time (aPTT) alone* - While **aPTT** monitoring is crucial for unfractionated heparin, it does not account for the risk of **heparin-induced thrombocytopenia (HIT)**. - Monitoring platelet count is equally important alongside aPTT in patients receiving heparin. *Prothrombin time alone* - **Prothrombin time (PT)** is used to monitor **warfarin** therapy, not unfractionated heparin. - Monitoring PT in this context would be inappropriate and would not provide information about the efficacy or safety of the prescribed heparin. *Platelet count alone* - Monitoring **platelet count** is important for detecting **heparin-induced thrombocytopenia (HIT)**, but it does not assess the therapeutic effect of heparin. - **aPTT** monitoring is essential to ensure adequate anticoagulation and prevent thrombotic events. *Prothrombin time and platelet count* - **Prothrombin time (PT)** is irrelevant for unfractionated heparin monitoring, as it measures the extrinsic pathway and is used for warfarin. - Although **platelet count** monitoring is important, relying on PT is incorrect for unfractionated heparin management.

Question 358: A 2-year-old boy had increased bleeding during a circumcision. His birth and delivery were uncomplicated, and his mother had no issues with prolonged bleeding during labor. Of note, his maternal grandfather has a history of bleeding complications. The boy's vital signs are stable and physical examination is notable for scattered bruises on his lower extremities. The lab results are as follows: Hemoglobin 12.8 gm % Hematocrit 35.4% WBC 8400/mm3 Platelets 215 x 109/L PT 14 s PTT 78 s What is the most likely diagnosis?

• A. Glanzmann thrombasthenia
• B. Hemophilia A (Correct Answer)
• C. Von Willebrand disease
• D. Scurvy
• E. Bernard-Soulier syndrome

Explanation: ***Hemophilia A*** - The patient's presentation with increased bleeding during circumcision, scattered bruises, and a **prolonged PTT** with normal PT and platelet count is highly suggestive of **Hemophilia A**. - The familial history of bleeding complications in the maternal grandfather points towards an **X-linked recessive inheritance pattern**, characteristic of Hemophilia A. - Hemophilia A results from **Factor VIII deficiency**, affecting the intrinsic coagulation pathway. *Glanzmann thrombasthenia* - This condition involves a defect in **platelet aggregation** due to deficiency of **GPIIb/IIIa**, which would typically manifest with a **normal platelet count** but abnormal platelet function tests. - While it causes bruising and bleeding, it would not affect the PTT, as coagulation factors are normal in this platelet function disorder. *Von Willebrand disease* - This is the **most common inherited bleeding disorder** and typically presents with mucocutaneous bleeding and menorrhagia in females. - While it can cause a **mildly prolonged PTT** due to low Factor VIII levels (vWF stabilizes Factor VIII), the PTT is typically only **mildly elevated**, not as significantly prolonged as seen here (78s vs normal ~25-35s). - The **X-linked family history** (affected maternal grandfather, not parents) strongly favors hemophilia over the **autosomal dominant** inheritance of most vWD cases. *Scurvy* - Scurvy results from **vitamin C deficiency** leading to impaired collagen synthesis. - While it can cause bleeding issues like petechiae and gingival bleeding, it would not cause a **prolonged PTT** or present with significant bleeding during a circumcision. - Coagulation tests remain normal in scurvy. *Bernard-Soulier syndrome* - This is a rare, inherited platelet disorder characterized by **giant platelets** and **thrombocytopenia**, resulting from a defect in the **glycoprotein Ib/IX/V complex**. - It would present with mucocutaneous bleeding and bruising, but the patient's **platelet count is normal** (215 × 10⁹/L) and the PTT would not be prolonged in this platelet function disorder.

Question 359: A 52-year-old woman is brought to the emergency department for a severe, sudden-onset headache, light-sensitivity, and neck stiffness that began 30 minutes ago. A CT scan of the head shows hyperdensity between the arachnoid mater and the pia mater. The patient undergoes an endovascular procedure. One week later, she falls as she is returning from the bathroom. Neurologic examination shows 3/5 strength in the right lower extremity and 5/5 in the left lower extremity. Treatment with which of the following drugs is most likely to have prevented the patient's current condition?

• A. Fosphenytoin
• B. Nitroglycerin
• C. Enalapril
• D. Fresh frozen plasma
• E. Nimodipine (Correct Answer)

Explanation: ***Nimodipine*** - The patient experienced a **subarachnoid hemorrhage (SAH)**, indicated by the sudden-onset severe headache, neck stiffness, light sensitivity, and hyperdensity between the arachnoid and pia mater on CT scan. - **Nimodipine**, a calcium channel blocker, is used to prevent **cerebral vasospasm** following SAH, which can lead to delayed cerebral ischemia and focal neurological deficits like the patient's new right lower extremity weakness. *Fosphenytoin* - **Fosphenytoin** is an **anticonvulsant** used to treat or prevent seizures. - While seizures can occur after SAH, there is no mention of seizure activity in this patient, and fosphenytoin would not prevent **vasospasm-induced ischemia**. *Nitroglycerin* - **Nitroglycerin** is a potent **vasodilator** primarily used to treat angina and heart failure. - It rapidly lowers blood pressure and would not be used to prevent cerebral vasospasm after SAH, and could potentially worsen cerebral perfusion if blood pressure drops too low. *Enalapril* - **Enalapril** is an **ACE inhibitor** used to treat hypertension and heart failure. - It is a long-acting antihypertensive and is not indicated for the prevention of **cerebral vasospasm** after SAH. *Fresh frozen plasma* - **Fresh frozen plasma (FFP)** is used to replace clotting factors in patients with coagulopathies or significant bleeding. - While SAH involves bleeding, FFP would be used to reverse anticoagulant effects or treat a severe clotting factor deficiency, not to prevent **delayed ischemic deficits** from vasospasm.

Question 360: A 57-year-old man with type 2 diabetes mellitus comes to the physician for a follow-up evaluation. He was recently diagnosed with hyperlipidemia, for which he takes several medications. His serum total cholesterol concentration is 295 mg/dL and serum high-density lipoprotein concentration is 19 mg/dL (N: > 40 mg/dL). The physician prescribes an additional drug that decreases hepatic production of triglycerides and reduces the release of VLDL and LDL through the inhibition of diacylglycerol acyltransferase 2. This patient should be advised to do which of the following?

• A. This medication may cause gastrointestinal upset; take it with food.
• B. Maintain a healthy diet and exercise regularly to maximize the drug's effect.
• C. Pruritus is a common side effect that usually resolves spontaneously.
• D. Report any signs of muscle pain or weakness immediately.
• E. Monitor liver function tests regularly while taking this medication. (Correct Answer)

Explanation: ***Monitor liver function tests regularly while taking this medication.*** - The drug described inhibits **diacylglycerol acyltransferase 2 (DGAT2)**, an enzyme that catalyzes the final step in **triglyceride synthesis** in the liver, thereby reducing **VLDL** and **LDL** production and release. - Drugs targeting hepatic lipid synthesis pathways, including DGAT2 inhibitors and related agents like **lomitapide** (an MTP inhibitor with similar effects on VLDL/LDL), carry a **BLACK BOX WARNING** for **hepatotoxicity**, including risk of hepatic steatosis, elevated transaminases, and potential liver failure. - Regular monitoring of **liver function tests (AST, ALT, alkaline phosphatase, total bilirubin)** is **mandatory** - typically before treatment, then monthly for the first year, and regularly thereafter to detect drug-induced liver injury early. *This medication may cause gastrointestinal upset; take it with food.* - While **gastrointestinal side effects** (diarrhea, nausea, dyspepsia) can occur with lipid-lowering agents affecting hepatic metabolism, this is not the most critical safety concern for drugs inhibiting triglyceride synthesis. - The primary and most serious risk is **hepatotoxicity**, making LFT monitoring the essential patient counseling point rather than routine GI symptom management. *Maintain a healthy diet and exercise regularly to maximize the drug's effect.* - **Lifestyle modifications** including diet (especially low-fat diet to reduce GI side effects and hepatic fat accumulation) and exercise are important adjuncts to all lipid-lowering therapy. - However, this is general health advice rather than a specific safety monitoring requirement related to the drug's mechanism of action and serious adverse effect profile (hepatotoxicity). *Pruritus is a common side effect that usually resolves spontaneously.* - **Pruritus** (itching) and flushing are characteristic side effects of **niacin** (nicotinic acid) due to prostaglandin-mediated cutaneous vasodilation, often prevented with aspirin pretreatment. - This is not a typical or prominent side effect of drugs targeting **DGAT2** or hepatic triglyceride synthesis pathways; the defining concern remains hepatotoxicity. *Report any signs of muscle pain or weakness immediately.* - **Myalgia**, **myopathy**, and **rhabdomyolysis** are well-recognized adverse effects of **statins** (HMG-CoA reductase inhibitors) due to effects on the mevalonate pathway and coenzyme Q10 depletion. - The mechanism described (inhibiting **DGAT2** and triglyceride synthesis) does not directly affect muscle metabolism or create significant risk for myopathy, making liver monitoring the appropriate priority for this specific drug class.

Question 361: A 20-year-old man presents to his primary care provider with a history of recurrent cough, wheezing, and breathlessness since early childhood. He was previously diagnosed with allergic rhinitis and bronchial asthma. For his allergic rhinitis, he uses intranasal fluticasone. For his asthma, he uses an albuterol inhaler as a rescue inhaler. It is decided to initiate a new medication for daily use. Which of the following medications, with its corresponding mechanism, is the next best step in therapy?

• A. Omalizumab acts by blocking both circulating and mast cell-bound IgE.
• B. Theophylline works through phosphodiesterase inhibition and has anti-inflammatory effects.
• C. Antileukotrienes (such as montelukast and zafirlukast) exert their beneficial effects in bronchial asthma by blocking CysLT1-receptors.
• D. β2-agonists reverse bronchoconstriction but do not control the underlying inflammation.
• E. Inhaled corticosteroids reduce inflammation by inhibiting the production of inflammatory mediators. (Correct Answer)

Explanation: ***Inhaled corticosteroids reduce inflammation by inhibiting the production of inflammatory mediators.*** * **Inhaled corticosteroids (ICS)** are the cornerstone of **long-term control therapy** for persistent asthma, as they effectively reduce airway inflammation. * Given the patient's history of recurrent symptoms and allergic rhinitis, suggesting a significant inflammatory component, **daily ICS** would be the most appropriate "next best step" for asthma management. *Omalizumab acts by blocking both circulating and mast cell-bound IgE.* * **Omalizumab** is an **anti-IgE antibody** used for severe persistent allergic asthma that is not well-controlled with high-dose ICS and other controllers. * It is typically considered for more severe cases and not as an initial "next best step" for daily use in a patient who is only on a rescue inhaler. *Theophylline works through phosphodiesterase inhibition and has anti-inflammatory effects.* * **Theophylline** is a **bronchodilator** with mild anti-inflammatory effects, but its use is limited by its narrow therapeutic window and potential for significant side effects like **arrhythmias** and **seizures**. * It is generally reserved for patients whose asthma is not well-controlled with ICS and long-acting beta-agonists (LABAs) due to its less favorable side effect profile compared to ICS. *Antileukotrienes (such as montelukast and zafirlukast) exert their beneficial effects in bronchial asthma by blocking CysLT1-receptors.* * **Antileukotrienes** are effective in asthma management, particularly for **aspirin-exacerbated respiratory disease** and **exercise-induced bronchoconstriction**, and have some anti-inflammatory properties. * While they can be used as an alternative or add-on therapy, **inhaled corticosteroids** are generally more potent anti-inflammatory agents and are considered first-line for daily control of persistent asthma. *β2-agonists reverse bronchoconstriction but do not control the underlying inflammation.* * **Short-acting beta2-agonists (SABAs)** like albuterol are primarily **rescue medications** that provide rapid relief from bronchoconstriction but do not address the underlying airway inflammation in asthma. * The question states the patient is already using an albuterol inhaler as a rescue and needs a new medication for "daily use," indicating a need for controller therapy, not another reliever.

Question 362: Two weeks after being hospitalized for acute pancreatitis, a 36-year-old man comes to the physician for a follow-up examination. Multiple family members have coronary artery disease. Physical examination shows multiple, yellow papular lesions on both upper eyelids. Fasting serum lipid studies show: Total cholesterol 280 mg/dl HDL-cholesterol 40 mg/dl LDL-cholesterol 185 mg/dl Triglycerides 1080 mg/dl Treatment with gemfibrozil is initiated. The expected beneficial effect of this drug is most likely due to which of the following mechanisms of action?

• A. Formation of bile acid complex
• B. Upregulation of lipoprotein lipase
• C. Inhibition of intestinal cholesterol absorption
• D. Inhibition of HMG-CoA reductase
• E. Activation of peroxisome proliferator-activated receptors (Correct Answer)

Explanation: ***Activation of peroxisome proliferator-activated receptors*** - **Gemfibrozil** is a **fibrate drug** that acts by activating **peroxisome proliferator-activated receptor alpha (PPAR-α)**. - Activation of **PPAR-α** leads to increased **lipoprotein lipase (LPL) activity**, enhanced fatty acid oxidation, and reduced hepatic VLDL production, ultimately lowering **triglycerides** and increasing **HDL-cholesterol**. *Formation of bile acid complex* - This mechanism of action is characteristic of **bile acid sequestrants** (e.g., cholestyramine, colesevelam), which bind to bile acids in the intestine, preventing their reabsorption. - Bile acid sequestrants primarily lower **LDL-cholesterol** and are not the primary mechanism of action for fibrates. *Upregulation of lipoprotein lipase* - While fibrates do lead to increased **lipoprotein lipase activity**, this is a *downstream effect* of their primary mechanism, which is the **activation of PPAR-α**. - Without the activation of PPAR-α, the upregulation of lipoprotein lipase would not occur. *Inhibition of intestinal cholesterol absorption* - This mechanism is characteristic of **cholesterol absorption inhibitors** such as **ezetimibe**, which specifically block the **Niemann-Pick C1-Like 1 (NPC1L1) protein** on enterocytes. - This mechanism is not associated with the action of fibrate drugs like gemfibrozil. *Inhibition of HMG-CoA reductase* - This is the primary mechanism of action for **statins** (e.g., atorvastatin, simvastatin), which inhibit the rate-limiting enzyme in **cholesterol biosynthesis** in the liver. - Statins are mainly used to lower **LDL-cholesterol**, whereas fibrates like gemfibrozil are primarily used for hypertriglyceridemia.

Question 363: A 22-year-old woman presents to the emergency department because of agitation and sweating. History shows she is currently being treated for depression with citalopram. She also takes tramadol for back pain. Her temperature is 38.6°C (101.5°F), the pulse is 108/min, the respirations are 18/min, and the blood pressure is 165/110 mm Hg. Physical examination shows hyperreflexia and mild tremors in all 4 extremities. Which of the following should be used in the next step of management for this patient?

• A. Diazepam
• B. Chlorpromazine
• C. Cyproheptadine
• D. Selegiline
• E. Discontinue tramadol and citalopram (Correct Answer)

Explanation: ***Discontinue tramadol and citalopram*** - This patient presents with symptoms highly suggestive of **serotonin syndrome**, characterized by **agitation, sweating, hyperthermia, tachycardia, hypertension, hyperreflexia, and tremors**, stemming from the concomitant use of **citalopram (SSRI)** and **tramadol (serotonergic properties)**. - The immediate priority in managing serotonin syndrome is to **discontinue all serotonergic agents** definitively, as continued exposure can worsen symptoms and lead to severe complications. *Diazepam* - While **benzodiazepines** like diazepam are often used to manage agitation and hyperreflexia in serotonin syndrome, they are **symptomatic treatments** and do not address the underlying cause. - Their use would be **adjunctive to discontinuing the causative agents**, not the primary next step. *Chlorpromazine* - **Chlorpromazine** is an antipsychotic with **dopamine-blocking effects** and anticholinergic properties; it is **not indicated** for the treatment of serotonin syndrome. - In fact, its use could **exacerbate certain symptoms** or lead to adverse effects due to its other pharmacological actions. *Cyproheptadine* - **Cyproheptadine** is a **serotonin antagonist** that can be used in some cases of severe serotonin syndrome to counteract the excessive serotonin activity. - However, the **initial and most critical step** is to discontinue the offending medications before considering pharmacologic interventions like cyproheptadine, which is typically reserved for moderate to severe cases after initial drug cessation. *Selegiline* - **Selegiline** is a **monoamine oxidase B (MAO-B) inhibitor** that increases dopamine levels and, at higher doses, can also inhibit MAO-A, leading to increased serotonin. - Administering another serotonergic agent would be **contraindicated** and potentially fatal in a patient experiencing serotonin syndrome.

Question 364: A 44-year-old man seeks evaluation at a clinic because he is experiencing a problem with his sexual health for the past month. He says he does not get erections like he used to, despite feeling the urge. In addition to heart failure, he has angina and hypertension. His regular oral medications include amlodipine, atorvastatin, nitroglycerin, spironolactone, and losartan. After a detailed evaluation of his current medications, it is concluded that he has drug-induced erectile dysfunction. Which one of the following medications may have caused this patient's symptom?

• A. Atorvastatin
• B. Amlodipine
• C. Spironolactone (Correct Answer)
• D. Losartan
• E. Nitroglycerin

Explanation: ***Spironolactone*** - **Spironolactone** is a **potassium-sparing diuretic with anti-androgenic effects** and can cause **gynecomastia** and **erectile dysfunction** due to competitive inhibition at androgen receptors and inhibition of testosterone biosynthesis. - The patient's history of **heart failure, angina, and hypertension** makes him susceptible to various medications, but spironolactone specifically targets hormonal pathways involved in sexual function. *Atorvastatin* - **Atorvastatin**, a **statin**, can rarely cause sexual dysfunction but is generally not a primary cause of erectile dysfunction. - Its main roles are in **cholesterol reduction** and **cardiovascular risk prevention**. *Amlodipine* - **Amlodipine**, a **calcium channel blocker**, manages hypertension and angina by dilating blood vessels. - It is **less likely to cause erectile dysfunction** compared to other antihypertensives like diuretics or beta-blockers. *Losartan* - **Losartan**, an **angiotensin receptor blocker (ARB)**, is used for hypertension and heart failure. - ARBs are generally well-tolerated and have a **low incidence of erectile dysfunction** compared to other antihypertensive classes. *Nitroglycerin* - **Nitroglycerin** is a vasodilator used for angina and has **no direct association with erectile dysfunction**. - Medications like sildenafil (Viagra) work via similar pathways (nitric oxide) and are used to treat erectile dysfunction.

Question 365: A 28-year-old man comes to the emergency department for an injury sustained while doing construction. Physical examination shows a long, deep, irregular laceration on the lateral aspect of the left forearm with exposed fascia. Prior to surgical repair of the injury, a brachial plexus block is performed using a local anesthetic. Shortly after the nerve block is performed, he complains of dizziness and then loses consciousness. His radial pulse is faint and a continuous cardiac monitor shows a heart rate of 24/min. Which of the following is the most likely mechanism of action of the anesthetic that was administered?

• A. Activation of acetylcholine receptors
• B. Inactivation of ryanodine receptors
• C. Inactivation of sodium channels (Correct Answer)
• D. Activation of GABA receptors
• E. Inactivation of potassium channels

Explanation: ***Inactivation of sodium channels*** - Local anesthetics primarily work by reversibly blocking **voltage-gated sodium channels** in nerves. - This prevents the influx of sodium ions, inhibiting the generation and propagation of **action potentials**, thus blocking pain signals. - The clinical presentation of dizziness, loss of consciousness, and bradycardia represents systemic toxicity from intravascular absorption of the local anesthetic. *Activation of acetylcholine receptors* - Activation of **nicotinic or muscarinic acetylcholine receptors** is the primary mechanism of action for neuromuscular stimulants or parasympathomimetics, not local anesthetics. - This would typically lead to muscle contraction or increased parasympathetic activity rather than analgesia and local nerve block. *Inactivation of ryanodine receptors* - Inactivation of **ryanodine receptors** primarily affects calcium release from the sarcoplasmic reticulum in muscle cells, crucial for excitation-contraction coupling. - This mechanism is associated with drugs like dantrolene used for malignant hyperthermia, not local anesthetics. *Activation of GABA receptors* - Activation of **GABA-A receptors** is the primary mechanism of action for benzodiazepines and barbiturates, leading to widespread CNS depression and sedation. - While systemic absorption of local anesthetics can cause CNS effects (as seen in toxicity), their primary therapeutic mechanism for nerve block is sodium channel inactivation, not GABA receptor activation. *Inactivation of potassium channels* - Inactivation of **potassium channels** would typically prolong repolarization and increase neuronal excitability or cause arrhythmias, depending on the specific channel. - This is not the mechanism of action for local anesthetics, which prevent depolarization by blocking sodium channel activation.

Question 366: A 9-year-old boy is brought to the physician by his mother to establish care after moving to a new city. He lives at home with his mother and older brother. He was having trouble in school until he was started on ethosuximide by a previous physician; he is now performing well in school. This patient is undergoing treatment for a condition that most likely presented with which of the following symptoms?

• A. Recurrent motor tics and involuntary obscene speech
• B. Episodic jerky movements of the arm and impaired consciousness
• C. Overwhelming daytime sleepiness and hypnagogic hallucinations
• D. Frequent episodes of blank staring and eye fluttering (Correct Answer)
• E. Limited attention span and poor impulse control

Explanation: ***Frequent episodes of blank staring and eye fluttering*** - The patient is taking **ethosuximide**, which is a primary treatment for **absence seizures**. - **Absence seizures** typically present as brief episodes of **blank staring**, unresponsiveness, and sometimes **eye fluttering**, often mistaken for daydreaming, which can impair school performance. *Recurrent motor tics and involuntary obscene speech* - This description is characteristic of **Tourette's disorder**, which involves both motor and phonic tics, and can include coprolalia (obscene speech). - Tourette's disorder is not typically treated with ethosuximide, nor does it commonly respond to it as a monotherapy. *Episodic jerky movements of the arm and impaired consciousness* - This presentation suggests a type of **myoclonic seizure** or a focal seizure with secondary generalization, depending on the extent of consciousness impairment. - While ethosuximide can sometimes be used as an adjunct, it is not the primary treatment for these types of seizures, and the classic description for absence seizures is distinct. *Overwhelming daytime sleepiness and hypnagogic hallucinations* - These symptoms are highly suggestive of **narcolepsy**, a chronic neurological condition characterized by overwhelming daytime sleepiness and other sleep-related phenomena. - Narcolepsy is treated with stimulants or other agents to promote wakefulness, not ethosuximide. *Limited attention span and poor impulse control* - These symptoms are hallmark features of **Attention-Deficit/Hyperactivity Disorder (ADHD)**, which can also affect school performance. - ADHD is treated with stimulants or non-stimulant medications targeting neurotransmitter systems, not ethosuximide.

Question 367: A 41-year-old woman is brought to the emergency department by ambulance because of a sudden onset severe headache. On presentation, the patient also says that she is not able to see well. Physical examination shows ptosis of the right eye with a dilated pupil that is deviated inferiorly and laterally. Based on the clinical presentation, neurosurgery is immediately consulted and the patient is taken for an early trans-sphenoidal surgical decompression. Which of the following will also most likely need to be supplemented in this patient?

• A. Erythropoietin
• B. Aldosterone
• C. Parathyroid hormone
• D. Insulin
• E. Corticosteroids (Correct Answer)

Explanation: ***Corticosteroids*** - This patient's presentation of sudden onset headache, visual disturbance, **ptosis of the right eye with a dilated pupil deviated inferiorly and laterally** strongly suggests a pituitary apoplexy, a life-threatening condition caused by hemorrhage or infarction of the pituitary gland. Patients with pituitary apoplexy can develop **adrenal insufficiency** due to disruption of the hypothalamic-pituitary-adrenal axis, necessitating immediate corticosteroid supplementation. - Neurosurgical decompression, especially **trans-sphenoidal surgery**, can further stress the adrenal axis and worsen adrenal insufficiency, making postoperative corticosteroid replacement vital to prevent **adrenal crisis**. *Erythropoietin* - **Erythropoietin** is a hormone involved in red blood cell production, primarily used to treat **anemia**, particularly in chronic kidney disease. - While patients undergoing surgery might experience some blood loss, there is no direct indication from the clinical presentation or immediate post-surgical needs for erythropoietin supplementation in this acute setting. *Aldosterone* - **Aldosterone** is a mineralocorticoid primarily involved in regulating blood pressure through sodium and potassium balance. - While adrenal insufficiency associated with pituitary apoplexy can lead to reduced aldosterone production, the primary life-threatening concern is **cortisol deficiency**, which is addressed by corticosteroid (glucocorticoid) supplementation. Aldosterone replacement is rarely the immediate and sole priority in acute adrenal crisis. *Parathyroid hormone* - **Parathyroid hormone** is crucial for **calcium and phosphorus regulation**. - There is no clinical information or direct physiological link between pituitary apoplexy or its surgical management and an immediate need for parathyroid hormone supplementation. *Insulin* - **Insulin** is a hormone essential for glucose metabolism and is primarily used to treat **diabetes mellitus**. - While pituitary dysfunction can sometimes lead to changes in glucose regulation, there is no immediate indication for insulin supplementation based on the presented symptoms of pituitary apoplexy. **Hypoglycemia** can be a concern with adrenal insufficiency if not managed with glucose and glucocorticoids, but insulin itself is not typically supplemented unless the patient has pre-existing or stress-induced hyperglycemia.

Question 368: A 70-year-old female with a history of congestive heart failure presents to the emergency room with dyspnea. She reports progressive difficulty breathing which began when she ran out of her furosemide and lisinopril prescriptions 1-2 weeks ago. She states the dyspnea is worse at night and when lying down. She denies any fever, cough, or GI symptoms. Her medication list reveals she is also taking digoxin. Physical exam is significant for normal vital signs, crackles at both lung bases and 2+ pitting edema of both legs. The resident orders the medical student to place the head of the patient's bed at 30 degrees. Additionally, he writes orders for the patient to be given furosemide, morphine, nitrates, and oxygen. Which of the following should be checked before starting this medication regimen?

• A. Basic metabolic panel (Correct Answer)
• B. Complete blood count
• C. Brain natriuretic peptide
• D. Urinalysis
• E. Chest x-ray

Explanation: ***Basic metabolic panel*** - A **basic metabolic panel (BMP)** is essential before starting this regimen to assess **kidney function** (creatinine, BUN) and **electrolytes**, particularly **potassium**. - **Critical safety consideration**: The patient is on **digoxin**, which has significantly increased toxicity when potassium is low. Furosemide (a loop diuretic) causes potassium loss, making baseline potassium assessment essential to prevent life-threatening digoxin toxicity. - **Renal function** must be checked before administering furosemide and lisinopril, both of which are renally cleared and can worsen renal function or accumulate in renal impairment. *Complete blood count* - A **complete blood count (CBC)** assesses for anemia, infection, and hematologic abnormalities. - While potentially useful, it doesn't provide the immediate biochemical information (renal function, electrolytes) needed to safely initiate the prescribed heart failure medications, especially given the digoxin interaction risk. *Brain natriuretic peptide* - **Brain natriuretic peptide (BNP)** is a biomarker of heart failure severity and can help differentiate cardiac from non-cardiac causes of dyspnea. - However, this patient's clinical presentation (orthopnea, bilateral crackles, pitting edema, medication non-adherence) already strongly confirms acute decompensated heart failure, making BNP less critical than checking renal function and electrolytes before medication administration. *Urinalysis* - **Urinalysis** can detect urinary tract infections, proteinuria, or other renal abnormalities. - This patient's symptoms are classic for acute decompensated heart failure due to medication non-adherence, making urinalysis less immediately relevant for managing her acute presentation and medication safety. *Chest x-ray* - A **chest x-ray** can confirm pulmonary edema (cardiomegaly, cephalization, Kerley B lines) and rule out other causes of dyspnea like pneumonia or pneumothorax. - While important for confirming the diagnosis, it is not required **before** starting medications and does not provide the critical biochemical information (renal function, electrolytes) needed to safely administer diuretics and ACE inhibitors in a patient on digoxin.

Question 369: A 41-year-old woman comes to the emergency room because she has been taking phenelzine for a few years and her doctor warned her that she should not eat aged cheese while on the medication. That night, she unknowingly ate an appetizer at a friend's party that was filled with cheese. She is concerned and wants to make sure that everything is all right. What vital sign or blood test is the most important to monitor in this patient?

• A. Oxygen saturation
• B. Blood pressure (Correct Answer)
• C. Temperature
• D. Creatine phosphokinase
• E. Heart rate

Explanation: ***Blood pressure*** - Phenelzine is a **monoamine oxidase inhibitor (MAOI)**, and consuming foods rich in **tyramine**, like aged cheese, can lead to a **hypertensive crisis**. - Monitoring blood pressure is crucial to detect and manage this potentially life-threatening elevation. *Oxygen saturation* - While overall patient stability is important, there is no direct physiological mechanism that would cause a critical drop in oxygen saturation due to a tyramine-induced hypertensive crisis. - This parameter would not be the primary or most important vital sign to monitor in this specific drug-food interaction. *Temperature* - Though fever can sometimes be a non-specific symptom in severe medical conditions, a significant change in body temperature is not a primary or direct anticipated sign of a **tyramine-induced hypertensive crisis**. - Monitoring temperature would not directly address the most immediate and critical complication associated with MAOI and tyramine interaction. *Creatine phosphokinase* - **Creatine phosphokinase (CPK)** levels are elevated in conditions involving muscle damage, such as rhabdomyolysis. - While severe complications of a hypertensive crisis could theoretically lead to organ damage, CPK is not the primary or most sensitive indicator for the initial assessment or immediate monitoring of a tyramine reaction with an MAOI. *Heart rate* - **Tachycardia** can occur during a hypertensive crisis; however, the primary danger is the elevation in blood pressure which can lead to stroke or myocardial infarction. - While important to monitor, heart rate is a secondary indicator compared to the direct measure of **blood pressure** in this specific scenario.

Question 370: A 69-year-old woman comes to the clinic for an annual well exam. She reports no significant changes to her health except for an arm fracture 3 weeks ago while she was lifting some heavy bags. Her diabetes is well controlled with metformin. She reports some vaginal dryness that she manages with adequate lubrication. She denies any weight changes, fevers, chills, palpitations, nausea/vomiting, incontinence, or bowel changes. A dual-energy X-ray absorptiometry (DEXA) scan was done and demonstrated a T-score of -2.7. She was subsequently prescribed a selective estrogen receptor modulator, in addition to vitamin and weight-bearing exercises, for the management of her symptoms. What is the mechanism of action of the prescribed medication?

• A. Estrogen antagonist in cervix and agonist in bone
• B. Estrogen agonist in bone and breast
• C. Estrogen antagonist in breast and agonist in bone (Correct Answer)
• D. Partial estrogen agonist in endometrium and bone
• E. Partial estrogen agonist in bone and antagonist in cervix

Explanation: ***Estrogen antagonist in breast and agonist in bone*** - Selective estrogen receptor modulators (SERMs) like **raloxifene** act as **estrogen agonists in bone**, helping to prevent osteoporosis by increasing bone mineral density. - They also act as **estrogen antagonists in breast tissue**, which can reduce the risk of breast cancer in high-risk postmenopausal women. - This is the mechanism of the medication prescribed for this patient's osteoporosis (T-score -2.7). *Estrogen antagonist in cervix and agonist in bone* - While SERMs are **agonists in bone**, they do not typically have significant antagonistic effects on the cervix, which is not a primary target for their therapeutic action or side effect profile. - The primary antagonism is observed in breast tissue, not the cervix. *Estrogen agonist in bone and breast* - This describes the action of **estrogen replacement therapy (ERT)**, which increases breast cancer risk, whereas SERMs are designed to avoid this by being antagonists in breast tissue. - The goal of SERMs is to achieve the beneficial bone effects of estrogen without the undesirable estrogenic effects on breast tissue. *Partial estrogen agonist in endometrium and bone* - Some SERMs, particularly **tamoxifen**, can act as a **partial estrogen agonist in the endometrium**, which can increase the risk of endometrial hyperplasia or cancer. - However, raloxifene (a common SERM for osteoporosis) is typically **neutral or minimally agonistic** on the endometrium, and the primary description here is for its breast and bone effects. *Partial estrogen agonist in bone and antagonist in cervix* - SERMs are indeed **agonists in bone**, but their antagonistic action is primarily in the breast, not the cervix. - The cervix is not a key target for either agonist or antagonist effects in the context of SERM therapeutic use for osteoporosis and breast cancer risk reduction.

Question 371: A 58-year-old man with a 10-year history of type 2 diabetes mellitus and hypertension comes to the physician for a routine examination. Current medications include metformin and captopril. His pulse is 84/min and blood pressure is 120/75 mm Hg. His hemoglobin A1c concentration is 9.5%. The physician adds repaglinide to his treatment regimen. The mechanism of action of this agent is most similar to that of which of the following drugs?

• A. Linagliptin
• B. Glyburide (Correct Answer)
• C. Pioglitazone
• D. Miglitol
• E. Metformin

Explanation: ***Glyburide*** - **Repaglinide** is a meglitinide, and **glyburide** is a sulfonylurea; both classes of drugs stimulate insulin release from pancreatic **beta cells** by closing ATP-sensitive potassium channels. - This action leads to depolarization of the beta cell membrane, opening of **voltage-gated calcium channels**, and subsequent release of insulin from storage granules. *Linagliptin* - **Linagliptin** is a **dipeptidyl peptidase-4 (DPP-4) inhibitor** that works by preventing the breakdown of incretins like GLP-1, thereby increasing postprandial insulin secretion and decreasing glucagon secretion. - Its mechanism is distinct from repaglinide's direct stimulation of insulin release. *Pioglitazone* - **Pioglitazone** is a **thiazolidinedione** that acts by activating **peroxisome proliferator-activated receptor-gamma (PPAR-γ)** in adipose tissue, increasing insulin sensitivity in peripheral tissues. - This mechanism centers on improving insulin utilization rather than stimulating insulin secretion. *Miglitol* - **Miglitol** is an **alpha-glucosidase inhibitor** that delays carbohydrate absorption in the gastrointestinal tract, leading to a flatter postprandial glucose curve. - Its action focuses on reducing glucose absorption, which is different from directly influencing insulin secretion or sensitivity. *Metformin* - **Metformin** is a biguanide that primarily reduces **hepatic glucose production** and improves insulin sensitivity in peripheral tissues. - It does not directly affect insulin secretion from the pancreas, distinguishing it from repaglinide.

Question 372: A 45-year-old woman comes to the clinic for complaints of abdominal pain and repeated watery stools for the past 2 days. She has a history of bowel complaints for the past 2 years consisting of periods of intermittent loose stools followed by the inability to make a bowel movement. Her past medical history is significant for diabetes controlled with metformin. She denies any abnormal oral intake, weight loss, fever, nausea/vomiting, or similar symptoms in her family. When asked to describe her stool, she reports that “it is just very watery and frequent, but no blood.” The physician prescribes a medication aimed to alleviate her symptoms. What is the most likely mechanism of action of this drug?

• A. Enteric nerve stimulation
• B. Substance P antagonist
• C. mu-opioid receptor agonist (Correct Answer)
• D. PGE1 analog
• E. D2 receptor antagonist

Explanation: ***mu-opioid receptor agonist*** - The patient's history of alternating **diarrhea and constipation**, absence of alarming features like weight loss or bloody stools, and chronic nature are highly suggestive of **Irritable Bowel Syndrome (IBS)**, specifically mixed type (IBS-M) or diarrhea-predominant (IBS-D) experiencing a flare. - Medications like **loperamide** (an over-the-counter mu-opioid receptor agonist) work by reducing **gastrointestinal motility** and increasing water absorption, effectively treating acute episodes of diarrhea in IBS. *Enteric nerve stimulation* - Medications that stimulate enteric nerves generally **increase gut motility**, which would worsen diarrhea rather than alleviate it. - This mechanism is characteristic of **prokinetic agents**, which are used to treat conditions like gastroparesis, not diarrhea. *Substance P antagonist* - **Substance P** is a neuropeptide involved in pain transmission and inflammation, and its antagonists have been investigated for conditions like IBS with pain. - However, they do not directly address the primary symptom of **watery stools** by altering motility or absorption. *PGE1 analog* - **PGE1 analogs** (e.g., misoprostol) are used to protect the gastric mucosa and can cause **diarrhea** as a side effect due to increased intestinal motility and fluid secretion. - This mechanism would exacerbate the patient's symptoms rather than relieve them. *D2 receptor antagonist* - **D2 receptor antagonists** (e.g., metoclopramide) are primarily antiemetics and prokinetic agents that **increase gastric emptying** and intestinal transit. - While they can relieve nausea and vomiting, they are not first-line treatments for diarrhea and could potentially worsen it in some cases due to increased motility.

Question 373: A 26-year-old woman is brought to the ED by her fiance with cyanosis and shortness of breath. Gradually over the last few days she has also experienced headaches, fatigue, and dizziness. Her past medical history is significant only for mild anemia attributed to menorrhagia, for which she takes an iron supplement. Per her fiance, she was recently laid-off, but is very excited about her new entrepreneurial endeavor of selling silk scarves that she dyes in their basement. She is afebrile, tachypneic, and tachycardic, and her oxygen saturation is 85% on room air, which seems high for her perceived degree of cyanosis. An arterial blood gas is drawn and the patient's blood is chocolate-colored. After a few minutes on 6 liters nasal canula, her oxygen saturation is still 85%. In addition to maintaining her airway, breathing, and circulation, what treatment should this patient also receive?

• A. Deferoxamine
• B. Dimercaprol
• C. Methylene blue (Correct Answer)
• D. Sodium bicarbonate
• E. Pralidoxime

Explanation: ***Methylene blue*** - The patient's symptoms (cyanosis, shortness of breath, headaches, dizziness, fatigue) coupled with **chocolate-colored blood**, **refractory hypoxemia despite oxygen supplementation**, and a history of exposure to **aniline dyes** (from dyeing silk scarves) are highly suggestive of **methemoglobinemia**. - **Methylene blue** acts as an electron acceptor for NADPH-methemoglobin reductase, converting ferric iron (Fe3+) in methemoglobin back to ferrous iron (Fe2+) in hemoglobin, thus restoring oxygen-carrying capacity. *Deferoxamine* - **Deferoxamine** is a **chelating agent** primarily used to treat **iron toxicity** or iron overload disorders like hemochromatosis. - While the patient has mild anemia and takes iron supplements, her presentation is not consistent with acute iron poisoning. *Dimercaprol* - **Dimercaprol** is a chelating agent used to treat poisoning by **heavy metals** such as arsenic, mercury, and lead. - There is no indication in the patient's history or symptoms to suggest heavy metal poisoning. *Sodium bicarbonate* - **Sodium bicarbonate** is primarily used to treat **metabolic acidosis**, hyperkalemia, or certain drug overdoses (e.g., tricyclic antidepressants). - Although the patient is tachypneic, there is no direct evidence of severe acidosis warranting bicarbonate, and it does not address the underlying cause of her hypoxemia. *Pralidoxime* - **Pralidoxime** (2-PAM) is a **cholinesterase reactivator** used as an antidote in conjunction with atropine for **organophosphate poisoning**. - The patient's symptoms are not consistent with cholinergic crisis from organophosphate exposure.

Question 374: A 35-year-old woman presents to the emergency room with fever, diarrhea, and dysuria for the past day. She also complains of palpitations, poor concentration, and severe anxiety. She was diagnosed with Graves disease 6 months ago but admits that she has missed some doses of her prescribed medications in the past couple of months due to stress. Her temperature is 103°F (39°C) and pulse is 132/minute. A urine culture is obtained and grows Escherichia coli. Which of the following drugs would be most effective in treating this patient’s acute condition?

• A. Amiodarone
• B. Methimazole
• C. Lithium
• D. Propranolol (Correct Answer)
• E. Nitrofurantoin

Explanation: ***Propranolol*** - This patient is likely experiencing a **thyroid storm** precipitated by her UTI and medication non-adherence, given her history of Graves disease, fever, tachycardia, anxiety, and GI symptoms. - **Propranolol**, a non-selective beta-blocker, is crucial in managing thyroid storm as it reduces the adrenergic symptoms (tachycardia, palpitations, anxiety) and also **inhibits the peripheral conversion of T4 to T3**. *Amiodarone* - **Amiodarone** contains a large amount of iodine, which can worsen hyperthyroidism or induce new-onset thyroid dysfunction. - It would be contraindicated in the acute management of a thyroid storm due to its potential to further increase thyroid hormone levels. *Methimazole* - **Methimazole** is an antithyroid drug that blocks the synthesis of thyroid hormones; however, its effects are not immediate. - While it is part of the long-term management of Graves disease, it would not be the most effective drug for the **acute symptoms** of a thyroid storm. *Lithium* - **Lithium** can inhibit the release of thyroid hormones and is sometimes used as an adjunct in treating hyperthyroidism, especially in cases of iodine sensitivity, but it is not a first-line agent. - It has a **narrow therapeutic window** and potential for significant side effects, making it less suitable for acute stabilization compared to beta-blockers. *Nitrofurantoin* - **Nitrofurantoin** is an antibiotic used to treat urinary tract infections (UTIs), which this patient also has (due to *E. coli*). - While treating the UTI is important, it will not address the **life-threatening symptoms of the thyroid storm**, such as tachycardia, fever, and anxiety.

Question 375: A 62-year-old man is brought to the emergency department because of a 4-hour history of abdominal pain, nausea, vomiting, and confusion. His wife reports that he had blurry vision on the way to the hospital. Two weeks ago, he lost his job and since then has been extremely worried about their financial situation and future. He has congestive heart failure and atrial fibrillation well controlled with combination medical therapy. His temperature is 36.5°C (97.7°F), pulse is 57/min and irregular, respirations are 14/min, and blood pressure is 118/63 mm Hg. The patient is oriented only to person. Serum studies show: Na+ 138 mEq/L Cl− 100 mEq/L K+ 5.3 mEq/L HCO3− 25 mEq/L Blood urea nitrogen 14 mg/dL Creatinine 0.9 mg/dL An ECG shows premature ventricular beats. The drug most likely responsible for this patient's symptoms has which of the following mechanisms of action?

• A. Blockade of aldosterone receptors
• B. Blockade of beta-adrenergic receptors
• C. Inhibition of Na+/K+-ATPase (Correct Answer)
• D. Inhibition of Na+-K+-2Cl--cotransporters
• E. Inhibition of funny channels

Explanation: ***Inhibition of Na+/K+-ATPase*** - The patient's symptoms (confusion, blurry vision, nausea, vomiting, abdominal pain, arrhythmia, hyperkalemia) are classic for **digoxin toxicity**, which occurs due to the inhibition of the **Na+/K+-ATPase pump**. - Inhibition of this pump leads to increased intracellular calcium, enhancing cardiac contractility but also causing hyperexcitability and arrhythmias like **premature ventricular beats**. *Blockade of aldosterone receptors* - This mechanism is characteristic of **aldosterone antagonists** (e.g., spironolactone, eplerenone) which are often used in heart failure. - While they can cause hyperkalemia, they typically do not cause the constellation of neurological (confusion, blurry vision) and gastrointestinal symptoms seen in this patient. *Blockade of beta-adrenergic receptors* - This is the mechanism of **beta-blockers** (e.g., carvedilol, metoprolol), also commonly used in heart failure and atrial fibrillation. - Symptoms of beta-blocker overdose usually include bradycardia, hypotension, and bronchospasm, but not the prominent GI or blurry vision symptoms seen here. *Inhibition of Na+-K+-2Cl--cotransporters* - This mechanism belongs to **loop diuretics** (e.g., furosemide), often used in congestive heart failure. - Loop diuretics primarily cause electrolyte imbalances such as hypokalemia and hypomagnesemia, and volume depletion, which does not match the patient's presentation of hyperkalemia and specific digoxin toxicity symptoms. *Inhibition of funny channels* - This is the mechanism of action of **ivabradine**, a selective inhibitor of the I_f current in the sinoatrial node, used to reduce heart rate in heart failure. - While it can cause bradycardia, it is not associated with the severe GI distress, neurological symptoms, or hyperkalemia observed in this patient.

Question 376: A 27-year-old woman comes to the physician because of a 2-month history of palpitations, diaphoresis, and a 5-kg (11-lb) weight loss. Her pulse is 101/min and blood pressure is 141/84 mm Hg. Physical examination shows a fine tremor when the fingers are outstretched. After confirmation of the diagnosis, treatment is begun with an antithyroid medication. The physician emphasizes the need for adequate contraception because of the increased risk of severe fetal malformations associated with the use of this medication, which is why its use is discouraged in the first trimester of pregnancy. Which of the following best describes the mechanism of action of this drug?

• A. Inhibition of thyroid hormone release
• B. Inhibition of peripheral conversion of T4 to T3
• C. Decreased iodide uptake by follicular cells
• D. Suppression of thyroid-stimulating hormone release
• E. Inhibition of iodide ion oxidation (Correct Answer)

Explanation: ***Inhibition of iodide ion oxidation*** - The patient's symptoms (palpitations, diaphoresis, weight loss, tremor, tachycardia, hypertension) are classic for **hyperthyroidism**, likely **Graves' disease**. - The antithyroid drug described, which is contraindicated in the first trimester due to teratogenicity, is **methimazole**. Methimazole (and propylthiouracil) primarily inhibits **thyroid peroxidase**, thereby preventing the **oxidation of iodide** and its subsequent organification into tyrosine residues on thyroglobulin, blocking thyroid hormone synthesis. *Inhibition of thyroid hormone release* - This mechanism is characteristic of **iodides** (e.g., Lugol's solution, potassium iodide), which acutely inhibit the release of pre-formed thyroid hormones from the thyroid gland. - While iodides can be used for rapid control of hyperthyroidism (e.g., before surgery or in thyroid storm), they are not the primary long-term antithyroid medications and do not carry the specific first-trimester teratogenicity risk described for PTU/methimazole. *Inhibition of peripheral conversion of T4 to T3* - This mechanism is primarily associated with **propylthiouracil (PTU)** (in addition to inhibiting thyroid hormone synthesis) and **beta-blockers** (like propranolol), as well as **glucocorticoids** and **amiodarone**. - While PTU also inhibits iodide oxidation, its unique ability to inhibit peripheral T4 to T3 conversion makes it the preferred antithyroid drug in the **first trimester of pregnancy** due to a lower teratogenic risk compared to methimazole, directly contrasting the drug described in the question. *Decreased iodide uptake by follicular cells* - This is the mechanism of action of **perchlorate** and **thiocyanate**, which are competitive inhibitors of the **sodium-iodide symporter (NIS)**, blocking iodide transport into follicular cells. - These agents are rarely used clinically due to toxicity concerns and are not the first-line antithyroid drugs with the described teratogenic profile. *Suppression of thyroid-stimulating hormone release* - **TSH release** from the pituitary is primarily suppressed by **negative feedback** from high levels of circulating thyroid hormones (T3 and T4), or by direct intervention with agents like **somatostatin analogs** (e.g., octreotide) in rare cases of TSH-producing pituitary adenomas. - Antithyroid drugs do not directly suppress TSH release; rather, by reducing thyroid hormone levels, they would eventually lead to an *increase* in TSH secretion if hyperthyroidism were adequately treated and feedback restored.

Question 377: A 58-year-old man comes to the physician because of a 3-month history of intermittent pain in his right calf that occurs after walking up more than 2 flights of stairs. He reports that the pain is associated with a tingling sensation and lasts for about 10 minutes. He is otherwise healthy. He has smoked 2 packs of cigarettes daily for 30 years and drinks 1 alcoholic beverage daily. He currently takes no medications. His pulse is 78/min, and blood pressure is 180/110 mm Hg. Physical examination shows yellow plaques below the lower eyelids bilaterally, loss of hair on the distal third of the right leg, and brittle toenails on the right foot. Femoral pulses are palpable bilaterally; right popliteal and pedal pulses are absent. Which of the following is the most appropriate management to prevent future morbidity and mortality of this patient's condition?

• A. Clopidogrel therapy (Correct Answer)
• B. Percutaneous transluminal angioplasty
• C. Cilostazol therapy
• D. Graded exercise therapy
• E. Pentoxifylline therapy

Explanation: ***Clopidogrel therapy*** - **Antiplatelet therapy** with clopidogrel (or aspirin) is crucial for **preventing future morbidity and mortality** in PAD patients by reducing the risk of **myocardial infarction**, stroke, and cardiovascular death. - PAD is a manifestation of systemic atherosclerosis, and these patients have significantly elevated cardiovascular risk. Antiplatelet therapy addresses this systemic risk and is a cornerstone of medical management. - Current guidelines (ACC/AHA) strongly recommend antiplatelet therapy for all patients with symptomatic PAD to reduce adverse cardiovascular events. *Graded exercise therapy* - **Graded exercise therapy** is highly effective for improving walking distance and reducing claudication symptoms by promoting collateral circulation and improving endothelial function. - While exercise is essential for symptom management and quality of life, it is **not the primary intervention for preventing mortality** in PAD patients, which is what this question specifically asks about. - Exercise should be recommended alongside antiplatelet therapy and risk factor modification. *Pentoxifylline therapy* - **Pentoxifylline** may improve red blood cell flexibility and microcirculation, but it has shown limited efficacy for symptom relief and **no proven benefit for reducing cardiovascular mortality**. - Its use is generally reserved for patients who cannot tolerate other treatments. *Percutaneous transluminal angioplasty* - **Revascularization** (PTA or surgical bypass) is typically reserved for patients with severe, lifestyle-limiting claudication unresponsive to medical therapy, or for critical limb ischemia. - This patient has intermittent claudication with moderate symptoms, making conservative medical management more appropriate initially. - Revascularization improves symptoms but does not reduce mortality compared to medical therapy alone. *Cilostazol therapy* - **Cilostazol** is a phosphodiesterase-3 inhibitor that improves walking distance and claudication symptoms through vasodilation and antiplatelet effects. - While effective for symptomatic relief, it does **not reduce cardiovascular mortality** and has a contraindication in heart failure patients. - It is used as an adjunct for symptom management, not as primary prevention of morbidity and mortality.

Question 378: A 55-year-old man presents to the emergency department with a 3-week history of shortness of breath. It started as exertional only, but progressed and is now present at rest. He says it's worse when he lies down; he has had a couple of episodes of waking up because of this shortness of breath with a choking sensation. He has not had any fever, cough, wheezing, or chest pain, but has noticed new swelling in his legs that has never happened before. He has also noticed that his hands and feet feel ‘weird’. Past medical history is unremarkable and social history is notable for drinking 4 vodka beverages per night for "as long as I can remember." On physical exam, his lungs have crackles up to the mid-lung fields. His bilateral lower extremities have 2+ pitting edema up to the mid-calf and he has jugular venous distension up to the angle of mandible. His bilateral hands and feet have sensory loss to pinprick and light touch with 4/5 strength on handgrip, wrist flexion and extension, ankle plantar flexion, and ankle dorsiflexion. This patient's presentation is most likely related to which of the following micronutrients?

• A. Vitamin B3
• B. Vitamin B12
• C. Vitamin B1 (Correct Answer)
• D. Vitamin B2
• E. Vitamin A

Explanation: ***Vitamin B1*** - This patient's symptoms, including **shortness of breath**, **orthopnea**, paroxysmal nocturnal dyspnea (PND), bilateral lower extremity **edema**, crackles, and jugular venous distension, are consistent with **heart failure**, a hallmark of **wet beriberi** (B1 deficiency). - The **neurological symptoms** (sensory loss, 4/5 strength) affecting hands and feet suggest **peripheral neuropathy**, characteristic of **dry beriberi**. Combined with a history of **chronic alcohol abuse**, which impairs thiamine absorption and leads to malnutrition, vitamin B1 deficiency is the most likely cause. *Vitamin B3* - Deficiency of vitamin B3 (**niacin**), known as **pellagra**, typically presents with the "3 Ds": **dermatitis**, **diarrhea**, and **dementia**. - While chronic alcohol use is a risk factor for pellagra, the patient's primary symptoms of heart failure and peripheral neuropathy are not characteristic of niacin deficiency. *Vitamin B12* - **Vitamin B12 deficiency** can cause **megaloblastic anemia** and neurological symptoms, including **peripheral neuropathy**, sensory disturbances, and subacute combined degeneration of the spinal cord. - However, the prominent signs of **heart failure** (shortness of breath, orthopnea, edema, JVD) are not typical features of B12 deficiency. *Vitamin B2* - **Vitamin B2 deficiency** (riboflavin) is characterized by symptoms such as **cheilosis** (cracks at the corners of the mouth), **glossitis** (inflammation of the tongue), and **seborrheic dermatitis**. - It does not typically cause heart failure or significant peripheral neuropathy as the primary presenting symptoms. *Vitamin A* - **Vitamin A deficiency** is primarily associated with **ocular symptoms** like **night blindness** and xerophthalmia, as well as impaired immune function and hyperkeratosis. - Heart failure and peripheral neuropathy are not recognized manifestations of vitamin A deficiency.

Question 379: A 60-year-old female sought a routine consultation in your clinic. She is diabetic and hypertensive. She had a history of myocardial infarction 2 years ago and is maintained on anticoagulants. When changing anticoagulants from heparin to warfarin, warfarin therapy is usually continued with heparin for the first 1–2 days. What is the rationale underlying the concurrent use of anticoagulants?

• A. Warfarin is metabolized slowly, thus leading to a delay in anticoagulation if heparin is not also administered.
• B. To compensate for the initial prothrombotic property of warfarin (Correct Answer)
• C. To prevent bleeding because heparin partially counteracts the warfarin hemorrhagic property
• D. Heparin decreases the clearance of warfarin, thus achieving a greater plasma drug concentration of warfarin.
• E. To achieve supraoptimal anticoagulation during critical periods of illness because warfarin and heparin have synergistic effects

Explanation: ***To compensate for the initial prothrombotic property of warfarin*** - Warfarin inhibits the synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and also **protein C** and **protein S**, which are natural anticoagulants. - Protein C has a shorter half-life than the procoagulant factors, leading to a temporary **hypercoagulable state** or **prothrombotic effect** initially, which requires bridging with heparin. *Warfarin is metabolized slowly, thus leading to a delay in anticoagulation if heparin is not also administered.* - While warfarin's full anticoagulant effect is delayed due to the half-lives of existing clotting factors, the primary reason for co-administration is to cover the initial **prothrombotic phase** from protein C depletion. - The slow metabolism is related to the time it takes for therapeutic effect, not directly the cause of initial hypercoagulation. *To prevent bleeding because heparin partially counteracts the warfarin hemorrhagic property* - This statement is incorrect; co-administration of heparin and warfarin increases the risk of bleeding, as both are anticoagulants. - The purpose of concurrent use is to maintain a therapeutic anticoagulant effect and prevent thrombosis, not to counteract bleeding. *Heparin decreases the clearance of warfarin, thus achieving a greater plasma drug concentration of warfarin.* - Heparin does not significantly interact with warfarin's metabolism or clearance to increase its plasma concentration. - Their mechanisms of action are distinct: heparin potentiates antithrombin, while warfarin inhibits vitamin K-dependent factor synthesis. *To achieve supraoptimal anticoagulation during critical periods of illness because warfarin and heparin have synergistic effects* - The goal is to achieve **therapeutic anticoagulation**, not "supraoptimal" levels, which would greatly increase bleeding risk. - While they have additive anticoagulant effects, the "synergistic" concept in this context is less accurate than addressing the initial prothrombotic state.

Question 380: A 49-year-old woman presents to the family medicine clinic with concerns about her weight. She has been constantly gaining weight for a decade now as she has not been able to control her diet. She has tried exercising but says that she is too lazy for this method of weight loss to work. Her temperature is 37° C (98.6° F), respirations are 15/min, pulse is 67/min, and blood pressure is 122/88 mm Hg. Her BMI is 30. Her labs from her past visit show: Fasting blood glucose: 149 mg/dL Glycated hemoglobin (HbA1c): 9.1% Triglycerides: 175 mg/dL LDL-Cholesterol: 102 mg/dL HDL-Cholesterol: 35 mg/dL Total Cholesterol: 180 mg/dL Serum creatinine: 1.0 mg/dL BUN: 12 mg/dL Serum: Albumin: 4.2 gm/dL Alkaline phosphatase: 150 U/L Alanine aminotransferase: 76 U/L Aspartate aminotransferase: 88 U/L After discussing the long term issues that will arise if her health does not improve, she agrees to modify her lifestyle and diet. Which of the following would be the best pharmacotherapy for this patient?

• A. Insulin
• B. Metformin (Correct Answer)
• C. Dietary modification alone
• D. Sitagliptin
• E. Glipizide

Explanation: ***Metformin*** - This patient has newly diagnosed **type 2 diabetes mellitus** (Fasting blood glucose 149 mg/dL, HbA1c 9.1%) in the setting of obesity (BMI 30). **Metformin** is the **first-line pharmacotherapy** for type 2 diabetes due to its efficacy, favorable safety profile, and potential for weight neutrality or modest weight loss. - Metformin works by **decreasing hepatic glucose production**, decreasing intestinal glucose absorption, and increasing insulin sensitivity. *Insulin* - While insulin is highly effective in lowering blood glucose, it is typically reserved for patients with **very high HbA1c** (often >10%), **symptomatic hyperglycemia**, or those who have failed oral pharmacotherapy, it can also cause **weight gain**. - Initiating insulin as first-line therapy can be overly aggressive and may lead to **hypoglycemia** in patients who can respond to oral agents. *Dietary modification alone* - Although **lifestyle changes** (diet and exercise) are crucial and can be remarkably effective, this patient's **HbA1c of 9.1%** indicates that **monotherapy with diet and exercise alone is insufficient** to achieve glycemic control. - Pharmacotherapy is generally recommended for HbA1c levels **above 7.5%**, even with a commitment to lifestyle changes. *Sitagliptin* - **Sitagliptin** is a **DPP-4 inhibitor** that increases insulin secretion and decreases glucagon secretion in a glucose-dependent manner. - It is often considered a **second-line agent** or an add-on therapy, as its HbA1c-lowering effect is generally less potent than metformin. *Glipizide* - **Glipizide** is a **sulfonylurea** that works by stimulating insulin release from pancreatic beta cells. - It can cause **weight gain** and has a significant risk of **hypoglycemia**, making it a less favorable first-line agent, especially in an obese patient, compared to metformin.

Question 381: A 57-year-old presents to your clinic complaining of baldness. He is overweight, has been diagnosed with BPH, and is currently taking atorvastatin for hyperlipidemia. The patient has tried several over-the-counter products for hair-loss; however, none have been effective. After discussing several options, the patient is prescribed a medication to treat his baldness that has the additional benefit of treating symptoms of BPH as well. Synthesis of which of the following compounds would be expected to decrease in response to this therapy?

• A. Testosterone
• B. FSH
• C. LH
• D. GnRH
• E. DHT (Correct Answer)

Explanation: ***DHT*** - The medication described is likely **finasteride**, a **5-alpha-reductase inhibitor**. This enzyme converts **testosterone** to **dihydrotestosterone (DHT)**. - Decreased DHT levels are beneficial for treating both **androgenetic alopecia (baldness)** and **benign prostatic hyperplasia (BPH)** due to its potent androgenic effects on hair follicles and prostate growth. *Testosterone* - While finasteride inhibits the conversion of testosterone to DHT, it does not directly decrease testosterone synthesis. In fact, **testosterone levels may slightly increase** as its conversion to DHT is blocked. - Testosterone itself is not the primary androgen responsible for male pattern baldness or BPH; it's its more potent metabolite, DHT. *FSH* - **Follicle-stimulating hormone (FSH)** is a gonadotropin released from the anterior pituitary that stimulates sperm production and ovarian follicle development. - The medication prescribed does not directly affect FSH synthesis or release; its action is peripheral, affecting androgen metabolism. *LH* - **Luteinizing hormone (LH)** is another gonadotropin that stimulates testosterone production in Leydig cells. - The drug's mechanism of action is local inhibition of an enzyme, not a central regulation of pituitary hormones like LH. *GnRH* - **Gonadotropin-releasing hormone (GnRH)** is released from the hypothalamus and stimulates the anterior pituitary to release FSH and LH. - This therapy specifically targets the conversion of an androgen and does not impact the hypothalamic-pituitary-gonadal axis at the level of GnRH.

Question 382: 29-year-old construction worker is brought to the emergency department after falling 10 ft (3 m) from the scaffolding at a construction site. He reports that he landed on his outstretched arms, which are now in severe pain (10/10 on a numeric scale). He has a history of opioid use disorder and is currently on methadone maintenance treatment. His pulse is 100/min, respirations are 20/min, and blood pressure is 140/90 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 98%. He is diaphoretic and in distress. Physical examination shows a hematoma on the patient's right forearm. X-ray of the right arm shows a nondisplaced fracture of the ulna. A CT of the abdomen and pelvis shows no abnormalities. The patient requests pain medication. In addition to managing the patient's injury, which of the following is the most appropriate next step in management?

• A. Administration of buprenorphine
• B. Psychiatric evaluation for drug-seeking behavior
• C. Increase of outpatient methadone regimen
• D. Urine toxicology screening
• E. Scheduled short-acting opioid administration (Correct Answer)

Explanation: ***Scheduled short-acting opioid administration*** - This patient is experiencing significant pain (10/10) from a verified injury (ulna fracture) and has a known history of **opioid use disorder** managed with methadone. - Providing **scheduled short-acting opioids** is appropriate for acute pain management in this context, addressing both the severe pain and the risk of withdrawal/escalated pain due to his opioid tolerance. *Administration of buprenorphine* - Administering buprenorphine in a patient currently on methadone for **opioid use disorder** could precipitate **acute opioid withdrawal** due to buprenorphine's partial agonist and high affinity properties. - Buprenorphine is typically used for **opioid dependence treatment** rather than acute pain management in someone currently maintained on methadone. *Psychiatric evaluation for drug-seeking behavior* - Attributing the patient's request for pain medication solely to "drug-seeking behavior" while he has a confirmed painful injury is **unethical and inappropriate**. - All patients, regardless of their substance use history, deserve adequate pain management for acute injuries. *Increase of outpatient methadone regimen* - Adjusting a stable outpatient methadone regimen for **acute pain management** is complex and typically requires coordination with the patient's opioid treatment program (OTP). - An isolated increase in methadone might not adequately address acute, incident pain from a fracture and could complicate subsequent long-term management. *Urine toxicology screening* - While a urine toxicology screen might be part of a comprehensive assessment in some contexts, it is **not the most appropriate immediate next step** for a patient presenting with severe acute pain from a confirmed injury. - The patient's pain needs immediate attention, and awaiting toxicology results would delay necessary pain relief.

Question 383: A 44-year-old man presents to the clinic worried about his risk for bladder cancer. His best friend who worked with him as a painter for the past 20-years died recently after being diagnosed with transitional cell carcinoma. He is worried that their long and heavy cigarette smoking history might have contributed to his death. He also reports that he has been feeling down since his friend's death 2 months ago and has not been eating or sleeping as usual. He took time off from work but now is running past due on some of his bills. He feels like he is moving a lot slower than usual. He would like to stop smoking but feels like it's impossible with just his willpower. What side-effect is most likely if this patient were started on his appropriate pharmacotherapy?

• A. Can decrease seizure threshold (Correct Answer)
• B. Can treat overdose with sodium bicarbonate
• C. Can cause restlessness at initiation or termination
• D. Can cause sedation and weight gain
• E. Can worsen uncontrolled hypertension

Explanation: ***Can decrease seizure threshold*** - The patient exhibits symptoms consistent with **major depressive disorder** (anhedonia, sleep/appetite disturbance, psychomotor retardation) and co-occurring **nicotine dependence**. - **Bupropion** is an appropriate pharmacotherapy as it treats both depression and aids in smoking cessation, but it carries a dose-dependent risk of **lowering the seizure threshold**. *Can treat overdose with sodium bicarbonate* - This statement is characteristic of **tricyclic antidepressant (TCA) overdose**, which leads to cardiac arrhythmias that can be mitigated by sodium bicarbonate. - Bupropion overdose is associated with seizures, blurred vision, and hallucinations, not typically managed with sodium bicarbonate for cardiac effects. *Can cause restlessness at initiation or termination* - This side effect is more commonly associated with **akathisia from antipsychotics** or sometimes **selective serotonin reuptake inhibitors (SSRIs)** during initiation or withdrawal. - While bupropion can cause agitation, "restlessness" in this context as a primary differentiating side effect for initiation/termination is less specific than the seizure risk. *Can cause sedation and weight gain* - **Sedation and weight gain** are common side effects of many antidepressants, particularly older TCAs and some newer atypical antidepressants like **mirtazapine**. - Bupropion is known for being **non-sedating** and can actually cause **weight loss**, making this option incorrect. *Can worsen uncontrolled hypertension* - While bupropion can cause a **mild increase in blood pressure**, sustained treatment with **MAOIs** (monoamine oxidase inhibitors) or **SNRIs** (serotonin-norepinephrine reuptake inhibitors) are more significantly associated with worsening uncontrolled hypertension. - The risk of seizure threshold lowering is a more distinct and clinically relevant side effect for bupropion compared to hypertension exacerbation.

Question 384: A 72-year-old man is brought in by ambulance to the hospital after being found down at home. On presentation, he appears cachectic and is found to be confused. Specifically, he does not answer questions appropriately and is easily distracted. His wife says that he has been losing weight over the last 3 months and he has a 40 pack-year history of smoking. His serum sodium is found to be 121 mEq/L and his urine osmolality is found to be 415 mOsm/kg. Chest radiograph shows a large central mass in the right lung. Which of the following treatments would be effective in addressing this patient's serum abnormality?

• A. Antipsychotic
• B. Antidiuretic hormone
• C. Normal saline
• D. Renin
• E. Demeclocycline (Correct Answer)

Explanation: ***Demeclocycline*** - This patient presents with **hyponatremia** and **concentrated urine** in the setting of lung cancer, suggestive of **SIADH**. Demeclocycline is a **tetracycline derivative** that inhibits the action of ADH on the renal tubules, promoting water excretion. - While other treatments like fluid restriction are first-line for SIADH, Demeclocycline is an effective pharmacological treatment, especially for **chronic or severe cases**. *Antipsychotic* - Antipsychotics are used to treat **psychotic disorders** and may induce hyponatremia as a side effect, but they do not directly treat the underlying mechanism of SIADH. - This patient's confusion is likely due to **hyponatremia** and his underlying medical condition, not a primary psychiatric disorder requiring antipsychotics. *Antidiuretic hormone* - **Antidiuretic hormone (ADH)**, also known as vasopressin, is the *cause* of SIADH (syndrome of inappropriate ADH secretion), where there is *excessive* ADH secretion. Administering more ADH would worsen the condition. - The goal of treatment in SIADH is to **reduce the effect or amount of ADH**, not increase it. *Normal saline* - Administering **normal saline (0.9% NaCl)** in SIADH can worsen hyponatremia. The kidneys will retain the free water due to ADH, while excreting the sodium, leading to a further drop in serum sodium. - Normal saline is used for **hypovolemic hyponatremia**, not euvolemic hyponatremia like SIADH. *Renin* - **Renin** is an enzyme involved in the **renin-angiotensin-aldosterone system** (RAAS), which primarily regulates blood pressure and fluid balance. It is not directly involved in the pathogenesis or treatment of SIADH. - The RAAS system's role in hyponatremia is distinct from the ADH-mediated pathology of SIADH.

Question 385: A 66-year-old man was referred for endoscopic evaluation due to iron deficiency anemia. He has had anorexia and weight loss for two months. Three years ago, the patient had coronary artery bypass grafting and aortic mechanical valve replacement. He has a 12-year history of diabetes mellitus and hypertension. He takes warfarin, lisinopril, amlodipine, metformin, aspirin, and carvedilol. His blood pressure is 115/65 mm Hg, pulse is 68/min, respirations are 14/min, temperature is 36.8°C (98.2°F), and blood glucose is 220 mg/dL. Conjunctivae are pale. Heart examination reveals a metallic click just before the carotid pulse. Which of the following is the most appropriate switch in this patient’s drug therapy before the endoscopy?

• A. Metformin to empagliflozin
• B. Aspirin to clopidogrel
• C. Lisinopril to losartan
• D. Warfarin to heparin (Correct Answer)
• E. Amlodipine to diltiazem

Explanation: ***Warfarin to heparin*** - The patient is on **warfarin** due to his **mechanical aortic valve**, which increases his risk of bleeding during endoscopy. - Switching to **heparin (bridging therapy)** allows for a shorter half-life and easier reversal if bleeding occurs, making it safer for the procedure. *Metformin to empagliflozin* - This change in **antidiabetic medication** does not address the immediate concern of bleeding risk for endoscopy. - **Empagliflozin** can cause **euglycemic diabetic ketoacidosis** and its benefits related to cardiovascular outcomes are long term, not relevant to peri-procedural management. *Aspirin to clopidogrel* - Both **aspirin** and **clopidogrel** are **antiplatelet agents** that increase bleeding risk. - Switching from one to the other does not mitigate the bleeding risk for endoscopy; often, one or both are held before such procedures if possible. *Lisinopril to losartan* - Both **lisinopril** and **losartan** are **antihypertensive medications** (ACE inhibitor and ARB, respectively) with similar effects on blood pressure. - This change would not impact the **bleeding risk** or the need for peri-procedural anticoagulation management. *Amlodipine to diltiazem* - Both **amlodipine** and **diltiazem** are **calcium channel blockers** used for hypertension and angina. - While they have different mechanisms, switching between them does not address the immediate safety concern of **bleeding risk** during endoscopy.

Question 386: A 69-year-old African American man is brought to the emergency department with sudden onset lower limb paralysis and back pain. He has had generalized bone pain for 2 months. He has no history of severe illnesses. He takes ibuprofen for pain. On examination, he is pale. The vital signs include: temperature 37.1°C (98.8°F), pulse 68/min, respiratory rate 16/min, and blood pressure 155/90 mm Hg. The neurologic examination shows paraparesis. The 8th thoracic vertebra is tender to palpation. An X-ray of the thoracic vertebrae confirms a compression fracture at the same level. The laboratory studies show the following: Laboratory test Hemoglobin 9 g/dL Mean corpuscular volume 95 μm3 Leukocyte count 5,000/mm3 Platelet count 240,000/mm3 ESR 85 mm/hour Serum Na+ 135 mEq/L K+ 4.2 mEq/L Cl− 113 mEq/L HCO3− 20 mEq/L Ca+ 11.5 mg/dL Albumin 4 g/dL Urea nitrogen 18 mg/dL Creatinine 1.2 mg/dL Serum electrophoresis shows a monoclonal protein level of 38 g/L. To reduce the likelihood of fracture recurrence, it is most appropriate to administer which of the following?

• A. Calcitonin
• B. Calcitriol
• C. Pamidronate (Correct Answer)
• D. Fluoride
• E. Testosterone

Explanation: ***Pamidronate*** - The patient's presentation with **bone pain**, **hypercalcemia**, **anemia**, **elevated ESR**, **renal insufficiency**, and a **monoclonal protein** in serum electrophoresis is highly suggestive of **multiple myeloma**. - **Bisphosphonates** like pamidronate are crucial in managing multiple myeloma by inhibiting osteoclast activity, reducing bone resorption, and thereby decreasing the risk of **pathological fractures** and managing **hypercalcemia**. *Calcitonin* - **Calcitonin** primarily works to lower serum calcium levels quickly but has a less sustained effect on bone remodeling compared to bisphosphonates. - While it can be used for acute hypercalcemia, its role in preventing long-term fracture recurrence in multiple myeloma is limited. *Calcitriol* - **Calcitriol**, the active form of **vitamin D**, promotes calcium absorption from the gut and bone mineralization. - Administering calcitriol in a patient with pre-existing hypercalcemia due to multiple myeloma would worsen the condition. *Fluoride* - **Fluoride** can increase bone density by affecting hydroxyapatite crystal formation. - However, high doses of fluoride can lead to **fluorosis** and paradoxically increase bone fragility, making it unsuitable for preventing fractures in multiple myeloma. *Testosterone* - **Testosterone** is an anabolic steroid that can improve bone density in individuals with **hypogonadism**. - It is not indicated for preventing fractures in the context of multiple myeloma, where bone destruction is driven by osteoclast activation due to plasma cell proliferation.

Question 387: One week after starting a new medication, a 16-year-old girl is brought to the emergency department by her mother because of a painful, blistering rash. She has a history of bipolar disorder. Her temperature is 39°C (102°F). Physical examination shows numerous coalescing bullae with epidermal detachment covering the face, trunk, and extremities. There are hemorrhagic erosions on the hard palate and buccal mucosa. When lateral pressure is applied to healthy-appearing skin at the edge of a bulla, a blister starts to form. Which of the following drugs is most likely responsible for this patient's current condition?

• A. Valproic acid
• B. Lithium
• C. Quetiapine
• D. Topiramate
• E. Lamotrigine (Correct Answer)

Explanation: ***Lamotrigine*** - The patient's symptoms (painful, blistering rash, coalescing bullae with epidermal detachment, hemorrhagic erosions on mucous membranes, fever, and positive **Nikolsky sign**) are classic for **Stevens-Johnson syndrome (SJS)** or **Toxic Epidermal Necrolysis (TEN)**. - **Lamotrigine** is a mood stabilizer commonly used in bipolar disorder and is a well-known high-risk drug for inducing SJS/TEN, especially when initiated rapidly or at high doses. *Valproic acid* - While used in bipolar disorder, **valproic acid** is generally not associated with a high risk of SJS/TEN. - Its common dermatological side effects are usually more benign, such as **alopecia** or **mild rash**, not severe blistering. *Lithium* - **Lithium** is a mood stabilizer for bipolar disorder, but it is rarely implicated in severe cutaneous adverse reactions like SJS/TEN. - Dermatologic side effects of lithium are typically mild, including **acneiform eruptions** or **psoriasiform rashes**. *Quetiapine* - **Quetiapine** is an antipsychotic sometimes used in bipolar disorder, but it has a low risk of causing SJS/TEN compared to lamotrigine. - While any drug can theoretically cause severe reactions, quetiapine is not a primary suspect for this presentation. *Topiramate* - **Topiramate** can cause various dermatological side effects, but it is not as strongly linked to SJS/TEN as lamotrigine. - Its use for bipolar disorder is often off-label, and its most serious skin reactions are less common than with specific anticonvulsants.

Question 388: A 34-year-old woman presents with blurred vision and ringing in her ears. She says she has a 6-month history of recurrent worsening bilateral pulsatile headaches that she manages with ibuprofen, which does very little to relieve the pain. For the past week, she says she has vomited nearly every morning and missed work due to the pain in her head. She first noticed vision problems 3 months ago that has occurred several times since then. Past medical history is significant for uncomplicated urinary tract infection for which she has just finished a course of antibiotics. She has a history of a mild urticarial reaction when she takes penicillin. Her vital signs include: blood pressure 115/74 mm Hg, pulse 75/min, and respiratory rate 16/min. Her body mass index (BMI) is 36 kg/m2. Physical examination is significant for bilateral peripheral visual field loss with preservation of visual acuity. Fundoscopic examination reveals blurring of the disc margins with vessel tortuosity. The remainder of her physical examination is unremarkable. A magnetic resonance image (MRI) of the brain is normal. Lumbar puncture (LP) is remarkable for a markedly elevated opening pressure. Which of the following is the next best step in the treatment of her condition?

• A. Ventriculoperitoneal shunting
• B. Furosemide
• C. Counseling for weight loss
• D. Optic nerve sheath fenestration
• E. Acetazolamide (Correct Answer)

Explanation: ***Acetazolamide*** - Given the diagnosis of **idiopathic intracranial hypertension (IIH)**, characterized by **elevated CSF opening pressure**, normal MRI, and symptoms like **pulsatile headaches**, blurred vision, and papilledema, **acetazolamide** is the first-line medical treatment. - **Acetazolamide** works by reducing **cerebrospinal fluid (CSF) production**, thereby lowering intracranial pressure and alleviating symptoms. *Ventriculoperitoneal shunting* - **Ventriculoperitoneal shunting** is a surgical intervention reserved for severe cases of **IIH** that are refractory to medical management or for patients with rapidly progressing vision loss. - It is not the initial treatment of choice when medical therapy with **acetazolamide** has not yet been attempted. *Furosemide* - While a diuretic, **furosemide** is not the primary treatment for **IIH**. It may be used as an adjunct in some cases, but it is less effective than acetazolamide in reducing CSF production. - Its main mechanism is to increase urinary output, not directly to decrease CSF pressure as effectively as a carbonic anhydrase inhibitor. *Counseling for weight loss* - **Weight loss** is a crucial long-term management strategy for **IIH**, as obesity is a significant risk factor and contributor to the condition. - However, it is a behavioral intervention that takes time to be effective and is not the immediate next best step for acute symptom management or to rapidly reduce elevated intracranial pressure. *Optic nerve sheath fenestration* - **Optic nerve sheath fenestration** is a surgical procedure considered for patients with **IIH** who experience progressive vision loss despite medical treatment, particularly when vision loss is severe or rapid. - It aims to directly relieve pressure on the optic nerve to prevent blindness and is not the initial treatment when **acetazolamide** has not been tried.

Question 389: A 56-year-old man with coronary artery disease agrees to participate in a pharmacological study. He takes an oral medication that leads to dephosphorylation of myosin light chains in venous smooth muscle cells. An investigator measures the plasma concentration of the drug over time after intravenous and then after oral administration. There is no statistically significant difference in the dose-corrected area under the curve for the 2 routes of administration. The patient most likely ingested which of the following drugs?

• A. Isosorbide mononitrate (Correct Answer)
• B. Nitroglycerine
• C. Nimodipine
• D. Nifedipine
• E. Nitroprusside

Explanation: ***Isosorbide mononitrate*** - **Isosorbide mononitrate** has nearly **100% oral bioavailability** due to minimal first-pass metabolism, which explains the comparable AUC between intravenous and oral administration. - This drug acts by releasing **nitric oxide**, leading to dephosphorylation of myosin light chains and subsequent **venous smooth muscle relaxation**, a mechanism consistent with the question stem. *Nitroglycerine* - **Nitroglycerine** undergoes extensive **first-pass metabolism** when taken orally, resulting in very low oral bioavailability and a significantly smaller AUC compared to intravenous administration. - It is typically administered sublingually or transdermally to avoid hepatic metabolism and achieve therapeutic effects. *Nimodipine* - **Nimodipine** is a **dihydropyridine calcium channel blocker** used for cerebral vasospasm, not primarily as a venous dilator acting via myosin light chain dephosphorylation. - While it can be given orally, its mechanism of action and primary clinical use are different from the description. *Nifedipine* - **Nifedipine** is another **dihydropyridine calcium channel blocker** primarily affecting arterial smooth muscle, not venous smooth muscle via myosin light chain dephosphorylation. - It undergoes significant first-pass metabolism, leading to variable oral bioavailability, which would likely result in a noticeable difference in AUC compared to IV administration. *Nitroprusside* - **Nitroprusside** is an **intravenously administered agent** that directly releases nitric oxide, but it has no oral formulation due to rapid degradation and toxicity. - Its use is limited to acute hypertensive emergencies and it does not fit the description of an orally administered drug with high bioavailability.

Question 390: A 50-year-old woman presents with sudden onset right upper quadrant abdominal pain. She says her symptoms started 6 hours ago after she had dinner. She describes the pain as cramping, radiating to her shoulders. She had similar episodes in the past, but they were less severe and resolved with over-the-counter analgesics. Her medical history is significant for hypertension and coronary artery disease. Her current medications include warfarin, hydrochlorothiazide, and fibrates. Her temperature is 37.7°C (99.9°F), blood pressure is 110/80 mm Hg, pulse is 80/min, and respirations are 15/min. Abdominal exam reveals severe right upper quadrant tenderness, and she catches her breath when palpated deeply just below the right costal margin. Surgical consult determines her to be surgically unfit for any intervention due to her high risk of bleeding. After treating her pain with appropriate analgesics, which of the following is the next best step in the management of this patient?

• A. Antispasmodic therapy (hyoscine butylbromide) (Correct Answer)
• B. Re-evaluate after few hours and perform laparoscopic cholecystectomy
• C. Discontinue fibrates
• D. Initiate stronger analgesic medications such as morphine
• E. No need for further treatment

Explanation: ***Antispasmodic therapy (hyoscine butylbromide)*** - The patient presents with symptoms highly suggestive of **biliary colic**, including right upper quadrant pain radiating to the shoulder, exacerbated by a fatty meal, and a positive Murphy's sign (catching her breath on deep palpation). Given she is surgically unfit due to anticoagulation, **medical management** for pain and spasm relief is the priority. - Hyoscine butylbromide is an **anticholinergic agent** that helps relax smooth muscles of the gastrointestinal tract, including the biliary tree, thereby reducing the painful spasms associated with biliary colic. *Re-evaluate after few hours and perform laparoscopic cholecystectomy* - While **laparoscopic cholecystectomy** is the definitive treatment for symptomatic cholelithiasis, the patient's current use of **warfarin** makes her surgically unfit due to a high bleeding risk. - Proceeding with surgery, even after re-evaluation, without addressing the anticoagulation and bleeding risk would be **unsafe** and could lead to severe hemorrhagic complications. *Discontinue fibrates* - Fibrates, like fenofibrate or gemfibrozil, can **increase the risk of gallstone formation** (cholelithiasis) by altering bile composition. However, discontinuing them acutely would not immediately resolve the current episode of biliary colic. - While it may be a consideration for **long-term management** to prevent future episodes, it is not the immediate best step for managing the acute symptomatic presentation. *Initiate stronger analgesic medications such as morphine* - Although the patient is in severe pain, **morphine** and other opioids can paradoxically **increase spasm of the sphincter of Oddi**, potentially worsening biliary colic rather than relieving it. - While effective for general pain relief, opioids like morphine are **generally avoided** in the initial management of suspected biliary colic due to this side effect. *No need for further treatment* - The patient is experiencing an acute, severe episode of **biliary colic** requiring urgent symptomatic relief. Her pain is significant, describing it as cramping, and she has a positive Murphy's sign. - Dismissing the need for further treatment would be **inappropriate** and would leave the patient suffering, potentially leading to complications if the obstruction is prolonged.

Question 391: A 70-year-old male immigrant from Asia is brought to the emergency room with complaints of palpitations and light-headedness for 1 hour. The patient was sitting in his chair watching television when he felt his heart racing and became dizzy. He was unable to stand up from his chair because of weakness and light-headedness. His past medical history is notable for mitral stenosis secondary to rheumatic fever as a child. On arrival to the emergency department, the patient's temperature is 99.7°F (37.6°C), blood pressure is 110/55 mmHg, pulse is 140/min, and respirations are 15/min. The patient appears comfortable but anxious. Electrocardiogram shows atrial fibrillation with rapid ventricular response. The patient is started on dofetilide. Which of the following would be expected in this patient’s cardiac action potential as a result of this drug?

• A. Decreased conduction velocity
• B. Increased QT interval (Correct Answer)
• C. Decreased calcium current
• D. Decreased slope of phase 0
• E. Decreased slope of phase 4

Explanation: ***Increased QT interval*** - **Dofetilide** is a **Class III antiarrhythmic** drug that primarily blocks the delayed rectifier **potassium channels (Ik)** in cardiomyocytes. - Blocking potassium efflux prolongs repolarization, which is reflected as a **prolonged action potential duration (APD)** and a lengthened **QT interval** on the electrocardiogram. *Decreased conduction velocity* - This effect is primarily associated with **Class I antiarrhythmic drugs** (e.g., flecainide, procainamide) which block **sodium channels**, thereby slowing the depolarization (Phase 0) and subsequent conduction velocity. - **Dofetilide**, a Class III agent, does not directly impact sodium channels or significantly decrease conduction velocity. *Decreased calcium current* - A decreased calcium current (Phase 2) is characteristic of **Class IV antiarrhythmic drugs** (**calcium channel blockers** like verapamil and diltiazem). - These drugs primarily act on nodal tissue to slow AV nodal conduction and heart rate, which is not the primary mechanism of action for **dofetilide**. *Decreased slope of phase 0* - The slope of **Phase 0 (depolarization)** is determined by the rapid influx of **sodium ions** into the cell. - A decreased slope of Phase 0 would be expected with **Class I antiarrhythmic drugs** (sodium channel blockers), not with **dofetilide**, which targets potassium channels. *Decreased slope of phase 4* - The slope of **Phase 4 (spontaneous depolarization)** in pacemaker cells is primarily influenced by the "funny current" (If) and calcium currents. - A decreased slope of Phase 4 is characteristic of **beta-blockers** (Class II antiarrhythmics) or **calcium channel blockers** that reduce the rate of spontaneous depolarization in nodal cells, thereby lowering heart rate. **Dofetilide** does not have this primary effect.

Question 392: A 57-year-old man calls his primary care physician to discuss the results of his annual laboratory exams. The results show that he has dramatically decreased levels of high-density lipoprotein (HDL) and mildly increased levels of low-density lipoprotein (LDL). The physician says that the HDL levels are of primary concern so he is started on the lipid level modifying drug that most effectively increases serum HDL levels. Which of the following is the most likely a side effect of this medication that the patient should be informed about?

• A. Hepatotoxicity
• B. Gallstones
• C. Flushing (Correct Answer)
• D. Malabsorption
• E. Myalgia

Explanation: ***Flushing*** - The medication that most effectively increases HDL levels is **niacin (vitamin B3)**. - A common and well-known side effect of niacin, especially at therapeutic doses, is **cutaneous flushing**, often accompanied by itching and warmth, due to prostaglandin release. *Hepatotoxicity* - While some lipid-modifying drugs, particularly statins, can cause hepatotoxicity, it is less characteristic of niacin directly affecting the liver. - **Niacin** can cause mild liver enzyme elevations but severe hepatotoxicity is rare with standard doses and monitoring. *Gallstones* - **Fibrates** (e.g., gemfibrozil, fenofibrate) are known to increase the risk of gallstone formation by increasing cholesterol excretion into bile. - Fibrates primarily lower triglycerides and can moderately increase HDL, but are not the *most effective* for significantly raising HDL. *Malabsorption* - **Bile acid sequestrants** (e.g., cholestyramine, colestipol) can cause malabsorption of fat-soluble vitamins and other drugs. - These drugs primarily lower LDL and have minimal effects on HDL levels. *Myalgia* - **Statins** (HMG-CoA reductase inhibitors) are well-known to cause muscle-related side effects, including myalgia, myopathy, and in severe cases, rhabdomyolysis. - Statins primarily lower LDL, and their effect on HDL is generally modest.

Question 393: A 53-year-old male presents to his primary care provider for tremor of his right hand. The patient reports that the shaking started a few months ago in his right hand but that he worries about developing it in his left hand as well. He reports that the shaking is worse when he is sitting still or watching television and improves as he goes about his daily activities. The patient has a past medical history of hypertension, hyperlipidemia, and diabetes mellitus, and his home medications are hydrochlorothiazide, lisinopril, and atorvastatin. He works as an accountant and drinks 1-2 beers per week. He has a 15-pack-year smoking history but quit ten years ago. On physical exam, the patient has bilateral hand tremors with a frequency of 4-5 Hz. The tremor improves on finger-to-nose testing. His upper extremities also display a mild resistance to passive movement, and he has 2+ reflexes throughout. He has no gait abnormalities, and he scores 29/30 on the Mini-Mental State Examination (MMSE). This patient should be started on which of the following classes of medications?

• A. Acetylcholinesterase inhibitor
• B. Sodium channel antagonist
• C. Anticholinergic (Correct Answer)
• D. Beta-blocker
• E. GABA receptor modulator

Explanation: ***Anticholinergic*** - The patient exhibits classic signs of **Parkinson's disease**, including a **resting tremor** (improves with activity, worse at rest), **bradykinesia** (mild resistance to passive movement), and a tremor frequency of **4-5 Hz**. - **Note on current practice**: While **dopaminergic agents (levodopa/carbidopa or dopamine agonists)** are the **preferred first-line treatment** for Parkinson's disease, they are not among the options listed. Among the available choices, **anticholinergics** like **benztropine** or **trihexyphenidyl** can be used for **tremor-predominant Parkinson's disease**, particularly in **younger patients** where tremor control is the primary goal. - **Anticholinergics** block muscarinic acetylcholine receptors, reducing the cholinergic overdrive associated with dopamine deficiency. However, they are now **used less frequently** due to adverse effects (cognitive impairment, dry mouth, urinary retention, constipation), especially in older adults. *Acetylcholinesterase inhibitor* - **Acetylcholinesterase inhibitors** (e.g., donepezil, rivastigmine) are used to treat **Alzheimer's disease** and other dementias by increasing acetylcholine levels. - They are **not indicated for Parkinson's disease tremor** and would likely **worsen motor symptoms** by further increasing cholinergic activity, which is already relatively excessive due to dopamine deficiency. *Sodium channel antagonist* - **Sodium channel antagonists** such as **carbamazepine** or **lamotrigine** are typically used as **antiepileptics** or for **mood stabilization** and neuropathic pain. - They are **not indicated for Parkinsonian tremor** and do not address the underlying dopaminergic deficiency in Parkinson's disease. *Beta-blocker* - **Beta-blockers** such as **propranolol** are the **first-line treatment for essential tremor**, which presents as an **action/postural tremor** that worsens with movement and goal-directed activity. - This patient's tremor is a **resting tremor** that **improves with activity**, which is characteristic of **Parkinson's disease, not essential tremor**. Beta-blockers would not be effective for resting tremor. *GABA receptor modulator* - **GABA receptor modulators** such as **benzodiazepines** (e.g., clonazepam) or **barbiturates** may be used for **essential tremor** as second-line agents or for **anxiety-induced tremor**. - They are **not a primary treatment for Parkinson's disease tremor** and do not address the underlying dopaminergic pathophysiology. Additionally, they carry risks of sedation, dependence, and cognitive impairment.

Question 394: A 52-year-old man with a history of hypertension and hyperlipidemia comes to the physician because of a 10-month history of substernal chest pain on exertion that is relieved with rest. His pulse is 82/min and blood pressure is 145/82 mm Hg. He is prescribed a drug that acts by forming free radical nitric oxide. The patient is most likely to experience which of the following adverse effects as a result of this drug?

• A. Pulsating headaches (Correct Answer)
• B. Erectile dysfunction
• C. Hypertensive urgency
• D. Lower extremity edema
• E. Nonproductive cough

Explanation: ***Pulsating headaches*** - The drug described is likely **nitroglycerin** or another **nitrate**, which acts by releasing **nitric oxide (NO)** to cause **vasodilation**. - **Vasodilation** in the cerebral vasculature is a common side effect of nitrates and can lead to **pulsating headaches**. *Erectile dysfunction* - **Erectile dysfunction** is not a direct adverse effect of nitrates; in fact, nitrates can be used to treat it, though their use with PDE5 inhibitors is contraindicated. - This condition is more commonly associated with the underlying cardiovascular disease rather than the medication used to treat angina. *Hypertensive urgency* - **Nitrates** cause **vasodilation** and typically **lower blood pressure**, making **hypotension** (not hypertension) a potential side effect. - **Hypertensive urgency** would indicate a sudden, severe elevation in blood pressure, which is antithetical to the drug's mechanism of action. *Lower extremity edema* - **Lower extremity edema** is generally not a direct side effect of nitrates; it is more commonly associated with conditions like **heart failure**, certain **calcium channel blockers**, or **venous insufficiency**. - While vasodilation can sometimes lead to fluid shifts, edema is not a prominent or expected adverse effect of this class of drugs. *Nonproductive cough* - A **nonproductive cough** is a common side effect of **ACE inhibitors** (e.g., lisinopril), which act on the **renin-angiotensin-aldosterone system**. - This symptom is not associated with **nitrates** because their mechanism of action is primarily through nitric oxide-mediated vasodilation, unrelated to the respiratory irritation seen with ACE inhibitors.

Question 395: A 68-year-old male with a history of congestive heart failure presents to his cardiologist complaining of mild dyspnea on exertion and swollen ankles. His past medical history is also significant for hypertension and alcohol abuse. He has a 50 pack-year smoking history. He currently takes lisinopril, aspirin, and metoprolol. His temperature is 99°F (37.2°C), blood pressure is 135/85 mmHg, pulse is 85/min, and respirations are 18/min. An echocardiogram reveals an ejection fraction of 35%. His cardiologist adds an additional medication to the patient’s regimen. Two weeks later, the patient notices yellow halos in his vision. Which of the following medications did this patient most likely start taking?

• A. Dobutamine
• B. Nitroprusside
• C. Hydralazine
• D. Digoxin (Correct Answer)
• E. Furosemide

Explanation: ***Digoxin*** - The patient's symptoms (dyspnea on exertion, swollen ankles, reduced ejection fraction) indicate **heart failure**. **Digoxin** is a cardiac glycoside used to improve cardiac output in heart failure. - **Yellow halos in vision** are a classic symptom of **digoxin toxicity**, which can occur if drug levels become too high. *Dobutamine* - **Dobutamine** is a **beta-1 adrenergic agonist** used as an inotrope in acute decompensated heart failure to improve cardiac contractility. - It is typically administered intravenously for short-term management and is not associated with yellow halos in vision. *Nitroprusside* - **Nitroprusside** is a potent **vasodilator** used for hypertensive emergencies and in some cases of acute decompensated heart failure to reduce preload and afterload. - It is also administered intravenously and is not associated with the visual disturbances described. *Hydralazine* - **Hydralazine** is a direct **arterial vasodilator** used to reduce afterload in heart failure, often in combination with nitrates. It can cause reflex tachycardia. - While used in chronic heart failure, it does not typically cause visual changes such as yellow halos. *Furosemide* - **Furosemide** is a **loop diuretic** used to reduce fluid overload in heart failure, alleviating symptoms like edema and dyspnea. - While it can cause ototoxicity at high doses or in renal impairment, it does not cause yellow halos in vision.

Question 396: A previously healthy 36-year-old woman comes to the emergency department because of a progressively worsening headache for 5 days. She vomited twice after waking up this morning. She does not smoke or drink alcohol. She is sexually active with one male partner and uses an oral contraceptive. Her temperature is 37.5°C (99.5°F), pulse is 105/min, and blood pressure is 125/80 mm Hg. Examination shows tearing of the right eye. The pupils are equal and reactive to light; right lateral gaze is limited. Fundoscopic examination shows bilateral optic disc swelling. The remainder of the examination shows no abnormalities. An MR venography of the head shows a heterogeneous intensity in the left lateral sinus. Which of the following is the most appropriate next step in management?

• A. Administer dalteparin (Correct Answer)
• B. Analyze cerebrospinal fluid
• C. Administer intravenous antibiotics
• D. Perform endovascular thrombolysis
• E. Measure D-dimer levels

Explanation: **Administer dalteparin** - The patient presents with classic signs and symptoms of **cerebral venous sinus thrombosis (CVST)**: worsening headache, vomiting, papilledema (optic disc swelling), and a risk factor (oral contraceptive use). The MR venography confirms a heterogeneous intensity in the left lateral sinus, consistent with a thrombus. **Anticoagulation with unfractionated or low molecular weight heparin (such as dalteparin)** is the first-line treatment to prevent clot propagation and recanalize the occluded sinus. - **Dalteparin** is a **low molecular weight heparin (LMWH)**, which is preferred over unfractionated heparin in many situations due to its predictable anticoagulant response and lower risk of heparin-induced thrombocytopenia. Prompt anticoagulation is crucial in preventing further neurological deficits and reducing morbidity. *Analyze cerebrospinal fluid* - While a **lumbar puncture** might show elevated opening pressure in CVST, it is **contraindicated prior to imaging** to exclude mass effect or obtundation, and in this case, imaging has already confirmed a thrombus. - CSF analysis is generally not the initial diagnostic or management priority in suspected CVST, especially when imaging has identified the thrombus. *Administer intravenous antibiotics* - The patient's symptoms are not suggestive of an **infectious etiology** like meningitis or encephalitis; despite a low-grade fever, there are no other clear signs of infection. - Administering antibiotics without a strong indication for infection would be inappropriate and delay the necessary treatment for the confirmed **thrombosis**. *Perform endovascular thrombolysis* - **Endovascular thrombolysis** is a more invasive procedure generally reserved for patients who **fail to improve with anticoagulation** or have severe neurological deficits that are rapidly progressing despite adequate medical management. - It carries higher risks compared to systemic anticoagulation and is not the first-line treatment for CVST. *Measure D-dimer levels* - While **elevated D-dimer levels** can indicate an active thrombotic process, they are **non-specific** and can be elevated in various conditions. - D-dimer testing would not provide additional diagnostic information beyond what the MR venography has already confirmed and would not guide immediate management.

Question 397: A 48-year-old man presents to the emergency department with complaints of substernal chest pain for the past 1 hour. The pain is crushing in nature and radiates to his neck and left arm. He rates the pain as 7/10. He gives a history of similar episodes in the past that resolved with rest. He is a non-smoker and drinks alcohol occasionally. On physical examination, the temperature is 37.0°C (98.6°F), the pulse rate is 130/min and irregular, the blood pressure is 148/92 mm Hg, and the respiratory rate is 18/min. The physician immediately orders an electrocardiogram, the findings of which are consistent with an acute Q-wave myocardial infarction (MI). After appropriate emergency management, he is admitted to the medical floor. He develops atrial fibrillation on the second day of admission. He is given a β-adrenergic blocking agent for the arrhythmia. On discharge, he is advised to continue the medication for at least 2 years. Which of the following β-adrenergic blocking agents was most likely prescribed to this patient?

• A. Atenolol (Correct Answer)
• B. Penbutolol
• C. Acebutolol
• D. Pindolol
• E. Celiprolol

Explanation: ***Atenolol*** - **Atenolol** is a **cardioselective β1-blocker** that is commonly prescribed for atrial fibrillation, especially post-MI, due to its efficacy in reducing heart rate and improving survival. - It lacks **intrinsic sympathomimetic activity (ISA)**, which is crucial for the post-MI setting to ensure adequate beta-blockade and prevent adverse cardiac events. *Penbutolol* - **Penbutolol** is a **non-selective β-blocker** with **intrinsic sympathomimetic activity (ISA)**. - Beta-blockers with ISA are generally **contraindicated or not preferred** in post-MI patients because their partial agonist activity might negate the protective effects of beta-blockade on myocardial oxygen demand and arrhythmogenesis. *Acebutolol* - **Acebutolol** is a **cardioselective β1-blocker** with **intrinsic sympathomimetic activity (ISA)**. - Like other beta-blockers with ISA, acebutolol is **not typically recommended** for long-term use after myocardial infarction due to concerns about reduced cardioprotective benefits. *Pindolol* - **Pindolol** is a **non-selective β-blocker** with **intrinsic sympathomimetic activity (ISA)**. - Its partial agonist activity can lead to **less reduction in heart rate and myocardial contractility** compared to beta-blockers without ISA, making it an unsuitable choice for post-MI management. *Celiprolol* - **Celiprolol** is a **cardioselective β1-blocker** that also has **β2-agonist properties** and **intrinsic sympathomimetic activity (ISA)**. - Its β2-agonist and ISA effects make it **less desirable post-MI** as it may not provide the full cardioprotective benefits of a pure β-blocker.

Question 398: A 73-year-old woman recently diagnosed with colonic adenocarcinoma comes to the physician because of a 1-week history of nausea and multiple episodes of vomiting. These symptoms started shortly after her first infusion of oxaliplatin and fluorouracil. The patient is started on an appropriate medication. Three weeks later, at a follow-up appointment, she states that she has developed headaches and constipation. The patient was most likely treated with a drug with which of the following mechanisms of action?

• A. 5-HT3 receptor antagonist (Correct Answer)
• B. H1 receptor antagonist
• C. NK1 receptor antagonist
• D. Cannabinoid receptor agonist
• E. M2 receptor antagonist

Explanation: ***5-HT3 receptor antagonist*** - The patient's symptoms of nausea and vomiting after **oxaliplatin and fluorouracil** chemotherapy are consistent with **chemotherapy-induced nausea and vomiting (CINV)**. - **5-HT3 receptor antagonists** (e.g., ondansetron) are the primary treatment for CINV, and their common side effects include **headache and constipation**. *H1 receptor antagonist* - **H1 receptor antagonists** (e.g., diphenhydramine) can be used as antiemetics, but they are generally less effective for severe CINV and are associated with side effects such as **sedation and anticholinergic effects** (e.g., dry mouth), not typically headache and constipation as the primary concern. - They work by blocking histamine-1 receptors in the **vomiting center**, but their efficacy in CINV is limited compared to 5-HT3 antagonists. *NK1 receptor antagonist* - **NK1 receptor antagonists** (e.g., aprepitant) are often used in combination with 5-HT3 antagonists and corticosteroids for highly emetogenic chemotherapy. - While effective, their common side effect profile does not typically highlight **headache and constipation** as prominently as 5-HT3 antagonists do, and they are usually not chosen as a monotherapy first-line for moderate CINV. *Cannabinoid receptor agonist* - **Cannabinoid receptor agonists** (e.g., dronabinol) are used for CINV, especially in patients who do not respond to other antiemetics, and also to stimulate appetite. - Their common side effects include **dizziness, euphoria, dysphoria**, and **hypotension**, but not typically headache and constipation as the most prominent adverse effects. *M2 receptor antagonist* - **M2 receptor antagonists** target muscarinic acetylcholine receptors, and while some anticholinergics might have antiemetic properties, using an M2-specific antagonist as a primary antiemetic for CINV is not standard practice. - There are no commonly used antiemetics for CINV that specifically act as **M2 receptor antagonists**, and this class of drugs is more relevant in contexts such as heart rate regulation.

Question 399: Two hours after undergoing elective cholecystectomy with general anesthesia, a 41-year-old woman is evaluated for decreased mental status. BMI is 36.6 kg/m2. Respirations are 18/min and blood pressure is 126/73 mm Hg. Physical examination shows the endotracheal tube in normal position. She does not respond to sternal rub and gag reflex is absent. Arterial blood gas analysis on room air shows normal PO2 and PCO2 levels. Which of the following anesthetic properties is the most likely cause of these findings?

• A. Low blood solubility
• B. High lipid solubility (Correct Answer)
• C. Low brain-blood partition coefficient
• D. High minimal alveolar concentration
• E. Low cytochrome P450 activity

Explanation: ***High lipid solubility*** - Anesthetics with **high lipid solubility** accumulate in **adipose tissue** and are slowly released, prolonging their effect, especially in obese patients. - The patient's **obesity (BMI 36.6 kg/m2)** contributes to a larger reservoir for lipid-soluble drugs, leading to delayed recovery and decreased mental status. *Low blood solubility* - **Low blood solubility** implies a rapid equilibrium between the lungs and the blood, leading to a **faster onset and offset** of anesthetic action. - This property would result in a quicker recovery from anesthesia, which contradicts the patient's prolonged unconsciousness. *Low brain-blood partition coefficient* - A **low brain-blood partition coefficient** means the anesthetic does not accumulate significantly in brain tissue relative to blood. - Agents with this property equilibrate quickly and leave the brain rapidly upon discontinuation, resulting in **fast recovery**, which is inconsistent with the patient's persistent decreased mental status. *High minimal alveolar concentration* - **High minimal alveolar concentration (MAC)** means that a higher concentration of the anesthetic gas is required to produce immobility in 50% of patients. - A high MAC describes the **potency** of an anesthetic and does not directly explain prolonged recovery or decreased mental status in an obese patient, but rather indicates that a larger dose or concentration was needed to achieve anesthesia. *Low cytochrome P450 activity* - **Low cytochrome P450 activity** would lead to slower metabolism of drugs that are primarily cleared by this system, potentially prolonging their effects. - While relevant for some drugs, the primary issue for inhaled anesthetics is their **physical distribution and elimination**, not typically metabolic clearance via Cytochrome P450 enzymes.

Question 400: A 56-year-old man with type 2 diabetes mellitus comes to the physician for a follow-up examination. Three months ago, the patient was started on metformin therapy after counseling on diet, exercise, and weight reduction failed to reduce his hyperglycemia. Physical examination shows no abnormalities. His hemoglobin A1c is 8.4%. Pioglitazone is added to the patient's medication regimen. Which of the following cellular changes is most likely to occur in response to this new drug?

• A. Depolarization of pancreatic β-cells
• B. Decreased sodium-dependent glucose cotransport
• C. Decreased breakdown of glucagon-like peptide 1
• D. Increased transcription of adipokines (Correct Answer)
• E. Autophosphorylation of receptor tyrosine kinase

Explanation: ***Increased transcription of adipokines*** - **Pioglitazone** is a **thiazolidinedione (TZD)** that acts as an **agonist for peroxisome proliferator-activated receptor-gamma (PPAR-γ)**. - Activation of PPAR-γ in adipocytes leads to increased transcription of genes involved in **glucose uptake and lipid metabolism**, including certain **adipokines** that improve insulin sensitivity. *Depolarization of pancreatic β-cells* - This is the mechanism of **sulfonylureas** (e.g., glipizide, glyburide) or **meglitinides** (e.g., repaglinide, nateglinide), which stimulate insulin release by closing K+ channels and depolarizing β-cells. - Pioglitazone does not directly stimulate insulin secretion from β-cells. *Decreased sodium-dependent glucose cotransport* - This is the mechanism of **SGLT2 inhibitors** (e.g., empagliflozin, canagliflozin, dapagliflozin), which reduce glucose reabsorption in the renal tubules. - Pioglitazone primarily acts by sensitizing peripheral tissues to insulin. *Decreased breakdown of glucagon-like peptide 1* - This is the mechanism of **DPP-4 inhibitors** (e.g., sitagliptin, saxagliptin), which prevent the degradation of GLP-1, thereby increasing its levels and effect. - Pioglitazone does not directly affect GLP-1 metabolism. *Autophosphorylation of receptor tyrosine kinase* - This is the initial step in the **insulin signaling pathway** when insulin binds to its receptor. - While pioglitazone improves insulin sensitivity, it does not directly cause autophosphorylation of the insulin receptor itself; rather, it upregulates pathways downstream or parallel to it that enhance insulin's effects.

Question 401: A 19-year-old male college student is brought to the emergency department by his girlfriend complaining of intense pain. They had been playing outside in the snow when the patient started to have severe hand and feet pain. He says the pain is 9 out of 10 and causing him to have trouble moving his fingers and toes. He also reports some difficulty “catching his breath.” He notes that he has been tiring easily for the past month but thought it was because he was studying and going out late. On physical examination, the patient appears uncomfortable. Bilateral conjunctivae are pale. His hands are swollen and tender to palpation. Cardiopulmonary examination is normal. Hemoglobin is 9.0 g/dL. An electrocardiogram shows mild sinus tachycardia. Hemoglobin electrophoresis is performed, which confirms sickle cell disease. The patient’s pain is managed, and he is discharged on hydroxyurea. Which of the following is the most likely to occur as a result of the new medication?

• A. Increase in hemoglobin with higher oxygen affinity
• B. Decrease in hemoglobin with higher oxygen affinity
• C. Increase in hemoglobin A
• D. Decrease in hemoglobin A
• E. Increase in fetal hemoglobin (Correct Answer)

Explanation: ***Increase in fetal hemoglobin*** - **Hydroxyurea** stimulates the production of **fetal hemoglobin (HbF)**, which reduces the polymerization of **hemoglobin S (HbS)** and sickling of red blood cells. - Increased HbF improves red blood cell survival and reduces the frequency of **vaso-occlusive crises** and other complications in **sickle cell disease**. *Increase in hemoglobin with higher oxygen affinity* - This option is too vague and does not describe the specific mechanism of hydroxyurea. - While **HbF** does have higher oxygen affinity than **HbA**, the therapeutic benefit comes specifically from **increasing HbF**, not from a general increase in hemoglobin with higher oxygen affinity. - The key mechanism is **HbF preventing sickling**, not simply having higher oxygen affinity. *Decrease in hemoglobin with higher oxygen affinity* - Hydroxyurea aims to *increase* functional hemoglobin and reduce anemia, not decrease it. - A *decrease* in total hemoglobin would be detrimental and is not a therapeutic effect of hydroxyurea. *Increase in hemoglobin A* - Patients with **sickle cell disease** produce little to no **hemoglobin A (HbA)**, as their beta-globin genes produce **hemoglobin S (HbS)**. - Hydroxyurea does not induce the production of **HbA**; its mechanism of action is through the upregulation of **HbF**. *Decrease in hemoglobin A* - Since patients with **sickle cell disease** already have an absence or very low levels of **hemoglobin A (HbA)**, a further decrease is not a relevant therapeutic effect. - Hydroxyurea's action is to increase **fetal hemoglobin (HbF)**, which acts as a protective factor against sickling.

Question 402: A 38-year-old male is brought to the emergency department by ambulance after a motor vehicle collision. He is found to have a broken femur and multiple soft tissue injuries and is admitted to the hospital. During the hospital course, he is found to have lower extremity swelling, redness, and pain, so he is given an infusion of a medication. The intravenous medication is discontinued in favor of an oral medication in preparation for discharge; however, the patient leaves against medical advice prior to receiving the full set of instructions. The next day, the patient is found to have black lesions on his trunk and his leg. The protein involved in this patient's underlying abnormality most likely affects the function of which of the following factors?

• A. Factor II only
• B. Factors II, VII, IX, and X
• C. Factors II and X
• D. Factors V and VIII (Correct Answer)
• E. Factor V only

Explanation: ***Factors V and VIII*** - The patient's initial presentation of **lower extremity swelling, redness, and pain** after trauma and immobilization is highly suggestive of **deep vein thrombosis (DVT)**, for which he received IV anticoagulation. The subsequent development of **black lesions on his trunk and leg** after switching to an oral anticoagulant and leaving against medical advice points to **warfarin-induced skin necrosis (WISN)**. - **Warfarin-induced skin necrosis** develops in patients with a congenital deficiency of **protein C** or, less commonly, **protein S**. Protein C, in its activated form (APC), functions to inactivate **Factor V (Va)** and **Factor VIII (VIIIa)**, which are crucial cofactors in the coagulation cascade. A deficiency means these factors remain active, leading to a **procoagulant state**. *Factor II only* - **Factor II (prothrombin)** is inactivated by protein C, but a deficiency in protein C primarily affects the inactivation of **Factors V and VIII**, which are the specific targets of activated protein C. - While factor II is part of the coagulation cascade, its regulation is not the primary mechanism by which protein C deficiency leads to the hypercoagulable state seen in WISN. *Factors II, VII, IX, and X* - These factors are **vitamin K-dependent coagulation factors**, which are inhibited by warfarin. While a deficiency in protein C can lead to an initial hypercoagulable state when warfarin is started (due to the faster drop in protein C levels compared to these factors), the primary function of protein C is to inactivate **Factors V and VIII**. - The problem described is a **protein C deficiency**, which specifically impacts the inactivation of factors V and VIII, not directly these other vitamin K-dependent factors. *Factors II and X* - Similar to Factor II only, these are **vitamin K-dependent factors** inhibited by warfarin. The core issue in warfarin-induced skin necrosis is a deficiency in protein C, which normally inactivates **Factors V and VIII**, leading to a transient prothrombotic state. - While Factor X is affected by warfarin, the direct regulatory role of protein C is predominantly on factors V and VIII. *Factor V only* - While **Factor V** is indeed a target of activated protein C inactivation, **Factor VIII** is also a critical target. Inactivating both **Factor V** and **Factor VIII** is essential for effective anticoagulation by protein C. - A deficiency in protein C affects both of these crucial cofactors, making the combined option more accurate.

Question 403: A 61-year-old woman comes to the physician because of a 6-month history of left knee pain and stiffness. Examination of the left knee shows tenderness to palpation along the joint line; there is crepitus with full flexion and extension. An x-ray of the knee shows osteophytes with joint-space narrowing. Arthrocentesis of the knee joint yields clear fluid with a leukocyte count of 120/mm3. Treatment with ibuprofen during the next week significantly improves her condition. The beneficial effect of this drug is most likely due to inhibition of which of the following?

• A. Conversion of hypoxanthine to urate
• B. Conversion of phospholipids to arachidonic acid
• C. Conversion of prostaglandin H2 to thromboxane A2
• D. Conversion of arachidonic acid to prostaglandin G2 (Correct Answer)
• E. Conversion of dihydroorotate to orotate

Explanation: ***Conversion of arachidonic acid to prostaglandin G2*** - This patient presents with symptoms and signs consistent with **osteoarthritis**, characterized by joint pain, stiffness, crepitus, and radiographic findings like **osteophytes** and **joint-space narrowing**. - **Ibuprofen is a non-selective NSAID** that inhibits **cyclooxygenase (COX-1 and COX-2) enzymes**, which catalyze the conversion of **arachidonic acid to prostaglandin G2 (PGG2)**, the first committed step in prostaglandin synthesis. - By blocking prostaglandin production, ibuprofen reduces inflammation and pain associated with osteoarthritis. *Conversion of hypoxanthine to urate* - This process is catalyzed by **xanthine oxidase** and is inhibited by medications like **allopurinol**, used in the treatment of **gout** to reduce uric acid levels. - Gout typically presents with acute, severe joint pain with signs of inflammation and monosodium urate crystals on joint aspiration, which are not characteristic of this patient's presentation. *Conversion of phospholipids to arachidonic acid* - This step is catalyzed by **phospholipase A2**, which is inhibited by **glucocorticoids** (via lipocortin induction). - While glucocorticoids have potent anti-inflammatory effects by working upstream of the arachidonic acid cascade, ibuprofen has a different mechanism targeting the COX enzymes downstream. *Conversion of prostaglandin H2 to thromboxane A2* - This reaction is catalyzed by **thromboxane synthase**, primarily important in platelet aggregation and vasoconstriction. - NSAIDs like ibuprofen do not specifically inhibit thromboxane synthase; rather, they inhibit COX enzymes upstream, which reduces production of both prostaglandins and thromboxanes. - Low-dose aspirin preferentially inhibits COX-1 in platelets, reducing thromboxane A2 for cardioprotection, but this is not ibuprofen's primary therapeutic mechanism in osteoarthritis. *Conversion of dihydroorotate to orotate* - This is a step in **pyrimidine synthesis**, inhibited by **leflunomide**, a disease-modifying antirheumatic drug (DMARD) used in rheumatoid arthritis. - This mechanism is unrelated to the action of NSAIDs or the treatment of osteoarthritis.

Question 404: A 31-year-old female receives a kidney transplant for autosomal dominant polycystic kidney disease (ADPKD). Three weeks later, the patient experiences acute, T-cell mediated rejection of the allograft and is given sirolimus. Which of the following are side effects of this medication?

• A. Nephrotoxicity, hypertension
• B. Hyperlipidemia, thrombocytopenia (Correct Answer)
• C. Nephrotoxicity, gingival hyperplasia
• D. Pancreatitis
• E. Cytokine release syndrome, hypersensitivity reaction

Explanation: ***Hyperlipidemia, thrombocytopenia*** - **Sirolimus** (rapamycin) is an **mTOR inhibitor** commonly used in transplant immunology, which frequently causes **hyperlipidemia** (elevated cholesterol and triglycerides) and **thrombocytopenia** (low platelet count). - Other common side effects include **myelosuppression** (leukopenia, anemia), **mouth ulcers**, and **impaired wound healing**. *Nephrotoxicity, hypertension* - **Nephrotoxicity** and **hypertension** are more characteristic side effects of **calcineurin inhibitors** like **tacrolimus** and **cyclosporine**, which are also used in transplant immunosuppression but have a different mechanism of action than sirolimus. - While sirolimus can indirectly affect kidney function, it is generally considered less nephrotoxic than calcineurin inhibitors. *Nephrotoxicity, gingival hyperplasia* - **Gingival hyperplasia** is a hallmark side effect of **cyclosporine**, a calcineurin inhibitor, along with **hirsutism** and **nephrotoxicity**. - Sirolimus does not typically cause gingival hyperplasia. *Pancreatitis* - While some immunosuppressants can rarely cause pancreatitis, it is not a common or characteristic side effect of **sirolimus**. - **Azathioprine** is more frequently associated with pancreatitis among immunosuppressive agents. *Cytokine release syndrome, hypersensitivity reaction* - **Cytokine release syndrome** and acute **hypersensitivity reactions** are more often associated with **monoclonal antibodies** (e.g., **basiliximab**, **daclizumab**) used for induction therapy or treatment of acute rejection, particularly within hours or days of administration. - Sirolimus is less likely to cause these immediate severe reactions.

Question 405: A 29-year-old woman presents to the primary care office for a recent history of falls. She has fallen 5 times over the last year. These falls are not associated with any preceding symptoms; she specifically denies dizziness, lightheadedness, or visual changes. However, she has started noticing that both of her legs feel weak. She's also noticed that her carpet feels strange beneath her bare feet. Her mother and grandmother have a history of similar problems. On physical exam, she has notable leg and foot muscular atrophy and 4/5 strength throughout her bilateral lower extremities. Sensation to light touch and pinprick is decreased up to the mid-calf. Ankle jerk reflex is absent bilaterally. Which of the following is the next best diagnostic test for this patient?

• A. MRI brain
• B. Ankle-brachial index
• C. Electromyography (including nerve conduction studies) (Correct Answer)
• D. Lumbar puncture
• E. Hemoglobin A1c

Explanation: ***Electromyography (including nerve conduction studies)*** - The patient's symptoms of **progressive weakness**, **sensory deficits** (carpet feels strange, decreased sensation up to mid-calf), **muscular atrophy**, and **absent ankle reflexes**, along with a **family history**, are highly suggestive of a **hereditary peripheral neuropathy** (e.g., Charcot-Marie-Tooth disease). - **Electromyography (EMG)** and **nerve conduction studies (NCS)** are essential for confirming peripheral neuropathy, differentiating between demyelinating and axonal involvement, and localizing the lesion. *MRI brain* - An MRI brain would be indicated for central nervous system pathology, but the patient's symptoms (distal weakness, sensory loss with a "stocking-glove" distribution, absent reflexes) are highly suggestive of a **peripheral neuropathy**. - There is no indication of upper motor neuron signs or other CNS involvement to warrant a brain MRI at this stage. *Ankle-brachial index* - Ankle-brachial index (ABI) is used to diagnose **peripheral artery disease (PAD)**, which typically presents with claudication (pain with exertion) and ischemic changes. - The patient's symptoms of sensory changes and progressive weakness are not characteristic of PAD. *Lumbar puncture* - A lumbar puncture is primarily used to analyze **cerebrospinal fluid (CSF)** for inflammatory, infectious, or neoplastic conditions affecting the CNS or nerve roots (e.g., Guillain-Barré syndrome, which has acute onset). - Given the chronic and progressive nature of her symptoms and a positive family history, it is less likely to be an acute inflammatory process of the nerve roots. *Hemoglobin A1c* - Hemoglobin A1c is used to screen for or monitor **diabetes mellitus**, which can cause a **diabetic neuropathy**. - While diabetes can cause peripheral neuropathy, the patient's young age, lack of typical diabetic risk factors, and strong family history point more strongly towards a hereditary condition. Glycemic control does not fully explain her presentation.

Question 406: A 3-year-old boy is brought in by his parents to the emergency department for lethargy and vomiting. The patient was fine until this afternoon, when his parents found him in the garage with an unlabeled open bottle containing an odorless liquid. On exam, the patient is not alert or oriented, but is responsive to touch and pain. The patient is afebrile and pulse is 90/min, blood pressure is 100/60 mmHg, and respirations are 20/min. Which of the following is an antidote for the most likely cause of this patient’s presentation?

• A. Glucagon
• B. Epinephrine
• C. Fomepizole (Correct Answer)
• D. Succimer
• E. Sodium bicarbonate

Explanation: ***Fomepizole*** - The patient's presentation with **lethargy**, **vomiting**, and altered mental status after unsupervised access to an **unlabeled, odorless liquid** highly suggests **toxic alcohol ingestion** (e.g., ethylene glycol or methanol). - **Fomepizole** is a competitive inhibitor of **alcohol dehydrogenase**, preventing the metabolism of toxic alcohols into their highly toxic acid metabolites (oxalic acid, formic acid), thus reducing organ damage. *Glucagon* - **Glucagon** is primarily used to treat severe **hypoglycemia**, especially in patients who cannot tolerate oral glucose or if intravenous access is difficult. - It is also indicated in the management of **beta-blocker overdose** to bypass beta-adrenergic receptors and increase cardiac contractility. *Epinephrine* - **Epinephrine** is a potent **vasopressor** and bronchodilator used in emergencies such as **anaphylaxis**, **cardiac arrest**, and severe asthma exacerbations. - It works by stimulating alpha- and beta-adrenergic receptors, leading to vasoconstriction, increased heart rate, and bronchodilation. *Succimer* - **Succimer** is a **chelating agent** primarily used in the treatment of **lead poisoning** in children with blood lead levels above a certain threshold. - It binds to lead ions, forming a stable complex that can be excreted in the urine. *Sodium bicarbonate* - **Sodium bicarbonate** is used to correct **metabolic acidosis**, which can occur in various conditions, including severe sepsis, diabetic ketoacidosis, and certain poisonings (e.g., salicylates, tricyclic antidepressants). - While toxic alcohol ingestion can cause metabolic acidosis, sodium bicarbonate addresses the acidosis itself, not the underlying toxic alcohol metabolism, for which fomepizole is the specific antidote.

Question 407: A 27-year-old woman was found lying unconscious on the side of the street by her friend. He immediately called the ambulance who were close to this neighborhood. On initial examination, she appears barely able to breathe. Her pupils are pinpoint. The needles she likely used were found on site but the drug she injected was unknown. The first responders were quick to administer a drug which is effectively used in these situations and her symptoms slowly began to reverse. She was taken to the nearest emergency department for further workup. Which of the following best describes the mechanism of action of the drug administered by the first responders?

• A. Alpha 2 receptor agonist
• B. Delta receptor antagonist
• C. Kappa receptor pure agonist
• D. NMDA receptor antagonist
• E. Mu receptor antagonist (Correct Answer)

Explanation: ***Mu receptor antagonist*** - The patient's symptoms (unconsciousness, barely breathing, pinpoint pupils) are classic for **opioid overdose**, which primarily acts on **mu opioid receptors**. - **Naloxone**, an opioid antagonist, is the drug of choice in such emergencies, reversing the effects by blocking opioid binding at the **mu receptor**. *Alpha 2 receptor agonist* - Alpha-2 receptor agonists like **clonidine** are used to treat **hypertension** and **opioid withdrawal symptoms**, not acute overdose. - They cause **sedation** and **reduced sympathetic outflow**, which would worsen the patient's respiratory depression in an overdose. *Delta receptor antagonist* - While delta opioid receptors are involved in pain modulation, **delta receptor antagonists** are not the primary treatment for acute opioid overdose. - Their role in reversing respiratory depression caused by mu-agonist opioids is limited compared to mu-receptor antagonists. *Kappa receptor pure agonist* - Kappa receptor agonists like **butorphanol** or **nalbuphine** can provide **analgesia** but can also cause **respiratory depression** and **sedation**. - Administering a kappa agonist would exacerbate the patient's overdose symptoms rather than reversing them. *NMDA receptor antagonist* - **NMDA receptor antagonists** (e.g., ketamine, phencyclidine) have dissociative anesthetic and analgesic properties. - They are not used to treat opioid overdose; their mechanism of action is unrelated to opioid receptors and their overdose symptoms differ.

Question 408: A 40-year-old man presents to the emergency department with a chief complaint of chest pain for the last 3 hours. His ECG shows normal sinus rhythm with ST-segment elevation in leads II, III, and aVF and reciprocal segment depression in leads V1–V6. On physical examination, cardiac sounds are normal on auscultation. His blood pressure is 92/64 mm Hg and heart rate is 93/min. A tissue plasminogen activator is administered to the patient intravenously within 1 hour of hospital arrival due to a lack of available percutaneous coronary intervention. After 6 hours of therapy, the patient's clinical condition starts to deteriorate. ECG on the monitor shows accelerated idioventricular rhythm, which within a couple of minutes changes to ventricular fibrillation. Before any measures could be started, the patient deteriorates further and must be transferred to the ICU. What is the most likely etiology of the ECG findings in this patient?

• A. Increase in cellular pH
• B. Inhibition of lipid peroxidation
• C. Free radical formation (Correct Answer)
• D. Calcium efflux
• E. Increased production of superoxide dismutase

Explanation: ***Free radical formation*** - **Reperfusion injury**, characterized by **free radical formation**, often involves the generation of **reactive oxygen species** upon the restoration of blood flow to ischemic tissue. - These free radicals cause significant cellular damage, contributing to the deterioration seen in this patient after successful thrombolysis. *Increase in cellular pH* - Ischemic tissue typically experiences a decrease in cellular pH due to the accumulation of **lactic acid** from anaerobic metabolism. - Upon reperfusion, while some buffering occurs, a significant increase in cellular pH *above normal* is not the primary mechanism of reperfusion injury. *Inhibition of lipid peroxidation* - **Lipid peroxidation** is a process by which free radicals attack membrane lipids, leading to cell damage. - Inhibition of lipid peroxidation would *protect* against reperfusion injury, not cause the deterioration observed in this patient. *Calcium efflux* - During ischemia and reperfusion, there is typically an *influx* of **calcium** into cells, leading to **calcium overload** and contributing to cell damage. - **Calcium efflux** (movement out of the cell) would generally be protective or indicates a different pathological process. *Increased production of superoxide dismutase* - **Superoxide dismutase (SOD)** is an important **antioxidant enzyme** that neutralizes superoxide radicals. - Therefore, increased production of SOD would *protect* against free radical damage and reperfusion injury, rather than causing clinical deterioration.

Question 409: A 50-year-old male is brought to the dermatologist's office with complaints of a pigmented lesion. The lesion is uniformly dark with clean borders and no asymmetry and has been increasing in size over the past two weeks. He works in construction and spends large portions of his day outside. The dermatologist believes that this mole should be biopsied. To prepare the patient for the biopsy, the dermatologist injects a small amount of lidocaine into the skin around the lesion. Which of the following nerve functions would be the last to be blocked by the lidocaine?

• A. Pain
• B. Touch
• C. Temperature
• D. Sympathetic stimulation
• E. Pressure (Correct Answer)

Explanation: ***Pressure*** - **Pressure** sensation is mediated by **Aβ fibers**, which are relatively **larger** and **myelinated**, making them more resistant to local anesthetic blockade. - Nerve fibers are blocked in a specific order, typically starting with smaller, unmyelinated fibers and ending with larger, myelinated fibers. *Pain* - **Pain** sensation is primarily carried by **unmyelinated C fibers** and **small myelinated Aδ fibers**, which are among the **first to be blocked** by local anesthetics. - These fibers have a **high surface-to-volume ratio**, making them more susceptible to the action of lidocaine. *Touch* - **Touch** sensation is mediated by a mix of **Aβ and Aδ fibers**; light touch is typically blocked relatively early due to the involvement of smaller fibers. - However, **crude touch** often persists longer than pain and temperature but is usually blocked before pressure. *Temperature* - **Temperature** sensation is primarily carried by **Aδ and C fibers**, making it one of the **earliest sensations to be blocked** by local anesthetic. - These fibers are generally small and have high sensitivity to local anesthetic agents. *Sympathetic stimulation* - **Sympathetic nerve fibers** are typically **small, unmyelinated C fibers** and are generally the **first to be blocked** by local anesthetics. - This early blockade can lead to **vasodilation** in the area due to the loss of sympathetic tone.

Question 410: An investigator is developing a drug that results in contraction of the pupillary dilator muscle when instilled topically. The drug works by increasing neurotransmitter release from the presynaptic nerve terminal. When administered intravenously, this drug is most likely to have which of the following additional effects?

• A. Acceleration of gut peristalsis
• B. Contraction of skeletal muscles
• C. Release of epinephrine by the adrenal medulla
• D. Relaxation of the bladder neck sphincter
• E. Increase in pyloric sphincter tone (Correct Answer)

Explanation: ***Increase in pyloric sphincter tone*** - The drug causes contraction of the **pupillary dilator muscle** by increasing neurotransmitter release from presynaptic terminals, indicating it is an **indirect sympathomimetic** (e.g., amphetamine, tyramine, ephedrine) - These drugs release **norepinephrine** from postganglionic sympathetic nerve terminals - The **pyloric sphincter** contains **α1-adrenergic receptors**, and sympathetic stimulation via norepinephrine causes **increased tone and contraction** - This would result in **increased pyloric sphincter tone**, consistent with generalized sympathetic activation *Relaxation of the bladder neck sphincter* - The **bladder neck sphincter** is under **α1-adrenergic control** - Sympathetic stimulation via α1-receptor activation causes **contraction**, not relaxation - An indirect sympathomimetic releasing norepinephrine would cause **contraction** of the bladder neck sphincter - Relaxation would require α1-blockade or parasympathetic activation, not sympathetic stimulation *Acceleration of gut peristalsis* - **Gut peristalsis** is primarily increased by the **parasympathetic nervous system** - The **sympathetic nervous system** generally **inhibits gut motility** through α- and β-adrenergic receptor activation - An indirect sympathomimetic would cause **decreased peristalsis**, not acceleration *Contraction of skeletal muscles* - **Skeletal muscle contraction** is mediated by **acetylcholine** at the **neuromuscular junction** acting on nicotinic receptors - Sympathetic neurotransmitters (norepinephrine/epinephrine) do not directly cause skeletal muscle contraction - While catecholamines can enhance muscle performance metabolically, they do not trigger contraction *Release of epinephrine by the adrenal medulla* - The **adrenal medulla** is stimulated by **preganglionic sympathetic neurons** that release **acetylcholine** at nicotinic receptors - Indirect sympathomimetics work at **postganglionic** nerve terminals by releasing norepinephrine - Since the drug releases NE from postganglionic terminals (not ACh from preganglionic terminals), it would **not significantly stimulate** the adrenal medulla to release epinephrine

Question 411: A 39-year-old man comes to the physician because of frequent urination for the past 2 months. He has been urinating 10–12 times during the day and 3–4 times during the night. He says he is drinking a lot of water to compensate for any dehydration. He has no history of serious illness and takes no medications. Vital signs are within normal limits. Physical examination shows no abnormalities. He is concerned he may have diabetes mellitus like his parents. Laboratory studies show: Hemoglobin 14.3 g/dL Serum Na+ 149 mEq/L K+ 3.9 mEq/L Cl- 102 mEq/L Glucose 90 mg/dL Osmolality 306 mOsmol/kg H2O Urine Osmolality 210 mOsmol/kg H2O A water deprivation test is conducted. After 2 hours of fluid restriction, his plasma osmolality is 315 mOsmol/kg H2O and his urine osmolality is 210 mOsmol/kg H2O. One hour after an ADH analog injection, his plasma osmolality is 276 mOsmol/kg H2O and his urine osmolality is 425 mOsmol/kg H2O. Which of the following is the most appropriate next step in management?

• A. Hydrochlorothiazide therapy
• B. Fluid restriction
• C. Desmopressin therapy (Correct Answer)
• D. Tolvaptan therapy
• E. Amiloride therapy

Explanation: ***Desmopressin therapy*** - The patient's urine osmolality significantly increased after exogenous **ADH analog (desmopressin)** administration during the water deprivation test, indicating a renal response to ADH. - This response points to **central diabetes insipidus**, where the body does not produce enough ADH, making desmopressin (an ADH analog) the appropriate replacement therapy. *Hydrochlorothiazide therapy* - **Thiazide diuretics** are sometimes used in **nephrogenic diabetes insipidus** (where kidneys don't respond to ADH) to induce a mild volume depletion, increasing proximal tubule reabsorption of water, but they are not the primary treatment for central DI. - The patient's response to exogenous ADH rules out nephrogenic DI as the primary problem. *Fluid restriction* - This patient is already experiencing **polyuria** and **polydipsia**, and fluid restriction would worsen his **hypernatremia** and dehydration without addressing the underlying ADH deficiency. - Fluid restriction is part of the diagnostic **water deprivation test**, not a therapeutic management for diabetes insipidus. *Tolvaptan therapy* - **Tolvaptan** is an **ADH receptor antagonist** used in conditions like **hyponatremia** due to SIADH to promote water excretion, which would be counterproductive in a patient with diabetes insipidus. - It would worsen the patient's condition by further impairing water reabsorption and increasing urine output. *Amiloride therapy* - **Amiloride**, a **potassium-sparing diuretic**, is primarily used for hypertension, heart failure, and to counteract potassium loss from other diuretics. - It has no role in the direct treatment of diabetes insipidus and would not address the ADH deficiency or renal unresponsiveness to ADH.

Question 412: A 36-year-old female presents to her primary care provider for tremor. She reports that she has always had a mild tremor but that she has begun noticing it more since learning to paint. She feels that she has trouble dipping her paintbrush in the paint and making precise strokes on the canvas. She has taken to painting while drinking wine, as she notices that the wine seems to improve her tremor. Her temperature is 97.6°F (36.4°C), blood pressure is 105/61 mmHg, pulse is 58/min, and respirations are 12/min. On exam, she has a high frequency bilateral hand tremor elicited on finger-to-nose testing. Her neurological exam is otherwise unremarkable. The patient is started on a new medication for her symptoms. One week later, she returns with a new complaint of abdominal pain for one day. She reports that she has noticed a darkening of her urine and now has difficulty raising her arms over her head to brush her hair. This patient was most likely treated with which of the following medications?

• A. Clozapine
• B. Propranolol
• C. Alprazolam
• D. Primidone (Correct Answer)
• E. Topiramate

Explanation: ***Correct Option: Primidone*** - The patient's initial presentation of a **high-frequency bilateral hand tremor** that improves with **alcohol consumption** is characteristic of **essential tremor**. - **Primidone** is a first-line treatment for essential tremor and is metabolized to **phenobarbital**, a barbiturate. - **Barbiturates are well-known porphyrinogenic drugs** that can precipitate **acute intermittent porphyria (AIP)**. - The new symptoms one week after starting treatment—**abdominal pain**, **dark urine** (due to porphobilinogen and porphyrins), and **proximal muscle weakness/neuropathy** (difficulty raising arms)—form the classic triad of an **acute porphyric crisis**. - This is a recognized adverse effect of primidone therapy. *Incorrect Option: Propranolol* - Propranolol is a **beta-blocker** and another first-line agent for essential tremor. - However, **propranolol is considered SAFE in porphyria** and is not a porphyrinogenic drug. - Beta-blockers do not precipitate acute porphyric crises. - Side effects of propranolol include bradycardia, bronchospasm, and fatigue, not the symptoms described. *Incorrect Option: Topiramate* - Topiramate is an **anticonvulsant** that can be used off-label for essential tremor, though it is not first-line. - Common side effects include **cognitive impairment**, **paresthesias**, **metabolic acidosis**, and **kidney stones**. - It does not cause acute porphyric crises with dark urine and proximal muscle weakness. *Incorrect Option: Alprazolam* - Alprazolam is a **benzodiazepine** used for anxiety disorders that may transiently reduce tremor due to **anxiolytic effects**. - It is not a primary treatment for essential tremor. - Side effects include sedation and dependence, not porphyric crises. *Incorrect Option: Clozapine* - Clozapine is an **atypical antipsychotic** used for **treatment-resistant schizophrenia**. - It is not indicated for tremor treatment. - Major side effects include **agranulocytosis**, **myocarditis**, and **seizures**, not acute porphyria.

Question 413: A 23-year-old G1P0 woman presents to the emergency department with regular and painful contractions that occur every 3 minutes. She was at home cooking dinner when she experienced a deluge of clear fluid between her legs followed by painful contractions. The patient has a past medical history of obesity. Her pregnancy was not followed by an obstetrician, but she notes that she experienced abdominal pain and headaches frequently towards the end of her pregnancy. Her temperature is 99.5°F (37.5°C), blood pressure is 187/128 mmHg, pulse is 110/min, respirations are 17/min, and oxygen saturation is 98% on room air. The patient is started on magnesium sulfate and labetalol. The patient delivers her baby vaginally 2 hours later. On the labor and delivery floor, the patient is notably somnolent. Vitals are notable for respirations of 6 per minute. Physical exam reveals a somnolent woman who is minimally responsive. Cardiopulmonary exam is notable for hypopnea. Neurological exam reveals absent deep tendon reflexes and 3/5 strength in her upper and lower extremities. Which of the following is the next best step in management?

• A. Discontinue current drug infusion (Correct Answer)
• B. Remove retained fetal parts
• C. Ultrasound
• D. CT scan of the head
• E. Supportive therapy

Explanation: ***Discontinue current drug infusion*** - The patient's symptoms, including **somnolence, respiratory depression (hypopnea, 6 respirations/minute), absent deep tendon reflexes, and muscle weakness (3/5 strength)**, are highly suggestive of **magnesium toxicity**. - Immediate discontinuation of the **magnesium sulfate infusion** is the critical first step to prevent further accumulation and worsening of toxicity. *Remove retained fetal parts* - This step is indicated for **postpartum hemorrhage** or infection due to retained placental fragments. - The patient's symptoms are neurological and respiratory, not related to uterine bleeding or infection. *Ultrasound* - An ultrasound might be useful to assess for retained products of conception or other intra-abdominal issues if there were signs of hemorrhage or infection. - However, the patient's primary symptoms indicate neurological and respiratory depression, which is not an indication for ultrasound. *CT scan of the head* - A CT scan of the head would be considered if there were concerns for **intracranial hemorrhage**, stroke, or other neurological emergencies, especially given her history of headaches and severe hypertension. - While hypertension is present, the constellation of absent deep tendon reflexes and respiratory depression points more directly to drug toxicity than to an acute intracranial event. *Supportive therapy* - Supportive therapy (e.g., **calcium gluconate as antidote**, airway management, mechanical ventilation) is essential and should be provided **concurrently** with stopping the magnesium infusion. - However, the *next best step* prioritizes **stopping the source of toxicity** first, as continued infusion would worsen the patient's condition despite supportive measures. - Without discontinuing the magnesium sulfate, supportive therapy alone would be insufficient to reverse the ongoing toxicity.

Question 414: An investigator is studying a drug that acts on the thyroid hormone pathway. Levels of serum free T3 and T4 in healthy participants are measured before and after administration of the drug. After administration, there is a decrease in the average serum free T3 level, while the average serum free T4 level is increased compared to initial serum studies. Inhibition of which of the following is the most likely mechanism of action of this drug?

• A. Thyroid-stimulating hormone
• B. Follicular iodotyrosine deiodinase
• C. Follicular thyroid peroxidase
• D. Peripheral 5'-deiodinase (Correct Answer)
• E. Follicular thyroid proteases

Explanation: ***Peripheral 5'-deiodinase*** - Inhibition of **peripheral 5'-deiodinase** would decrease the conversion of **T4 to T3** in the periphery, resulting in lower **free T3** and higher **free T4** levels. - This enzyme is crucial for activating T4 into the more potent T3, and its blockade explains the observed changes in hormone levels. *Thyroid-stimulating hormone* - Inhibition of **TSH** would lead to a decrease in the production and release of both **T3 and T4** from the thyroid gland. - This contradicts the observed increase in **free T4** levels. *Follicular iodotyrosine deiodinase* - This enzyme is involved in recycling iodine from **monoiodotyrosine (MIT)** and **diiodotyrosine (DIT)** within the thyroid follicular cells, which is important for efficient thyroid hormone synthesis. - Its inhibition would primarily affect iodine availability and synthesis, not directly lead to increased T4 and decreased T3 in the periphery. *Follicular thyroid peroxidase* - **Thyroid peroxidase (TPO)** is critical for the **iodination of tyrosine residues** on thyroglobulin and the **coupling of MIT and DIT** to form T3 and T4. - Inhibition of TPO would decrease the synthesis of both **T3 and T4**, contrary to the observed increase in **free T4**. *Follicular thyroid proteases* - **Thyroid proteases** cleave thyroglobulin to release mature **T3 and T4** into the bloodstream. - Inhibition of these proteases would lead to a decrease in the release of both **T3 and T4**, which does not align with the observed increase in **free T4**.

Question 415: A 48-year-old man comes to the emergency room for a persistent painful erection for the last 4 hours. Three weeks ago, he had a deep vein thrombosis following a 13-hour flight. He also has a history of sickle cell trait, gastroesophageal reflux disease, major depressive disorder, and hypertension. He has smoked 1 pack of cigarette daily for the past 9 years. He takes warfarin, propranolol, citalopram, trazodone, lisinopril, and omeprazole. He is alert and oriented but in acute distress. His temperature is 37°C(98.6°F), pulse is 109/min, and blood pressure is 139/88 mm Hg. Examination shows a rigid erection with no evidence of trauma, penile discharge, injection, or prosthesis. Which of the following is the most likely cause of his condition?

• A. Sickle cell trait
• B. Trazodone (Correct Answer)
• C. Citalopram
• D. Warfarin
• E. Cigarette smoking

Explanation: ***Trazodone*** - **Trazodone** is an antidepressant known to cause **priapism** as a rare but serious side effect (approximately 1 in 6,000 patients) - Mechanism: **Alpha-1 adrenergic receptor blockade** leads to impaired venous outflow from the corpus cavernosum - The patient's presentation of **persistent, painful erection for 4 hours** in the context of trazodone use is highly suspicious for drug-induced priapism - This is a **medical emergency** requiring immediate intervention to prevent ischemic damage *Sickle cell trait* - While **sickle cell disease** is a common cause of priapism due to vaso-occlusion, **sickle cell trait** (heterozygous state) typically only causes priapism under extreme conditions (high altitude, severe dehydration, extreme exertion) - The patient's clinical context does not suggest these extreme precipitants - Given clear medication history with trazodone, drug-induced priapism is more likely *Citalopram* - **Citalopram** is an SSRI (selective serotonin reuptake inhibitor) - SSRIs are **not associated with priapism**; they more commonly cause sexual dysfunction (decreased libido, anorgasmia) - Priapism is not a recognized adverse effect of this drug class *Warfarin* - **Warfarin** is an anticoagulant that inhibits vitamin K-dependent clotting factors - Primary adverse effects involve **bleeding complications**, not priapism - Does not directly affect erectile mechanisms or cause prolonged erections *Cigarette smoking* - **Smoking** is associated with **erectile dysfunction** (ED) due to endothelial damage and reduced nitric oxide bioavailability - Smoking causes **difficulty achieving/maintaining erections**, not persistent unwanted erections - Not a cause of priapism

Question 416: A 37-year-old woman, gravida 3, para 2, at 28 weeks' gestation comes to the physician for a follow-up examination. One week ago, an oral glucose tolerance screening test showed elevated serum glucose levels. She has complied with the recommended diet and lifestyle modifications. Over the past week, home blood glucose monitoring showed elevated fasting and post-prandial blood glucose levels. Which of the following describes the mechanism of action of the most appropriate pharmacotherapy for this patient?

• A. Inhibition of alpha-glucosidase
• B. Closure of ATP-dependent K+-channels
• C. Inhibition of dipeptidyl peptidase 4
• D. Activation of peroxisome proliferator-activated receptor-gamma
• E. Binding to receptors with tyrosine kinase activity (Correct Answer)

Explanation: ***Binding to receptors with tyrosine kinase activity*** - This mechanism describes **insulin**, which is the **first-line pharmacotherapy for gestational diabetes mellitus (GDM)** that is not controlled by diet and lifestyle modifications. Insulin binds to its receptor, activating **tyrosine kinase activity** and initiating a cascade of intracellular signaling that promotes glucose uptake and utilization. - Given the **elevated fasting and post-prandial blood glucose levels** despite dietary changes, insulin therapy is indicated to manage GDM, which relies on this mechanism of action. *Inhibition of alpha-glucosidase* - **Alpha-glucosidase inhibitors** (e.g., acarbose, miglitol) delay carbohydrate absorption in the gut, primarily targeting post-prandial hyperglycemia. - While these can be used in some forms of diabetes, they are generally **not preferred for GDM due to potential gastrointestinal side effects** and less effective control over fasting hyperglycemia compared to insulin. *Closure of ATP-dependent K+-channels* - Drugs like **sulfonylureas** (e.g., glyburide) act by **closing ATP-dependent K+-channels** on pancreatic beta cells, leading to depolarization and insulin release. - **Glyburide** can be used in GDM but is a controversial choice due to its potential to **cross the placenta** and cause fetal hypoglycemia. *Inhibition of dipeptidyl peptidase 4* - **Dipeptidyl peptidase-4 (DPP-4) inhibitors** (e.g., sitagliptin, saxagliptin) enhance the action of incretin hormones, stimulating glucose-dependent insulin release and suppressing glucagon secretion. - There is **limited data on the safety and efficacy of DPP-4 inhibitors in pregnancy**, and they are not typically recommended for GDM. *Activation of peroxisome proliferator-activated receptor-gamma* - This mechanism describes **thiazolidinediones (TZDs)**, such as pioglitazone and rosiglitazone, which improve insulin sensitivity. - **TZDs are contraindicated in pregnancy** due to potential adverse effects on the fetus, including increased risk of cardiovascular defects and fluid retention.

Question 417: A 33-year-old man comes into the urgent care clinic with an intensely itchy rash on the bilateral mid-lower extremities, with a fine linear demarcation approximately an inch above his socks. The rash is arranged in streaks of erythema with superimposed vesicular lesions. The patient states that he recently began hiking in the woods behind his house, but he denies any local chemical exposures to his lower extremities. His vital signs include: blood pressure of 127/76, heart rate of 82/min, and respiratory rate of 12/min. Of the following options, which is the mechanism of his reaction?

• A. Type III–immune complex-mediated hypersensitivity reaction
• B. Type IV–cell-mediated (delayed) hypersensitivity reaction (Correct Answer)
• C. Type II–cytotoxic hypersensitivity reaction
• D. Type I–anaphylactic hypersensitivity reaction
• E. Type III and IV–mixed immune complex and cell-mediated hypersensitivity reactions

Explanation: **Type IV–cell-mediated (delayed) hypersensitivity reaction** - The described rash with **erythema**, **vesicular lesions**, and a **linear demarcation** after hiking is classic for **allergic contact dermatitis**, often caused by plants like poison ivy, which is a **Type IV hypersensitivity reaction**. - This reaction is **delayed**, usually appearing 24-72 hours after exposure, and is mediated by **T lymphocytes** and **macrophages** reacting to the antigen. *Type III–immune complex-mediated hypersensitivity reaction* - This type of reaction involves the formation of **immune complexes** (antigen-antibody), leading to inflammation and tissue damage. - Clinically, it often presents as **vasculitis**, **serum sickness**, or conditions like **lupus nephritis**, which do not match the localized, vesicular rash described. *Type II–cytotoxic hypersensitivity reaction* - This reaction involves **antibodies** (IgG or IgM) binding to antigens on cell surfaces, leading to cell destruction or dysfunction. - Examples include **hemolytic transfusion reactions** and **autoimmune hemolytic anemia**, which are distinct from allergic contact dermatitis. *Type I–anaphylactic hypersensitivity reaction* - This is an **immediate hypersensitivity** reaction mediated by **IgE antibodies** binding to mast cells, leading to histamine release. - Symptoms typically include **urticaria**, **angioedema**, **bronchospasm**, and **anaphylaxis**, occurring rapidly after exposure. *Type III and IV–mixed immune complex and cell-mediated hypersensitivity reactions* - While some conditions can involve features of both Type III and Type IV, the clinical picture of **allergic contact dermatitis** is predominantly a **pure Type IV (delayed cell-mediated) reaction**. - The primary mechanism of the described rash does not involve immune complex deposition.

Question 418: An 8-year-old boy is brought to the pediatrician by his parents due to recurrent episodes of wheezing for the last 2 years. He uses a salbutamol inhaler for relief from wheezing, but his symptoms have recently worsened. He often coughs during the night, which awakens him from sleep almost every other day. He is not able to play football because he starts coughing after 10–15 minutes of play. His current physical examination is completely normal and auscultation of his chest does not reveal any abnormal breath sounds. His peak expiratory flow rate (PEFR) is 75% of expected for his age, gender, and height. After a complete diagnostic evaluation, the pediatrician prescribes a low-dose inhaled fluticasone daily for at least 3 months. He also mentions that the boy may require continuing inhaled corticosteroid (ICS) therapy for a few years if symptoms recur after discontinuation of ICS. However, the parents are concerned about the side effects of corticosteroids. Which of the following corticosteroid-related adverse effects is most likely?

• A. Suppression of hypothalamus-pituitary-adrenal (HPA) axis
• B. Short stature
• C. Posterior subcapsular cataract
• D. Steroid psychosis
• E. Hoarseness of voice (Correct Answer)

Explanation: ***Hoarseness of voice*** - **Hoarseness (dysphonia)** is the **most common local side effect** of inhaled corticosteroids (ICS) due to irritation of the vocal cords or laryngeal deposition. - Other local effects include **oral candidiasis (thrush)**, though less common in children than adults. - These adverse effects are localized to the upper airway and are generally **mild and reversible**. - Can be **minimized** by using a spacer device and rinsing the mouth after each use. *Suppression of hypothalamus-pituitary-adrenal (HPA) axis* - While systemic corticosteroids can cause HPA axis suppression, **low-dose inhaled corticosteroids** have minimal systemic absorption (typically <1% bioavailability). - HPA suppression is unlikely unless used at **very high doses** (>800 mcg/day fluticasone equivalent) or for prolonged periods. - The pediatrician prescribed a **low-dose ICS**, significantly reducing the risk of this systemic effect. *Short stature* - Some studies have shown a small, **transient reduction in growth velocity** (approximately 1 cm in the first year) during ICS therapy in children. - This effect is typically **minor and does not significantly impact final adult height**. - The benefits of asthma control **far outweigh** this minimal growth effect. - Poorly controlled asthma itself can impair growth more than ICS therapy. *Posterior subcapsular cataract* - **Systemic corticosteroids**, particularly with prolonged use, are a known risk factor for posterior subcapsular cataracts. - **Low-dose inhaled corticosteroids** have a **very low risk** of causing cataracts due to minimal systemic exposure. - Risk increases only with high doses (>1000 mcg/day) used for many years. *Steroid psychosis* - **Steroid psychosis** is a rare but serious neuropsychiatric side effect primarily associated with **high-dose systemic corticosteroids**. - It is **highly unlikely** to occur with **low-dose inhaled corticosteroids** due to their limited systemic bioavailability. - This effect is not relevant to the clinical scenario presented.

Question 419: A 36 year-old woman presents to the doctor’s office for evaluation of substernal chest pain and a metallic taste in her mouth. The patient has a history of metabolic syndrome and hypothyroidism. She takes levothyroxine daily. The patient’s vital signs are currently stable. On examination, she appears to be in mild discomfort, but is alert and oriented. The abdomen is mildly tender to palpation without guarding. Which of the following is the most appropriate treatment choice based on her history and physical examination?

• A. Omeprazole (Correct Answer)
• B. Famotidine
• C. Metoclopramide
• D. Magnesium hydroxide
• E. Bismuth subsalicylate

Explanation: ***Omeprazole*** - The patient's symptoms of **substernal chest pain** and **metallic taste** are highly suggestive of **gastroesophageal reflux disease (GERD)**. - **Omeprazole** is a **proton pump inhibitor (PPI)**, which is the most effective class of medications for suppressing gastric acid production and treating GERD. *Famotidine* - **Famotidine** is an **H2 receptor antagonist** that reduces gastric acid production. - While it can be used for GERD, PPIs like omeprazole are generally more effective and provide superior symptom relief and healing of erosive esophagitis. *Metoclopramide* - **Metoclopramide** is a **prokinetic agent** that increases gastrointestinal motility. - It could be considered an adjunct in GERD management, especially if there's evidence of gastroparesis, but it is not a first-line treatment for typical GERD symptoms. *Magnesium hydroxide* - **Magnesium hydroxide** is an **antacid** that provides temporary relief by neutralizing stomach acid. - It does not address the underlying pathology of GERD (acid reflux) and is not suitable for long-term or definitive treatment. *Bismuth subsalicylate* - **Bismuth subsalicylate** primarily acts as an **antidiarrheal** and has some **antimicrobial properties** (e.g., against *H. pylori*). - It is not a primary treatment for GERD and would not effectively address substernal chest pain or a metallic taste related to acid reflux.

Question 420: A 45-year-old Caucasian man is given nitroglycerin for the management of his stable angina. Nitroglycerin given for the rapid relief of acute angina would most likely be given through what route of administration?

• A. Subcutaneous injection
• B. Intramuscular injection
• C. Intravenous injection
• D. Sublingual (Correct Answer)
• E. Oral

Explanation: ***Sublingual*** - **Sublingual** administration provides rapid absorption into the bloodstream through the oral mucosa, bypassing first-pass metabolism, which is crucial for quick relief of acute angina. - This route allows the medication to exert its vasodilatory effects within 1-3 minutes, alleviating chest pain efficiently. - It is the **standard of care** for outpatient management of acute angina episodes due to ease of self-administration. *Subcutaneous injection* - **Subcutaneous injection** has a slower onset of action compared to sublingual administration, making it unsuitable for rapid relief of acute angina. - While it avoids first-pass metabolism, the absorption rate is not fast enough for emergency situations. *Intramuscular injection* - **Intramuscular injection** also has a relatively slower onset of action and is less predictable for rapid relief compared to sublingual routes. - It is not a standard route for acute angina management due to the need for immediate action. *Intravenous injection* - **Intravenous administration** provides immediate systemic availability and is used for continuous infusion in unstable angina or acute coronary syndromes in hospital settings. - However, it is **not practical for outpatient or self-administered rapid relief** due to the need for IV access, medical personnel, and monitoring. - While highly effective in critical care, it is not the route for typical acute angina episodes outside the hospital. *Oral* - **Oral administration** undergoes significant **first-pass metabolism** in the liver, which delays the onset of action and reduces bioavailability, rendering it ineffective for rapid relief of acute angina. - The delayed absorption (typically 30-60 minutes) makes it impractical for emergency situations where immediate vasodilation is needed. - Oral nitrates are used for prophylaxis, not acute relief.

Question 421: A 28-year-old man comes to his general practitioner for a regular checkup. He has had trouble breathing lately with coughing, shortness of breath, and wheezing. Problems first started when he went running (outside), but he is also observing the problems when taking a light walk or resting. As a child, he suffered from atopic dermatitis, just like his father and sister. He also has a history of hay fever. What is the most likely cause of his symptoms?

• A. Smoking
• B. Chronic obstructive pulmonary disease
• C. Type I hypersensitivity (Correct Answer)
• D. Type IV hypersensitivity
• E. Exercise

Explanation: ***Type I hypersensitivity*** - The patient's presentation with **coughing, shortness of breath, and wheezing** suggests **bronchial asthma**, which is a classic manifestation of **Type I hypersensitivity** (allergic reaction). - The history of **atopic dermatitis** (eczema) and **hay fever** indicates an **atopic diathesis**, which is a strong predisposing factor for allergic asthma. This forms the **atopic triad**. *Smoking* - While smoking can cause respiratory symptoms like coughing and shortness of breath, it typically does not cause acute wheezing that improves with rest in a young, otherwise healthy individual. - The patient's personal history of atopic dermatitis and hay fever, and running in the family does not suggest smoking. *Chronic obstructive pulmonary disease* - **COPD** usually develops in older individuals, often with a history of significant smoking or environmental exposure, and is characterized by **progressive, non-reversible airflow limitation**. - The patient's young age and history of atopic conditions make COPD a less likely diagnosis compared to asthma. *Type IV hypersensitivity* - **Type IV hypersensitivity**, or **delayed-type hypersensitivity**, typically manifests as contact dermatitis (e.g., poison ivy) or granulomatous reactions, which are T-cell mediated and develop over 24-72 hours. - It does not cause acute respiratory symptoms like wheezing, nor is it linked to atopic conditions such as hay fever and asthma. *Exercise* - Exercise can trigger **exercise-induced bronchoconstriction (asthma)**, which presents as shortness of breath and wheezing during or after physical activity. - However, the patient also experiences symptoms during light walks or at rest, and has a strong atopic history, indicating that exercise is a trigger for underlying asthma (Type I hypersensitivity) rather than the sole cause of symptoms.

Question 422: A 66-year-old gentleman presents to a new primary care physician to establish care after a recent relocation. His past medical history is significant for gout, erectile dysfunction, osteoarthritis of bilateral knees, mitral stenosis, and diabetic peripheral neuropathy. He denies any past surgeries along with the use of any tobacco, alcohol, or illicit drugs. He has no known drug allergies and cannot remember the names of the medications he is taking for his medical problems. He states that he has recently been experiencing chest pain with strenuous activities. What part of the patient's medical history must be further probed before starting him on a nitrate for chest pain?

• A. Erectile dysfunction (Correct Answer)
• B. Diabetic peripheral neuropathy
• C. Gout
• D. Arthritis
• E. Mitral stenosis

Explanation: ***Erectile dysfunction*** - Patients often take **phosphodiesterase-5 (PDE5) inhibitors** (e.g., sildenafil, tadalafil) for erectile dysfunction, which are absolutely contraindicated with nitrates. - **Co-administration** can lead to a severe and potentially fatal drop in blood pressure due to enhanced vasodilation. *Diabetic peripheral neuropathy* - While important for overall health assessment, **diabetic peripheral neuropathy** does not directly contraindicate the use of nitrates for chest pain. - It might influence medication choices if a patient has orthostatic hypotension, but not a direct contraindication. *Gout* - **Gout** is a joint condition and has no direct contraindication with nitrate use. - Medications for gout, such as allopurinol or colchicine, do not interact adversely with nitrates. *Arthritis* - **Arthritis** (including osteoarthritis mentioned) is a musculoskeletal condition and does not contraindicate nitrate therapy. - Pain management for arthritis does not typically involve drugs that interact dangerously with nitrates. *Mitral stenosis* - While **mitral stenosis** can affect cardiac function and hemodynamics, it is generally not an absolute contraindication to nitrate use. - Nitrates can even be used cautiously in **mitral stenosis** to manage angina, though their use requires careful monitoring of preload.

Question 423: A 7-year-old boy with asthma is brought to the emergency department because of a 1-day history of shortness of breath and cough. Current medications are inhaled albuterol and beclomethasone. His temperature is 37°C (98.6°F) and respirations are 24/min. Pulmonary examination shows bilateral expiratory wheezing. Serum studies show increased concentrations of interleukin-5. Which of the following is the most likely effect of the observed laboratory finding in this patient?

• A. Suppression of MHC class II expression
• B. Recruitment of eosinophils (Correct Answer)
• C. Induction of immunoglobulin class switching to IgE
• D. Differentiation of bone marrow stem cells
• E. Secretion of acute phase reactants

Explanation: ***Recruitment of eosinophils*** - **Interleukin-5 (IL-5)** is a key cytokine primarily responsible for the **differentiation, maturation, and activation of eosinophils**. - In asthma, an increase in IL-5 leads to the **recruitment of eosinophils** to the airways, contributing to inflammation and bronchoconstriction. *Suppression of MHC class II expression* - **MHC class II expression** is mainly modulated by other cytokines such as **IFN-γ** (upregulation) and **IL-10** (downregulation), not IL-5. - IL-5's primary role is in **eosinophil biology**, not in antigen presentation regulation. *Induction of immunoglobulin class switching to IgE* - **Immunoglobulin class switching to IgE** is primarily driven by **IL-4** and **IL-13**, in synergy with **CD40-CD40L interactions**. - While IgE is involved in allergic asthma, IL-5 directly influences **eosinophils**, not IgE class switching. *Differentiation of bone marrow stem cells* - The **differentiation of various bone marrow stem cells** into specific lineages is a complex process involving a wide array of **colony-stimulating factors** and interleukins (e.g., GM-CSF, G-CSF, M-CSF, IL-3). - While IL-5 promotes eosinophil development, it is not broadly responsible for the differentiation of all bone marrow stem cells. *Secretion of acute phase reactants* - **Acute phase reactants** (e.g., CRP, ESR) are primarily secreted by the liver in response to IL-1, IL-6, and TNF-α during **acute inflammation**. - IL-5 is not a primary inducer of acute phase reactant secretion.

Question 424: A 62-year-old man comes to the physician because of tremors in both hands for the past few months. He has had difficulty buttoning his shirts and holding a cup of coffee without spilling its content. He has noticed that his symptoms improve after a glass of whiskey. His maternal uncle began to develop similar symptoms around the same age. He has bronchial asthma controlled with albuterol and fluticasone. Examination shows a low-amplitude tremor bilaterally when the arms are outstretched that worsens during the finger-to-nose test. Which of the following is the most appropriate pharmacotherapy in this patient?

• A. Levodopa
• B. Propranolol
• C. Valproic acid
• D. Alprazolam
• E. Primidone (Correct Answer)

Explanation: ***Primidone*** - The patient exhibits symptoms consistent with **essential tremor**, characterized by an **action tremor** that improves with alcohol and a family history. Primidone is a first-line agent, and an **anticonvulsant** used to treat essential tremor. - While **propranolol** is also a first-line treatment, it is contraindicated in this patient due to his history of **bronchial asthma**. *Levodopa* - **Levodopa** is the primary treatment for **Parkinson's disease**, which typically presents with a **resting tremor**, bradykinesia, rigidity, and postural instability. - The patient's tremor is an **action tremor**, not a resting tremor, and he lacks other parkinsonian features. *Propranolol* - **Propranolol** is a first-line treatment for essential tremor, effective in reducing tremor severity. - However, it is a **non-selective beta-blocker** and is contraindicated in patients with **asthma** due to the risk of bronchospasm. *Valproic acid* - **Valproic acid** is primarily an antiepileptic drug and mood stabilizer, and is not a first-line treatment for essential tremor. - Its use for tremor is generally reserved for other types of tremors or as an **adjunctive therapy** in refractory cases, not as a primary treatment for essential tremor. *Alprazolam* - **Alprazolam** is a benzodiazepine used to treat anxiety and panic disorders, and can sometimes help with **anxiety-potentiated tremors**. - While it may temporarily reduce tremor due to its sedative effects, it is not a primary or long-term treatment for essential tremor due to issues like **tolerance, dependence, and sedation**.

Question 425: A 28-year-old woman presents to a psychiatrist with a 10-year history of unexplained anxiety symptoms. To date, she has not visited any psychiatrist, because she believes that she should not take medicines to change her emotions or thoughts. However, after explaining the nature of her disorder, the psychiatrist prescribes daily alprazolam. When she comes for her first follow-up, she reports excellent relief from her symptoms without any side-effects. The psychiatrist encourages her to continue her medication for the next 3 months and then return for a follow-up visit. After 3 months, she tells her psychiatrist that she has been experiencing excessive sedation and drowsiness over the last few weeks. The psychiatrist finds that she is taking alprazolam in the correct dosage, and she is not taking any other medication that causes sedation. Upon asking her about any recent changes in her lifestyle, she mentions that for the last 2 months, she has made a diet change. The psychiatrist tells her that diet change may be the reason why she is experiencing excessive sedation and drowsiness. Which of the following is the most likely diet change the psychiatrist is talking about?

• A. Daily consumption of tomatoes
• B. Daily consumption of St. John's wort
• C. Daily consumption of cruciferous vegetables
• D. Daily consumption of grapefruit juice (Correct Answer)
• E. Daily consumption of charcoal-broiled foods

Explanation: ***Daily consumption of grapefruit juice*** - **Grapefruit juice** is a potent inhibitor of the **CYP3A4 enzyme**, which is responsible for the metabolism of **alprazolam**. - Inhibition of CYP3A4 leads to **increased plasma concentrations of alprazolam**, enhancing its sedative effects and causing drowsiness. *Daily consumption of tomatoes* - **Tomatoes** do not significantly interact with the metabolism of **alprazolam** or other benzodiazepines. - They are a healthy food item with no known common drug interactions relevant to alprazolam's side effects. *Daily consumption of St. John's wort* - **St. John's wort** is a known **CYP3A4 inducer**, meaning it would *decrease* alprazolam levels, potentially leading to reduced efficacy. - It would not cause increased sedation or drowsiness due to higher alprazolam concentrations. *Daily consumption of cruciferous vegetables* - **Cruciferous vegetables** (e.g., broccoli, cabbage) can induce certain CYP enzymes but generally do not significantly interfere with **alprazolam metabolism** to cause increased sedation. - Their effects on drug metabolism are usually less pronounced or specific to other enzyme systems. *Daily consumption of charcoal-broiled foods* - **Charcoal-broiled foods** can induce **CYP1A2 enzymes**, but **alprazolam** is primarily metabolized by CYP3A4. - Therefore, this dietary change is unlikely to significantly impact alprazolam metabolism or lead to increased sedation.

Question 426: A 45-year-old man comes to the physician because of a 3-month history of recurrent headaches. The headaches are of a dull, nonpulsating quality. The patient denies nausea, vomiting, photophobia, or phonophobia. Neurologic examination shows no abnormalities. The physician prescribes a drug that irreversibly inhibits cyclooxygenase-1 and cyclooxygenase-2 by covalent acetylation. Which of the following medications was most likely prescribed by the physician?

• A. Prednisolone
• B. Indomethacin
• C. Aspirin (Correct Answer)
• D. Carbamazepine
• E. Celecoxib

Explanation: **Aspirin** - Aspirin is a non-steroidal anti-inflammatory drug (**NSAID**) that **covalently acetylates** and irreversibly inhibits both **COX-1** and **COX-2** enzymes. - The described mechanism of action (irreversible inhibition of COX-1 and COX-2 by covalent acetylation) is characteristic of aspirin. *Prednisolone* - **Prednisolone** is a corticosteroid, which inhibits inflammation by affecting **gene transcription** and protein synthesis, rather than directly inhibiting cyclooxygenase enzymes. - Its mechanism involves suppressing the immune system and reducing inflammatory mediators, distinct from COX inhibition. *Indomethacin* - **Indomethacin** is a non-selective NSAID that reversibly inhibits COX-1 and COX-2. - It does not involve covalent acetylation for its inhibitory action, unlike aspirin. *Carbamazepine* - **Carbamazepine** is an anticonvulsant medication primarily used for epilepsy and trigeminal neuralgia. - Its mechanism of action involves blocking **voltage-gated sodium channels**, thereby stabilizing neuronal membranes and reducing seizure propagation. *Celecoxib* - **Celecoxib** is a selective **COX-2 inhibitor**, meaning it primarily targets COX-2 enzymes while sparing COX-1. - Furthermore, it is a reversible inhibitor, not an irreversible one through covalent acetylation.

Question 427: A 67-year-old woman is admitted to the hospital because of a 2-day history of fever, headache, jaw pain, and decreased vision in the right eye. Her erythrocyte sedimentation rate is 84 mm per hour. Treatment with methylprednisolone is initiated but her symptoms do not improve. The physician recommends the administration of a new drug. Three days after treatment with the new drug is started, visual acuity in the right eye increases. The beneficial effect of this drug is most likely due to inhibition of which of the following molecules?

• A. Leukotriene D4
• B. Interleukin-4
• C. Complement component 5
• D. Interleukin-6 (Correct Answer)
• E. Thromboxane A2

Explanation: ***Interleukin-6*** - The patient's symptoms (fever, headache, jaw pain, decreased vision, elevated ESR) are classic for **giant cell arteritis (GCA)**. GCA involves transmural inflammation of medium to large arteries, often affecting the temporal artery and ophthalmic artery. - **Tocilizumab**, a monoclonal antibody that targets the **IL-6 receptor**, is an approved treatment for GCA, especially in cases unresponsive to corticosteroids or for steroid-sparing effects. Its efficacy in improving vision and reducing inflammation supports its action on IL-6. *Leukotriene D4* - **Leukotriene D4** is a potent bronchoconstrictor and mediator in allergic and asthmatic responses. - Inhibitors of leukotriene D4, such as montelukast, are used to treat **asthma** and **allergic rhinitis**, not vasculitis like GCA. *Interleukin-4* - **Interleukin-4** is a key cytokine in the **Th2 immune response**, promoting B-cell activation, **IgE production**, and allergic inflammation. - Drugs targeting IL-4 (or its receptor) are used in conditions like **atopic dermatitis** and **asthma**, not GCA, which is primarily a Th1-mediated inflammatory disease. *Complement component 5* - **Complement component 5 (C5)** is a central molecule in the **complement cascade**, playing a role in inflammation and cell lysis. - While the complement system can be involved in various inflammatory conditions, specific C5 inhibition is primarily seen with drugs like **Eculizumab** for paroxysmal nocturnal hemoglobinuria or atypical hemolytic uremic syndrome, which are distinct from GCA. *Thromboxane A2* - **Thromboxane A2** is a potent vasoconstrictor and platelet aggregator, primarily produced by platelets. - Its inhibition, typically by **aspirin**, is used for **antiplatelet effects** in cardiovascular disease and stroke prevention, not for the direct treatment of large vessel vasculitis or to rapidly resolve visual loss in GCA.

Question 428: A 43-year-old woman presents to her primary care provider for follow-up of her glucose levels. At her last visit 3 months ago, her fasting serum glucose was 128 mg/dl. At that time, she was instructed to follow a weight loss regimen consisting of diet and exercise. Her family history is notable for a myocardial infarction in her father and type II diabetes mellitus in her mother. She does not smoke and drinks 2-3 glasses of wine per week. Her temperature is 99°F (37.2°C), blood pressure is 131/78 mmHg, pulse is 80/min, and respirations are 17/min. Her BMI is 31 kg/m^2. On exam, she is well-appearing and appropriately interactive. Today, despite attempting to make the appropriate lifestyle changes, a repeat fasting serum glucose is 133 mg/dl. The patient is prescribed the first-line oral pharmacologic agent for her condition. Which of the following is the correct mechanism of action of this medication?

• A. Inhibition of hepatic gluconeogenesis (Correct Answer)
• B. Activation of peroxisome proliferator-activating receptors
• C. Inhibition of the sodium-glucose cotransporter
• D. Closure of potassium channels in pancreatic beta cells
• E. Inhibition of alpha-glucosidase in the intestinal brush border

Explanation: ***Inhibition of hepatic gluconeogenesis*** - This patient's fasting glucose levels (128 mg/dL and 133 mg/dL on repeat testing) meet the diagnostic criteria for **type 2 diabetes mellitus** (fasting glucose ≥126 mg/dL on two separate occasions). Given her elevated BMI, family history, and persistent hyperglycemia despite lifestyle modifications, the most appropriate first-line pharmacologic agent is **metformin**. - **Metformin** primarily acts by **decreasing hepatic glucose production**, mainly through the inhibition of gluconeogenesis, and also improves insulin sensitivity in peripheral tissues. *Activation of peroxisome proliferator-activating receptors* - This is the mechanism of action for **thiazolidinediones (TZDs)**, such as pioglitazone and rosiglitazone. - While TZDs improve insulin sensitivity, they are generally **not considered first-line agents** due to potential side effects like weight gain, edema, and cardiovascular risks. *Inhibition of the sodium-glucose cotransporter* - This describes the mechanism of action for **SGLT2 inhibitors**, such as empagliflozin and canagliflozin. - SGLT2 inhibitors block glucose reabsorption in the kidneys, leading to **glucose excretion in the urine**, and are typically used as second-line therapy or in patients with cardiovascular disease or chronic kidney disease. *Closure of potassium channels in pancreatic beta cells* - This is the mechanism of action for **sulfonylureas**, such as glipizide and glyburide, and **meglitinides**. - These medications **stimulate insulin secretion** from pancreatic beta cells, but they carry a higher risk of hypoglycemia and weight gain compared to metformin. *Inhibition of alpha-glucosidase in the intestinal brush border* - This is the mechanism of action for **alpha-glucosidase inhibitors**, such as acarbose and miglitol. - These drugs **delay carbohydrate absorption** in the gut, which can help reduce postprandial glucose levels, but they are not typically considered first-line for overall glucose control due to gastrointestinal side effects.

Question 429: A previously healthy 52-year-old man comes to the physician because of a 4-month history of recurrent abdominal pain, foul-smelling, greasy stools, and a 5-kg (11-lb) weight loss despite no change in appetite. Physical examination shows pain on palpation of the right upper quadrant. His fasting serum glucose concentration is 186 mg/dL. Abdominal ultrasound shows multiple round, echogenic foci within the gallbladder lumen with prominent posterior acoustic shadowing. The serum concentration of which of the following substances is most likely to be increased in this patient?

• A. Glucagon
• B. Serotonin
• C. Insulin
• D. Somatostatin (Correct Answer)
• E. Vasoactive intestinal peptide

Explanation: ***Somatostatin*** - Elevated **somatostatin** levels can inhibit the release of various gastrointestinal hormones and enzymes, leading to malabsorption, **steatorrhea (foul-smelling, greasy stools)**, and **weight loss**, as seen in this patient. - The abdominal pain, gallstones (echogenic foci with posterior acoustic shadowing), and elevated fasting glucose suggest a possible **somatostatinoma**, a rare neuroendocrine tumor producing somatostatin. *Glucagon* - **Glucagon** primarily increases blood glucose, which is elevated here, but its excess typically presents with a characteristic **necrolytic migratory erythema** and severe weight loss, not malabsorption as the primary GI symptom. - While high blood glucose is present, malabsorption symptoms and gallstones are not typical features of a glucagonoma. *Insulin* - **Insulin** lowers blood glucose, so an increased concentration would lead to **hypoglycemia**, not the hyperglycemia (186 mg/dL) observed in this patient. - Symptoms of insulin excess (e.g., insulinoma) would include neuroglycopenic symptoms and weight gain, not malabsorption and weight loss. *Serotonin* - Increased **serotonin** levels are associated with **carcinoid syndrome**, which typically presents with flushing, diarrhea, bronchospasm, and valvular heart disease. - Although diarrhea can be a symptom, the specific features of malabsorption, recurrent abdominal pain, gallstones, and hyperglycemia do not align well with carcinoid syndrome. *Vasoactive intestinal peptide* - Elevated **vasoactive intestinal peptide (VIP)**, as in **VIPoma**, causes severe watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome). - While weight loss can occur due to fluid loss, the presence of steatorrhea, gallstones, and hyperglycemia makes VIPoma a less likely diagnosis.

Question 430: A 77-year-old woman with congestive heart failure is admitted to the hospital for evaluation prior to cardiac transplantation. During her stay at the hospital, the physician prescribes a drug to improve cardiac contractility. The drug works by selectively inhibiting an isoenzyme that is responsible for the degradation of cyclic adenosine monophosphate. Which of the following is the most likely adverse effect of this drug?

• A. Hyperkalemia
• B. QT interval prolongation
• C. Hyperglycemia
• D. Bronchospasm
• E. Hypotension (Correct Answer)

Explanation: ***Hypotension*** - The drug described is likely a **phosphodiesterase-3 inhibitor** (e.g., milrinone), which increases cyclic AMP in cardiac myocytes and vascular smooth muscle cells. - Increased **cyclic AMP** in vascular smooth muscle leads to **vasodilation**, causing a drop in systemic vascular resistance and subsequently **hypotension**. *Hyperkalemia* - **Hyperkalemia** is not a characteristic adverse effect of phosphodiesterase inhibitors. It is associated with drugs like **ACE inhibitors**, **ARBs**, or **aldosterone antagonists**. - These drugs primarily affect the **renin-angiotensin-aldosterone system** or potassium excretion. *QT interval prolongation* - While some **phosphodiesterase inhibitors** can cause **QT prolongation**, it is not the *most likely* adverse effect compared to hypotension, especially in a patient with heart failure. - Furthermore, **QT prolongation** is a more prominent concern with drugs like **antiarrhythmics** (e.g., amiodarone, sotalol) or certain **antibiotics** (e.g., macrolides). *Hyperglycemia* - **Hyperglycemia** is typically associated with drugs that interfere with **insulin secretion** or **insulin sensitivity**, such as **corticosteroids** or some **atypical antipsychotics**. - Phosphodiesterase inhibitors do not directly cause significant **glucose disturbances**. *Bronchospasm* - **Bronchospasm** is a common side effect of **beta-blockers** due to their antagonism of beta-2 adrenergic receptors in the airways. - Phosphodiesterase inhibitors, by increasing **cyclic AMP**, would theoretically cause **bronchodilation**, not bronchospasm.

Question 431: A 20-year-old girl presents to a physician following unprotected coitus with her boyfriend about 10 hours ago. She tells the doctor that although they usually use a barrier method of contraception, this time they forgot. She does not want to become pregnant. She also mentions that she has major depression and does not want to take an estrogen-containing pill. After necessary counseling, the physician prescribes an enteric-coated pill containing 1.5 mg of levonorgestrel. Which of the following is the primary mechanism of action of this drug?

• A. Atrophy of the endometrium
• B. Reduction in motility of cilia in the fallopian tubes
• C. Mucosal hypertrophy and polyp formation in cervix
• D. Thickening of the cervical mucus
• E. Delayed ovulation through inhibition of follicular development (Correct Answer)

Explanation: ***Delayed ovulation through inhibition of follicular development*** - The primary mechanism of action of **levonorgestrel** as emergency contraception is to **inhibit or delay ovulation** by suppressing the luteinizing hormone (LH) surge. - This prevents the release of an egg, thereby averting fertilization if intercourse has recently occurred. *Atrophy of the endometrium* - While progestins can cause endometrial changes, **atrophy** is not the primary mechanism of action for high-dose levonorgestrel in emergency contraception. - Significant endometrial changes that would prevent implantation typically require longer-term exposure or different formulations. *Reduction in motility of cilia in the fallopian tubes* - This is not a primary mechanism of action for **levonorgestrel** as an emergency contraceptive. - While hormonal changes can influence fallopian tube function, the main contraceptive effect is pre-fertilization. *Mucosal hypertrophy and polyp formation in cervix* - **Levonorgestrel** typically causes changes like **thickening of cervical mucus**, not hypertrophy or polyp formation, to impede sperm. - Mucosal hypertrophy and polyp formation are not considered mechanisms of contraception. *Thickening of the cervical mucus* - While **levonorgestrel** does **thicken cervical mucus**, making it harder for sperm to reach the egg, this is a secondary mechanism. - The primary and most effective action for emergency contraception is the delay of ovulation.

Question 432: A 55-year-old man is discharged from the hospital after being treated for a ST-elevation myocardial infarction. The patient became hypotensive to 87/48 mmHg with a pulse of 130/min. He was properly resuscitated, and a cardiac catheterization with stent placement was performed. Upon being discharged, the patient was started on metoprolol, lisinopril, aspirin, atorvastatin, and nitroglycerin. Upon presentation to the patient’s primary care doctor today, his liver enzymes are elevated with an AST of 55 U/L and an ALT of 57 U/L. Which of the following is the most likely etiology of these laboratory abnormalities?

• A. Metoprolol
• B. Ischemic hepatitis
• C. Lisinopril
• D. Nitroglycerin
• E. Atorvastatin (Correct Answer)

Explanation: ***Atorvastatin*** - **Statins** (like atorvastatin) are a common cause of drug-induced liver injury, manifesting as elevated liver enzymes (AST and ALT). - Regular monitoring of liver function tests is recommended when initiating or adjusting statin therapy due to this known side effect. *Metoprolol* - While metoprolol can rarely cause liver enzyme elevations, it is **much less common** and typically less pronounced than elevations seen with statins. - Its primary mechanism of action is related to beta-adrenergic blockade, not direct hepatic toxicity. *Ischemic hepatitis* - **Ischemic hepatitis**, also known as shock liver, typically causes a **much more severe and acute increase** in AST/ALT (often in the thousands), usually transiently after a hypotensive episode. - The mild, persistent elevations described after resuscitation for hypotension make drug-induced injury more likely than resolution of acute ischemic hepatitis. *Lisinopril* - **ACE inhibitors** like lisinopril can cause liver enzyme elevations, but this is a **rare adverse effect** and generally not considered a primary contributor in the context of multiple medications, especially when a statin is also prescribed. - Its hepatic side effects are overshadowed by the more common potential for hyperkalemia or angioedema. *Nitroglycerin* - **Nitroglycerin** primarily acts as a vasodilator and is **not commonly associated** with significant elevations in liver enzymes. - Its metabolism does not typically lead to hepatotoxicity as a common or dose-limiting side effect.

Question 433: A 45-year-old man undergoes an esophagogastroduodenoscopy for his recurrent episodes of epigastric pain. He also lost a significant amount of weight in the last 6 months. He says that he has been taking a number of dietary supplements "to cope". His past medical history is insignificant, and a physical examination is within normal limits. The endoscopy shows a bleeding ulcer in the proximal duodenum. Lab tests reveal a serum iron level of 130 μg/dL. However, his stool guaiac test is negative for occult blood. Over-ingestion of which of the following substances is the most likely cause for this patient’s lab findings?

• A. Red meat
• B. Folate
• C. Tocopherol
• D. Ascorbic acid (Correct Answer)
• E. Thiamine

Explanation: **Ascorbic acid** - **Excessive intake of ascorbic acid (vitamin C)** can lead to false-negative stool guaiac tests because it reduces the orthotolidine reagent, interfering with the peroxidase reaction that detects hemoglobin. - While the patient has a bleeding ulcer, the negative guaiac test despite active bleeding is explained by this **reductive interference** from large doses of vitamin C, which he might be taking as part of his "dietary supplements." *Red meat* - **Red meat intake** can cause **false-positive** stool guaiac tests due to the presence of peroxidases in the meat. - This is the opposite of the patient's presentation, which shows a **false-negative** result. *Folate* - **Folate (vitamin B9)** does not significantly interfere with the chemical reaction used in the guaiac test. - High doses of folate are not known to cause either false-positive or false-negative results in stool occult blood testing. *Tocopherol* - **Tocopherol (vitamin E)** does not interfere with the chemical reaction of the guaiac test for occult blood. - While vitamin E can have some anticoagulant properties at very high doses, it does not directly affect the chemical detection of blood in stool. *Thiamine* - **Thiamine (vitamin B1)** does not interfere with the chemical reaction of the guaiac test for occult blood. - There is no known mechanism by which thiamine supplementation would lead to false-negative results in a stool guaiac test.

Question 434: A 28-year-old man makes an appointment with his general practitioner for a regular check-up. He has recently been diagnosed with asthma and was given a short-acting β2-agonist to use during acute exacerbations. He said he usually uses the medication 1–2 times per week. Which of the following is the most appropriate treatment in this case?

• A. He should start using a short-acting β2-agonist every day, not just when he has symptoms.
• B. Long-acting β2-agonists should be added to his treatment regimen.
• C. Inhaled corticosteroids should be added as controller therapy. (Correct Answer)
• D. Systemic corticosteroids should be added to his treatment regimen.
• E. He should continue with current treatment.

Explanation: ***Inhaled corticosteroids should be added as controller therapy.*** - The patient's use of a **short-acting β2-agonist (SABA)** 1-2 times per week indicates **persistent asthma** that is not well-controlled, suggesting the need for daily controller therapy. - **Inhaled corticosteroids (ICS)** are the most effective anti-inflammatory controller medication for asthma and are recommended as the first-line add-on therapy when SABA use exceeds twice a week. *He should start using a short-acting β2-agonist every day, not just when he has symptoms.* - **SABAs** are **rescue medications** for acute symptom relief and do not address the underlying airway inflammation in asthma. - Daily SABA use indicates **poor asthma control** and can lead to adverse effects like **tachycardia** and **tremors**, and may even mask worsening disease. *Long-acting β2-agonists should be added to his treatment regimen.* - **Long-acting β2-agonists (LABAs)** should typically **not be used as monotherapy** in asthma due to a potential risk of severe exacerbations and asthma-related deaths. - LABAs are generally added to an **ICS regimen** when asthma remains uncontrolled despite adequate ICS therapy. *Systemic corticosteroids should be added to his treatment regimen.* - **Systemic corticosteroids** are reserved for **severe asthma exacerbations** or for patients with very severe persistent asthma unresponsive to other treatments, given their significant side effects with long-term use. - The patient's current symptoms do not warrant the immediate use of systemic corticosteroids, which carry risks such as **osteoporosis**, **diabetes**, and **hypertension**. *He should continue with current treatment.* - Continuing with SABA monotherapy when used 1-2 times per week indicates **persistent asthma**, which is **suboptimally controlled**. - Current guidelines suggest that SABA use more than twice weekly warrants a step-up in therapy to include daily controller medication like **inhaled corticosteroids**.

Question 435: A 48-year-old woman visits the clinic with unintentional weight loss for the past 3 months. She is also concerned about difficulty swallowing solid food. She also has early satiety and mild abdominal discomfort. An upper gastrointestinal endoscopy is advised along with a biopsy. The histopathological report reveals gastric adenocarcinoma. She then undergoes a subtotal gastrectomy and is started on an adjuvant chemotherapy regimen with platinum and fluoropyrimidine. 2 weeks later she develops acute respiratory distress and chest pain. A D-dimer test is positive. Her blood pressure is 125/78, heart rate is 110/min, and oxygen saturation is 88%. CT scan of the chest reveals a clot in the anterior segmental artery in the right upper lung. Which of the following therapies should the patient be started on for her acute condition?

• A. Warfarin
• B. Low-molecular weight heparin (Correct Answer)
• C. Aspirin
• D. Clopidogrel
• E. Ticagrelor

Explanation: ***Low-molecular weight heparin*** - The patient presents with **acute pulmonary embolism (PE)** secondary to cancer, which significantly increases the risk of recurrent VTE. **LMWH** is the preferred treatment for cancer-associated VTE due to its superior efficacy and lower risk of recurrence compared to warfarin. - Given her **acute respiratory distress**, **chest pain**, **tachycardia**, and **hypoxemia**, immediate anticoagulation is crucial, and LMWH provides a rapid and predictable anticoagulant effect without the need for immediate laboratory monitoring. *Warfarin* - While warfarin is an anticoagulant, it has a **slow onset of action** and requires several days to achieve therapeutic levels, making it unsuitable for acute PE. - Warfarin also interacts with many drugs and requires frequent **INR monitoring**, which can be challenging in a patient receiving chemotherapy for gastric adenocarcinoma. *Aspirin* - Aspirin is an **antiplatelet agent** primarily used for arterial thrombosis prophylaxis and is **ineffective in treating acute venous thromboembolism (VTE)** like PE. - It does not provide sufficient anticoagulation to prevent further clot formation or address the existing pulmonary embolus. *Clopidogrel* - Clopidogrel is an **antiplatelet agent** that inhibits platelet aggregation and is used for arterial thrombotic events, such as acute coronary syndromes or prevention of stroke. - It is **not indicated for the treatment of acute PE** as it does not target the coagulation cascade involved in venous thrombosis. *Ticagrelor* - Ticagrelor is another **antiplatelet agent** primarily used in similar indications as clopidogrel (e.g., acute coronary syndromes). - Like other antiplatelet drugs, it is **ineffective for the treatment of acute venous thromboembolism (VTE)**, which requires anticoagulation.

Question 436: A 57-year-old man comes to the physician because of a 4-week history of constipation, episodic bloody stools, progressive fatigue, and a 5-kg (10.2-lb) weight loss. Digital rectal examination shows a hard, 1.5-cm rectal mass. A biopsy confirms the diagnosis of colorectal carcinoma. The patient begins treatment with a combination chemotherapy regimen that includes a drug that is also used in the treatment of wet age-related macular degeneration. This drug most likely acts by inhibiting which of the following substances?

• A. Vascular endothelial growth factor (Correct Answer)
• B. Interferon-alpha
• C. Metalloproteinase
• D. Fibroblast growth factor
• E. Epidermal growth factor

Explanation: ***Vascular endothelial growth factor*** - The drug described is likely **bevacizumab**, a monoclonal antibody that targets **VEGF**. - **VEGF** plays a crucial role in **angiogenesis**, promoting tumor growth and the abnormal blood vessel formation seen in **wet age-related macular degeneration**. *Interferon-alpha* - **Interferon-alpha** is an **immunomodulatory cytokine** used in treating certain cancers (e.g., melanoma, renal cell carcinoma) and viral infections (e.g., hepatitis B and C). - It does not have a role in the direct treatment of **wet age-related macular degeneration**. *Metalloproteinase* - **Metalloproteinases** are enzymes involved in **extracellular matrix remodeling** and can contribute to tumor invasion and metastasis, but are not the primary target for the drug described. - While inhibitors of MMPs have been explored, they are not the class of drugs recognized for dual use in **colorectal cancer** and **wet AMD**. *Fibroblast growth factor* - **Fibroblast growth factor (FGF)** is involved in diverse cellular processes including **cell growth, proliferation, and angiogenesis**. - While FGF signaling can promote tumor growth, it is not the main target of the drug used for both **colorectal carcinoma** and **wet AMD**. *Epidermal growth factor* - **Epidermal growth factor (EGF)** and its receptor **EGFR** are targets for certain cancer therapies (e.g., cetuximab, panitumumab) that inhibit cell proliferation and survival. - However, **EGFR inhibitors** are not used in the treatment of **wet age-related macular degeneration**.

Question 437: A 56-year-old postmenopausal woman comes to the physician because of a 6-month history of worsening pain and swelling in her left knee. She has a history of peptic ulcer disease for which she takes cimetidine. Examination shows palpable crepitus and limited range of motion of the left knee. Which of the following is the most appropriate pharmacotherapy for this patient’s symptoms?

• A. Acetylsalicylic acid
• B. Diclofenac
• C. Meloxicam
• D. Celecoxib (Correct Answer)
• E. Ketorolac

Explanation: ***Celecoxib*** - This patient suffers from **osteoarthritis** (evidenced by her age, postmenopausal status, knee pain, crepitus, and limited range of motion) and has a history of **peptic ulcer disease (PUD)**. **Celecoxib** is a **COX-2 selective NSAID**, which reduces the risk of gastrointestinal side effects compared to non-selective NSAIDs. - Given her history of PUD, a COX-2 selective NSAID is the most appropriate choice to manage her pain while minimizing the risk of a PUD exacerbation or bleed. *Acetylsalicylic acid* - **Aspirin** (acetylsalicylic acid) is a non-selective NSAID and would pose a significant risk of **gastrointestinal bleeding** or ulcer exacerbation in a patient with a history of **peptic ulcer disease**. - While it has anti-inflammatory properties, its adverse effect profile makes it unsuitable for this patient's chronic pain management. *Diclofenac* - **Diclofenac** is a **non-selective NSAID**, meaning it inhibits both COX-1 and COX-2 enzymes. - Due to its inhibition of COX-1, it carries an increased risk of **gastric ulcers** and bleeding, making it less safe for a patient with a history of **peptic ulcer disease**. *Meloxicam* - **Meloxicam** is a partially COX-2 selective NSAID, but it still has some affinity for COX-1 at higher doses, conferring a risk for **gastrointestinal adverse effects**. - Although it may have a slightly better GI safety profile than non-selective NSAIDs, **celecoxib** offers superior GI protection. *Ketorolac* - **Ketorolac** is a potent **non-selective NSAID** primarily used for short-term management of moderate to severe acute pain, often administered parenterally. - Its use is associated with a high risk of **gastrointestinal toxicity** and renal impairment, making it inappropriate for chronic pain management in a patient with **peptic ulcer disease**.

Question 438: A 45-year-old man presents with a persistent cough for the past month. He says it started off with a runny nose and fever, from which he recovered in a week, but he says that the cough persists after the resolution of the fever. The patient denies any expectoration, chest pain, weight loss, or breathlessness. He reports no history of recent travel or sick contacts. Past medical history is significant for chronic constipation. He reports a 15-pack-year smoking history but denies any alcohol or current recreational drug use. He says he did use intravenous drugs in his late twenties but quit after going through a drug rehabilitation program. Physical examination is unremarkable. Laboratory findings and a chest radiograph are normal. Which of the following would be the best choice as a cough suppressant in this patient?

• A. Oxymetazoline
• B. Pseudoephedrine
• C. Guaifenesin
• D. Dextromethorphan (Correct Answer)
• E. Codeine

Explanation: ***Dextromethorphan*** - Dextromethorphan is a commonly used **cough suppressant** that acts on the cough center in the medulla, making it a good choice for **non-productive coughs** after ruling out serious etiologies. - Its mechanism of action involves elevating the **cough threshold**, providing symptomatic relief for the persistent cough described. *Oxymetazoline* - **Oxymetazoline** is a topical **nasal decongestant** that causes vasoconstriction in the nasal passages. - It is primarily used for the relief of **nasal congestion** and rhinitis, not as a cough suppressant. *Pseudoephedrine* - **Pseudoephedrine** is an oral **decongestant** that works by vasoconstriction to reduce nasal and sinus congestion. - It does not directly suppress cough and is primarily indicated for symptoms related to **upper airway congestion**. *Guaifenesin* - **Guaifenesin** is an **expectorant** that thins bronchial secretions, making them easier to clear. - It is used for **productive coughs** to help expel mucus, not to suppress a dry, non-productive cough. *Codeine* - **Codeine** is an opioid that effectively suppresses cough but carries risks of **sedation**, **constipation**, and potential for **abuse**. - Given the patient's history of chronic constipation and past intravenous drug use, **opioid-based cough suppressants** like codeine should be avoided due to potential for adverse effects and relapse.

Question 439: A 65-year-old man presents to the emergency department with shortness of breath. He was at home cleaning his yard when his symptoms began. The patient is a farmer and does not have regular medical care. He has smoked two packs of cigarettes every day for the past 40 years. The patient lives alone and admits to feeling lonely at times. His temperature is 99.5°F (37.5°C), blood pressure is 159/95 mmHg, pulse is 90/min, respirations are 19/min, and oxygen saturation is 86% on room air. On physical exam, you note a man in distress. Pulmonary exam reveals poor air movement, wheezing, and bibasilar crackles. Cardiac exam is notable for an S4 heart sound. The patient is started on appropriate therapy and his symptoms improve. Prior to discharge he is no longer distressed when breathing and his oxygen saturation is 90% on room air. Which of the following interventions could improve mortality the most in this patient?

• A. Varenicline (Correct Answer)
• B. Albuterol
• C. Ipratropium
• D. Home oxygen
• E. Magnesium

Explanation: ***Varenicline*** - This patient presents with symptoms highly suggestive of an **acute exacerbation of COPD** (shortness of breath, poor air movement, wheezing, significant smoking history). **Smoking cessation** is the single most effective intervention to improve mortality in patients with COPD, and varenicline is a highly effective medication for this purpose. - While other interventions manage acute symptoms, quitting smoking addresses the underlying progressive lung damage and **reduces the risk of future exacerbations and overall mortality**. *Albuterol* - **Albuterol** is a **short-acting beta-agonist (SABA)** used as a rescue inhaler to provide rapid bronchodilation during an acute exacerbation of COPD. - While essential for **symptomatic relief** and managing acute episodes, it does not impact the long-term progression of COPD or overall mortality. *Ipratropium* - **Ipratropium** is a **short-acting muscarinic antagonist (SAMA)** that also causes bronchodilation and is used in the acute management of COPD exacerbations, often in combination with SABAs. - Like albuterol, it provides **symptomatic relief** but does not alter the disease course or improve long-term mortality. *Home oxygen* - **Home oxygen therapy** is indicated for patients with severe, chronic hypoxemia (PaO2 < 55 mmHg or SaO2 < 88%) on room air to improve quality of life and decrease mortality. - While beneficial for select patients with **chronic hypoxemia**, it is not a primary intervention for acute exacerbations or a more impactful mortality-reducing strategy than smoking cessation for a patient who continues to smoke. *Magnesium* - **Intravenous magnesium sulfate** can be considered in severe, life-threatening asthma exacerbations or acute COPD exacerbations that are unresponsive to standard bronchodilator therapy. - It works by inducing **bronchial smooth muscle relaxation** but is a therapy for acute rather than chronic management or mortality improvement.

Question 440: A 24-year-old woman comes to the physician because of excessive hair growth. She has noticed increasing numbers of dark hairs on her upper lip and on her abdomen over the past 8 years. Menarche was at the age of 13 years. Menses occur at regular 28-day intervals and last 5–6 days with moderate flow. She is sexually active with one male partner. Her only medication is a combination oral contraceptive. She is 168 cm (5 ft 6 in) tall and weighs 88 kg (193 lb); BMI is 31 kg/m2. Vital signs are within normal limits. Physical examination shows coarse dark hair on the upper lip and periumbilical and periareolar skin. Her external genitalia appear normal. The remainder of the examination shows no abnormalities. Midcycle serum studies show: Fasting glucose 95 mg/dL Dehydroepiandrosterone sulfate 3.1 μg/mL (N = 0.5–5.4) Luteinizing hormone 95 mIU/mL Follicle-stimulating hormone 75 mIU/mL 17α-Hydroxyprogesterone 190 ng/dL (N = 20–300) Testosterone 1.1 nmol/L (N < 3.5) Dihydrotestosterone 435 pg/mL (N < 300) A urine pregnancy test is negative. Which of the following is the most likely underlying cause of this patient's symptom?

• A. Peripheral insulin resistance
• B. Deficiency of 21-hydroxylase
• C. Androgen-producing tumor of the adrenals
• D. Increased activity of 5-alpha reductase (Correct Answer)
• E. Tumor of granulosa-theca cells of the ovary

Explanation: ***Increased activity of 5-alpha reductase*** - This patient presents with signs of **hirsutism** (excessive dark hair growth on the upper lip, abdomen, and peri-areolar areas) along with **normal testosterone levels** and elevated **dihydrotestosterone (DHT)**. Elevated DHT despite normal testosterone strongly suggests increased peripheral conversion of testosterone to DHT by **5-alpha reductase**. - **5-alpha reductase** converts testosterone into the more potent androgen **dihydrotestosterone (DHT)** in target tissues like hair follicles. The normal LH/FSH ratio, regular menses, and combination oral contraceptive use make conditions like PCOS less likely to be the primary cause of the androgen excess in this context. *Peripheral insulin resistance* - While **insulin resistance** is common in obese individuals (BMI 31) and can contribute to hirsutism, it typically leads to **elevated ovarian androgen production** (e.g., higher testosterone). Here, the testosterone is within the normal range, making it less likely to be the direct cause of the elevated DHT. - The fasting glucose is normal (95 mg/dL), which does not strongly support overt insulin resistance as the primary cause of excess androgenization in this clinical scenario. *Deficiency of 21-hydroxylase* - **21-hydroxylase deficiency (Congenital Adrenal Hyperplasia)** would typically present with significantly **elevated 17α-hydroxyprogesterone** levels, often into thousands of ng/dL, and signs of precocious puberty or virilization from childhood. - This patient's 17α-hydroxyprogesterone level is **190 ng/dL**, which is within the normal range (20–300 ng/dL), ruling out this condition. *Androgen-producing tumor of the adrenals* - An **adrenal androgen-producing tumor** would typically cause a **rapid onset** of severe hirsutism/virilization and often markedly elevated **DHEA-S** levels. - This patient's hirsutism developed gradually over 8 years, and her DHEA-S level is normal (3.1 μg/mL), making an adrenal tumor unlikely. *Tumor of granulosa-theca cells of the ovary* - While ovarian tumors (such as **granulosa-theca cell tumors**) can produce androgens and lead to hirsutism, they usually cause a **rapid onset** of symptoms and significantly **elevated testosterone levels**, often above 3.5 nmol/L. - This patient has a gradual onset of symptoms and normal testosterone levels, making an ovarian tumor less likely.

Question 441: A 14-year-old female with no past medical history presents to the emergency department with nausea and abdominal pain. On physical examination, her blood pressure is 78/65, her respiratory rate is 30, her breath has a fruity odor, and capillary refill is > 3 seconds. Serum glucose is 820 mg/dL. After starting IV fluids, what is the next best step in the management of this patient?

• A. Intravenous Dextrose in water
• B. Subcutaneous insulin glargine
• C. Intravenous regular insulin (Correct Answer)
• D. Intravenous glucagon
• E. Subcutaneous insulin lispro

Explanation: ***Intravenous regular insulin*** - The patient presents with **diabetic ketoacidosis (DKA)**, characterized by **hyperglycemia**, **fruity breath** (due to ketones), and **hypotension**. Prompt administration of **intravenous regular insulin** is crucial to lower blood glucose and resolve ketoacidosis. - **Regular insulin** is preferred intravenously due to its **rapid onset** and short duration of action, allowing for precise titration and continuous adjustment based on glucose levels. *Intravenous Dextrose in water* - **Dextrose** would further increase the already severely elevated blood glucose level in a patient with DKA, worsening the metabolic derangements. - Dextrose is typically initiated only after blood glucose drops to safe levels (<200 mg/dL) to prevent **hypoglycemia** during insulin infusion. *Subcutaneous insulin glargine* - **Insulin glargine** is a **long-acting insulin** designed for basal insulin coverage, not for acute management of severe hyperglycemia or DKA. - Its **slow onset of action** and prolonged effect make it unsuitable for the urgent and rapid glucose reduction required in DKA. *Intravenous glucagon* - **Glucagon** is a hormone that **raises blood glucose levels**, counteracting the effects of insulin. - Administering glucagon would exacerbate the severe hyperglycemia present in DKA and is used only in cases of severe hypoglycemia. *Subcutaneous insulin lispro* - **Insulin lispro** is a **rapid-acting insulin analog** but is typically given subcutaneously. - While faster than regular insulin subcutaneously, the **subcutaneous route** has variable absorption in critically ill patients, and the immediate and precisely controllable effect of intravenous regular insulin is needed in DKA.

Question 442: A 52-year-old man comes to the physician because of increasing weakness of his arms and legs over the past year. He has also had difficulty speaking for the past 5 months. He underwent a partial gastrectomy for gastric cancer 10 years ago. His temperature is 37.1°C (98.8°F), pulse is 88/min, and blood pressure is 118/70 mm Hg. Examination shows dysarthria. There is mild atrophy and twitching of the tongue. Muscle strength is decreased in all extremities. Muscle tone is decreased in the right lower extremity and increased in the other extremities. Deep tendon reflexes are absent in the right lower extremity and 4+ in the other extremities. Plantar reflex shows an extensor response on the left. Sensation is intact in all extremities. Which of the following is the most appropriate pharmacotherapy for this patient?

• A. Nusinersen
• B. Riluzole (Correct Answer)
• C. Glatiramer acetate
• D. Vitamin B12
• E. Corticosteroids

Explanation: ***Riluzole*** - This patient's presentation with progressive weakness, dysarthria, muscle atrophy, fasciculations (twitching of the tongue), and a mix of **upper motor neuron signs** (increased tone, 4+ reflexes, extensor plantar response) and **lower motor neuron signs** (decreased tone in one extremity, absent reflexes in another) is highly suggestive of **amyotrophic lateral sclerosis (ALS)** - **Riluzole** is an FDA-approved medication for ALS that reduces **glutamate-mediated excitotoxicity**, which is thought to contribute to neuronal degeneration in ALS - It has been shown to **extend survival** and **delay the need for tracheostomy** in patients with ALS *Nusinersen* - Nusinersen is an antisense oligonucleotide used to treat **spinal muscular atrophy (SMA)**, a genetic disorder characterized by alpha motor neuron degeneration - SMA presents differently from ALS, typically starting in infancy or childhood with progressive muscle weakness and hypotonia, **without the prominent upper motor neuron signs** seen in this patient *Glatiramer acetate* - Glatiramer acetate is an immunomodulatory drug used in the treatment of **multiple sclerosis (MS)** - MS is characterized by demyelination in the central nervous system, leading to a variety of neurological symptoms that can include weakness, but typically with **sensory disturbances** and often **relapsing-remitting courses**, which are not characteristic of this patient's presentation *Vitamin B12* - **Vitamin B12 deficiency** can cause neurological symptoms, including weakness, paresthesias, and gait abnormalities due to subacute combined degeneration of the spinal cord and peripheral neuropathy - While the patient had a partial gastrectomy (a risk factor for B12 deficiency), his clinical picture with **prominent upper motor neuron signs, dysarthria, and fasciculations is not typical for B12 deficiency**, which primarily affects sensory and peripheral motor function *Corticosteroids* - Corticosteroids are potent anti-inflammatory and immunosuppressive agents used in various neurological conditions such as **multiple sclerosis exacerbations**, **myasthenia gravis**, or inflammatory myopathies - They are **not effective in treating ALS** and may even worsen muscle weakness in some individuals

Question 443: A 56-year-old man with substernal chest pain calls 911. When paramedics arrive, they administer drug X sublingually for the immediate relief of angina. What is the most likely site of action of drug X?

• A. Pulmonary arteries
• B. Large veins (Correct Answer)
• C. Cardiac muscle
• D. Large arteries
• E. Arterioles

Explanation: ***Large veins*** - Drug X is most likely **nitroglycerin**, which is administered sublingually for rapid relief of angina. - Its primary mechanism of action involves **vasodilation of large veins**, leading to **decreased preload** and reduced myocardial oxygen demand. *Pulmonary arteries* - While nitroglycerin can cause some pulmonary vasodilation, its primary therapeutic effect in angina is not focused on the **pulmonary arteries**. - Medications targeting pulmonary arteries are typically used for conditions like **pulmonary hypertension**. *Cardiac muscle* - Nitroglycerin does not directly act on **cardiac muscle** to improve angina; its effects are primarily vascular. - It does not directly enhance contractility or directly reduce oxygen consumption at the myocardial cellular level. *Large arteries* - Nitroglycerin does cause some **arterial vasodilation**, but this effect is less prominent than its venodilating effect at typical anti-anginal doses. - Significant arterial dilation can lead to **hypotension**, which is a side effect, not the primary therapeutic mechanism for angina relief. *Arterioles* - Nitroglycerin causes **less vasodilation of resistance arterioles** compared to its venodilating effects. - While some arteriolar dilation occurs, it mainly contributes to a decrease in **afterload**, but the predominant effect for angina relief is preload reduction.

Question 444: A 78-year-old woman with a history of cerebrovascular accident (CVA) presents to the emergency department with slurred speech, diplopia and dizziness that has persisted for eight hours. Upon further questioning you find that since her CVA one year ago, she has struggled with depression and poor nutrition. Her dose of paroxetine has been recently increased. Additionally, she is on anti-seizure prophylaxis due to sequelae from her CVA. CT scan reveals an old infarct with no acute pathology. Vital signs are within normal limits. On physical exam you find the patient appears frail. She is confused and has nystagmus and an ataxic gait. What would be an appropriate next step?

• A. Lower the dose of her anti-seizure medication (Correct Answer)
• B. Start total parenteral nutrition (TPN)
• C. Administer tissue plasminogen activator (tPA)
• D. Start trimethoprim-sulfamethoxazole (TMP-SMX)
• E. Increase the dose of her anti-seizure medication

Explanation: ***Lower the dose of her anti-seizure medication*** - The patient presents with classic symptoms of **anti-seizure medication toxicity**, including **slurred speech, diplopia, dizziness, nystagmus, and ataxia**, which are common with drugs like **phenytoin** or **carbamazepine**. - Given her **frailty**, poor nutrition, and recent CVA, she is likely more susceptible to adverse drug effects, making a dose reduction the most appropriate next step to resolve the toxicity. *Start total parenteral nutrition (TPN)* - While the patient has **poor nutrition**, her acute symptoms are neurological and suggest a drug-related issue, not a primary nutritional emergency requiring TPN. - TPN carries its own risks and is not indicated as an immediate treatment for drug toxicity or acute neurological symptoms in this context. *Administer tissue plasminogen activator (tPA)* - The patient's symptoms have been present for **eight hours**, exceeding the typical **time window for thrombolytic therapy** for acute ischemic stroke, which is generally 3 to 4.5 hours. - The **CT scan shows an old infarct** with no acute pathology, ruling out an acute ischemic stroke that would warrant tPA. *Start trimethoprim-sulfamethoxazole (TMP-SMX)* - There is **no indication of an infection** in the provided clinical picture; her symptoms are neurological and consistent with medication toxicity. - Administering an antibiotic without evidence of infection is inappropriate and could lead to unnecessary side effects. *Increase the dose of her anti-seizure medication* - The patient is exhibiting clear signs of **anti-seizure medication toxicity** (slurred speech, diplopia, dizziness, nystagmus, ataxia). - Increasing the dose would exacerbate these symptoms and could lead to more severe adverse events, making it a dangerous and inappropriate action.

Question 445: A patient in a phase 1 trial for a novel epoxide reductase inhibitor, being studied for stroke prophylaxis, develops pain and erythema on the right thigh two days after starting the trial. This rapidly progresses to a purpuric rash with necrotic bullae within 24 hours. Lab results show a PTT of 29 seconds, PT of 28 seconds, and INR of 2.15. What is the most likely pathogenesis of this condition?

• A. Decreased plasmin activity
• B. Decreased platelet count
• C. Decreased protein C levels (Correct Answer)
• D. Increased factor VIII activity
• E. Decreased antithrombin III activity

Explanation: ***Decreased protein C levels*** - The clinical presentation of **pain and erythema progressing to purpuric rash with necrotic bullae** within 2-3 days of starting therapy, along with elevated PT/INR, is **pathognomonic for warfarin-induced skin necrosis**. - This novel **epoxide reductase inhibitor** works like warfarin by inhibiting **vitamin K epoxide reductase**, which depletes all vitamin K-dependent factors. - **Protein C and protein S** (natural anticoagulants) have **short half-lives** (6-8 hours) and drop rapidly, while procoagulant factors II, VII, IX, and X have longer half-lives (24-60 hours). - This creates a **transient hypercoagulable state** in the first 2-3 days of therapy with **low protein C/S** but relatively preserved procoagulant factors, leading to **microvascular thrombosis** and skin necrosis. - Most common in patients with **hereditary protein C or S deficiency** or those receiving loading doses. *Decreased antithrombin III activity* - Antithrombin III is **not a vitamin K-dependent factor** and is not directly affected by epoxide reductase inhibitors. - Decreased antithrombin III would cause thrombosis but does not explain the **specific temporal relationship** and mechanism of warfarin-induced skin necrosis. - Antithrombin III deficiency causes **venous thromboembolism**, not the characteristic cutaneous necrosis pattern. *Decreased plasmin activity* - Plasmin is involved in **fibrinolysis** and is not affected by vitamin K epoxide reductase inhibitors. - Decreased plasmin activity would impair clot breakdown but does not explain the **early hypercoagulable state** specific to warfarin initiation. - This mechanism is not relevant to warfarin-induced skin necrosis. *Decreased platelet count* - The lab values provided show **elevated PT/INR**, consistent with coagulation factor depletion, not thrombocytopenia. - Thrombocytopenia causes **petechiae and mucosal bleeding**, not the large **necrotic bullae** seen here. - Platelet count is not affected by epoxide reductase inhibitors. *Increased factor VIII activity* - Factor VIII is **not a vitamin K-dependent factor** and is not depleted by epoxide reductase inhibitors. - While elevated factor VIII can contribute to hypercoagulability, it does not explain the **specific mechanism and timeline** of warfarin-induced skin necrosis. - This is not the primary pathogenesis of this condition.

Question 446: A 32-year-old man comes to the physician because of a 2-week history of diarrhea. During this period, he has had about 10 bowel movements per day. He states that his stools are light brown and watery, with no blood or mucus. He also reports mild abdominal pain and nausea. Over the past year, he has had 6 episodes of diarrhea that lasted several days and resolved spontaneously. Over this time, he also noticed frequent episodes of reddening in his face and neck. He returned from a 10-day trip to Nigeria 3 weeks ago. There is no personal or family history of serious illness. He has smoked a pack of cigarettes daily for the past 13 years. His temperature is 37°C (98.6°F), pulse is 110/min, and blood pressure is 100/60 mm Hg. Physical examination shows dry mucous membranes. The abdomen is tender with no rebound or guarding. The remainder of the examination shows no abnormalities. Serum studies show: Na+ 136 mEq/L Cl- 102 mEq/L K+ 2.3 mEq/L HCO3- 22 mEq/L Mg2+ 1.7 mEq/L Ca2+ 12.3 mg/dL Glucose (fasting) 169 mg/dL Nasogastric tube aspiration reveals significantly decreased gastric acid production. Which of the following is the most likely underlying cause of this patient's symptoms?

• A. Excessive accumulation of mast cells
• B. Increased conversion of 5-hydroxytryptophan to serotonin
• C. Functional gastrointestinal disorder
• D. Transmural inflammation of the intestinal walls
• E. Elevated serum VIP concentration (Correct Answer)

Explanation: ***Elevated serum VIP concentration*** - The patient's symptoms, including **chronic watery diarrhea**, **hypokalemia**, **hypercalcemia**, **impaired gastric acid secretion**, and **flushing**, are classic manifestations of a **VIPoma**. - **Vasoactive intestinal peptide (VIP)** directly stimulates intestinal fluid and electrolyte secretion, inhibits gastric acid secretion, and can cause cutaneous flushing and systemic effects. *Excessive accumulation of mast cells* - **Systemic mastocytosis** can cause diarrhea and flushing due to the release of histamine and other mediators. - However, it typically presents with **urticaria pigmentosa** (skin lesions), bone pain, and hepatosplenomegaly, and would not explain the **hypokalemia**, **hypercalcemia**, or **impaired gastric acid secretion** seen in this patient. *Increased conversion of 5-hydroxytryptophan to serotonin* - This describes **carcinoid syndrome**, which presents with **diarrhea**, **flushing**, and sometimes **cardiac valvular lesions** or **bronchospasm**. - While diarrhea and flushing are present, the patient's **hypokalemia**, **hypercalcemia**, and especially **achlorhydria** (decreased gastric acid production) are not typical features of carcinoid syndrome. *Functional gastrointestinal disorder* - Functional GI disorders like **irritable bowel syndrome (IBS)** can cause chronic diarrhea and abdominal pain. - However, they do not cause the systemic findings such as **flushing**, **hypokalemia**, **hypercalcemia**, or **hypochlorhydria** observed in this patient. *Transmural inflammation of the intestinal walls* - **Inflammatory bowel diseases (IBD)**, such as Crohn's disease, involve transmural inflammation and can cause chronic diarrhea, abdominal pain, and weight loss. - While IBD can cause diarrhea, it typically presents with **bloody stools**, fever, and does not explain the flushing, hypokalemia, hypercalcemia, or achlorhydria found here.

Question 447: A 25-year-old man is rushed to the emergency department following a motor vehicle accident. After an initial evaluation, he is found to have bilateral femoral fractures. After surgical fixation of his fractures, he suddenly starts to feel nauseated and becomes agitated. Past medical history is significant for a thyroid disorder. His temperature is 40.0°C (104°F), blood pressure is 165/100 mm Hg, pulse is 170/min and irregularly irregular, and respirations are 20/min. On physical examination, the patient is confused and delirious. Oriented x 0. Laboratory studies are significant for the following: Thyroxine (T4), free 5 ng/dL Thyroid stimulating hormone (TSH) 0.001 mU/L The patient is started on propranolol to control his current symptoms. Which of the following best describes the mechanism of action of this new medication?

• A. Inhibition of an underlying autoimmune process
• B. Interference with enterohepatic circulation and recycling of thyroid hormones
• C. Inhibition of release of thyroid hormones
• D. Inhibition of thyroid peroxidase enzyme
• E. Decrease the peripheral conversion of T4 to T3 (Correct Answer)

Explanation: ***Decrease the peripheral conversion of T4 to T3*** - **Propranolol**, a non-selective beta-blocker, plays a crucial role in thyroid storm management by **blocking beta-adrenergic receptors**, thereby mitigating the cardiovascular symptoms like tachycardia and hypertension. - Furthermore, at high doses, propranolol directly **inhibits the peripheral conversion of T4 to T3**, which is the more biologically active thyroid hormone, thus reducing the overall thyroid hormone effect. *Inhibition of an underlying autoimmune process* - This mechanism describes drugs like **glucocorticoids** or **immunosuppressants**, which are effective in autoimmune thyroid diseases like Graves' disease but are not the primary mechanism of action for propranolol. - While thyroid storm is often triggered by **Graves' disease**, initial management focuses on symptom control and blocking hormone effects, not primarily immune suppression by propranolol. *Interference with enterohepatic circulation and recycling of thyroid hormones* - This mechanism is characteristic of **cholestyramine** or **iodinated contrast agents**, which bind to thyroid hormones in the gut, preventing their reabsorption and increasing their fecal excretion. - Propranolol does not significantly influence the enterohepatic circulation or recycling of thyroid hormones. *Inhibition of release of thyroid hormones* - This action is primarily achieved by **iodine preparations** (e.g., Lugol's iodine, potassium iodide) given after antithyroid drugs, which acutely block the release of preformed thyroid hormones from the gland. - Although propranolol can reduce some aspects of sympathetic stimulation, it does not directly inhibit the release of thyroid hormones from the thyroid gland. *Inhibition of thyroid peroxidase enzyme* - This mechanism is specific to **thionamides** like **propylthiouracil (PTU)** and **methimazole**, which block the organification of iodine and coupling of iodotyrosines, thereby inhibiting thyroid hormone synthesis. - Propranolol does not directly affect the thyroid peroxidase enzyme or thyroid hormone synthesis.

Question 448: A 31-year-old man presents with a headache, myalgias, nausea, irritability, and forgetfulness. He developed these symptoms gradually over the past 3 months. He is a motor mechanic, and he changed his place of work 4 months ago. He smokes a half a pack of cigarettes per day. His vaccinations are up to date. On presentation, his vital signs are as follows: blood pressure is 145/70 mm Hg, heart rate is 94/min, respiratory rate is 17/min, and temperature is 36.8℃ (98.2℉). Physical examination reveals diffuse erythema of the face and chest and slight abdominal distention. Neurological examination shows symmetrical brisk upper and lower extremities reflexes. Blood tests show the following results: pH 7.31 Po2 301 mm Hg Pco2 28 mm Hg Na+ 141 mEq/L K+ 4.3 mEq/L Cl- 109 mEq/L HCO3- 17 mEq/L Base Excess -3 mEq/L Carboxyhemoglobin 38% Methemoglobin 1% Serum cyanide 0.35 mcg/mL (Reference range 0.5–1 mcg/mL) Which of the following statements about the patient’s condition is true?

• A. Viral infection should be suspected in this patient.
• B. Chronic cyanide exposure is the main cause of patient’s condition.
• C. The patient’s symptoms are a consequence of his essential hypertension.
• D. This patient’s symptoms are due to CO-induced inactivation of cytochrome oxidase and carboxyhemoglobin formation. (Correct Answer)
• E. This patient has disrupted glycolysis due to inactivation of fructose-bisphosphate aldolase.

Explanation: ***This patient’s symptoms are due to CO-induced inactivation of cytochrome oxidase and carboxyhemoglobin formation.*** - The elevated **carboxyhemoglobin (COHb)** level of 38% indicates significant **carbon monoxide (CO) poisoning**. CO binds to **hemoglobin** with much greater affinity than oxygen, forming COHb, which impairs **oxygen transport** to tissues and causes **hypoxia**. - CO also directly binds to and inhibits **cytochrome c oxidase** in the **electron transport chain**, disrupting cellular respiration and ATP production, which contributes to systemic symptoms like **headache**, **myalgias**, and **neurological dysfunction** (irritability, forgetfulness), consistent with this patient's presentation. *Viral infection should be suspected in this patient.* - While headache and myalgias can be seen in **viral infections**, the presence of severely elevated **carboxyhemoglobin** and the patient's occupation as a mechanic strongly point towards carbon monoxide poisoning. - The other specific findings, such as **diffuse erythema** and **neurological changes**, are not typical or sufficient to primarily suspect a viral infection in light of the lab results. *Chronic cyanide exposure is the main cause of patient’s condition.* - The **serum cyanide level** is below the reference range (0.35 mcg/mL vs. 0.5–1 mcg/mL), indicating that **cyanide poisoning** is not present and therefore not the cause of his symptoms. - **Cyanide poisoning** would typically cause more acute and severe symptoms related to cellular **hypoxia**, often with a normal PCO2 and lactate production. *The patient’s symptoms are a consequence of his essential hypertension.* - While the patient has **elevated blood pressure** (145/70 mmHg), which could be a sign of **hypertension**, this alone does not explain the full constellation of symptoms, especially the **erythema** and severe **neurological impairment** described. - Most importantly, **hypertension** would not account for the significantly elevated **carboxyhemoglobin** levels, which are the primary driver of the patient's symptoms. *This patient has disrupted glycolysis due to inactivation of fructose-bisphosphate aldolase.* - There is no clinical or laboratory evidence to suggest disruption of **glycolysis** or inactivation of **fructose-bisphosphate aldolase**. - This enzyme is crucial for glycolysis, and its dysfunction would lead to different metabolic derangements, distinct from the signs and symptoms of **carbon monoxide poisoning**, which directly impacts oxygen delivery and utilization.

Question 449: A 79-year-old man presents to a physician’s office for a routine appointment. He had a myocardial infarction 3 years ago and was started on aspirin, carvedilol, captopril, and high-dose atorvastatin. He denies shortness of breath or cough. He exercises regularly and is on a healthy diet that is good for his heart. The vital signs include: pulse 80/min, respirations 16/min and blood pressure 122/80 mm Hg. The physical examination reveals an overweight male with a body mass index (BMI) of 28 kg/m2. The fasting lipid profile is as follows: Total cholesterol 200 mg/dL High-density lipoprotein (HDL) 35 mg/dL Low-density lipoprotein (LDL) 140 mg/dL Triglycerides 120 mg/dL Which of the following drugs should be added to his regimen?

• A. Niacin
• B. Losartan
• C. Furosemide
• D. Orlistat
• E. Ezetimibe (Correct Answer)

Explanation: ***Correct: Ezetimibe*** - This patient is on a **high-dose statin (atorvastatin)** and already has a history of **myocardial infarction (MI)**. His **LDL is still elevated at 140 mg/dL**, which indicates that he is at high risk for future cardiovascular events. - According to **ACC/AHA guidelines**, for patients with established **atherosclerotic cardiovascular disease (ASCVD)** and persistently high LDL (target <70 mg/dL) despite maximal statin therapy, a **non-statin agent** like **ezetimibe** should be added to further lower LDL and reduce cardiovascular risk. - The **IMPROVE-IT trial** demonstrated that adding ezetimibe to statin therapy in post-ACS patients significantly reduces cardiovascular events. *Incorrect: Niacin* - While niacin can increase **HDL** and decrease **triglycerides** and **LDL**, it has fallen out of favor for routine use in ASCVD prevention. - Large clinical trials (AIM-HIGH, HPS2-THRIVE) have shown that adding niacin to statin therapy does not provide additional cardiovascular benefit and is associated with significant side effects like **flushing, pruritus, and increased risk of diabetes**. *Incorrect: Losartan* - Losartan is an **angiotensin receptor blocker (ARB)**, typically used for **hypertension** or **heart failure**, or as an alternative to ACE inhibitors in patients who develop cough. - The patient's **blood pressure is well-controlled (122/80 mm Hg)**, and he is already on an **ACE inhibitor (captopril)**, so losartan is not indicated. *Incorrect: Furosemide* - Furosemide is a **loop diuretic** primarily used to treat **fluid retention** due to heart failure, liver disease, or kidney disease. - The patient has no signs or symptoms of **fluid overload** (e.g., shortness of breath, edema), making furosemide unnecessary. *Incorrect: Orlistat* - Orlistat is a lipase inhibitor used for **weight loss** by reducing dietary fat absorption. - While the patient is overweight (BMI 28 kg/m²), his primary issue here is uncontrolled LDL despite maximal statin therapy post-MI, not simply weight management, and **ezetimibe directly targets the LDL problem**.

Question 450: A 21-year-old primigravid woman comes to the physician at 10 weeks' gestation because of progressive fatigue for the past 3 weeks. She reports that she has had a 3.2-kg (7-lb) weight loss after conceiving despite an increase in appetite. She has become increasingly anxious and has trouble falling asleep. There is no personal or family history of serious illness. Medications include folic acid and a multivitamin. She is 165 cm (5 ft 5 in) tall and weighs 55 kg (120 lb); BMI is 20 kg/m2. Her temperature is 37.4°C (99.4°F), pulse is 120/min, respirations are 18/min, and blood pressure is 150/70 mm Hg. The globes of the eyes are prominent. The thyroid gland is firm and diffusely enlarged. Neurologic examination shows a fine resting tremor of the hands. There is a midsystolic click at the apex and a grade 2/6 early systolic murmur at the upper left sternal border. Serum thyroid-stimulating hormone concentration is 0.1 μU/mL. An ECG is normal except for sinus tachycardia. Which of the following is the most appropriate next step in management?

• A. Radioactive iodine ablation
• B. Lugol's iodine
• C. Atenolol
• D. Propylthiouracil (Correct Answer)
• E. Thyroidectomy

Explanation: ***Propylthiouracil*** - The patient presents with classic symptoms of **hyperthyroidism** (**fatigue, weight loss despite increased appetite, anxiety, tachycardia, prominent globes, fine tremor, diffusely enlarged thyroid**, and a **TSH of 0.1 μU/mL**), likely **Graves' disease** given her age and presentation. - **Propylthiouracil (PTU)** is the preferred antithyroid drug during the **first trimester of pregnancy** due to a lower risk of teratogenicity compared to methimazole, especially preventing **embryopathy** (aplasia cutis). *Radioactive iodine ablation* - **Radioactive iodine (RAI) ablation** is **contraindicated in pregnancy** as it crosses the placenta and can cause **fetal hypothyroidism** and **cretinism** by destroying the fetal thyroid gland. - It is typically used for definitive treatment of hyperthyroidism in non-pregnant individuals or post-pregnancy. *Lugol's iodine* - **Lugol's iodine (potassium iodide)** is used in the short term to acutely block thyroid hormone release, primarily as preparation for thyroidectomy or in **thyroid storm**. - It is not a primary long-term treatment for hyperthyroidism and can be problematic in pregnancy due to potential for fetal goiter and hypothyroidism with prolonged use. *Atenolol* - **Atenolol**, a **beta-blocker**, can relieve adrenergic symptoms of hyperthyroidism like tachycardia, tremors, and anxiety. - However, it does not address the underlying **excessive thyroid hormone production** and has been associated with **fetal growth restriction** and **bradycardia** in pregnancy. **Propranolol** is a safer beta-blocker if needed during pregnancy but should be used cautiously. *Thyroidectomy* - **Thyroidectomy** is a definitive treatment for hyperthyroidism but is usually reserved for patients who fail medical therapy or have large goiters causing compressive symptoms, and its preferred timing is during the **second trimester of pregnancy** if indicated, to minimize risks to both mother and fetus. - It is not the most appropriate initial management step for an uncomplicated presentation of hyperthyroidism in early pregnancy.

Question 451: A 55-year-old woman with type 2 diabetes mellitus presents to her physician with intermittent nausea for the past 2 months. Her symptoms are exacerbated within one hour after eating. She has no other history of a serious illness. She takes metformin and injects insulin. Her vitals are normal. Abdominal examination is normal. An ECG shows normal sinus rhythm with no evidence of ischemia. Hemoglobin A1c is 7%. A gastric emptying scan shows 60% of her meal in the stomach 75 minutes after eating. Which of the following is the most appropriate pharmacotherapy at this time?

• A. Dimenhydrinate
• B. Octreotide
• C. Lorazepam
• D. Metoclopramide (Correct Answer)
• E. Ondansetron

Explanation: ***Metoclopramide*** - This patient presents with symptoms and gastric emptying scan results consistent with **diabetic gastroparesis**. Metoclopramide is a **prokinetic agent** that increases gastrointestinal motility and reduces nausea and vomiting. - As a **dopamine D2 receptor antagonist**, it enhances cholinergic stimulation of the GI tract, promoting gastric emptying. *Dimenhydrinate* - This is an **antihistamine** primarily used for motion sickness. While it can help with nausea, it does not address the underlying **gastroparesis** and would not improve gastric emptying. - It also has **sedative side effects** that often limit its use. *Octreotide* - **Octreotide** is a **somatostatin analog** used to treat conditions like VIPomas, acromegaly, and esophageal varices. It can actually *slow* gastric emptying. - It is not indicated for the treatment of **gastroparesis** and would likely worsen symptoms. *Lorazepam* - **Lorazepam** is a **benzodiazepine** used for anxiety and sometimes as an antiemetic due to its anxiolytic and sedative properties, not due to direct effects on gastrointestinal motility. - It does not address the underlying pathology of **gastroparesis** and its use would be inappropriate as a primary treatment. *Ondansetron* - **Ondansetron** is a **5-HT3 receptor antagonist** that effectively treats chemotherapy-induced nausea and vomiting. - While it helps with nausea, it does not improve **gastric motility** or address the delayed gastric emptying seen in gastroparesis.

Question 452: A 50-year-old man comes to the emergency department because of a severely painful right eye. The pain started an hour ago and is accompanied by frontal headache and nausea. The patient has vomited twice since the onset of the pain. He has type 2 diabetes mellitus. He immigrated to the US from China 10 years ago. He works as an engineer at a local company and has been under a great deal of stress lately. His only medication is metformin. Vital signs are within normal limits. The right eye is red and is hard on palpation. The right pupil is mid-dilated and nonreactive to light. The left pupil is round and reactive to light and accommodation. Which of the following agents is contraindicated in this patient?

• A. Oral acetazolamide
• B. Topical epinephrine (Correct Answer)
• C. Topical timolol
• D. Topical apraclonidine
• E. Topical pilocarpine

Explanation: ***Topical epinephrine*** - **Epinephrine** is a **sympathomimetic** agent that can **dilate the pupil** (mydriasis). - In a patient experiencing **acute angle-closure glaucoma**, mydriasis will further narrow the angle and **exacerbate the sudden rise in intraocular pressure**, making it contraindicated. *Oral acetazolamide* - **Acetazolamide** is a **carbonic anhydrase inhibitor** that **reduces aqueous humor production**, thereby lowering intraocular pressure. - It is often used as a first-line systemic treatment for **acute angle-closure glaucoma** and is not contraindicated. *Topical timolol* - **Timolol** is a **beta-adrenergic blocker** that **reduces aqueous humor production** without affecting pupil size. - It is a common topical medication for lowering intraocular pressure in various forms of glaucoma, including acute angle-closure. *Topical apraclonidine* - **Apraclonidine** is an **alpha-2 adrenergic agonist** that lowers intraocular pressure primarily by **reducing aqueous humor production** and to a lesser extent by increasing uveoscleral outflow. - It is used as an adjunctive treatment for acute angle-closure glaucoma and is not contraindicated. *Topical pilocarpine* - **Pilocarpine** is a **cholinergic agonist** that causes **pupillary miosis** and **contraction of the ciliary muscle**, which **opens the trabecular meshwork** and facilitates aqueous outflow. - It is often used after initial pressure reduction in acute angle-closure glaucoma to reverse the pupillary block.

Question 453: A 25-year-old man is brought to the emergency department after his girlfriend discovered him at home in a minimally responsive state. He has a history of drinking alcohol excessively and using illicit drugs. On arrival, he does not respond to commands but withdraws all extremities to pain. His pulse is 90/min, respirations are 8/min, and blood pressure is 130/90 mm Hg. Pulse oximetry while receiving bag-valve-mask ventilation shows an oxygen saturation of 95%. Examination shows cool, dry skin, with scattered track marks on his arms and legs. The pupils are pinpoint and react sluggishly to light. His serum blood glucose level is 80 mg/dL. The most appropriate next step in management is intravenous administration of which of the following?

• A. Fomepizole
• B. Naltrexone
• C. Methadone
• D. Naloxone (Correct Answer)
• E. Phentolamine

Explanation: ***Naloxone*** - The patient presents with classic signs of **opioid overdose**: altered mental status, **respiratory depression** (8/min), and **pinpoint pupils**. - **Naloxone** is an opioid antagonist that rapidly reverses the effects of opioid toxicity and is the most appropriate first-line treatment in this scenario. *Fomepizole* - This medication is used as an antidote for **methanol** and **ethylene glycol poisoning**, which typically present with metabolic acidosis and renal failure, not pinpoint pupils and respiratory depression. - There are no clinical signs in this patient indicative of methanol or ethylene glycol ingestion. *Naltrexone* - **Naltrexone** is an opioid antagonist used for long-term management of opioid use disorder or alcohol dependence, but it is not used in acute overdose resuscitation due to its slower onset and formulation (oral or long-acting injectable). - Its primary role is to prevent relapse, not to reverse acute respiratory depression. *Methadone* - **Methadone** is a long-acting opioid agonist used for opioid replacement therapy and chronic pain management. - Administering methadone would worsen the patient's opioid-induced respiratory depression and central nervous system depression. *Phentolamine* - **Phentolamine** is an alpha-adrenergic blocker used to treat hypertensive crises, particularly those caused by pheochromocytoma or extravasation of vasopressors. - It has no role in managing opioid overdose and could lead to hypotension in this patient.

Question 454: A 23-year-old male presents to the emergency room following a gunshot wound to the leg. On arrival his temperature is 99°F (37.2°C), blood pressure is 90/60 mmHg, pulse is 112/min, respirations are 21/min, and pulse oximetry is 99% on room air. Two large bore IVs are placed and he receives crystalloid fluid replacement followed by 2 units of crossmatched packed red blood cells. Immediately following transfusion, his temperature is 102.2°F (39°C), blood pressure is 93/64 mmHg, pulse is 112/min, respirations are 21/min, and pulse oximetry is 99% on room air. There is oozing from his IV sites. You check the records and realize there was a clerical error with the blood bank. What is the mechanism for his current condition?

• A. IgE mediated reaction
• B. Deposition of immune complexes
• C. Production of leukotrienes
• D. Preformed antibodies (Correct Answer)
• E. T lymphocyte reaction

Explanation: ***Preformed antibodies*** - The patient's symptoms, including **fever**, persistent **hypotension**, and **oozing from IV sites** (which suggests **DIC**), immediately following a transfusion due to a clerical error, are classic signs of an **acute hemolytic transfusion reaction (AHTR)**. - AHTRs are caused by the recipient's **preformed antibodies** (e.g., anti-A, anti-B) reacting with donor red blood cell antigens, leading to rapid **intravascular hemolysis**, cytokine release, and activation of the coagulation cascade. *IgE mediated reaction* - An **IgE-mediated reaction** (Type I hypersensitivity) typically presents with symptoms like **hives, angioedema, bronchospasm, or anaphylaxis**. - While transfusion reactions can involve allergic components, the clinical picture of severe hemolysis and DIC points away from a primary IgE-mediated anaphylactic response. *Deposition of immune complexes* - **Immune complex deposition** (Type III hypersensitivity) is characteristic of conditions like **serum sickness** or **lupus**. - These reactions usually manifest hours to days after exposure and typically involve features like **arthritis** or **glomerulonephritis**, which are not seen in this acute scenario. *Production of leukotrienes* - **Leukotrienes** are mediators of inflammation and bronchoconstriction, prominently involved in **asthma** and some allergic reactions. - While they may play a secondary role in the inflammatory response, they are not the primary mechanism initiating an **acute hemolytic transfusion reaction**. *T lymphocyte reaction* - **T lymphocyte reactions** are central to **delayed-type hypersensitivity** (Type IV) and **graft-versus-host disease (GVHD)**. - These reactions have a delayed onset (**days to weeks**) and primarily involve cellular immunity, which does not explain the immediate and severe hemolytic reaction observed.

Question 455: A 61-year-old man presents to the emergency department for the evaluation of polyuria, polydipsia, and confusion. He has a history of the psychiatric disease but is unable to provide additional details. He is admitted to the hospital and his home medications are continued. Routine testing is unrevealing for the etiology of his symptoms. Desmopressin acetate (DDAVP) is given, but no effect is seen on urine output or urine osmolarity. Which of the following medications could have induced this syndrome?

• A. Lithium (Correct Answer)
• B. Omeprazole
• C. Nafcillin
• D. Nitrofurantoin
• E. Ranitidine

Explanation: ***Lithium*** - The patient exhibits symptoms of **polyuria, polydipsia, and confusion**, which are classic signs of **nephrogenic diabetes insipidus (NDI)**. - The lack of response to **desmopressin (DDAVP)** confirms the diagnosis of NDI, and considering his history of psychiatric illness, **lithium** is a well-known cause of drug-induced NDI by interfering with the action of **vasopressin** in the renal tubules. *Omeprazole* - **Omeprazole** is a proton pump inhibitor primarily used for conditions like **GERD** and **peptic ulcers**. - It is not associated with causing nephrogenic diabetes insipidus or significant renal toxicity leading to polyuria and polydipsia. *Nafcillin* - **Nafcillin** is a penicillinase-resistant penicillin used to treat staphylococcal infections. - While it can cause **interstitial nephritis** in rare cases, leading to renal dysfunction, it does not typically induce nephrogenic diabetes insipidus directly or cause severe polyuria and polydipsia in this manner. *Nitrofurantoin* - **Nitrofurantoin** is an antibiotic used for urinary tract infections. - Its main side effects include **gastrointestinal upset**, **pulmonary fibrosis (rare)**, and **peripheral neuropathy**, but it is not associated with nephrogenic diabetes insipidus. *Ranitidine* - **Ranitidine** is an H2-receptor antagonist used to reduce stomach acid production. - It is not known to cause nephrogenic diabetes insipidus or significant renal adverse effects that would manifest as polyuria and polydipsia unresponsive to DDAVP.

Question 456: A 51-year-old woman schedules an appointment with her physician with complaints of upper abdominal pain, nausea, and early satiety for the last 6 months. She has type 1 diabetes for the past 10 years and is on subcutaneous insulin therapy. She complains of occasional heartburn and lost 4.5 kg (10 lb) in the past 6 months without any changes in her diet. The medical history is significant for long QT syndrome. The vital signs include: pulse 74/min, respirations 18/min, temperature 37.7°C (99.9°F), and blood pressure 140/84 mm Hg. Abdominal examination is negative for organomegaly or a palpable mass, but there is a presence of succussion splash. She has slightly decreased vision in both her eyes and fundoscopy reveals diabetic changes in the retina. Esophagogastroduodenoscopy is performed, which is negative for obstruction, but a small ulcer is noted near the cardiac end of the stomach with some food particles. Which of the following drugs would be inappropriate in the management of this patient's condition?

• A. Bethanechol
• B. Domperidone
• C. Erythromycin
• D. Promethazine
• E. Cisapride (Correct Answer)

Explanation: ***Cisapride*** - Cisapride is a **prokinetic agent** that was largely withdrawn due to its propensity to cause **QT prolongation** and life-threatening arrhythmias, which is critically contraindicated in patients with a history of **long QT syndrome**. - The patient's history of **long QT syndrome** makes cisapride an inappropriate and dangerous choice for managing her diabetic gastroparesis. *Bethanechol* - Bethanechol is a **muscarinic agonist** that can increase gastric motility, but it is not typically first-line for gastroparesis due to potential systemic cholinergic side effects. - While it aids in stomach emptying, its use must be weighed against its side-effect profile, though it doesn't directly interact with QT interval. *Domperidone* - Domperidone is a **dopamine D2 receptor antagonist** that acts as a prokinetic and antiemetic, primarily in the periphery, minimizing central nervous system side effects. - While generally safer regarding QT prolongation than some other prokinetics, it can still prolong the QT interval in high doses or in susceptible individuals, but less severely than cisapride. *Erythromycin* - Erythromycin is a **macrolide antibiotic** that acts as a **motilin receptor agonist**, significantly increasing gastric emptying. - It's a useful prokinetic for gastroparesis, although long-term use can be limited by antibiotic resistance and potential for **QT prolongation**, though less severe than cisapride. *Promethazine* - Promethazine is an **antihistamine** with antiemetic properties, often used for nausea and vomiting, but it is **not a prokinetic agent**. - It would address the nausea symptomatically but would not improve gastric emptying in a patient with gastroparesis.

Question 457: A 30-year-old man comes to the physician for follow-up evaluation for hypertension. He reports a 1-month history of episodic throbbing headaches, palpitations, and paroxysmal sweating. Blood pressure is 160/90 mm Hg. He appears pale but physical examination is otherwise unremarkable. Laboratory studies show elevated urine and plasma metanephrines. A CT scan of the abdomen shows a mass in the left adrenal gland. Which of the following is the most appropriate initial pharmacotherapy for this patient?

• A. Propranolol
• B. Phenoxybenzamine (Correct Answer)
• C. Hydrochlorothiazide
• D. Octreotide
• E. Clonidine

Explanation: ***Phenoxybenzamine*** - This patient presents with symptoms highly suggestive of a **pheochromocytoma** (episodic throbbing headaches, palpitations, paroxysmal sweating, hypertension), confirmed by **elevated metanephrines** and an **adrenal mass**. - **Alpha-blockade** with phenoxybenzamine is the initial and crucial step for blood pressure control to prevent a **hypertensive crisis** during surgical tumor removal. *Propranolol* - **Beta-blockers** like propranolol should only be administered *after* adequate alpha-blockade has been established. - Giving a beta-blocker first can lead to **unopposed alpha-adrenergic stimulation**, worsening hypertension and potentially causing a hypertensive crisis. *Hydrochlorothiazide* - This is a **thiazide diuretic** used for essential hypertension and is not appropriate for the acute management of a **pheochromocytoma-induced hypertensive crisis**. - It does not address the underlying catecholamine excess and would be ineffective in preventing a crisis. *Octreotide* - **Octreotide** is a somatostatin analog primarily used to treat neuroendocrine tumors like **carcinoid syndrome** or VIPomas. - It has no role in the management of pheochromocytoma, which arises from chromaffin cells and secretes catecholamines. *Clonidine* - **Clonidine** is an **alpha-2 adrenergic agonist** that reduces sympathetic outflow from the central nervous system. - While it can lower blood pressure, it is not the first-line agent for pheochromocytoma and does not provide the comprehensive, irreversible alpha-blockade needed for surgical preparation.

Question 458: Thirty minutes after vaginal delivery of a 2780-g (6-lb 2-oz) newborn at term, a 25-year-old woman, gravida 1, para 1, has heavy vaginal bleeding. Her pregnancy was complicated by pre-eclampsia. Her pulse is 111/min and blood pressure is 95/65 mm Hg. Physical examination shows a fundal height 2 inches below the xiphoid process of the sternum. A drug with which of the following mechanisms of action is most appropriate for this patient?

• A. Activation of phospholipase C (Correct Answer)
• B. Depolarization of the motor end plate
• C. Increased synthesis of cyclic AMP
• D. Inhibition of norepinephrine reuptake
• E. Binding to prostaglandin I2 receptors

Explanation: ***Activation of phospholipase C*** - This patient presents with **postpartum hemorrhage (PPH)**, characterized by heavy vaginal bleeding, tachycardia, hypotension, and a poorly contracted uterus (normal fundal height is at the umbilicus immediately after delivery; 2 inches below the xiphoid is high indicating uterine atony). - The most appropriate first-line treatment for uterine atony is **oxytocin**, which acts by binding to G protein-coupled receptors, leading to the **activation of phospholipase C** and an increase in intracellular calcium, causing uterine muscle contraction. *Depolarization of the motor end plate* - This mechanism describes the action of **neuromuscular blocking agents** or agonists at the nicotinic acetylcholine receptor, which are not used for treating postpartum hemorrhage. - The motor end plate is involved in skeletal muscle contraction, not smooth muscle contraction of the uterus. *Increased synthesis of cyclic AMP* - **Increased cyclic AMP** generally leads to smooth muscle relaxation (e.g., beta-2 agonists like terbutaline), which would worsen uterine atony and postpartum hemorrhage. - Tocolytic agents that would cause uterine relaxation would be contraindicated in this scenario. *Inhibition of norepinephrine reuptake* - This mechanism describes the action of certain **antidepressants** (e.g., tricyclic antidepressants, SNRIs) or **stimulants**, which primarily affect the central nervous system and are not used to manage postpartum hemorrhage. - This action does not directly cause uterine contraction. *Binding to prostaglandin I2 receptors* - **Prostaglandin I2 (PGI2)**, also known as prostacyclin, is a potent vasodilator and inhibitor of platelet aggregation. Binding to its receptors would lead to smooth muscle relaxation and would increase bleeding, directly worsening postpartum hemorrhage. - Uterotonic agents like carboprost (PGF2α analog) act on different prostaglandin receptors to induce uterine contraction.

Question 459: A 64-year-old woman otherwise healthy presents with acute onset severe rectal bleeding. The patient says that 2 hours ago bleeding began suddenly after a difficult bowel movement. She says the blood is bright red, and, initially, bleeding was brisk but now has stopped. The patient denies having any similar symptoms in the past. She has noticed that she bled more easily while having her regular manicure/pedicure for the past 3 months but thought it was nothing serious. No significant past medical history and the patient does not take any current medications. Family history is unremarkable. Review of systems is positive for mild dyspnea on exertion the past 2-3 months. Her vital signs include: temperature 37.0°C (98.6°F), blood pressure 100/65 mm Hg, pulse 95/min, respiratory rate 15/min, and oxygen saturation 97% on room air. A cardiac examination is significant for a 2/6 systolic murmur loudest at the right upper sternal border. Rectal exam shows no evidence of external hemorrhoids, fissures, or lesions. No active bleeding is noted. The stool is guaiac positive. Deficiency of which of the following is most likely the cause of this patient’s condition?

• A. Factor VIII
• B. von Willebrand factor (Correct Answer)
• C. Antithrombin III
• D. Vitamin K
• E. ADAMTS13 gene mutation

Explanation: **von Willebrand factor** - The patient's **acute rectal bleeding** after a difficult bowel movement, along with a history of **easy bleeding** during manicures/pedicures, suggests a **primary hemostasis** defect. These symptoms, coupled with findings suggestive of **aortic stenosis** (systolic murmur, possible GI angiodysplasia due to her age), are highly indicative of acquired **von Willebrand syndrome (AVWS)**. - **AVWS** can be precipitated by **aortic stenosis** due to the shearing of large von Willebrand factor (vWF) multimers as they pass through the stenotic valve, leading to their degradation and impaired platelet plug formation. The patient's **mild dyspnea on exertion** and the **2/6 systolic murmur** at the right upper sternal border point to potential aortic stenosis. *Factor VIII* - A deficiency in **Factor VIII** causes **hemophilia A**, which typically presents with **deep tissue bleeding**, hemarthroses, and intracranial hemorrhages, rather than mucocutaneous bleeding and easy bruising. - Hemophilia A is an **X-linked recessive disorder**, primarily affecting males, and would typically manifest much earlier in life with more severe bleeding episodes. *ADAMTS13 gene mutation* - A mutation in the **ADAMTS13 gene** leads to **thrombotic thrombocytopenic purpura (TTP)**, characterized by microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal dysfunction, and fever. - The patient's presentation of acute, bright red rectal bleeding and easy bruising is not consistent with the typical thrombotic and hemolytic features of TTP. *Antithrombin III* - **Antithrombin III deficiency** is associated with an **increased risk of venous and arterial thrombosis**, not bleeding. - Patients with this deficiency are prone to conditions like deep vein thrombosis and pulmonary embolism, which are the opposite of the bleeding tendency seen in this patient. *Vitamin K* - **Vitamin K deficiency** impairs the synthesis of **coagulation factors II, VII, IX, and X**, as well as proteins C and S, leading to a **coagulopathy** with prolonged PT and aPTT. - While it can cause bleeding, the specific presentation with easy bruising and **GI bleeding associated with potential aortic stenosis** points more directly to acquired von Willebrand syndrome rather than generalized clotting factor deficiency.

Question 460: A 21-year-old man undergoes orthopedic surgery for a leg fracture that he has sustained in a motorbike accident. After induction of anesthesia with desflurane, the patient's respiratory minute ventilation decreases notably. Which of the following additional effects is most likely to occur in response to this drug?

• A. Decreased seizure threshold
• B. Increased intracranial pressure (Correct Answer)
• C. Increased skeletal muscle tonus
• D. Increased cerebral metabolic rate
• E. Increased glomerular filtration rate

Explanation: ***Increased intracranial pressure*** - **Desflurane**, like other volatile anesthetics, causes **cerebral vasodilation**, leading to increased cerebral blood flow and consequently **increased intracranial pressure (ICP)**. - This effect is particularly pronounced with desflurane and is a key concern, especially in patients with pre-existing elevated ICP. *Decreased seizure threshold* - While some anesthetics can lower the seizure threshold, **desflurane** is generally considered to be **seizure-neutral** or even anticonvulsant at higher concentrations. - **Enflurane** is an example of an inhaled anesthetic known to reliably induce epileptiform activity. *Increased skeletal muscle tonus* - **Volatile anesthetics** generally cause **skeletal muscle relaxation**, which is why they are often used with neuromuscular blockers during surgery. - An increase in skeletal muscle tonus is seen in conditions like **malignant hyperthermia**, which can be triggered by desflurane, but this is a rare, life-threatening genetic disorder, not a typical effect of the drug. *Increased cerebral metabolic rate* - **Desflurane** typically causes a **dose-dependent reduction in the cerebral metabolic rate for oxygen (CMRO2)**, indicating a decrease in brain activity. - This is often beneficial during anesthesia, providing **neuroprotection**, despite the concurrent cerebral vasodilation. *Increased glomerular filtration rate* - **Volatile anesthetics**, including desflurane, tend to cause a **dose-dependent decrease in renal blood flow and glomerular filtration rate (GFR)** due to systemic vasodilation and decreased cardiac output. - Renal function is generally preserved in healthy individuals, but the GFR does not increase with the use of desflurane.

Question 461: A 64-year-old woman with osteoarthritis is brought to the emergency room because of a 2-day history of nausea and vomiting. Over the past few weeks, she has been taking acetaminophen frequently for worsening knee pain. Examination shows scleral icterus and tender hepatomegaly. She appears confused. Serum alanine aminotransferase (ALT) level is 845 U/L, aspartate aminotransferase (AST) is 798 U/L, and alkaline phosphatase is 152 U/L. Which of the following is the most likely underlying mechanism of this patient's liver failure?

• A. N-acetyl-p-benzoquinoneimine formation (Correct Answer)
• B. Sulfate-conjugate formation
• C. Glucuronide-conjugate formation
• D. Salicylic acid formation
• E. N-acetylcysteine formation

Explanation: ***N-acetyl-p-benzoquinoneimine formation*** - This patient's clinical presentation, including the history of frequent acetaminophen use, nausea, vomiting, scleral icterus, tender hepatomegaly, confusion, and significantly elevated AST/ALT levels (**845 U/L and 798 U/L respectively**), is highly indicative of **acetaminophen-induced hepatotoxicity**. - **N-acetyl-p-benzoquinoneimine (NAPQI)** is a highly reactive and toxic metabolite of acetaminophen, formed when the normal metabolic pathways (sulfation and glucuronidation) become saturated due to excessive dosing. NAPQI depletes **glutathione** stores, leading to **oxidative stress** and direct hepatocellular injury causing liver failure. *Sulfate-conjugate formation* - **Sulfate-conjugation** is one of the primary and non-toxic pathways for acetaminophen metabolism at therapeutic doses. - This pathway becomes saturated with acetaminophen overdose, leading to increased metabolism through the **cytochrome P450 pathway** and subsequent NAPQI production. *Glucuronide-conjugate formation* - **Glucuronide-conjugation** is another primary and non-toxic pathway for acetaminophen metabolism, similar to sulfation. - Like sulfation, this pathway is also saturated in cases of acetaminophen overdose, shunting more of the drug to the toxic P450-mediated pathway. *Salicylic acid formation* - **Salicylic acid** is a metabolite of aspirin (acetylsalicylic acid), not acetaminophen. - Overdose of aspirin can cause metabolic acidosis, tinnitus, and hyperthermia, but not typically the pattern of liver injury associated with this patient's findings. *N-acetylcysteine formation* - **N-acetylcysteine** is the antidote for acetaminophen overdose; it is not a metabolite of acetaminophen. - It replenishes **glutathione**, which helps detoxify NAPQI and prevent further liver damage.

Question 462: A 14-year-old girl with a history of severe persistent asthma presents to her pediatrician after a recent hospital discharge for asthma exacerbation. Her mother is concerned that her daughter continues to wheeze and cough multiple nights per week. She is also concerned that her daughter frequently uses the bathroom to urinate despite no recent change in her diet. She has allergies to pollen and shellfish, but her mother denies any recent exposure. The patient's medications include albuterol, salmeterol, and both inhaled and oral prednisone. What alternative drug can the pediatrician recommend for this patient?

• A. Omalizumab (Correct Answer)
• B. Natalizumab
• C. Imatinib
• D. Trastuzumab
• E. Nivolumab

Explanation: ***Omalizumab*** - This patient presents with **severe persistent asthma** despite treatment with oral and inhaled corticosteroids, indicating a need for additional therapy beyond standard bronchodilators and anti-inflammatory agents. - Given her history of allergies and nocturnal symptoms, **omalizumab**, an **anti-IgE monoclonal antibody**, is a suitable option for patients with severe persistent allergic asthma not controlled by conventional treatments. *Natalizumab* - **Natalizumab** is a **monoclonal antibody** that targets the α4-integrin, used primarily in the treatment of **multiple sclerosis** and **Crohn's disease**. - It is not indicated for the treatment of asthma and would not address her allergic symptoms or severe airway inflammation. *Imatinib* - **Imatinib** is a **tyrosine kinase inhibitor** used in the treatment of various cancers, such as **chronic myelogenous leukemia (CML)** and **gastrointestinal stromal tumors (GIST)**. - It has no role in the management of asthma. *Trastuzumab* - **Trastuzumab** is a **monoclonal antibody** that targets the **HER2/neu receptor**, commonly used in the treatment of **HER2-positive breast cancer** and **gastric cancer**. - This medication is not indicated for asthma. *Nivolumab* - **Nivolumab** is a **PD-1 checkpoint inhibitor**, a type of **immunotherapy** used in several advanced cancers to boost the immune response against tumor cells. - It has no therapeutic indication for asthma and could even exacerbate immune-related conditions.

Question 463: A 19-year-old woman comes to the physician because of episodic, bilateral finger pain and discoloration that occurs with cold weather. Her fingers first turn white, then blue, before eventually returning to a normal skin color. The symptoms have been occurring daily and limit her ability to work. She has no history of serious illness and takes no medication. She does not smoke. Physical examination shows normal capillary refill of the nail beds. The radial pulse is palpable bilaterally. The remainder of the examination shows no abnormalities. Which of the following is the most appropriate pharmacotherapy for this patient?

• A. Nifedipine (Correct Answer)
• B. Phenylephrine
• C. Isosorbide dinitrate
• D. Prednisone
• E. Ergotamine

Explanation: ***Nifedipine*** - This patient's symptoms of **episodic, bilateral finger pain and discoloration** (white, then blue, then red) triggered by cold are classic for **Raynaud phenomenon**. - **Calcium channel blockers** like nifedipine are the **first-line pharmacotherapy** for severe or frequent Raynaud symptoms, as they cause vasodilation and improve blood flow. *Phenylephrine* - **Phenylephrine** is an **alpha-1 adrenergic agonist** that causes vasoconstriction, which would worsen Raynaud phenomenon. - It is used as a decongestant or to increase blood pressure, directly opposing the desired therapeutic effect for Raynaud. *Isosorbide dinitrate* - **Isosorbide dinitrate** is a **nitrate** used to treat angina by causing vasodilation, primarily of veins. - While it causes vasodilation, it is not the primary or most effective treatment for peripheral vasoconstriction seen in Raynaud phenomenon, and can have significant side effects like headache and hypotension. *Prednisone* - **Prednisone** is a corticosteroid used for inflammatory conditions and autoimmune diseases. - Raynaud phenomenon itself is primarily a **vasospastic disorder** and not an inflammatory process that would respond to corticosteroids unless associated with an underlying inflammatory autoimmune disease, which is not indicated here. *Ergotamine* - **Ergotamine** is an **ergot alkaloid** used to treat migraines due to its vasoconstrictive properties at specific serotonin receptors. - Its potent **vasoconstrictive effects** would significantly worsen the symptoms of Raynaud phenomenon.

Question 464: A 5-year-old African-American boy is brought to the physician because of fatigue and night sweats for the past month. During this time, he has also lost 3 kg (6.6 lbs). Before the onset of symptoms, he had been healthy except for a febrile seizure as an infant. His brother had chickenpox 2 months ago. He is at the 75th percentile for height and 50th percentile for weight. He appears markedly fatigued. His temperature is 38°C (100.4°F), pulse is 95/min, respirations are 19/min, and blood pressure is 100/60 mm Hg. Lung and cardiac examination is normal. There are enlarged, nontender lymph nodes bilaterally in the neck. The abdomen is soft and nontender. A complete blood count shows: Leukocyte count 8,000/mm³ Hemoglobin 9.1 g/dL Hematocrit 26.9% Platelet count 34,000/mm³ Serum Na+ 135 mEq/L K+ 4.5 mEq/L Cl- 101 mEq/L HCO3- 27 mEq/L Urea nitrogen 9 mg/dL Creatinine 0.7 mg/dL Ca2+ 8.8 mg/dL PCR testing demonstrates a 9:22 chromosomal translocation. The patient is diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia. Which of the following is the most appropriate targeted therapy component?

• A. Cladribine
• B. Imatinib (Correct Answer)
• C. Hydroxyurea
• D. All-trans retinoic acid
• E. Transfuse platelets

Explanation: ***Imatinib*** - The patient has **Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)**, indicated by the **9:22 chromosomal translocation** (BCR-ABL fusion gene). - **Imatinib** is a tyrosine kinase inhibitor (TKI) that specifically targets the **BCR-ABL fusion protein**, making it the most appropriate targeted therapy for Ph+ ALL. *Cladribine* - **Cladribine** is a purine analog primarily used in the treatment of **hairy cell leukemia** and some forms of lymphoma. - It is not a targeted therapy for the **BCR-ABL fusion gene** in Ph+ ALL. *Hydroxyurea* - **Hydroxyurea** is a myelosuppressive agent used to rapidly lower high blood counts in conditions like **chronic myeloid leukemia (CML)** or **myeloproliferative neoplasms**. - It does not target the specific genetic abnormality of Ph+ ALL. *All-trans retinoic acid* - **All-trans retinoic acid (ATRA)** is a form of vitamin A used in the treatment of **acute promyelocytic leukemia (APL)**. - ATRA induces differentiation of promyelocytes and is not effective for Ph+ ALL. *Transfuse platelets* - While the patient has **thrombocytopenia** (platelet count 34,000/mm³), **platelet transfusion** is a supportive measure, not a targeted therapy for leukemia. - It addresses a complication of the disease rather than the underlying oncogenic driver.

Question 465: A 65-year-old man with decompensated cirrhosis secondary to hepatitis C is brought to the emergency department with 2 episodes of massive hematemesis that started 2 hours ago. He is a liver transplant candidate. The blood pressure is 110/85 mm Hg in the supine position and 90/70 mm Hg after sitting for 3 minutes. The pulse is 110/min, the respirations are 22/min, and the temperature is 36.1°C (97.0°F). The physical examination shows spider angiomata, palmar erythema, and symmetric abdominal distension with positive shifting dullness. The lung and heart examination shows no abnormalities. Two large-bore intravenous lines are obtained. Saline (0.9%) is initiated. Laboratory tests are pending. The most important next step is to administer which of the following intravenous therapies?

• A. Fresh frozen plasma
• B. Octreotide (Correct Answer)
• C. Packed red blood cells (RBCs)
• D. Propranolol
• E. Pantoprazole

Explanation: ***Octreotide*** - This patient's presentation with **massive hematemesis**, **decompensated cirrhosis**, and signs of portal hypertension strongly suggests **esophageal variceal bleeding**. - **Octreotide**, a somatostatin analog, is critical in managing variceal bleeding by causing **splanchnic vasoconstriction**, which reduces portal blood flow and pressure, thereby decreasing active bleeding. *Fresh frozen plasma* - While patients with **cirrhosis often have coagulopathy**, administering fresh frozen plasma (FFP) without documented severe coagulopathy or active bleeding requiring immediate reversal (e.g., before an invasive procedure) is not the highest priority. - **FFP transfusions** can paradoxically increase portal pressure and volume, potentially worsening variceal bleeding. *Packed red blood cells (RBCs)* - Though the patient is likely anemic due to massive hematemesis, **transfusion of RBCs** should be guided by hemoglobin levels and clinical signs of hemodynamic instability, with a goal to achieve **hemodynamic stability** rather than over-transfusing. - While important, **stopping the bleeding** with octreotide takes precedence before optimal RBC transfusion thresholds are determined. *Propranolol* - **Propranolol** is a non-selective beta-blocker used for **primary and secondary prophylaxis** of variceal bleeding. - It is **contraindicated in acute bleeding** as it can worsen hypotension and interfere with the body's compensatory mechanisms during hypovolemic shock. *Pantoprazole* - **Pantoprazole**, a **proton pump inhibitor (PPI)**, is used to suppress stomach acid and is beneficial in managing **peptic ulcer bleeding**. - However, it has no direct role in controlling **variceal bleeding**, which originates from esophageal varices rather than acid-related gastric or duodenal mucosa.

Question 466: Two-hours into recovery from general anesthesia for an orthopedic fracture, a 34-year-old woman develops fever and masseter muscle rigidity with lockjaw. She has no history of a similar episode. She has no history of serious illness and takes no medications. She appears confused. In the recovery room, her blood pressure is 78/50 mm Hg, the pulse is 128/min, the respirations are 42/min, and the temperature is 40.3°C (104.5°F). Cardiopulmonary examination shows no abnormalities. Laboratory studies show: Serum Na+ 145 mEq/L K+ 6.5 mEq/L Arterial blood gas on room air pH 7.01 PCO2 78 mm Hg HCO3− 14 mEq/L PO2 55 mm Hg The patient is reintubated. Which of the following is the most appropriate next step in pharmacotherapy?

• A. Lorazepam
• B. Diphenhydramine
• C. Dantrolene (Correct Answer)
• D. Labetalol
• E. Cyproheptadine

Explanation: ***Dantrolene*** - The patient exhibits classic signs of **malignant hyperthermia**, including **masseter muscle rigidity**, **fever (40.3°C)**, **tachycardia (128/min)**, **tachypnea (42/min)**, and **hypotension (78/50 mm Hg)**. The **elevated potassium (6.5 mEq/L)**, **acidosis (pH 7.01)**, and **hypercapnia (PCO2 78 mm Hg)** further support this diagnosis. - **Dantrolene** is the only specific antidote for malignant hyperthermia as it acts as a **ryanodine receptor antagonist**, inhibiting calcium release from the sarcoplasmic reticulum and thereby reducing muscle contracture and heat production. *Lorazepam* - **Lorazepam** is a benzodiazepine used for treating seizures, anxiety, and agitation, but it does **not address the underlying pathophysiology of malignant hyperthermia**. - While the patient appears confused, this is likely secondary to the metabolic derangements and hyperthermia, not a primary indication for lorazepam. *Diphenhydramine* - **Diphenhydramine** is an antihistamine used to treat allergic reactions or sedation; it has no role in the management of malignant hyperthermia. - It would not alleviate the muscle rigidity, hyperthermia, or metabolic abnormalities seen in this patient. *Labetalol* - **Labetalol** is a beta-blocker used to manage hypertension and tachycardia, but these are symptoms of malignant hyperthermia rather than the root cause. - While it could temporarily lower heart rate and blood pressure, it **does not address the excessive calcium release** in skeletal muscle, which is the hallmark of malignant hyperthermia. *Cyproheptadine* - **Cyproheptadine** is a serotonin antagonist used in the treatment of serotonin syndrome. - Malignant hyperthermia and serotonin syndrome share some clinical features like hyperthermia, but the **trigger (anesthetic agents)** and underlying mechanisms are different, making cyproheptadine ineffective here.

Question 467: A 45-year-old-man presents to the physician with complaints of intermittent episodes of severe headaches and palpitations. During these episodes, he notices that he sweats profusely and becomes pale in complexion. He describes the episodes as coming and going within the past 2 months. His temperature is 99.3°F (37.4°C), blood pressure is 165/118 mmHg, pulse is 126/min, respirations are 18/min, and oxygen saturation is 90% on room air. Which of the following would be the first medication given to treat this patient’s most likely diagnosis?

• A. Phentolamine
• B. Pilocarpine
• C. Prazosin
• D. Phenoxybenzamine (Correct Answer)
• E. Propranolol

Explanation: ***Phenoxybenzamine*** - The patient exhibits classic symptoms of a **pheochromocytoma**, such as paroxysmal hypertension, headaches, palpitations, and sweating. - **Alpha-blockade with phenoxybenzamine** should always be initiated **before** beta-blockade to prevent a hypertensive crisis due to unopposed alpha-adrenergic stimulation. *Phentolamine* - This is a **short-acting alpha-blocker** used for acute management of hypertensive crises in pheochromocytoma, not for initial chronic preparation. - It would be used in an **emergency** or during surgery if blood pressure spikes, but not for preoperative stabilization. *Pilocarpine* - This is a **cholinergic agonist** primarily used in ophthalmology to treat glaucoma or xerostomia. - It has no role in the management of hypertension or pheochromocytoma. *Prazosin* - This is a **selective alpha-1 blocker**, which can be used in pheochromocytoma but is typically less preferred for initial broad alpha-blockade. - **Phenoxybenzamine** is a non-selective, long-acting alpha-blocker, often favored for its comprehensive blockade. *Propanolol* - This is a **beta-blocker** which should only be added after adequate alpha-blockade has been established to control tachycardia. - Giving a beta-blocker alone without prior alpha-blockade can worsen hypertension by blocking vasodilatory beta-2 receptors, leading to unopposed alpha-1 vasoconstriction.

Question 468: A 63-year-old man with a history of hypertension and atrial fibrillation is brought into the emergency room and found to have a ventricular tachyarrhythmia. Ibutilide is discontinued and the patient is switched to another drug that also prolongs the QT interval but is associated with a decreased risk of torsades de pointes. Which drug was most likely administered in this patient?

• A. Esmolol
• B. Digoxin
• C. Sotalol
• D. Amiodarone (Correct Answer)
• E. Quinidine

Explanation: ***Amiodarone*** - **Amiodarone** prolongs the **QT interval** but has a lower risk of **torsades de pointes** compared to other **Class III antiarrhythmics** due to its mixed ion channel blocking properties and consistent action potential prolongation. - It's a broad-spectrum **antiarrhythmic drug** effective for both **atrial** and **ventricular arrhythmias**, making it a good choice for someone with a history of **atrial fibrillation** presenting with **ventricular tachyarrhythmia**. *Esmolol* - **Esmolol** is a **beta-blocker** that does not prolong the **QT interval**; it is used to slow heart rate and can be used for rhythm control but not by **QT prolongation**. - Its primary action is on **beta-1 receptors**, reducing **myocardial contractility** and **heart rate**, primarily used for acute control of **tachyarrhythmias** or **hypertensive emergencies**. *Digoxin* - **Digoxin** is a **cardiac glycoside** that does not prolong the **QT interval**; it primarily works by inhibiting the **Na+/K+-ATPase pump** and increasing **vagal tone**. - It is used to control **ventricular rate** in **atrial fibrillation** and to manage **heart failure**, but it is not an **antiarrhythmic** in the sense of directly terminating **ventricular tachyarrhythmias** by affecting **QT prolongation**. *Sotalol* - **Sotalol** is a **beta-blocker** with **Class III antiarrhythmic properties** that prolongs the **QT interval** and has a significant **dose-related risk of torsades de pointes**, particularly at higher doses. - While it's effective for both **ventricular** and **supraventricular arrhythmias**, its risk of **TdP** is a major concern, making **amiodarone** a safer alternative when **TdP risk** is to be minimized. *Quinidine* - **Quinidine** is a **Class IA antiarrhythmic** that significantly prolongs the **QT interval** and is known for a high risk of causing **torsades de pointes**. - It primarily blocks **fast sodium channels** and also **potassium channels**, contributing to its **proarrhythmic effects** and making it a less favored option when **TdP risk** needs to be decreased.

Question 469: A 13-year-old boy with a history of asthma and seasonal allergies is currently using albuterol to manage his asthma symptoms. Recently, his use of albuterol increased from 1–2 days/week to 4 times/week over the past several weeks, though he does not experience his symptoms daily. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 74/min, and respiratory rate 14/min. His physical examination shows clear, bilateral breath sounds and normal heart sounds. What change should be made to his current treatment regimen?

• A. Add tiotropium
• B. Add formoterol + budesonide twice daily
• C. Add montelukast 5 mg daily
• D. Add fluticasone daily (Correct Answer)
• E. Add salmeterol twice daily

Explanation: ***Add fluticasone daily*** - This patient currently has **mild persistent asthma** based on his increased albuterol use (4 times/week, but not daily). The guideline-recommended step-up for mild persistent asthma is the daily addition of a **low-dose inhaled corticosteroid (ICS)** like fluticasone. - Adding fluticasone daily addresses the underlying inflammation of asthma, reducing symptoms and the need for frequent albuterol rescue inhaler use. *Add tiotropium* - Tiotropium, a **long-acting muscarinic antagonist (LAMA)**, is primarily used for asthma as an add-on therapy for patients whose symptoms are not well-controlled with ICS and long-acting beta-2 agonists (LABAs). - It is not a first-line agent for initiating controller therapy in mild persistent asthma. *Add formoterol + budesonide twice daily* - This combination, a **LABA/ICS**, is indicated for moderate to severe persistent asthma, not mild persistent asthma, or can be used as a reliever in older children/adults with mild asthma (SMART therapy). - Prescribing it twice daily would be an over-treatment for this patient's current asthma severity. *Add montelukast 5 mg daily* - Montelukast, a **leukotriene receptor antagonist**, is an alternative for mild persistent asthma, but **ICS are generally preferred** due to superior efficacy in controlling inflammation. - While it could be considered, fluticasone (an ICS) is a more effective first-line option for controller therapy in mild persistent asthma. *Add salmeterol twice daily* - Salmeterol is a **long-acting beta-2 agonist (LABA)** that should never be used as monotherapy in asthma due to the risk of severe exacerbations and asthma-related death. - LABAs should always be used in combination with an **inhaled corticosteroid (ICS)**.

Question 470: A 25-year-old woman is brought to the emergency department 12 hours after ingesting 30 tablets of an unknown drug in a suicide attempt. The tablets belonged to her father, who has a chronic heart condition. She has had nausea and vomiting. She also reports blurring and yellowing of her vision. Her temperature is 36.7°C (98°F), pulse is 51/min, and blood pressure is 108/71 mm Hg. Abdominal examination shows diffuse tenderness with no guarding or rebound. Bowel sounds are normal. An ECG shows prolonged PR-intervals and flattened T-waves. Further evaluation is most likely to show which of the following electrolyte abnormalities?

• A. Increased serum K+ (Correct Answer)
• B. Decreased serum K+
• C. Decreased serum Na+
• D. Increased serum Na+
• E. Increased serum Ca2+

Explanation: ***Increased serum K+*** - The patient presents with classic symptoms of **digoxin toxicity**, including **nausea, vomiting, blurry and yellow vision, bradycardia**, and ECG changes like **prolonged PR interval** and **flattened T-waves**. - **Digoxin inhibits the Na+/K+-ATPase pump**, leading to an increase in extracellular potassium as potassium cannot enter the cells. *Decreased serum K+* - While hypokalemia can exacerbate digoxin toxicity by increasing digoxin binding to the Na+/K+-ATPase, digoxin overdose itself typically causes **hyperkalemia** due to its direct effect on the pump. - ECG changes like **flattened T-waves** can be seen in hypokalemia, but the overall clinical picture, especially the history of overdose and bradycardia, points more strongly to digoxin toxicity with hyperkalemia. *Decreased serum Na+* - **Hyponatremia** is not a characteristic feature of acute digoxin overdose. - Digoxin primarily affects potassium and calcium channels, with less direct impact on sodium levels, unless related to fluid status changes which are not indicated here. *Increased serum Na+* - **Hypernatremia** is not typically associated with digoxin toxicity. - Digoxin's mechanism of action does not directly lead to increased serum sodium; rather, it primarily inhibits the Na+/K+-ATPase. *Increased serum Ca2+* - Digoxin **increases intracellular calcium** by inhibiting the Na+/K+-ATPase, which indirectly leads to increased Na+/Ca2+ exchanger activity. - However, this primarily affects intracellular levels and **does not typically result in increased serum calcium**.

Question 471: A 52-year-old woman complains of severe vomiting for the past 2 hours. She recently had a chemotherapy session for breast cancer. She denies a history of any relevant gastrointestinal diseases, including GERD. The physical exam does not demonstrate any epigastric or abdominal tenderness. The last bowel movement was yesterday and was normal. What is the primary mechanism of the drug which would be prescribed to treat her chief complaint?

• A. 5-HT3 blocker (Correct Answer)
• B. 5-HT1 blocker
• C. D1 blocker
• D. 5-HT2 blocker
• E. 5-HT4 blocker

Explanation: ***5-HT3 blocker*** - **Chemotherapy-induced nausea and vomiting (CINV)** is primarily mediated by the release of **serotonin (5-HT)** from enterochromaffin cells in the gastrointestinal tract, which then acts on **5-HT3 receptors**. - **5-HT3 receptor antagonists** (e.g., ondansetron, granisetron, palonosetron) are highly effective in preventing and treating CINV by blocking these receptors in the gut and the **chemoreceptor trigger zone (CTZ)**. *5-HT1 blocker* - **5-HT1 receptors** are generally associated with other functions, such as **vasoconstriction** and **neuronal inhibition**, and are not the primary target for antiemetic therapy in CINV. - Triptans, for example, are **5-HT1B/1D agonists** used for migraine, not antiemesis. *D1 blocker* - **D1 blockers** (dopamine D1 receptor antagonists) are not typically used as antiemetics. - **D2 receptor antagonists** (e.g., metoclopramide, prochlorperazine) are antiemetics, acting primarily in the CTZ, but **5-HT3 antagonists** are generally preferred for severe CINV due to their superior efficacy and tolerability. *5-HT2 blocker* - **5-HT2 receptors** are involved in various physiological processes, including platelet aggregation and smooth muscle contraction, but are not the main target for antiemetic agents in CINV. - Some atypical antipsychotics have **5-HT2A blocking activity**, but this is not their primary antiemetic mechanism. *5-HT4 blocker* - **5-HT4 receptor blockers** are not used as antiemetics for CINV. - In contrast, **5-HT4 receptor agonists** (e.g., cisapride, prucalopride) are **prokinetic agents** that stimulate gastrointestinal motility, but these are not indicated for acute chemotherapy-induced vomiting.

Question 472: A 55-year-old male is hospitalized for acute heart failure. The patient has a 20-year history of alcoholism and was diagnosed with diabetes mellitus type 2 (DM2) 5 years ago. Physical examination reveals ascites and engorged paraumbilical veins as well as 3+ pitting edema around both ankles. Liver function tests show elevations in gamma glutamyl transferase and aspartate transaminase (AST). Of the following medication, which most likely contributed to this patient's presentation?

• A. Glargine
• B. Pramlintide
• C. Pioglitazone (Correct Answer)
• D. Glipizide
• E. Metformin

Explanation: ***Pioglitazone*** - **Pioglitazone**, a thiazolidinedione, is known to cause **fluid retention** and can exacerbate or precipitate **congestive heart failure**. - The patient's presentation with **ascites**, **pitting edema**, and **acute heart failure** is consistent with the adverse effects of this medication, especially in a patient with risk factors like alcoholism. *Glargine* - **Glargine** is a **long-acting insulin** analog primarily used to control blood glucose levels in diabetes. - It does not typically cause **fluid retention** or worsen **heart failure** directly, making it an unlikely contributor to these specific symptoms. *Pramlintide* - **Pramlintide** is an **amylin analog** used to improve glycemic control by slowing gastric emptying and suppressing glucagon secretion. - It is not associated with **fluid retention** or the exacerbation of **heart failure**. *Glipizide* - **Glipizide** is a **sulfonylurea** that stimulates insulin release from pancreatic beta cells. - While it can cause hypoglycemia, it does not typically contribute to **fluid retention** or worsen **heart failure**. *Metformin* - **Metformin** is a **biguanide** that reduces hepatic glucose production and increases insulin sensitivity. - It is generally considered **cardioprotective** and does not cause **fluid retention** or exacerbate **heart failure**.

Question 473: A patient with Graves' disease is treated with thiocyanate (a historical antithyroid agent). Thiocyanate helps reduce thyroid hormone production by:

• A. Inhibiting thyroid peroxidase
• B. Inhibiting 5'-deiodinase
• C. Inhibiting iodide follicular uptake (Correct Answer)
• D. Inhibiting beta-adrenergic receptors
• E. Inhibiting thyroid deiodinase

Explanation: ***Inhibiting iodide follicular uptake*** - Thiocyanate is a competitive inhibitor of the **sodium-iodide symporter (NIS)** on thyroid follicular cells, blocking the uptake of iodide into the thyroid gland. - By preventing iodide entry, thiocyanate reduces the raw material needed for thyroid hormone synthesis, thereby mitigating the **hyperthyroidism** seen in Graves' disease. *Inhibiting thyroid peroxidase* - This is the mechanism of action for **thionamide drugs** (e.g., methimazole, propylthiouracil), which block the oxidation of iodide and its organification. - While effective in Graves' disease, thiocyanate does not directly inhibit thyroid peroxidase activity. *Inhibiting 5'-deiodinase* - **Propylthiouracil (PTU)**, but not thiocyanate, inhibits the peripheral conversion of T4 to the more active T3 by blocking 5'-deiodinase enzymes. - This action helps to reduce the overall effect of thyroid hormones in the body. *Inhibiting beta-adrenergic receptors* - **Beta-blockers** (e.g., propranolol) are used to manage the symptomatic effects of hyperthyroidism, such as palpitations, tremor, and anxiety. - They do not affect thyroid hormone synthesis or release, but rather block the peripheral actions of thyroid hormones on adrenergic receptors. *Inhibiting thyroid deiodinase* - This option refers to the enzymes responsible for removing iodine from thyroid hormones, which is part of the normal catabolism of these hormones or for converting T4 to T3. - Thiocyanate does not primarily act by inhibiting these deiodinase enzymes within the thyroid gland or peripherally; its main action is on iodide uptake.

Question 474: A 42-year-old woman, gravida 1, para 0, at 10 weeks' gestation comes to the physician for a prenatal examination. She has no history of significant medical illness. Physical examination shows a uterus consistent with a 10-week gestation. Cell-free fetal DNA testing shows a karyotype of 47,XXY. If the fetus's condition had not been diagnosed until puberty, which of the following sets of hormonal changes would most likely be found at that time? $$$ Follicle-stimulating hormone %%% Luteinizing hormone %%% Testosterone %%% Estrogen $$$

• A. ↑ ↑ ↓ ↑ (Correct Answer)
• B. ↓ ↓ normal ↑
• C. ↑ ↑ normal normal
• D. ↓ ↓ ↓ ↓
• E. ↑ ↑ ↑ ↓

Explanation: ***↑ ↑ ↓ ↑*** - This hormonal pattern is characteristic of **Klinefelter syndrome (47,XXY)** at puberty, where testicular dysfunction leads to **primary hypogonadism**. - **Decreased testosterone** due to impaired Leydig cell function causes **increased LH and FSH** (due to a lack of negative feedback), while aromatization of excess androgens in peripheral tissues results in **increased estrogen**. *↓ ↓ normal ↑* - This pattern (low FSH, low LH, normal testosterone, high estrogen) would suggest **secondary hypogonadism** or an estrogen-producing tumor, which is not consistent with Klinefelter syndrome. - In secondary hypogonadism, the pituitary is the primary problem, leading to insufficient gonadotropin production; however, in Klinefelter, the problem is primarily testicular. *↑ ↑ normal normal* - While FSH and LH are elevated in Klinefelter syndrome, testosterone is typically *decreased*, not normal, and estrogen is often *increased*, not normal. - This option does not fully capture the classic hormonal profile of **primary hypogonadism with feminization** seen in Klinefelter syndrome. *↓ ↓ ↓ ↓* - This pattern of universally low hormone levels is not typical for Klinefelter syndrome. - Such widespread reduction in hormones might be seen in severe **panhypopituitarism**, which affects multiple endocrine axes and is a distinct condition. *↑ ↑ ↑ ↓* - While FSH and LH are elevated, and testosterone is decreased, estrogen is typically *increased* (due to peripheral conversion of androgens) in Klinefelter syndrome, not decreased. - A decrease in estrogen along with elevated gonadotropins and decreased testosterone would indicate a different type of hormonal imbalance, possibly associated with **severe ovarian failure** if it were a female.

Question 475: A 30-year-old woman with a 1-year history of medically-managed Graves disease visits her endocrinologist to discuss her desire to become pregnant and whether pregnancy is safe with her medications. Her temperature is 98.4°F (36.9°C), blood pressure is 110/66 mmHg, pulse is 78/min, respirations are 12/min. The endocrinologist advises that the patient may pursue pregnancy, but first needs to be switched from methimazole to propylthiouracil for her Graves disease due to pregnancy safety considerations. Which of the following is a possible side effect of propylthiouracil that represents a greater risk compared to methimazole?

• A. Thyroid storm
• B. Agranulocytosis
• C. Fulminant hepatic necrosis (Correct Answer)
• D. Skin rash
• E. Aplastic anemia

Explanation: ***Fulminant hepatic necrosis*** - Propylthiouracil (PTU) carries a **black box warning** for severe liver injury, including **fulminant hepatic necrosis**, which is a greater risk compared to methimazole. - This risk is particularly relevant in the context of pregnancy, as PTU is often preferred in the first trimester due to lower teratogenic risk, but its hepatotoxicity must be closely monitored. *Thyroid storm* - **Thyroid storm** is a life-threatening exacerbation of hyperthyroidism and is not a direct side effect of antithyroid medications like PTU or methimazole. - It is a complication of inadequately treated or untreated hyperthyroidism. *Agranulocytosis* - **Agranulocytosis** is a rare but serious side effect of both propylthiouracil and methimazole. - While it is a concern, the risk of fulminant hepatic necrosis is specifically highlighted as being higher with PTU. *Skin rash* - **Skin rash** is a common and usually mild side effect that can occur with both methimazole and propylthiouracil. - It is not typically considered a more severe or distinguishing risk for PTU compared to methimazole. *Aplastic anemia* - **Aplastic anemia** is an extremely rare but severe side effect that can be associated with antithyroid drugs, including both PTU and methimazole. - Although serious, the risk of fulminant hepatic necrosis is a more specifically emphasized and distinct concern for PTU.

Question 476: A 52-year-old male with ischemic cardiomyopathy presents to his cardiologist for worsening shortness of breath on exertion. He denies any recent episodes of chest pain and has been compliant with his medications, which include metoprolol, lisinopril, spironolactone, and furosemide. The patient’s vitals signs are as follows: Temperature is 98.7 deg F (37.1 deg C), blood pressure is 163/78 mmHg, pulse is 92/min, respirations are 14/min, and oxygen saturation is 98% on room air. A repeat echocardiogram reveals a stable LVEF of 25-35%. The physician decides to start hydralazine and isosorbide dinitrate. Which of the following is true regarding this medication combination?

• A. Has anti-inflammatory properties to reduce the risk of coronary artery thrombosis
• B. Improves symptoms but does not have an overall mortality benefit in patients with congestive heart failure
• C. Increases the volume of blood that enters the heart to improve ventricular contraction
• D. Has positive effects on cardiac remodeling
• E. Decreases the volume and work placed on the left ventricle (Correct Answer)

Explanation: ***Decreases the volume and work placed on the left ventricle*** - The combination of **hydralazine** and **isosorbide dinitrate** acts as a **balanced vasodilator**, reducing both preload and afterload. - **Hydralazine** primarily reduces **afterload** by dilating arterioles, while **isosorbide dinitrate** primarily reduces **preload** by dilating venules, thereby decreasing the volume and work on the left ventricle. - This hemodynamic benefit reduces myocardial oxygen demand and improves cardiac output in patients with **HFrEF**. *Has anti-inflammatory properties to reduce the risk of coronary artery thrombosis* - This medication combination does **not possess anti-inflammatory properties** and is not used to reduce the risk of **coronary artery thrombosis**. - **Anti-inflammatory drugs** (like NSAIDs) and **antiplatelet agents** (like aspirin) would be used for such purposes, but they have different mechanisms. *Improves symptoms but does not have an overall mortality benefit in patients with congestive heart failure* - This statement is incorrect; the combination of **hydralazine and isosorbide dinitrate** has been shown to improve **mortality** in specific populations, particularly **African Americans with heart failure**, as evidenced by the **A-HeFT trial**. - The combination showed a **43% reduction in mortality** and significant improvement in quality of life in this population. - Medications that primarily improve symptoms without mortality benefit include **diuretics** in the absence of congestion. *Increases the volume of blood that enters the heart to improve ventricular contraction* - This combination aims to **decrease the volume** and pressure within the heart (preload and afterload), not increase it. - Increasing ventricular filling volume could worsen shortness of breath in patients with **heart failure** by further engorging the heart chambers and increasing pulmonary congestion. *Has positive effects on cardiac remodeling* - While this combination does have some favorable effects on cardiac remodeling through **nitric oxide donation** and reduction in ventricular wall stress, these effects are **less prominent** compared to **ACE inhibitors**, **ARBs**, and **beta-blockers**, which are the cornerstone neurohormonal antagonists. - The primary benefit of hydralazine-isosorbide dinitrate is through **direct hemodynamic effects** (reducing preload and afterload), which indirectly reduce ventricular wall stress. - The **most accurate** answer focuses on the direct mechanism: decreasing volume and work on the left ventricle.

Question 477: A 52-year-old man presents to the emergency department with nausea, palpitations, and lightheadedness after consuming a drink prepared from the leaves of yellow oleander (Thevetia peruviana). He had read somewhere that such a drink is healthy. As he liked the taste, he consumed 3 glasses of the drink before the symptoms developed. He also vomited twice. There is no past medical history suggestive of any significant medical condition. On physical examination, he is disoriented. The temperature is 36.5°C (97.8°F), the pulse is 140/min and irregular, the blood pressure is 94/58 mm Hg, and the respiratory rate is 14/min. Auscultation of the heart reveals an irregularly irregular heartbeat, while auscultation of the lungs does not reveal any significant abnormalities. The abdomen is soft and the pupillary reflexes are intact. An electrocardiogram shows peaked T waves. A botanist confirms that yellow oleander leaves contain cardiac glycosides. In addition to controlling the airway, breathing, and circulation with supportive therapy, which of the following medications is indicated?

• A. Procainamide
• B. Digoxin immune Fab (Correct Answer)
• C. Atropine
• D. Quinidine
• E. Propranolol

Explanation: ***Digoxin immune Fab*** - The patient exhibits symptoms of **cardiac glycoside toxicity**, including nausea, palpitations, lightheadedness, hypotension, and an irregularly irregular heartbeat with peaked T waves on ECG. Yellow oleander contains cardiac glycosides, and **Digoxin immune Fab (Digifab)** specifically binds to and inactivates these toxins. - This medication is crucial for reversing the effects of severe cardiac glycoside poisoning by preventing them from binding to their target receptors, the **Na+/K+-ATPase pumps**, thereby restoring normal cardiac function. - The peaked T waves indicate **hyperkalemia**, which occurs in cardiac glycoside toxicity due to inhibition of Na+/K+-ATPase pumps, preventing potassium from entering cells. *Procainamide* - **Procainamide** is an antiarrhythmic drug used for various reentrant and ectopic arrhythmias, but it is **contraindicated in digoxin toxicity** as it can worsen myocardial depression and AV blocks. - Its use in the presence of cardiac glycoside-induced bradyarrhythmias or conduction blocks could be detrimental due to its own negative chronotropic and dromotropic effects. *Atropine* - **Atropine** is primarily used to treat **bradycardia** and AV blocks by blocking muscarinic receptors. - While the patient has an irregular pulse, the primary issue is cardiac glycoside intoxication affecting the Na+/K+-ATPase pump, which can cause various arrhythmias, not solely bradycardia, and atropine does not address the underlying toxin. *Quinidine* - **Quinidine** is a Class IA antiarrhythmic that inhibits the **Na+/K+-ATPase pump**, similar to cardiac glycosides. - Its co-administration with cardiac glycosides can significantly **increase digoxin levels** and exacerbate toxicity, making it an inappropriate choice. *Propranolol* - **Propranolol** is a **beta-blocker** that slows sinus heart rate and AV nodal conduction. - While it might control some tachyarrhythmias, it can worsen **bradycardia and hypotension**, which may be present in cardiac glycoside toxicity, and does not address the underlying toxic mechanism.

Question 478: A group of researchers wish to develop a clinical trial assessing the efficacy of a specific medication on the urinary excretion of amphetamines in intoxicated patients. They recruit 50 patients for the treatment arm and 50 patients for the control arm of the study. Demographics are fairly balanced between the two groups. The primary end points include (1) time to recovery of mental status, (2) baseline heart rate, (3) urinary pH, and (4) specific gravity. Which medication should they use in order to achieve a statistically significant result positively favoring the intervention?

• A. Potassium citrate
• B. Ascorbic acid (Correct Answer)
• C. Tap water
• D. Sodium bicarbonate
• E. Aluminum hydroxide

Explanation: ***Ascorbic acid*** - Urinary excretion of **weak bases** like amphetamines is enhanced in an **acidic urine environment**. Ascorbic acid, or vitamin C, is an acidic substance that, when administered, can significantly **lower urinary pH**. - By acidifying the urine, ascorbic acid promotes the **ionization of amphetamines** in the renal tubules, making them less lipid-soluble and decreasing their reabsorption, thereby **increasing their urinary excretion**. *Potassium citrate* - Potassium citrate is a **urinary alkalinizer**, meaning it would increase the pH of the urine. - Increasing urinary pH would **decrease the excretion of acidic drugs** and **increase the reabsorption of basic drugs** like amphetamines, which is the opposite of the desired effect. *Tap water* - Administering tap water would primarily lead to **diuresis** (increased urine production) but would have a **negligible effect on urinary pH**. - While increased urine volume can dilute the concentration of amphetamines, it does not significantly alter the **renal clearance rate based on pH**, which is crucial for weak bases. *Sodium bicarbonate* - Sodium bicarbonate is a potent **urinary alkalinizer**, used to increase the pH of the urine. - Just like potassium citrate, a higher urinary pH would **inhibit the excretion of amphetamines** by promoting their non-ionized, lipid-soluble form and increasing their reabsorption. *Aluminum hydroxide* - Aluminum hydroxide is primarily an **antacid** and phosphate binder, used for conditions like GERD or hyperphosphatemia; it has **no significant direct effect on urinary pH or amphetamine excretion**. - Its action is largely confined to the gastrointestinal tract, and it does not get absorbed in a way that would acidify the urine.

Question 479: A 57-year-old woman with a history of diabetes and hypertension accidentally overdoses on antiarrhythmic medication. Upon arrival in the ER, she is administered a drug to counteract the effects of the overdose. Which of the following matches an antiarrhythmic with its correct treatment in overdose?

• A. Propafenone and glucose
• B. Sotalol and norepinephrine
• C. Encainide and epinephrine
• D. Quinidine and insulin
• E. Esmolol and glucagon (Correct Answer)

Explanation: ***Esmolol and glucagon*** - **Esmolol** is a **beta-blocker**, and **glucagon** can be used in **beta-blocker overdose** to activate adenylate cyclase independently of beta-receptors, increasing intracellular cAMP and improving cardiac contractility and heart rate. - This pair represents a correct antiarrhythmic drug (esmolol) with its appropriate antidote (glucagon) for overdose management. *Propafenone and glucose* - **Propafenone** is a **Class IC antiarrhythmic** that can cause **QRS widening**, but **glucose** is not a specific antidote for its overdose. - Overdose management for propafenone typically involves sodium bicarbonate for QRS widening and supportive care. *Sotalol and norepinephrine* - **Sotalol** is a **beta-blocker** with **Class III antiarrhythmic** properties, and **norepinephrine** is a **vasopressor**. - While norepinephrine might be used for **hypotension** in sotalol overdose, it is not the primary or specific antidote for reversing the beta-blocking effects; **glucagon** would be more appropriate for the cardiac effects. *Encainide and epinephrine* - **Encainide** is a **Class IC antiarrhythmic** drug, and its overdose treatment would generally focus on **sodium bicarbonate** for QRS widening and supportive measures. - **Epinephrine** is a **vasopressor** and might be used for **hypotension** but is not a specific antidote for encainide overdose. *Quinidine and insulin* - **Quinidine** is a **Class IA antiarrhythmic** that primarily blocks **sodium channels** and can cause **QT prolongation** and **QRS widening**. - **Insulin** is primarily used for **hyperglycemia** or in high-dose insulin therapy for certain drug overdoses (e.g., calcium channel blockers or beta-blockers), but it is not a direct antidote for quinidine overdose.

Question 480: A 14-year-old boy has undergone kidney transplantation due to stage V chronic kidney disease. A pre-transplantation serologic assessment showed that he is negative for past or present HIV infection, viral hepatitis, EBV, and CMV infection. He has a known allergy for macrolides. The patient has no complaints 1 day after transplantation. His vital signs include: blood pressure 120/70 mm Hg, heart rate 89/min, respiratory rate 17/min, and temperature 37.0°C (98.6°F). On physical examination, the patient appears to be pale, his lungs are clear on auscultation, heart sounds are normal, and his abdomen is non-tender on palpation. His creatinine is 0.65 mg/dL (57.5 µmol/L), GFR is 71.3 mL/min/1.73 m2, and urine output is 0.9 mL/kg/h. Which of the following drugs should be used in the immunosuppressive regimen in this patient?

• A. Belatacept
• B. Sirolimus
• C. Omalizumab
• D. Daclizumab
• E. Basiliximab (Correct Answer)

Explanation: **Basiliximab** - **Basiliximab** is a **monoclonal antibody** that targets the **IL-2 receptor (CD25)** on activated T cells, preventing their proliferation and inducing immunosuppression. - It is commonly used as **induction therapy** in kidney transplant recipients due to its good safety profile, especially in pediatric patients, without the nephrotoxicity associated with calcineurin inhibitors, minimizing acute rejection risks immediately post-transplant. *Belatacept* - **Belatacept** works by co-stimulation blockade, binding to **CD80 and CD86** on antigen-presenting cells to prevent T-cell activation. - It is typically reserved for patients who cannot tolerate calcineurin inhibitors due to **nephrotoxicity** or require a steroid-sparing regimen, which is not indicated as an immediate need in this patient. *Sirolimus* - **Sirolimus** is an **mTOR inhibitor** that works by blocking T-cell proliferation and B-cell differentiation. - It is associated with several side effects, including **delayed wound healing**, **thrombocytopenia**, and **hyperlipidemia**, which are undesirable in the immediate post-transplant period, especially in a growing adolescent. *Omalizumab* - **Omalizumab** is an **anti-IgE monoclonal antibody** primarily used for allergic asthma and chronic spontaneous urticaria. - It has no role in **immunosuppression for organ transplantation** as its mechanism of action is unrelated to preventing graft rejection. *Daclizumab* - **Daclizumab** is another **monoclonal antibody** that also targets the **IL-2 receptor (CD25)**, similar to basiliximab. - However, daclizumab has been **withdrawn from the market** due to serious adverse effects including severe liver injury and autoimmune encephalitis, making it unavailable for clinical use in transplantation.

Question 481: A 10-year-old boy presents to the emergency department with a swollen and painful elbow after accidentally bumping his arm into the kitchen table. His mom notes that he seems to bruise and bleed easily, but this is the first time he has had a swollen joint. She also remembers that her uncle had a bleeding disorder, but cannot remember the diagnosis. Physical exam reveals a warm and tender elbow joint, but is otherwise unremarkable. Based on clinical suspicion, a bleeding panel is ordered with the following findings: Bleeding time: 3 minutes Prothrombin time (PT): 13 seconds Partial thromboplastin time (PTT): 54 seconds Which of the following treatments would most likely be effective in preventing further bleeding episodes for this patient?

• A. von Willebrand factor replacement
• B. Platelet administration
• C. Vitamin K supplementation
• D. Factor VIII replacement (Correct Answer)
• E. Intravenous immunoglobulin

Explanation: ***Factor VIII replacement*** - The prolonged **PTT (54 seconds)** with normal PT and bleeding time, combined with a history of **easy bruising and bleeding** and **hemarthrosis** (swollen, painful elbow), is highly indicative of **hemophilia A**, which is caused by a deficiency of Factor VIII. - **Factor VIII replacement therapy** directly addresses the underlying deficiency in hemophilia A, preventing future bleeding episodes and treating acute bleeds. *von Willebrand factor replacement* - **von Willebrand disease** typically presents with a prolonged bleeding time (which is normal in this patient) and can have a prolonged PTT (due to Factor VIII being carried by vWF), but the primary defect is usually in platelet adhesion. - While vWF replacement is used for von Willebrand disease, this patient's presentation with a normal bleeding time makes it less likely to be the primary cause compared to hemophilia A. *Platelet administration* - **Platelet administration** is indicated for conditions involving **thrombocytopenia** (low platelet count) or **platelet dysfunction**, which would typically manifest as a prolonged bleeding time. - This patient has a **normal bleeding time** and no indication of thrombocytopenia, making platelet administration inappropriate. *Vitamin K supplementation* - **Vitamin K** is essential for the synthesis of Factors II, VII, IX, and X, as well as proteins C and S. Deficiency often leads to a **prolonged PT and PTT**. - This patient has a **normal PT**, ruling out common causes of vitamin K deficiency or liver dysfunction as the primary issue. *Intravenous immunoglobulin* - **Intravenous immunoglobulin (IVIG)** is typically used for conditions involving **immune-mediated platelet destruction** (like immune thrombocytopenic purpura, ITP) or certain autoimmune diseases. - This patient's presentation and lab findings do not suggest an **immune-mediated disorder** or a primary platelet problem that would warrant IVIG.

Question 482: A 45-year-old woman, suspected of having colon cancer, is advised to undergo a contrast-CT scan of the abdomen. She has no comorbidities and no significant past medical history. There is also no history of drug allergy. However, she reports that she is allergic to certain kinds of seafood. After tests confirm normal renal function, she is taken to the CT scan room where radiocontrast dye is injected intravenously and a CT scan of her abdomen is conducted. While being transferred to her ward, she develops generalized itching and urticarial rashes, with facial angioedema. She becomes dyspneic. Her pulse is 110/min, the blood pressure is 80/50 mm Hg, and the respirations are 30/min. Her upper and lower extremities are pink and warm. What is the most appropriate management of this patient?

• A. Administer broad-spectrum IV antibiotics
• B. Administer vasopressors (norepinephrine and dopamine)
• C. Administer IM epinephrine 1:1,000, followed by steroids and antihistamines (Correct Answer)
• D. Perform IV resuscitation with colloids
• E. Obtain an arterial blood gas analysis

Explanation: ***Administer IM epinephrine 1:1,000, followed by steroids and antihistamines*** - This patient is experiencing **anaphylaxis** due to **radiocontrast dye**, characterized by generalized itching, urticarial rashes, angioedema, dyspnea, hypotension, and tachycardia. **Intramuscular epinephrine (1:1,000 dilution, 0.3-0.5 mg)** is the first-line treatment for anaphylaxis to reverse bronchospasm and hypotension. - Subsequent administration of **steroids and antihistamines** helps to prevent recurrent or protracted reactions and to reduce inflammatory responses initiated by histamine and other mediators. *Administer broad-spectrum IV antibiotics* - This patient's symptoms are consistent with an **allergic reaction (anaphylaxis)**, not an infection, making antibiotics inappropriate. - There is no clinical evidence of bacterial infection, such as fever, localized inflammation, or signs of sepsis beyond anaphylactic shock. *Administer vasopressors (norepinephrine and dopamine)* - While vasopressors can raise blood pressure, they are **second-line agents** for anaphylaxis after epinephrine. - Epinephrine addresses both the **vasodilation** and **bronchoconstriction** components of anaphylaxis, making it superior as the initial treatment. *Perform IV resuscitation with colloids* - **IV fluid resuscitation** is crucial for treating the hypovolemic component of anaphylactic shock, but **crystalloids** are generally preferred over colloids initially. - **Colloids** do not offer a significant advantage over crystalloids in anaphylaxis, and administering fluids alone would not address the bronchospasm or diffuse mediator release. *Obtain an arterial blood gas analysis* - While an ABG can provide information on oxygenation and acid-base status, it is **not the priority** during an acute, life-threatening anaphylactic reaction. - Immediate management of **airway, breathing, and circulation (ABC)** with epinephrine takes precedence to stabilize the patient.

Question 483: A 60-year-old man comes to the emergency room for a persistent painful erection for the last 5 hours. He has a history of sickle cell trait, osteoarthritis, insomnia, social anxiety disorder, gout, type 2 diabetes mellitus, major depressive disorder, and hypertension. He drinks 1 can of beer daily, and smokes marijuana on the weekends. He takes propranolol, citalopram, trazodone, allopurinol, metformin, glyburide, lisinopril, and occasionally ibuprofen. He is alert and oriented but in acute distress. Temperature is 36.5°C(97.7°F), pulse is 105/min, and blood pressure is 145/95 mm Hg. Examination shows a rigid erection with no evidence of trauma, penile discharge, injection, or prosthesis. Which of the following is the most likely cause of his condition?

• A. Citalopram
• B. Propranolol
• C. Marijuana use
• D. Trazodone (Correct Answer)
• E. Sickle cell trait

Explanation: ***Trazodone*** - **Trazodone** is well-known to cause **priapism** as a rare but serious side effect, even at therapeutic doses for insomnia or depression. - The patient's presentation of a **persistent, painful erection** for 5 hours is highly consistent with priapism induced by this medication. *Citalopram* - While citalopram (an **SSRI**) can affect sexual function, it typically causes **erectile dysfunction** or ejaculatory problems, not priapism. - Priapism is not a recognized or common side effect of citalopram. *Propranolol* - Propranolol is a **beta-blocker** and is not associated with priapism. - Its effects on erection are more commonly related to **erectile dysfunction** due to its role in cardiovascular regulation. *Marijuana use* - Although marijuana use can impact cardiovascular and neurological systems, there is **no clear evidence** to strongly link it to sustained priapism as a direct cause. - While theoretically possible through vasodilation, it's a less common cause than certain medications. *Sickle cell trait* - While **sickle cell disease** is a common cause of priapism due to venous occlusion, **sickle cell trait** is generally not considered a direct or common cause of priapism. - Priapism in sickle cell trait is rare and usually associated with other confounding factors or extreme conditions.

Question 484: A 56-year-old man comes to the physician for a follow-up examination. One month ago, he was diagnosed with a focal seizure and treatment with a drug that blocks voltage-gated sodium channels was begun. Today, he reports that he has not had any abnormal body movements, but he has noticed occasional double vision. His serum sodium is 132 mEq/L, alanine aminotransferase is 49 U/L, and aspartate aminotransferase is 46 U/L. This patient has most likely been taking which of the following drugs?

• A. Carbamazepine (Correct Answer)
• B. Topiramate
• C. Lamotrigine
• D. Gabapentin
• E. Levetiracetam

Explanation: ***Carbamazepine*** - This patient's symptoms of **double vision (diplopia)**, **hyponatremia** (serum sodium 132 mEq/L), and mild elevation in **liver enzymes** (ALT 49 U/L, AST 46 U/L) are classic side effects of carbamazepine. - Carbamazepine blocks **voltage-gated sodium channels**, which is consistent with the initial treatment description for focal seizures. - Hyponatremia occurs due to **SIADH (syndrome of inappropriate antidiuretic hormone secretion)**, a well-known adverse effect. *Topiramate* - Common side effects include **cognitive slowing**, **paresthesias**, and **kidney stones**, which are not reported by the patient. - While it can cause weight loss and metabolic acidosis, **diplopia** and **hyponatremia** are not typical adverse effects. *Lamotrigine* - Also blocks voltage-gated sodium channels but has a different side effect profile. - The most significant and potentially life-threatening side effect is a severe skin rash known as **Stevens-Johnson syndrome (SJS)** or toxic epidermal necrolysis (TEN). - It does not commonly cause **diplopia** or significant **hyponatremia**. *Gabapentin* - Primarily acts by binding to the **α2δ subunit of voltage-gated calcium channels** and is NOT a sodium channel blocker. - Side effects typically include **dizziness**, **somnolence**, and peripheral edema, not the constellation of symptoms presented. *Levetiracetam* - Its mechanism of action involves binding to the **synaptic vesicle protein 2A (SV2A)**, a unique target, and it is NOT a voltage-gated sodium channel blocker. - Common side effects include behavioral changes (**irritability**, **aggression**) and **somnolence**, but not diplopia or hyponatremia.

Question 485: A 22-year-old woman comes to the physician to discuss the prescription of an oral contraceptive. She has no history of major medical illness and takes no medications. She does not smoke cigarettes. She is sexually active with her boyfriend and has been using condoms for contraception. Physical examination shows no abnormalities. She is prescribed combined levonorgestrel and ethinylestradiol tablets. Which of the following is the most important mechanism of action of this drug in the prevention of pregnancy?

• A. Inhibition of rise in luteinizing hormone (Correct Answer)
• B. Suppression of ovarian folliculogenesis
• C. Thickening of cervical mucus
• D. Prevention of endometrial proliferation
• E. Increase of sex-hormone binding globulin

Explanation: ***Inhibition of rise in luteinizing hormone*** - Combined oral contraceptives (COCs) primarily prevent pregnancy by **suppressing the hypothalamic-pituitary-ovarian axis**, which inhibits the mid-cycle **Luteinizing Hormone (LH) surge** necessary for ovulation. - Without the LH surge, the mature follicle does not rupture, and the **ovum is not released**. *Suppression of ovarian folliculogenesis* - While COCs do **suppress follicular development**, this is a consequence of the feedback inhibition on FSH secretion, and not the primary contraceptive mechanism. - The direct **prevention of ovulation** via LH surge inhibition is the most crucial step. *Thickening of cervical mucus* - Progestin components of COCs cause the **cervical mucus to become thick and impermeable** to sperm, acting as a secondary contraceptive mechanism. - However, this is not the most important or primary mechanism, as ovulation can still be theoretically prevented even without this effect. *Prevention of endometrial proliferation* - The progestin in COCs causes the endometrium to become **thin and atrophic**, making it less receptive to implantation. - This is an **ancillary contraceptive effect** but not the primary way pregnancy is prevented, as preventing ovulation is more fundamental. *Increase of sex-hormone binding globulin* - Estrogen in COCs can **increase levels of sex hormone-binding globulin (SHBG)**, affecting the bioavailability of endogenous androgens. - This effect is largely responsible for reducing symptoms of androgen excess (e.g., acne) but plays **no direct role in contraception**.

Question 486: A 64-year-old woman presents to the clinic with a history of 3 fractures in the past year with the last one being last month. Her bone-density screening from last year reported a T-score of -3.1 and she was diagnosed with osteoporosis. She was advised to quit smoking and was asked to adapt to a healthy lifestyle to which she complied. She was also given calcium and vitamin D supplements. After a detailed discussion with the patient, the physician decides to start her on weekly alendronate. Which of the following statements best describes this patient’s new therapy?

• A. It should be stopped after 10 years due to the risk of esophageal cancer
• B. It is typically used as a second-line therapy for her condition after raloxifene
• C. It can cause hot flashes, flu-like symptoms, and peripheral edema
• D. It must be taken with the first meal of the day due to the significant risk of GI upset
• E. The patient must stay upright for at least 30 minutes after taking this medication (Correct Answer)

Explanation: ***The patient must stay upright for at least 30 minutes after taking this medication*** - This instruction is crucial for **alendronate** (a bisphosphonate) to prevent **esophageal irritation** and potential esophagitis or ulcers. - Alendronate must be taken with a full glass of plain water on an **empty stomach** at least 30-60 minutes before the first food, beverage, or other medication of the day, and the patient must remain upright. *It should be stopped after 10 years due to the risk of esophageal cancer* - The main concern with long-term bisphosphonate use (usually >5 years for oral agents) is the risk of **atypical femoral fractures** and **osteonecrosis of the jaw**, not esophageal cancer. - While esophageal irritation is a known side effect, the risk of esophageal cancer is **not the primary reason** for treatment discontinuation after 10 years. *It is typically used as a second-line therapy for her condition after raloxifene* - **Alendronate** (an oral bisphosphonate) is considered a **first-line therapy** for postmenopausal osteoporosis, especially in patients with a history of fractures and low T-scores. - **Raloxifene** is a selective estrogen receptor modulator (SERM) typically used when bisphosphonates are contraindicated or not tolerated, or there is a need to also treat breast cancer risk, and it is **less potent** in reducing non-vertebral fractures. *It can cause hot flashes, flu-like symptoms, and peripheral edema* - These side effects (hot flashes, flu-like symptoms, peripheral edema) are **not typically associated** with alendronate. - **Hot flashes** are more common with estrogen-modulating drugs like raloxifene, while **flu-like symptoms** can occur with IV bisphosphonates (like zoledronic acid) or certain anabolic agents. *It must be taken with the first meal of the day due to the significant risk of GI upset* - This statement is incorrect; alendronate must be taken on an **empty stomach** (at least 30-60 minutes before the first food or drink) to ensure adequate absorption. - Taking it with food or other beverages significantly **reduces its absorption**, making it less effective, and the risk of GI upset (specifically esophageal irritation) is why remaining upright and taking with water are stressed.

Question 487: A 7-year-old boy presents to an urgent care clinic from his friend’s birthday party after experiencing trouble breathing. His father explains that the patient had eaten peanut butter at the party, and soon after, he developed facial flushing and began scratching his face and neck. This has never happened before but his father says that they have avoided peanuts and peanut butter in the past because they were worried about their son having an allergic reaction. The patient has no significant medical history and takes no medications. His blood pressure is 94/62 mm Hg, heart rate is 125/min, and respiratory rate is 22/min. On physical examination, his lips are edematous and he has severe audible stridor. Of the following, which type of hypersensitivity reaction is this patient experiencing?

• A. Type II hypersensitivity reaction
• B. Type III hypersensitivity reaction
• C. Type I hypersensitivity reaction (Correct Answer)
• D. Type IV hypersensitivity reaction
• E. Combined type I and type III hypersensitivity reactions

Explanation: ***Type I hypersensitivity reaction*** - This patient is experiencing **anaphylaxis** due to **peanut exposure**, a classic example of a **Type I hypersensitivity reaction**. This involves **IgE-mediated mast cell and basophil degranulation**, releasing histamines and other inflammatory mediators. - The symptoms like **facial flushing, itching, angioedema (edematous lips), stridor (upper airway obstruction), tachycardia**, and potentially **hypotension** (blood pressure 94/62 mmHg in a child suggests relative hypotension) are all consistent with a severe systemic allergic reaction. *Type II hypersensitivity reaction* - Type II hypersensitivity involves **antibody-mediated cytotoxicity**, where **IgG or IgM antibodies** bind to antigens on cell surfaces, leading to cell destruction. - This type of reaction typically manifests as **hemolytic anemia, thrombocytopenia**, or **Goodpasture syndrome**, which are distinct from the patient's acute allergic presentation. *Type III hypersensitivity reaction* - Type III hypersensitivity is characterized by the formation of **immune complexes** (antigen-antibody complexes) that deposit in tissues, leading to inflammation and tissue damage. - Conditions like **serum sickness, lupus nephritis**, or **Arthus reaction** are examples of Type III reactions and do not fit the acute, IgE-mediated symptoms seen in this patient. *Type IV hypersensitivity reaction* - Type IV hypersensitivity is a **delayed-type hypersensitivity** reaction mediated by **T-cells**, not antibodies. It takes 24-72 hours to develop. - Examples include **contact dermatitis (e.g., poison ivy)**, **tuberculin skin test reactions**, or **graft rejection**, which are much slower and have different mechanisms than the immediate anaphylactic response described. *Combined type I and type III hypersensitivity reactions* - While some complex immune conditions might involve multiple types of hypersensitivity over time, the patient's acute, rapid-onset symptoms after peanut ingestion are overwhelmingly characteristic of a **primary Type I hypersensitivity reaction**. - There is no clinical evidence in this presentation to suggest the involvement of **immune complex deposition** (Type III) in addition to the immediate IgE-mediated response.

Question 488: A group of researchers is studying various inhaled substances to determine their anesthetic properties. In particular, they are trying to identify an anesthetic with fast onset and quick recovery for use in emergencies. They determine the following data: Inhalational anesthetic Blood-gas partition coefficient A 0.15 B 0.92 C 5.42 Which of the following statements is accurate with regard to these inhaled anesthetic substances?

• A. Agent C has the fastest onset of action
• B. Agent A has the fastest onset of action (Correct Answer)
• C. Agent B is the most potent
• D. Agent B has the fastest onset of action
• E. Agent A is the most potent

Explanation: ***Agent A has the fastest onset of action*** - **Agent A** has the lowest blood-gas partition coefficient (0.15), indicating very low solubility in blood. - A **low blood-gas partition coefficient** means the anesthetic quickly equilibrates between the lungs and blood, leading to a rapid rise in partial pressure in the brain and thus **fast onset of action** and **quick recovery**. *Agent C has the fastest onset of action* - **Agent C** has the highest blood-gas partition coefficient (5.42), indicating high solubility in blood. - High solubility means the anesthetic takes longer to saturate the blood and reach the brain, resulting in a **slow onset of action** and **slow recovery**. *Agent B is the most potent* - **Potency** of an inhaled anesthetic is inversely related to its **Minimum Alveolar Concentration (MAC)**, not directly to its blood-gas partition coefficient. - While a higher blood-gas coefficient can sometimes correlate with other properties, it does not directly determine potency. *Agent B has the fastest onset of action* - **Agent B** has a blood-gas partition coefficient of 0.92, which is higher than Agent A (0.15). - A higher blood-gas partition coefficient means the anesthetic is more soluble in blood, leading to a **slower onset of action** compared to Agent A. *Agent A is the most potent* - **Agent A** has the lowest blood-gas partition coefficient (0.15), which indicates **fast onset** and **rapid recovery**, but not necessarily high potency. - **Potency** is determined by MAC (Minimum Alveolar Concentration), which is the concentration of anesthetic at 1 atmosphere that produces immobility in 50% of patients challenged with a surgical incision.

Question 489: A 25-year-old man comes to the physician because of an 8-hour history of painful leg cramping, runny nose, chills, diarrhea, and abdominal pain. Examination shows cool, damp skin with piloerection. The pupils are 7 mm in diameter and equal in size. Deep tendon reflexes are 3+ bilaterally. The diagnosis of opioid withdrawal is made. After the patient is stabilized, the physician initiates a withdrawal regimen with methadone. Which of the following characteristics makes this drug a suitable substance for the treatment of this patient's addiction?

• A. Rapid onset of action
• B. Low tolerance potential
• C. Long elimination half-life (Correct Answer)
• D. Low dependence risk
• E. Limited potency

Explanation: ***Long elimination half-life*** - **Methadone's long half-life** allows for steady drug levels, preventing the rapid fluctuations that trigger severe withdrawal symptoms. - This characteristic enables **once-daily dosing**, simplifying treatment and reducing the likelihood of illicit drug-seeking behavior. *Rapid onset of action* - While methadone does have a relatively quick onset, it's not its primary advantage in **opioid addiction treatment**. - **Buprenorphine** often has a faster onset and is used in a different capacity for induction of treatment. *Low tolerance potential* - **Methadone** is an opioid agonist and, like other opioids, patients can develop **tolerance** to its effects over time. - Its utility in addiction treatment comes from its ability to stabilize opioid receptors, not from a lack of tolerance development. *Low dependence risk* - **Methadone** is an opioid and carries a significant risk of **physical dependence**. - The goal of methadone maintenance is to manage this dependence in a controlled medical setting, reducing harm associated with illicit opioid use. *Limited potency* - **Methadone** is a potent opioid, similar in potency to morphine, which contributes to its effectiveness in managing severe withdrawal symptoms and cravings. - Its high potency is a key factor in its therapeutic benefit, not a limitation.

Question 490: An 82-year-old male with a history of congestive heart failure presented with new-onset atrial fibrillation. He was initially started on carvedilol, but he now requires an additional agent for rate control. He is started on a medicine and is warned by his physician of the following potential side effects associated with this therapy: nausea, vomiting, confusion, blurry yellow vision, electrolyte abnormalities, and potentially fatal arrhythmia. Which of the following is most likely to increase this patient's susceptibility to the toxic effects associated with this medication?

• A. Hyperkalemia
• B. Elevated AST and ALT
• C. Increased GFR with normal creatinine
• D. Hypokalemia (Correct Answer)
• E. Hyponatremia

Explanation: ***Hypokalemia*** - The symptoms described (nausea, vomiting, confusion, blurry yellow vision, potentially fatal arrhythmias) are classic for **digoxin toxicity**. - **Hypokalemia** increases the binding of digoxin to the **Na+/K+-ATPase pump**, exacerbating its effects and increasing the risk of toxicity. *Hyperkalemia* - **Hyperkalemia** actually **inhibits** digoxin binding to the Na+/K+-ATPase pump. - This can reduce the therapeutic efficacy and the toxic effects of digoxin. *Elevated AST and ALT* - Elevated AST and ALT indicate **liver dysfunction**, which can affect the metabolism of certain drugs. - However, digoxin is primarily eliminated by the **kidneys**, so liver enzyme abnormalities are not a primary risk factor for digoxin toxicity. *Increased GFR with normal creatinine* - An increased **Glomerular Filtration Rate (GFR)** would lead to more rapid renal clearance of digoxin. - This would **decrease** the risk of digoxin accumulation and toxicity, rather than increase it. *Hyponatremia* - While electrolyte imbalances can be associated with cardiac conditions, **hyponatremia** itself does not directly increase the susceptibility to digoxin toxicity. - The most critical electrolyte imbalance for digoxin toxicity is **hypokalemia**.

Question 491: A 22-year-old woman presents to the emergency department feeling lightheaded and states that her heart is racing. She does not have a history of any chronic medical conditions. She is a college sophomore and plays club volleyball. Although she feels stressed about her upcoming final exams next week, she limits her caffeine intake to 3 cups of coffee per day to get a good night sleep. She notes that her brother takes medication for some type of heart condition, but she does not know the name of it. Both her parents are alive and well. She denies recent illness, injuries, or use of cigarettes, alcohol, or recreational drugs. The pertinent negatives from the review of systems include an absence of fever, nausea, vomiting, sweating, fatigue, or change in bowel habits. The vital signs include: temperature 36.8°C (98.2°F), heart rate 125/min, respiratory rate 15/min, blood pressure 90/75 mm Hg, and oxygen saturation of 100% on room air. The laboratory results are within normal limits. The ECG is significant for a shortened PR interval and widened QRS. Which of the following medications should the patient avoid in this scenario?

• A. Amlodipine
• B. Procainamide
• C. Diltiazem
• D. Verapamil (Correct Answer)
• E. Metoprolol

Explanation: ***Verapamil*** - The ECG findings of a **shortened PR interval** and **widened QRS** are characteristic of **Wolff-Parkinson-White (WPW) syndrome**, an accessory pathway that can bypass the AV node. - Verapamil is a **non-dihydropyridine calcium channel blocker** that blocks the AV node and can paradoxically increase conduction down the accessory pathway in WPW, potentially leading to **ventricular fibrillation** if an atrial tachyarrhythmia is present. - **Verapamil is the most classically contraindicated medication in WPW syndrome** and is the prototype drug to avoid in this condition. *Amlodipine* - Amlodipine is a **dihydropyridine calcium channel blocker** primarily used for hypertension and angina. - It has minimal effect on the AV node and does not carry the same risk as non-dihydropyridine calcium channel blockers in WPW syndrome. *Procainamide* - **Procainamide is a Class Ia antiarrhythmic** that can be used to treat tachyarrhythmias related to WPW syndrome, as it prolongs the refractory period of the accessory pathway. - It would be a potential **treatment option**, not a medication to avoid, especially for antidromic atrioventricular reentrant tachycardia (AVRT) in WPW. *Diltiazem* - Similar to verapamil, diltiazem is a **non-dihydropyridine calcium channel blocker** that blocks the AV node. - While it carries similar risks to verapamil in WPW syndrome, **verapamil is more classically emphasized** as the prototypical contraindicated medication in medical education and board examinations. *Metoprolol* - Metoprolol is a **beta-blocker** that slows conduction through the AV node. - While beta-blockers are also generally **avoided in WPW syndrome with atrial fibrillation**, **AV nodal blocking calcium channel blockers (especially verapamil) are considered the primary contraindication** due to more pronounced effects on accessory pathway conduction.

Question 492: A 71-year-old man with recently diagnosed small-cell lung cancer sees his physician because of increasing weakness over the past 3 months. He is unable to climb stairs or comb his hair. His weakness is worse after inactivity and improves with exercise. He is a former smoker with a 30-pack-year history. He is currently preparing for initiation of chemotherapy. His vital signs are within normal limits. On examination, ptosis of both eyelids is seen. Dry oral mucosa is notable. Significant weakness is detected in all four proximal extremities. The patellar and biceps reflexes are absent. Auscultation of the lungs reveals generalized wheezing and rhonchi. Which of the following is the most likely underlying mechanism for this patient’s weakness?

• A. Acute autoimmune demyelination of axons
• B. Endomysial CD8+ T cell infiltration with vacuoles and inclusion bodies
• C. Necrotizing vasculitis with granuloma formation
• D. Reduced number of available postsynaptic acetylcholine receptors
• E. Autoantibody-impaired acetylcholine release from nerve terminals (Correct Answer)

Explanation: ***Autoantibody-impaired acetylcholine release from nerve terminals*** - This patient's progressive, proximal muscle weakness, **ptosis**, and **absent deep tendon reflexes**, particularly with improvement upon exercise, are classic signs of **Lambert-Eaton myasthenic syndrome (LEMS)**. - LEMS is a **paraneoplastic syndrome** strongly associated with **small-cell lung cancer (SCLC)**, caused by autoantibodies targeting presynaptic **voltage-gated calcium channels**, thus impairing acetylcholine release. *Acute autoimmune demyelination of axons* - This description is characteristic of **Guillain-Barré syndrome (GBS)**, which typically presents with **ascending paralysis** and is often preceded by an infection. - Unlike LEMS, GBS usually causes worsening weakness with activity and is not directly associated with cancer in this paraneoplastic manner. *Endomysial CD8+ T cell infiltration with vacuoles and inclusion bodies* - This pathological finding is characteristic of **inclusion body myositis (IBM)**, a progressive muscle disease. - IBM typically affects older adults and causes **asymmetric weakness**, often involving distal muscles, which is not consistent with the patient's presentation. *Necrotizing vasculitis with granuloma formation* - This describes conditions like **Granulomatosis with Polyangiitis (GPA)**, which primarily affects **small and medium-sized blood vessels**, often involving the upper and lower respiratory tracts and kidneys. - While it can cause muscle weakness due to vasculitic neuropathy or myopathy, it does not typically present with the specific "improvement with exercise" seen in this patient, and the presentation is not consistent with LEMS. *Reduced number of available postsynaptic acetylcholine receptors* - This is the underlying mechanism for **myasthenia gravis (MG)**, another autoimmune neuromuscular junction disorder. - While MG also causes fluctuating weakness and ptosis, its weakness typically **worsens with activity** and improves with rest, the opposite of the waxing and waning seen in LEMS.

Question 493: A 50-year-old woman comes to the physician for the evaluation of excessive hair growth on her chin over the past 2 weeks. She also reports progressive enlargement of her gums. Three months ago, she underwent a liver transplantation due to Wilson disease. Following the procedure, the patient was started on transplant rejection prophylaxis. She has a history of poorly-controlled type 2 diabetes mellitus. Temperature is 37°C (98.6°F), pulse is 80/min, respirations are 22/min, and blood pressure is 150/80 mm Hg. Physical examination shows dark-pigmented, coarse hair on the chin, upper lip, and chest. The gingiva and the labial mucosa are swollen. There is a well-healed scar on her right lower abdomen. Which of the following drugs is the most likely cause of this patient's findings?

• A. Daclizumab
• B. Cyclosporine (Correct Answer)
• C. Sirolimus
• D. Methotrexate
• E. Tacrolimus

Explanation: **Cyclosporine** * This patient's **combination of hirsutism** (excessive hair growth) **and gingival hyperplasia** (gum enlargement) is the classic presentation of cyclosporine toxicity, an immunosuppressant commonly used for transplant rejection prophylaxis. * Cyclosporine is a **calcineurin inhibitor** that prevents T-cell activation and is highly effective in preventing graft rejection. * The **simultaneous presence of both hirsutism and prominent gingival hyperplasia** is particularly characteristic of cyclosporine. *Daclizumab* * **Daclizumab** is a **monoclonal antibody** targeting the IL-2 receptor, which was previously used for transplant prophylaxis but has been discontinued for this indication. * It is not associated with hirsutism or gingival hyperplasia. *Sirolimus* * **Sirolimus** is an **mTOR inhibitor** used as an immunosuppressant, known for side effects like hyperlipidemia, myelosuppression, and delayed wound healing. * It does **not** typically cause hirsutism or gingival hyperplasia. *Methotrexate* * **Methotrexate** is an **antimetabolite** and immunosuppressant commonly used in autoimmune diseases and cancer, with side effects including bone marrow suppression, mucositis, and liver toxicity. * Hirsutism and gingival hyperplasia are **not** characteristic side effects of methotrexate. *Tacrolimus* * **Tacrolimus** is another **calcineurin inhibitor**, similar to cyclosporine, but with a different side effect profile. While tacrolimus can cause hirsutism, **gingival hyperplasia is significantly less common** with tacrolimus compared to cyclosporine. * The **presence of prominent gingival hyperplasia alongside hirsutism strongly favors cyclosporine** over tacrolimus. * Tacrolimus is more commonly associated with **neurotoxicity** (e.g., tremor) and **nephrotoxicity**.

Question 494: A 54-year-old man comes to the emergency department because of episodic palpitations for the past 12 hours. He has no chest pain. He has coronary artery disease and type 2 diabetes mellitus. His current medications include aspirin, insulin, and atorvastatin. His pulse is 155/min and blood pressure is 116/77 mm Hg. Physical examination shows no abnormalities. An ECG shows monomorphic ventricular tachycardia. An amiodarone bolus and infusion is given, and the ventricular tachycardia converts to normal sinus rhythm. He is discharged home with oral amiodarone. Which of the following is the most likely adverse effect associated with long-term use of this medication?

• A. Angle-closure glaucoma
• B. Hepatic adenoma
• C. Shortened QT interval on ECG
• D. Progressive multifocal leukoencephalopathy
• E. Chronic interstitial pneumonitis (Correct Answer)

Explanation: ***Chronic interstitial pneumonitis*** - **Amiodarone** is known to cause several dose-dependent adverse effects, including **pulmonary toxicity** in the form of **interstitial pneumonitis** or fibrosis. - This adverse effect can manifest as progressive dyspnea, cough, and infiltrates on chest imaging, requiring careful monitoring during long-term use. *Angle-closure glaucoma* - While some medications can cause **angle-closure glaucoma**, it is **not a classic or common adverse effect of amiodarone**. - **Topiramate** and **sulfonamides** are more commonly associated with acute angle-closure glaucoma. *Hepatic adenoma* - **Hepatic adenomas** are typically associated with **oral contraceptive use** and sometimes **anabolic steroid use**, not amiodarone. - Amiodarone can cause **hepatic toxicity** (elevated transaminases, hepatitis), but not specifically hepatic adenoma. *Shortened QT interval on ECG* - **Amiodarone** is a Class III antiarrhythmic drug that **prolongs the QT interval** by blocking potassium channels, which is its mechanism of action for suppressing arrhythmias. - Therefore, a shortened QT interval is the **opposite of what would be expected with amiodarone use**. *Progressive multifocal leukoencephalopathy* - **Progressive multifocal leukoencephalopathy (PML)** is a rare, severe opportunistic infection of the brain caused by the **JC virus**, typically seen in immunocompromised individuals. - It is **not an adverse effect of amiodarone**; drugs like natalizumab or rituximab, which affect the immune system, are associated with PML.

Question 495: A 34-year-old female presents to the emergency room with headache and palpitations. She is sweating profusely and appears tremulous on exam. Vital signs are as follows: HR 120, BP 190/110, RR 18, O2 99% on room air, and Temp 37C. Urinary metanephrines and catechols are positive. Which of the following medical regimens is contraindicated as a first-line therapy in this patient?

• A. Labetalol
• B. Propranolol (Correct Answer)
• C. Nitroprusside
• D. Lisinopril
• E. Phenoxybenzamine

Explanation: ***Propranolol*** - This patient's presentation with headache, palpitations, sweating, hypertension, and tachycardia, along with elevated urinary metanephrines and catechols, is highly suggestive of a **pheochromocytoma**. - **Pure beta-blockers** (like propranolol) are **absolutely contraindicated** as first-line therapy because blocking $\beta_2$ receptors without initial $\alpha$-blockade leads to unopposed $\alpha$-adrenergic stimulation, causing severe **vasoconstriction** and a dangerous **hypertensive crisis**. - This is the **most contraindicated** option among the choices listed. *Labetalol* - Labetalol is a **non-selective $\beta$-blocker with some $\alpha_1$-blocking activity** (β:α blockade ratio ~7:1). - While **not recommended** as first-line monotherapy in pheochromocytoma due to predominant beta-blockade, it has **some alpha-blocking properties** that distinguish it from pure beta-blockers. - In practice, it's typically avoided as initial therapy, but it carries **less risk** than pure beta-blockers because of its partial alpha-blockade. - Some sources consider it relatively contraindicated, but propranolol (pure beta-blocker) is more definitively contraindicated. *Nitroprusside* - **Nitroprusside** is a potent **vasodilator** that acts on both arterial and venous beds, making it effective for **rapid blood pressure reduction** in hypertensive emergencies. - It is **not contraindicated** and can be used in a pheochromocytoma crisis for acute blood pressure control, though it should ideally be combined with alpha-blockade. - It does not directly address catecholamine effects but provides symptomatic BP control. *Lisinopril* - **Lisinopril** is an **ACE inhibitor**, which works by preventing the conversion of angiotensin I to angiotensin II, leading to vasodilation and reduced aldosterone secretion. - It is **not contraindicated** but is **inappropriate** as first-line therapy in pheochromocytoma crisis because it does not directly counteract the massive catecholamine release. - It would be ineffective for managing the acute hypertensive emergency. *Phenoxybenzamine* - **Phenoxybenzamine** is an **irreversible, non-selective $\alpha$-adrenergic blocker** that is the **gold standard first-line therapy** for pheochromocytoma. - It effectively blocks the vasoconstrictive effects of catecholamines, allowing for adequate blood pressure control before any $\beta$-blockade is considered. - This is the **correct first-line medication**, not contraindicated.

Question 496: A 3-year-old toddler was rushed to the emergency department after consuming peanut butter crackers at daycare. The daycare staff report that the patient has a severe allergy to peanut butter and he was offered the crackers by mistake. The patient is in acute distress. The vital signs include: blood pressure 60/40 mm Hg and heart rate 110/min. There is audible inspiratory stridor and the respiratory rate is 27/min. Upon examination, his chest is covered in a maculopapular rash. Intubation is attempted and failed due to extensive laryngeal edema. The decision for cricothyrotomy is made. Which of the following is the most likely mechanism of this pathology?

• A. C3b interaction
• B. Deposition of antigen-antibody complexes
• C. C5a production
• D. IL-2 secretion
• E. Mast cell degranulation and histamine release (Correct Answer)

Explanation: ***Mast cell degranulation and histamine release*** - The clinical scenario describes **anaphylaxis**, a severe, life-threatening allergic reaction, which is predominantly mediated by **IgE antibodies** binding to mast cells and basophils. - Upon re-exposure to the allergen (**peanut butter**), the allergen cross-links IgE molecules on the cell surface, leading to rapid **mast cell degranulation** and the release of preformed mediators like **histamine**, tryptase, and newly synthesized mediators like leukotrienes and prostaglandins. These mediators cause vasodilation, increased vascular permeability (leading to hypotension and edema), bronchoconstriction (leading to stridor), and pruritus/rash. *C3b interaction* - **C3b** is a component of the **complement system** and primarily functions in **opsonization** and the formation of the membrane attack complex (MAC). - While the complement system can be activated in allergic reactions, C3b interaction itself is not the primary mechanism responsible for the acute, severe symptoms of anaphylaxis. *Deposition of antigen-antibody complexes* - This mechanism describes a **Type III hypersensitivity reaction** (e.g., serum sickness, lupus nephritis), where immune complexes deposit in tissues leading to inflammation. - The symptoms described (acute respiratory distress, hypotension, stridor, rash) are characteristic of a **Type I hypersensitivity reaction** mediated by IgE, not immune complex deposition. *C5a production* - **C5a** is a powerful **anaphylatoxin** and chemoattractant produced during **complement activation**. - While C5a can contribute to some features of anaphylaxis by promoting mast cell degranulation, it is a downstream mediator and not the primary initiating mechanism of IgE-mediated anaphylaxis. *IL-2 secretion* - **IL-2** (interleukin-2) is a cytokine primarily involved in the **proliferation and differentiation of T cells**, particularly in **cell-mediated immunity** (Type IV hypersensitivity reactions) and immune regulation. - It does not play a direct, immediate role in the acute mast cell degranulation and mediator release characteristic of anaphylaxis.

Question 497: A 59-year-old healthy woman presents to her primary care physician’s office six weeks after undergoing an elective breast augmentation procedure in the Dominican Republic. She was told by her surgeon to establish post-operative care once back in the United States. Today she is bothered by nausea and early satiety. Her past medical history is significant only for GERD for which she takes ranitidine. Since the surgery, she has also taken an unknown opioid pain medication that was given to her by the surgeon. She reports that she has been taking approximately ten pills a day. On examination she is afebrile with normal vital signs and her surgical incisions are healing well. Her abdomen is distended and tympanitic. The patient refuses to stop her pain medicine and laxatives are not effective; what medication could be prescribed to ameliorate her gastrointestinal symptoms?

• A. Naloxegol (Correct Answer)
• B. Senna
• C. Pantoprazole
• D. Metoclopramide
• E. Naproxen

Explanation: ***Naloxegol*** - This patient is experiencing **opioid-induced constipation (OIC)** due to chronic opioid use, evidenced by nausea, early satiety, abdominal distension, and ineffective laxatives. **Naloxegol** is a peripherally acting mu-opioid receptor antagonist (PAMORA) that blocks opioid effects in the gastrointestinal tract without reversing central analgesia. - It helps ameliorate OIC symptoms by reducing the constipating effects of opioids while the patient continues to take their pain medication, which is crucial given her refusal to stop. *Senna* - **Senna** is a stimulant laxative that works by irritating the bowel mucosa to promote peristalsis. - While useful for some forms of constipation, it is often ineffective in severe OIC because the primary problem is opioid-mediated reduction in gut motility, not simply a lack of stimulation, and the patient reports laxatives have already been ineffective. *Pantoprazole* - **Pantoprazole** is a proton pump inhibitor (PPI) used to reduce stomach acid production and treat conditions like GERD. - While the patient has a history of GERD, her current symptoms of nausea, early satiety, and abdominal distension are primarily related to opioid use and not acid reflux, making pantoprazole an inappropriate treatment for her current GI complaints. *Metoclopramide* - **Metoclopramide** is a dopamine antagonist that acts as a prokinetic agent, increasing gastrointestinal motility. - Although it can help with nausea and gastric emptying, it primarily addresses the upper GI tract and may not be sufficient for the severe, generalized reduction in motility seen in OIC, and its central dopamine blocking effects can lead to side effects like tardive dyskinesia with chronic use. *Naproxen* - **Naproxen** is a nonsteroidal anti-inflammatory drug (NSAID) used for pain and inflammation. - It has no role in treating gastrointestinal motility disorders or opioid-induced constipation; in fact, chronic NSAID use can cause GI side effects like gastritis and ulcers.

Question 498: A 35-year-old female presents to her primary care physician complaining of right upper quadrant pain over the last 6 months. Pain is worst after eating and feels like intermittent squeezing. She also admits to lighter colored stools and a feeling of itchiness on her skin. Physical exam demonstrates a positive Murphy's sign. The vitamin level least likely to be affected by this condition is associated with which of the following deficiency syndromes?

• A. Rickets and osteomalacia
• B. Hemolytic anemia
• C. Night blindness
• D. Increased prothrombin time and easy bleeding
• E. Scurvy (Correct Answer)

Explanation: ***Scurvy*** - This condition is likely **cholestasis** due to common bile duct obstruction, given the RUQ pain after eating, light-colored stools, itchiness, and **positive Murphy's sign**. - Cholestasis impairs the absorption of **fat-soluble vitamins** (A, D, E, K), but not **water-soluble vitamins** like vitamin C, which prevents scurvy. *Rickets and osteomalacia* - These conditions are caused by **vitamin D deficiency**, which is a **fat-soluble vitamin**. - Impaired fat absorption in cholestasis would significantly impact vitamin D levels, leading to increased risk of rickets in children and osteomalacia in adults. *Hemolytic anemia* - This can be caused by **vitamin E deficiency**, a **fat-soluble vitamin**. - Cholestasis impairs vitamin E absorption, which can lead to increased red blood cell fragility and hemolytic anemia. *Night blindness* - This is a classic symptom of **vitamin A deficiency**, which is a **fat-soluble vitamin**. - Impaired fat absorption in cholestasis would reduce vitamin A uptake, contributing to night blindness. *Increased prothrombin time and easy bleeding* - These symptoms are indicative of **vitamin K deficiency**, a **fat-soluble vitamin**. - Vitamin K is essential for the synthesis of clotting factors, and its absorption is severely hindered in cholestasis, leading to coagulopathies.

Question 499: A 59-year-old male with a 1-year history of bilateral knee arthritis presents with epigastric pain that intensifies with meals. He has been self-medicating with aspirin, taking up to 2,000 mg per day for the past six months. Which of the following medications, if taken instead of aspirin, could have minimized his risk of experiencing this epigastric pain?

• A. Naproxen
• B. Celecoxib (Correct Answer)
• C. Indomethacin
• D. Ibuprofen
• E. Ketorolac

Explanation: ***Celecoxib*** - **Celecoxib** is a selective **COX-2 inhibitor**, which preferentially inhibits the COX-2 enzyme responsible for inflammation and pain, while largely sparing COX-1. - Sparing **COX-1** reduces the inhibition of **prostaglandins** that protect the gastric mucosa, thereby lowering the risk of GI side effects like epigastric pain and ulcers compared to non-selective NSAIDs. *Naproxen* - **Naproxen** is a **non-selective NSAID** that inhibits both COX-1 and COX-2 enzymes. - Inhibition of **COX-1** interferes with the production of protective prostaglandins in the stomach, increasing the risk of gastrointestinal adverse effects such as epigastric pain, ulcers, and bleeding, similar to aspirin. *Indomethacin* - **Indomethacin** is a potent **non-selective NSAID** with significant inhibition of both COX-1 and COX-2. - Its strong **COX-1 inhibition** makes it particularly prone to causing gastrointestinal side effects including severe epigastric pain, nausea, and dyspepsia. *Ibuprofen* - **Ibuprofen** is a **non-selective NSAID** commonly used for pain and inflammation that inhibits both COX-1 and COX-2 enzymes. - Although generally better tolerated than indomethacin or high-dose aspirin, it still carries a dose-dependent risk of **GI adverse effects** due to COX-1 inhibition. *Ketorolac* - **Ketorolac** is a potent **non-selective NSAID** primarily used for short-term management of acute moderate to severe pain. - It has a high risk of **gastrointestinal complications**, including gastric ulcers and bleeding, making it unsuitable for long-term use and not a safer alternative to aspirin in terms of GI risk.

Question 500: A 62-year-old man presents to his primary care provider complaining of leg pain with exertion for the past 6 months. He notices that he has bilateral calf cramping with walking. He states that it is worse in his right calf than in his left, and it goes away when he stops walking. He has also noticed that his symptoms are progressing and that this pain is occurring sooner than before. His medical history is remarkable for type 2 diabetes mellitus and 30-pack-year smoking history. His ankle-brachial index (ABI) is found to be 0.80. Which of the following can be used as initial therapy for this patient's condition?

• A. Endovascular revascularization
• B. Arthroscopic resection
• C. Duloxetine
• D. Heparin
• E. Cilostazol (Correct Answer)

Explanation: ***Cilostazol*** - This patient presents with symptoms highly suggestive of **peripheral artery disease (PAD)**, characterized by **intermittent claudication** (leg pain with exertion relieved by rest) and a **low ankle-brachial index (ABI)** of 0.80. - **Cilostazol** is a phosphodiesterase inhibitor specifically approved for the symptomatic relief of **intermittent claudication** in patients with PAD, improving walking distance and quality of life. *Endovascular revascularization* - **Endovascular revascularization** (e.g., angioplasty, stenting) is typically reserved for patients with more severe symptoms, such as **rest pain**, **non-healing ulcers**, or **gangrene**, or for those who have failed appropriate medical therapy. - Initial management of **intermittent claudication** usually begins with lifestyle modifications and pharmacotherapy, given the less severe presentation and the current guidelines. *Arthroscopic resection* - **Arthroscopic resection** is a surgical procedure primarily used for joint-related problems, such as removing damaged cartilage or bone spurs from a joint. - It is not indicated for the treatment of **peripheral artery disease** or **intermittent claudication**, which is a vascular condition. *Duloxetine* - **Duloxetine** is a serotonin-norepinephrine reuptake inhibitor (SNRI) primarily used for the treatment of **neuropathic pain**, depression, and generalized anxiety disorder. - While the patient has diabetes (a risk factor for neuropathy), the symptom of **intermittent claudication associated with exertion** and a low ABI points away from neuropathic pain as the primary cause. *Heparin* - **Heparin** is an anticoagulant used to prevent blood clot formation, typically in acute settings like **deep vein thrombosis (DVT)**, **pulmonary embolism (PE)**, or acute limb ischemia. - It is not indicated for the long-term management of stable **peripheral artery disease** with intermittent claudication, as it does not address the underlying atherosclerotic process.

Question 501: A 26-year-old G1P0 woman is brought to the emergency room by her spouse for persistently erratic behavior. Her spouse reports that she has been sleeping > 1 hour a night, and it sometimes seems like she’s talking to herself. She has maxed out their credit cards on baby clothes. The patient’s spouse reports this has been going on for over a month. Since first seeing a physician, she has been prescribed multiple first and second generation antipsychotics, but the patient’s spouse reports that her behavior has failed to improve. Upon examination, the patient is speaking rapidly and occasionally gets up to pace the room. She reports she is doing “amazing,” and that she is “so excited for the baby to get here because I’m going to be the best mom.” She denies illicit drug use, audiovisual hallucinations, or suicidal ideation. The attending psychiatrist prescribes a class of medication the patient has not yet tried to treat the patient’s psychiatric condition. In terms of this new medication, which of the following is the patient’s newborn most likely at increased risk for?

• A. Ototoxicity
• B. Attention deficit hyperactivity disorder
• C. Right ventricular atrialization (Correct Answer)
• D. Renal defects
• E. Caudal regression syndrome

Explanation: ***Right ventricular atrialization*** - The patient's presentation of persistent **erratic behavior**, **reduced sleep**, rapid speech, and increased spending, enduring for over a month, is highly suggestive of a **manic episode** in the context of **bipolar I disorder**. Since antipsychotics have been ineffective, the next step is often **lithium**. - **Lithium** exposure during the first trimester of pregnancy is associated with an increased risk of **Ebstein's anomaly**, a congenital heart defect characterized by **right ventricular atrialization** (displacement of the tricuspid valve leaflets into the right ventricle), leading to tricuspid regurgitation and right heart failure. *Ototoxicity* - **Ototoxicity** in newborns is typically associated with exposure to medications such as **aminoglycoside antibiotics** (e.g., gentamicin) or certain diuretics (e.g., furosemide) during pregnancy. - Lithium is not known to cause ototoxicity as a primary birth defect. *Attention deficit hyperactivity disorder* - While various prenatal exposures can influence neurodevelopment, there is currently **no strong evidence** linking in-utero lithium exposure specifically to an increased risk of **ADHD** in offspring. - ADHD is a complex neurodevelopmental disorder with multifactorial origins, including genetic and environmental factors. *Renal defects* - While lithium is primarily excreted by the kidneys and can cause **renal dysfunction** in adults (e.g., nephrogenic diabetes insipidus), it is not a prominent teratogen known to cause specific **structural renal defects** in newborns when exposed during pregnancy. - Renal anomalies are more commonly associated with other medications or genetic syndromes. *Caudal regression syndrome* - **Caudal regression syndrome** is a severe congenital anomaly affecting the development of the lower spine and limbs. It is strongly associated with **poorly controlled maternal diabetes**. - There is no established link between in-utero lithium exposure and caudal regression syndrome.

Question 502: A 27-year-old man presents to the emergency department for bizarre behavior. The patient had boarded up his house and had been refusing to leave for several weeks. The police were called when a foul odor emanated from his property prompting his neighbors to contact the authorities. Upon questioning, the patient states that he has been pursued by elves for his entire life. He states that he was tired of living in fear, so he decided to lock himself in his house. The patient is poorly kempt and has very poor dentition. The patient has a past medical history of schizophrenia which was previously well controlled with olanzapine. The patient is restarted on olanzapine and monitored over the next several days. Which of the following needs to be monitored long term in this patient?

• A. CBC
• B. HbA1c levels (Correct Answer)
• C. ECG
• D. Monitoring for acute dystonia
• E. Renal function studies

Explanation: ***HbA1c levels*** - **Olanzapine** is associated with significant metabolic side effects, including **weight gain**, **dyslipidemia**, and **new-onset diabetes mellitus**, necessitating long-term monitoring of **glucose metabolism** - **HbA1c** provides an average of blood glucose levels over the past 2-3 months, making it an excellent indicator for assessing the risk and progression of **diabetes** in patients on olanzapine. *CBC* - While some antipsychotics can cause hematological side effects like **agranulocytosis** (e.g., **clozapine**), **olanzapine** is not typically associated with severe bone marrow suppression requiring routine, long-term CBC monitoring. - CBC monitoring would be more relevant in the short-term if there were specific concerns for infection or adverse drug reactions. *ECG* - Some atypical antipsychotics can prolong the **QTc interval**, which would warrant ECG monitoring, but this adverse effect is less commonly associated with **olanzapine** compared to other antipsychotics like **ziprasidone** or **haloperidol**. - While a baseline ECG might be considered, long-term routine ECG monitoring is not typically indicated without specific cardiac risk factors or symptoms. *Monitoring for acute dystonia* - **Acute dystonia** is an extrapyramidal symptom that typically occurs early in treatment with antipsychotics, especially first-generation agents or at the initiation of therapy with second-generation agents like **olanzapine**. - While important to monitor acutely, it is not a long-term monitoring requirement once the patient is stable on the medication. *Renal function studies* - **Olanzapine** is primarily metabolized by the liver, and **renal excretion** plays a minor role in its elimination. - Therefore, long-term monitoring of renal function is not routinely recommended for patients on olanzapine unless there are pre-existing kidney conditions or other nephrotoxic medications.

Question 503: A 53-year-old man is brought to the emergency department because of wheezing and shortness of breath that began 1 hour after he took a new medication. Earlier in the day he was diagnosed with stable angina pectoris and prescribed a drug that irreversibly inhibits cyclooxygenase-1 and 2. He has chronic rhinosinusitis and asthma treated with inhaled β-adrenergic agonists and corticosteroids. His respirations are 26/min. Examination shows multiple small, erythematous nasal mucosal lesions. After the patient is stabilized, therapy for primary prevention of coronary artery disease should be switched to a drug with which of the following mechanisms of action?

• A. Direct inhibition of Factor Xa
• B. Sequestration of Ca2+ ions
• C. Potentiation of antithrombin III
• D. Blockage of P2Y12 component of ADP receptors (Correct Answer)
• E. Inhibition of vitamin K epoxide reductase

Explanation: ***Blockage of P2Y12 component of ADP receptors*** - The patient experienced an asthma exacerbation suspected to be due to **aspirin-exacerbated respiratory disease (AERD)**, which is triggered by **aspirin** (a non-selective COX inhibitor). - Given the need for antiplatelet therapy for CAD, a **P2Y12 receptor antagonist** such as **clopidogrel** is a suitable alternative to aspirin in patients with AERD, as it does not interact with the cyclooxygenase pathway. *Direct inhibition of Factor Xa* - This mechanism of action describes drugs like **rivaroxaban** or **apixaban**, which are primarily used as anticoagulants for conditions like atrial fibrillation or venous thromboembolism. - While they prevent clot formation, they are not typically used for primary prevention of **coronary artery disease (CAD)** in lieu of antiplatelet agents like aspirin or P2Y12 inhibitors. *Sequestration of Ca2+ ions* - This refers to **calcium channel blockers (CCBs)**, which are used to treat hypertension, angina, and certain arrhythmias. - While CCBs can be used to manage angina symptoms, they do not provide the necessary **antiplatelet effect** for primary prevention of cardiovascular events in CAD. *Potentiation of antithrombin III* - This is the mechanism of action for **heparins** (e.g., unfractionated heparin, low molecular weight heparin) and related drugs like fondaparinux. - **Heparins are anticoagulants** used for acute thrombosis or prophylaxis in specific situations, but they are not used for chronic **primary prevention of CAD** in stable patients. *Inhibition of vitamin K epoxide reductase* - This describes the mechanism of **warfarin**, a vitamin K antagonist used as an anticoagulant for conditions like atrial fibrillation, prosthetic heart valves, or venous thromboembolism. - Warfarin is an anticoagulant, not an antiplatelet agent, and is not indicated for **primary prevention of CAD** in this context.

Question 504: A 37-year-old man presents with back pain which began 3 days ago when he was lifting heavy boxes. The pain radiates from the right hip to the back of the thigh. The pain is exacerbated when he bends at the waist. He rates the severity of the pain as 6 out of 10. The patient has asthma and mitral insufficiency due to untreated rheumatic fever in childhood. He has a smoking history of 40 pack-years. His family history is remarkable for rheumatoid arthritis, diabetes, and hypertension. Vital signs are within normal limits. On physical examination, the pain is elicited when the patient is asked to raise his leg without extending his knee. The patient has difficulty walking on his heels. Peripheral pulses are equal and brisk bilaterally. No hair loss, temperature changes, or evidence of peripheral vascular disease is observed. Which of the following is considered the best management option for this patient?

• A. Referral for surgery
• B. Prescription of opioids
• C. Over-the-counter NSAIDs (Correct Answer)
• D. Observation
• E. Stenting

Explanation: ***Over-the-counter NSAIDs*** - The patient's symptoms are highly suggestive of **acute sciatica caused by disc herniation**, given the radiating back pain, exacerbation with bending, and a positive straight leg raise test. - **Over-the-counter NSAIDs** (such as ibuprofen or naproxen) are the recommended first-line treatment for acute low back pain and radiculopathy due to their anti-inflammatory and analgesic effects. - **Important consideration**: While this patient has asthma and mitral insufficiency, NSAIDs remain the most appropriate option among those listed. However, **selective COX-2 inhibitors or acetaminophen** might be considered as safer alternatives given his comorbidities. NSAIDs should be used at the lowest effective dose for the shortest duration, with monitoring for bronchospasm or fluid retention. *Referral for surgery* - **Surgical intervention** is typically reserved for cases where conservative management fails after 6-12 weeks, or if there are signs of progressive neurological deficits, severe weakness, or **cauda equina syndrome**. - The patient's presentation does not indicate an urgent need for surgery, as his symptoms are acute (3 days) and there are no severe neurological deficits described. *Prescription of opioids* - **Opioids** are not recommended as a first-line treatment for acute low back pain, especially in the absence of severe, intractable pain. - Long-term use of opioids carries risks of **addiction**, **tolerance**, and **adverse effects**, and evidence suggests limited efficacy over NSAIDs for acute low back pain. *Observation* - While many cases of acute low back pain resolve spontaneously, **observation alone** without any pain management is inappropriate for a patient experiencing pain rated 6/10 and functional impairment (difficulty walking on heels). - Providing symptomatic relief and encouraging continued activity are important aspects of initial management to prevent chronicity and improve function. *Stenting* - **Stenting** is a procedure primarily used to open narrowed arteries to treat conditions like **coronary artery disease** or **peripheral arterial disease**. - This patient's symptoms are musculoskeletal and neuropathic in origin, with no signs or symptoms of vascular compromise (normal peripheral pulses, no claudication, no evidence of peripheral vascular disease) that would warrant stenting.

Question 505: A 17-year-old white male is brought to the emergency department after being struck by a car. He complains of pain in his right leg and left wrist, and slowly recounts how he was hit by a car while being chased by a lion. In between sentences of the story, he repeatedly complains of dry mouth and severe hunger and requests something to eat and drink. His mother arrives and is very concerned about this behavior, noting that he has been withdrawn lately and doing very poorly in school the past several months. Notable findings on physical exam include conjunctival injection bilaterally and a pulse of 107. What drug is this patient most likely currently abusing?

• A. Cocaine
• B. Heroin
• C. Marijuana (Correct Answer)
• D. Benzodiazepines
• E. Phencyclidine (PCP)

Explanation: ***Marijuana*** - The patient's **conjunctival injection**, **dry mouth**, and **increased appetite** (the "munchies") are classic signs of marijuana intoxication. His distorted perception of reality (being chased by a lion) and altered mental status are also consistent with marijuana use. - The history of being withdrawn and poor school performance over several months suggests chronic use and potential cannabis use disorder. *Cocaine* - Cocaine intoxication typically presents with **psychomotor agitation**, **tachycardia**, **mydriasis (dilated pupils)**, and potentially paranoia, but not typically increased appetite or conjunctival injection. - The patient's presentation of a prolonged, elaborate delusional story is less characteristic for cocaine, which tends to produce more acute and often paranoid psychosis. *Heroin* - Heroin (opioid) intoxication primarily causes **CNS depression**, **respiratory depression**, **miosis (pinpoint pupils)**, and euphoria, none of which are prominent in this patient's presentation. - While he has an elevated pulse, the other distinct symptoms of dry mouth, hunger, and conjunctival injection point away from opioid use. *Benzodiazepines* - Benzodiazepine intoxication causes **CNS depression**, **sedation**, **ataxia**, and slurred speech, but typically does not cause conjunctival injection, dry mouth, or increased appetite. - The patient's agitated storytelling and specific physical signs are not consistent with benzodiazepine overdose. *Phencyclidine (PCP)* - PCP intoxication is associated with severe behavioral changes including **aggressiveness**, **nystagmus**, **hallucinations**, **dissociative states**, and often a high pain tolerance, which might fit some aspects of the story and trauma. - However, characteristic signs like **nystagmus** (horizontal or vertical), **hypertension**, and a more profound **dissociative amnesia** or violence are usually more pronounced than what is described.

Question 506: A 70-year-old woman with history of coronary artery disease status-post coronary artery bypass graft presents with a stroke due to an infarction in the right middle cerebral artery territory. She is admitted to the intensive care unit for neurological monitoring following a successful thrombectomy. Overnight, the patient complains of difficulty breathing, chest pain, and jaw pain. Her temperature is 98.6°F (37°C), blood pressure is 160/80 mmHg, pulse is 100/min, respirations are 30/min, and oxygen saturation is 90% on 2L O2 via nasal cannula. Rales are heard in the lower lung bases. Electrocardiogram reveals left ventricular hypertrophy with repolarization but no acute ST or T wave changes. Troponin is 2.8 ng/mL. Chest radiograph reveals Kerley B lines. After administration of oxygen, aspirin, carvedilol, and furosemide, the patient improves. The next troponin is 3.9 ng/mL. Upon further discussion with the consulting cardiologist and neurologist, a heparin infusion is started. After transfer to a general medicine ward floor four days later, the patient complains of a headache. The patient's laboratory results are notable for the following: Hemoglobin: 11 g/dL Hematocrit: 36% Leukocyte count: 11,000 /mm^3 with normal differential Platelet count: 130,000 /mm^3 On admission, the patient's platelet count was 300,000/mm^3. What medication is appropriate at this time?

• A. Enoxaparin
• B. Argatroban (Correct Answer)
• C. Protamine
• D. Dalteparin
• E. Tinzaparin

Explanation: ***Argatroban*** - This patient presents with a **new headache** and a significant drop in **platelet count** (from 300,000 to 130,000 /mm^3) while on **heparin**, which is highly suggestive of **heparin-induced thrombocytopenia (HIT)**. Argatroban is a **direct thrombin inhibitor** and is the preferred anticoagulant in patients with HIT, especially those with renal insufficiency. - HIT is a prothrombotic disorder, and immediate cessation of heparin and initiation of a non-heparin anticoagulant like argatroban is crucial to prevent life-threatening thrombotic complications. *Enoxaparin* - **Enoxaparin** is a **low molecular weight heparin (LMWH)**. All heparins, including LMWH and unfractionated heparin, are contraindicated in HIT because they can cross-react with antibodies formed against the heparin-platelet factor 4 complex, exacerbating the condition. - Using enoxaparin would worsen the patient's HIT and increase the risk of thrombosis. *Protamine* - **Protamine sulfate** is used to **reverse the anticoagulant effects of heparin** by binding to it. - While it reverses heparin, it does not address the underlying **prothrombotic state** of HIT and would not be an appropriate anticoagulant to use. *Dalteparin* - **Dalteparin** is another **low molecular weight heparin (LMWH)**. Similar to enoxaparin, all heparins are contraindicated in **heparin-induced thrombocytopenia (HIT)**. - Using dalteparin could still trigger platelet activation and thrombosis in a patient with HIT. *Tinzaparin* - **Tinzaparin** is also a **low molecular weight heparin (LMWH)**. As with other heparins, it should be avoided in patients with **heparin-induced thrombocytopenia (HIT)**. - Continuing any form of heparin would perpetuate the immune response and the risk of new thrombotic events.

Question 507: A 55-year-old man presents to the emergency department with shortness of breath and weakness. Past medical history includes coronary artery disease, arterial hypertension, and chronic heart failure. He reports that the symptoms started around 2 weeks ago and have been gradually worsening. His temperature is 36.5°C (97.7°F), blood pressure is 135/90 mm Hg, heart rate is 95/min, respiratory rate is 24/min, and oxygen saturation is 94% on room air. On examination, mild jugular venous distention is noted. Auscultation reveals bilateral loud crackles. Pitting edema of the lower extremities is noted symmetrically. His plasma brain natriuretic peptide level on rapid bedside assay is 500 pg/mL (reference range < 125 pg/mL). A chest X-ray shows enlarged cardiac silhouette. He is diagnosed with acute on chronic left heart failure with pulmonary edema and receives immediate care with furosemide. The physician proposes a drug trial with a new BNP stabilizing agent. Which of the following changes below are expected to happen if the patient is enrolled in this trial?

• A. Increased potassium release from cardiomyocytes
• B. Increased water reabsorption by the renal collecting ducts
• C. Increased blood pressure
• D. Inhibition of funny sodium channels
• E. Restricted aldosterone release (Correct Answer)

Explanation: ***Restricted aldosterone release*** - **BNP** acts to counter the **RAAS** system. By stabilizing BNP, there will be increased **natriuresis** and reduced levels of aldosterone due to its inhibitory effect on **renin secretion**. - This **aldosterone** restriction contributes to **diuresis** and vasodilation, which ultimately helps to reduce cardiac preload and afterload. *Increased potassium release from cardiomyocytes* - An increase in **potassium release** from cardiomyocytes is not a direct or expected effect of a **BNP stabilizing agent**. - BNP primarily influences **sodium** and **water balance** through renal and vascular effects, not direct cardiomyocyte potassium regulation. *Increased water reabsorption by the renal collecting ducts* - **BNP** promotes **natriuresis** and **diuresis**, leading to decreased water reabsorption in the renal collecting ducts. - A BNP stabilizing agent would therefore **decrease water reabsorption**, working against the action of **ADH**. *Increased blood pressure* - **BNP** acts as a **vasodilator** and promotes fluid excretion, which typically leads to a **reduction** in blood pressure. - Stabilizing BNP would therefore be expected to maintain or reduce **blood pressure**, not increase it. *Inhibition of funny sodium channels* - **Funny channels** (If channels) are primarily found in the **pacemaker cells** of the heart and are involved in controlling heart rate. - While BNP can influence heart rate indirectly, its primary mechanism of action does not involve direct **inhibition of funny sodium channels**.

Question 508: A 13-year-old boy is brought to the emergency room by his mother for a generalized tonic-clonic seizure that occurred while attending a laser light show. His mother says that he has been otherwise healthy but “he often daydreams”. Over the past several months, he has reported recurrent episodes of jerky movements of his fingers and arms. These episodes usually occurred shortly after waking up in the morning. He has not lost consciousness during these episodes. Which of the following is the most appropriate treatment for this patient's condition?

• A. Carbamazepine
• B. Tiagabine
• C. Vigabatrin
• D. Diazepam
• E. Valproate (Correct Answer)

Explanation: ***Valproate*** - This patient presents with symptoms characteristic of **juvenile myoclonic epilepsy (JME)** including **myoclonic jerks** upon awakening, **absences** ("daydreaming"), and generalized tonic-clonic seizures, especially those triggered by **photic stimulation** (laser light show). - **Valproate** is considered the first-line and most effective treatment for JME, offering broad-spectrum efficacy against all seizure types seen in this syndrome. *Carbamazepine* - **Carbamazepine** is primarily used for **focal seizures** and **generalized tonic-clonic seizures** that are not associated with myoclonus or absence seizures. - It can potentially **exacerbate myoclonic and absence seizures** in patients with JME, making it an inappropriate choice. *Tiagabine* - **Tiagabine** is an **adjunctive treatment** for **focal onset seizures** and works by inhibiting GABA reuptake. - It is **not effective** for generalized seizure types like those seen in JME and can even worsen them. *Vigabatrin* - **Vigabatrin** is an **irreversible inhibitor of GABA transaminase** used primarily for **infantile spasms** and refractory focal seizures. - Its use is limited by a high risk of **permanent ophthalmic damage** (retinal toxicity), making it unsuitable for JME. *Diazepam* - **Diazepam** is a **fast-acting benzodiazepine** primarily used for the **acute termination of seizures**, particularly status epilepticus. - It is not a suitable long-term maintenance treatment for epilepsy due to issues like **tolerance** and **sedation**.

Question 509: A 25-year-old G1P1 with a history of diabetes and epilepsy gives birth to a female infant at 32 weeks gestation. The mother had no prenatal care and took no prenatal vitamins. The child's temperature is 98.6°F (37°C), blood pressure is 100/70 mmHg, pulse is 130/min, and respirations are 25/min. On physical examination in the delivery room, the child's skin is pink throughout and she cries on stimulation. All four extremities are moving spontaneously. A tuft of hair is found overlying the infant's lumbosacral region. Which of the following medications was this patient most likely taking during her pregnancy?

• A. Valproic acid (Correct Answer)
• B. Warfarin
• C. Gentamicin
• D. Lithium
• E. Ethosuximide

Explanation: ***Valproic acid*** - The presence of a **tuft of hair over the lumbosacral region** strongly suggests an underlying **neural tube defect**, such as spina bifida. - **Valproic acid** is an antiepileptic drug known for its significant association with an increased risk of neural tube defects when taken during pregnancy, especially in the first trimester. *Warfarin* - **Warfarin** is a known teratogen associated with **fetal warfarin syndrome**, characterized by bone abnormalities (e.g., nasal hypoplasia, stippled epiphyses), not primarily neural tube defects. - It works as a **vitamin K antagonist** and causes bleeding if taken during pregnancy. *Gentamicin* - **Gentamicin** is an aminoglycoside antibiotic primarily associated with **ototoxicity** (hearing loss) and **nephrotoxicity** in the fetus. - It is not known to cause neural tube defects. *Lithium* - **Lithium** is a mood stabilizer linked to **Ebstein's anomaly**, a congenital heart defect affecting the tricuspid valve, when taken during pregnancy. - It is not associated with neural tube defects. *Ethosuximide* - **Ethosuximide** is an antiepileptic drug primarily used for absence seizures. - While all antiepileptic drugs carry some teratogenic risk, ethosuximide has a lower risk of neural tube defects compared to valproic acid.

Question 510: A 50-year-old man presents to the office with the complaint of pain in his left great toe. The pain started 2 days ago and has been progressively getting worse to the point that it is difficult to walk even a few steps. He adds that his left big toe is swollen and hot to the touch. He has never had similar symptoms in the past. He normally drinks 2–3 cans of beer every night but recently binge drank 3 nights ago. Physical examination is notable for an overweight gentleman (BMI of 35) in moderate pain, with an erythematous, swollen, and exquisitely tender left great toe. Laboratory results reveal a uric acid level of 9 mg/dL. A complete blood count shows: Hemoglobin % 12 gm/dL Hematocrit 45% Mean corpuscular volume (MCV) 90 fL Platelets 160,000/mm3 Leukocytes 8,000/mm3 Segmented neutrophils 65% Lymphocytes 25% Eosinophils 3% Monocytes 7% RBCs 5.6 million/mm3 Synovial fluid analysis shows: Cell count 55,000 cells/mm3 (80% neutrophils) Crystals negatively birefringent crystals present Culture pending Gram stain no organisms seen Which of the following is the mechanism of action of the drug that will most likely be used in the long-term management of this patient?

• A. Activates adenosine monophosphate (AMP) deaminase
• B. Inhibits renal clearance of uric acid
• C. Activates inosine monophosphate (IMP) dehydrogenase
• D. Inhibits xanthine oxidase (Correct Answer)
• E. Increases renal clearance of uric acid

Explanation: ***Inhibits xanthine oxidase*** - The patient's symptoms (acute, severe pain in the **great toe**, swelling, erythema, elevated **uric acid** 9 mg/dL, and presence of **negatively birefringent crystals** in synovial fluid) are classic for an acute **gout attack**. - **Allopurinol** and **febuxostat** are long-term management drugs that work by inhibiting **xanthine oxidase**, an enzyme crucial for uric acid production, thereby reducing serum uric acid levels and preventing future attacks. *Activates adenosine monophosphate (AMP) deaminase* - This is not a mechanism of action for common long-term gout medications. AMP deaminase is involved in purine metabolism but is not a direct target for uric acid lowering. - Manipulating AMP deaminase activity is not a recognized therapeutic approach for chronic gout management. *Inhibits renal clearance of uric acid* - This mechanism would *increase* serum uric acid levels, which is contraindicated in the long-term management of gout. - Drugs that inhibit renal clearance of uric acid would exacerbate the condition, leading to more frequent and severe gout attacks. *Activates inosine monophosphate (IMP) dehydrogenase* - This is not a mechanism of action for long-term gout medications. IMP dehydrogenase is involved in de novo purine synthesis. - Inhibitors of IMP dehydrogenase, like **mycophenolate mofetil**, are used in transplant medicine and autoimmune conditions, not for lowering uric acid. *Increases renal clearance of uric acid* - Drugs like **probenecid** act as **uricosurics** by increasing the renal excretion of uric acid. While this helps lower uric acid, it is specifically contraindicated in patients with **renal stones** or impaired renal function due to the risk of stone formation. - **Uricosurics** are generally second-line agents for long-term management in patients who **under-excrete uric acid** and have good renal function.

Question 511: A 55-year-old man comes to the physician because of a 4-month history of fatigue, increased sweating, and a 5.4-kg (12-lb) weight loss. Over the past 3 weeks, he has had gingival bleeding when brushing his teeth. Twenty years ago, he was diagnosed with a testicular tumor and treated with radiation therapy. His temperature is 37.8°C (100°F), pulse is 70/min, respirations are 12/min, and blood pressure is 130/80 mm Hg. He takes no medications. Cardiopulmonary examination shows no abnormalities. The spleen is palpated 4 cm below the left costal margin. Laboratory studies show: Hemoglobin 9 g/dL Mean corpuscular volume 86 μm3 Leukocyte count 110,000/mm3 Segmented neutrophils 24% Metamyelocytes 6% Myelocytes 34% Promyelocytes 14% Blasts 1% Lymphocytes 11% Monocytes 4% Eosinophils 4% Basophils 2% Platelet count 650,000/mm3 Molecular testing confirms the diagnosis. Which of the following is the most appropriate next step in treatment?

• A. Phlebotomy
• B. Cytarabine and daunorubicin therapy
• C. Rituximab therapy
• D. Low-dose aspirin therapy
• E. Imatinib therapy (Correct Answer)

Explanation: ***Imatinib therapy*** - The patient's presentation with **fatigue**, **sweating**, **weight loss**, **gingival bleeding**, **splenomegaly**, and remarkable lab findings (**leukocytosis** with a left shift including **myelocytes**, **promyelocytes**, low blast count, **thrombocytosis**, and **anemia**) is highly suggestive of **Chronic Myeloid Leukemia (CML)**. - Molecular testing would confirm the presence of the **Philadelphia chromosome (BCR-ABL1 fusion gene)**, which is the target of **imatinib**, a tyrosine kinase inhibitor (TKI) and the first-line treatment for CML. *Phlebotomy* - **Phlebotomy** is a treatment for **polycythemia vera**, a myeloproliferative neoplasm characterized by an *elevated red blood cell count*, which is not present here (patient has anemia). - It aims to reduce blood viscosity and iron overload, which are not the primary issues in this patient. *Cytarabine and daunorubicin therapy* - This combination therapy (often termed "7+3" regimen) is standard induction chemotherapy for **Acute Myeloid Leukemia (AML)**. - The patient's **low blast count (1%)** and presence of various myeloid precursor stages define a chronic phase of a myeloproliferative neoplasm, not acute leukemia (which requires >20% blasts). *Rituximab therapy* - **Rituximab** is a monoclonal antibody that targets the **CD20 antigen** found on B-cells and is primarily used in the treatment of **B-cell non-Hodgkin lymphomas** and **Chronic Lymphocytic Leukemia (CLL)**. - This patient presents with a myeloid proliferation, not a lymphoid malignancy. *Low-dose aspirin therapy* - **Low-dose aspirin** is used for its antiplatelet effects to prevent thrombotic events, particularly in conditions like **essential thrombocythemia** or **polycythemia vera** where platelet counts or red cell mass are significantly elevated sometimes requiring aspirin if clots are forming. - While this patient has thrombocytosis, treating the underlying CML with imatinib is the priority and will typically normalize platelet counts, making aspirin a secondary or adjunct consideration if thrombosis risk is high and CML treatment is not yet effective.

Question 512: A 72-year-old woman with a history of atrial fibrillation on warfarin, diabetes, seizure disorder and recent MRSA infection is admitted to the hospital. She subsequently begins therapy with another drug and is found to have a supratherapeutic International Normalized Ratio (INR). Which of the following drugs is likely contributing to this patient's elevated INR?

• A. Carbamazepine
• B. Phenobarbital
• C. Glipizide
• D. Rifampin
• E. Valproic acid (Correct Answer)

Explanation: ***Valproic acid*** - **Valproic acid** inhibits the **CYP2C9** enzyme and can displace **warfarin** from **plasma protein binding sites**, increasing free warfarin levels and leading to a **supratherapeutic INR**. - This interaction is particularly relevant in patients on warfarin, as it directly potentiates its anticoagulant effect. *Carbamazepine* - **Carbamazepine** is a potent **CYP450 enzyme inducer**, which would typically **decrease** warfarin levels and **lower** the INR. - It would counteract the anticoagulant effect of warfarin, not enhance it. *Phenobarbital* - **Phenobarbital** is another strong **CYP450 enzyme inducer**, similar to carbamazepine. - Its use would likely **reduce** the plasma concentration of warfarin, resulting in a **subtherapeutic INR**. *Glipizide* - **Glipizide** is an **oral hypoglycemic agent** and does not have a significant direct interaction with warfarin that would elevate the INR. - While some sulfonylureas can have minor anticoagulant effects, they are not a primary cause of **supratherapeutic INR** in this context. *Rifampin* - **Rifampin** is a powerful **CYP450 enzyme inducer**, known to significantly **reduce** the effectiveness of many drugs, including warfarin. - It would lead to a **lower** INR, increasing the risk of thrombotic events.

Question 513: A 42-year-old man presents to his family physician for evaluation of oral pain. He states that he has increasing pain in a molar on the top left of his mouth. The pain started 1 week ago and has been progressively worsening since then. His medical history is significant for hypertension and type 2 diabetes mellitus, both of which are currently controlled with lifestyle modifications. His blood pressure is 124/86 mm Hg, heart rate is 86/min, and respiratory rate is 14/min. Physical examination is notable for a yellow-black discoloration of the second molar on his left upper mouth. The decision is made to refer him to a dentist for further management of this cavity. The patient has never had any dental procedures and is nervous about what type of sedation will be used. Which of the following forms of anesthesia utilizes solely an oral or intravenous anti-anxiety medication?

• A. Minimal Sedation (Correct Answer)
• B. Dissociation
• C. Regional anesthesia
• D. Epidural anesthesia
• E. Deep sedation

Explanation: ***Minimal Sedation*** - This involves using **oral** or **intravenous anti-anxiety medications** to help a patient relax while remaining conscious and responsive. - The patient can still respond to verbal commands but is in a state of decreased anxiety and awareness. *Dissociation* - This is a state induced by certain drugs, like **ketamine**, where the patient feels detached from their body and environment. - While it can be achieved intravenously, it is not solely an anti-anxiety medication effect and involves a different neurological state. *Regional anesthesia* - This involves injecting a **local anesthetic** near nerves to numb a specific part of the body, such as a limb or a jaw section for dental procedures. - It primarily provides pain relief by blocking nerve signals and does not typically involve anti-anxiety medication as its sole component for sedation. *Epidural anesthesia* - This form of regional anesthesia involves injecting a **local anesthetic** into the **epidural space** surrounding the spinal cord to block pain signals. - It is used for pain control during surgery or childbirth and does not involve oral or intravenous anti-anxiety medication as the primary method of sedation. *Deep sedation* - This involves a more profound depression of consciousness than minimal sedation, where the patient may be difficult to arouse but still responds purposefully to repeated or painful stimulation. - While it can use intravenous medications, it typically involves a combination of sedatives and analgesics to achieve a deeper state of unresponsiveness, beyond just anti-anxiety medication.

Question 514: A 23-year-old male presents with complaints of polydipsia and frequent, large-volume urination. Laboratory testing does not demonstrate any evidence of diabetes; however, a reduced urine osmolality of 120 mOsm/L is measured. Which of the following findings on a desmopressin test would be most consistent with a diagnosis of central diabetes insipidus?

• A. Reduction in urine osmolality to 60 mOsm/L following desmopressin administration
• B. No detectable change in urine osmolality following desmopressin administration
• C. Increase in urine osmolality to 400 mOsm/L following desmopressin administration (Correct Answer)
• D. Increase in urine osmolality to 130 mOsm/L following desmopressin administration
• E. Reduction in urine osmolality to 110 mOsm/L following desmopressin administration

Explanation: ***Increase in urine osmolality to 400 mOsm/L following desmopressin administration*** - In **central diabetes insipidus**, the kidneys are still able to respond to **vasopressin** (ADH), but the body doesn't produce enough of it. Therefore, administering **desmopressin** (a synthetic ADH analog) will significantly increase **urine osmolality** as the kidneys resorb more water. - A significant increase, such as from 120 mOsm/L to 400 mOsm/L, indicates that the underlying problem is a lack of ADH production, characteristic of **central diabetes insipidus**. *Increase in urine osmolality to 130 mOsm/L following desmopressin administration* - A minor increase from 120 mOsm/L to 130 mOsm/L following desmopressin administration would suggest that the kidneys are largely **unresponsive** to ADH, which is characteristic of **nephrogenic diabetes insipidus**. - In central diabetes insipidus, a more substantial increase in **urine osmolality** is expected, as the kidney's ability to respond to ADH is intact. *Reduction in urine osmolality to 60 mOsm/L following desmopressin administration* - A reduction in **urine osmolality** after desmopressin administration would be an unexpected and contradictory finding. - Desmopressin is meant to increase water reabsorption, leading to concentrated urine, not more dilute urine. *Reduction in urine osmolality to 110 mOsm/L following desmopressin administration* - Similar to the previous option, a reduction in **urine osmolality** following desmopressin administration is clinically inconsistent with the expected action of ADH. - This result would not align with either central nor nephrogenic diabetes insipidus scenarios, where an increase or no change, respectively, would be anticipated. *No detectable change in urine osmolality following desmopressin administration* - If there is no detectable change or only a very small change in **urine osmolality** after desmopressin administration, it suggests that the kidneys are not responding to ADH. - This would be consistent with **nephrogenic diabetes insipidus**, where the kidneys themselves are resistant to ADH, rather than central DI, where the problem is ADH deficiency.

Question 515: A 52-year-old man is seen by his endocrinologist for routine followup of his type 2 diabetes. Although he has previously been on a number of medication regimens, his A1C has remained significantly elevated. In order to try to better control his glucose level, the endocrinologist prescribes a new medication. He explains that this new medication works by blocking the ability of his kidneys to reabsorb glucose and therefore causes glucose wasting in the urine. Which of the following medications has this mechanism of action?

• A. Canagliflozin (Correct Answer)
• B. Acarbose
• C. Metformin
• D. Glyburide
• E. Exenatide

Explanation: ***Canagliflozin*** - **Canagliflozin** is an **SGLT2 inhibitor** that works by blocking the reabsorption of glucose in the renal tubules, leading to glucose excretion in the urine. - This mechanism of action directly matches the description provided: "blocking the ability of his kidneys to reabsorb glucose and therefore causes glucose wasting in the urine." *Acarbose* - **Acarbose** is an **alpha-glucosidase inhibitor** that delays the digestion and absorption of carbohydrates in the small intestine. - Its primary action is in the gastrointestinal tract, not by directly affecting renal glucose reabsorption. *Metformin* - **Metformin** is a **biguanide** that primarily works by decreasing hepatic glucose production and improving insulin sensitivity. - It does not directly affect the kidney's ability to reabsorb glucose. *Glyburide* - **Glyburide** is a **sulfonylurea** that stimulates insulin secretion from pancreatic beta cells. - Its mechanism involves increasing insulin release, independent of renal glucose handling. *Exenatide* - **Exenatide** is a **GLP-1 receptor agonist** that enhances glucose-dependent insulin secretion, suppresses glucagon secretion, slows gastric emptying, and promotes satiety. - Its actions are mainly related to insulin and glucagon regulation, not direct renal glucose filtration.

Question 516: A 25-year-old woman presents to her college campus clinic with the complaint of being unable to get up for her morning classes. She says that, because of this, her grades are being affected. For the past 6 weeks, she says she has been feeling depressed because her boyfriend dumped her. She finds herself very sleepy, sleeping in most mornings, eating more snacks and fast foods, and feeling drained of energy. She is comforted by her friend’s efforts to cheer her up but still feels guarded around any other boy that shows interest in her. The patient says she had similar symptoms 7 years ago for which she was prescribed several selective serotonin reuptake inhibitors (SSRIs) and a tricyclic antidepressant (TCA). However, none of the medications provided any long-term relief. She has prescribed a trial of Phenelzine to treat her symptoms. Past medical history is significant for a long-standing seizure disorder well managed with phenytoin. Which of the following statements would most likely be relevant to this patient’s new medication?

• A. “This medication is known to cause anorgasmia during treatment.”
• B. “You will have a risk for cardiotoxicity from this medication.”
• C. “A common side effect of this medication is sedation.”
• D. “While taking this medication, you should avoid drinking red wine.” (Correct Answer)
• E. “While on this medication, you may have a decreased seizure threshold.”

Explanation: ***"While taking this medication, you should avoid drinking red wine."*** - Phenelzine is a **monoamine oxidase inhibitor (MAOI)**. MAOIs inhibit the breakdown of **tyramine**, an amine found in fermented foods like red wine, aged cheeses, cured meats, and pickled foods. - Consuming tyramine-rich foods with an MAOI can lead to a **hypertensive crisis**, characterized by a sudden, severe increase in blood pressure which can cause headaches, palpitations, and potentially stroke. - This dietary counseling is **essential and immediately actionable** patient education when starting an MAOI. *"This medication is known to cause anorgasmia during treatment."* - While sexual dysfunction can occur with many antidepressants, **anorgasmia** is much more common and severe with **SSRIs (Selective Serotonin Reuptake Inhibitors)** than with MAOIs. - MAOIs like phenelzine have a different mechanism of action and generally have a lower incidence of sexual side effects compared to SSRIs. *"You will have a risk for cardiotoxicity from this medication."* - **Cardiotoxicity** is a significant concern with **tricyclic antidepressants (TCAs)**, especially in overdose, due to their effects on cardiac sodium channels and potential for arrhythmias. - While MAOIs can cause **orthostatic hypotension**, direct cardiotoxicity is not a primary concern with phenelzine. *"A common side effect of this medication is sedation."* - Phenelzine is generally considered **activating** rather than sedating, and can sometimes lead to insomnia or agitation. - The patient's current hypersomnia is a symptom of her **atypical depression**, not a predicted side effect of phenelzine. In fact, phenelzine may help improve this symptom. *"While on this medication, you may have a decreased seizure threshold."* - This statement is actually **medically accurate** - MAOIs including phenelzine can lower (decrease) the seizure threshold, meaning they increase seizure risk. - This is relevant given the patient's seizure disorder managed with phenytoin and warrants monitoring. - However, the **dietary tyramine restriction** is the more critical and immediately actionable counseling point when initiating MAOI therapy, as hypertensive crisis can occur with the very first exposure to tyramine-rich foods.

Question 517: A 54-year-old male has a history of gout complicated by several prior episodes of acute gouty arthritis and 3 prior instances of nephrolithiasis secondary to uric acid stones. He has a serum uric acid level of 11 mg/dL (normal range 3-8 mg/dL), a 24 hr urine collection of 1300 mg uric acid (normal range 250-750 mg), and a serum creatinine of 0.8 mg/dL with a normal estimated glomerular filtration rate (GFR). Which of the following drugs should be avoided in this patient?

• A. Probenecid (Correct Answer)
• B. Naproxen
• C. Indomethacin
• D. Allopurinol
• E. Colchicine

Explanation: ***Probenecid*** - This patient is an **overproducer of uric acid**, as evidenced by his high 24-hour urinary uric acid excretion. **Uricosuric agents** like probenecid are contraindicated in patients who excrete more than 800 mg of uric acid per 24 hours, as they increase the risk of **renal calculi (uric acid stones)**. - He has a history of prior nephrolithiasis secondary to uric acid stones, which makes probenecid a poor choice, further exacerbating his risk of stone formation by increasing uric acid excretion. *Naproxen* - **NSAIDs** like naproxen are commonly used to treat acute gouty arthritis by reducing inflammation. - They do not affect uric acid levels and are appropriate for managing the pain and inflammation of gout flares, not to be avoided. *Indomethacin* - **Indomethacin** is another NSAID frequently used for the treatment of **acute gout attacks**. - It works by reducing inflammation and pain and does not interfere with uric acid metabolism in a way that would be detrimental in this patient's case. *Allopurinol* - **Allopurinol** is a **xanthine oxidase inhibitor** that reduces uric acid production and is the drug of choice for patients who are **overproducers of uric acid** or have recurrent gout attacks. - This medication treats hyperuricemia and would be beneficial in this patient to lower his serum uric acid and prevent further attacks and stone formation. *Colchicine* - **Colchicine** is used to treat **acute gout flares** and is also used for prophylaxis against flares when initiating uric acid-lowering therapy. - It works by inhibiting neutrophil migration and activation, and its use is not contraindicated in this patient.

Question 518: A 28-year-old woman has a follow-up visit with her physician. She was diagnosed with allergic rhinitis and bronchial asthma at 11 years of age. Her regular controller medications include daily high-dose inhaled corticosteroids and montelukast, but she still needs to use a rescue inhaler 3–4 times a week following exercise. She also becomes breathless with moderate exertion. After a thorough evaluation, the physician explains that her medication dosages need to be increased. She declines taking oral corticosteroids daily due to concerns about side effects. The physician prescribes omalizumab, which is administered subcutaneously every 3 weeks. Which of the following best explains the mechanism of action of the new medication that has been added to the controller medications?

• A. Prevention of binding of IgE antibodies to mast cell receptors (Correct Answer)
• B. Inhibition of synthesis of interleukin-4 (IL-4)
• C. Inhibition of synthesis of IgE antibodies
• D. Selective binding to interleukin-3 (IL-3) and inhibition of its actions
• E. Prevention of binding of interleukin-5 (IL-5) to its receptors

Explanation: ***Prevention of binding of IgE antibodies to mast cell receptors*** - **Omalizumab** is a **monoclonal antibody** that specifically targets and binds to **free IgE** in the bloodstream, preventing it from attaching to high-affinity IgE receptors on **mast cells** and **basophils**. - By reducing surface IgE, omalizumab **downregulates IgE receptors** on these cells, thereby reducing the release of inflammatory mediators upon allergen exposure, which is beneficial in **allergic asthma** uncontrolled by standard therapies. *Inhibition of synthesis of interleukin-4 (IL-4)* - **IL-4** is a cytokine primarily involved in **Th2 differentiation** and **IgE class switching**, but omalizumab's action is not directly blocking its synthesis. - While *omalizumab* indirectly reduces IgE levels, its primary mechanism isn't to inhibit the production of IL-4 itself, but rather to prevent the effects of existing IgE. *Inhibition of synthesis of IgE antibodies* - **Omalizumab** does not inhibit the *synthesis* of IgE antibodies; instead, it binds to already synthesized **free IgE** circulating in the blood. - This binding effectively neutralizes IgE, preventing it from contributing to the allergic cascade, but it doesn't stop B cells from producing more IgE. *Selective binding to interleukin-3 (IL-3) and inhibition of its actions* - **IL-3** is a cytokine involved in the growth and differentiation of various **hematopoietic cells**, including mast cells and basophils, but it is not the target of omalizumab. - Omalizumab specifically targets **IgE** and has no known direct action on IL-3 signaling pathways. *Prevention of binding of interleukin-5 (IL-5) to its receptors* - **IL-5** is a key cytokine in the **eosinophilic inflammatory pathway** and is targeted by other therapies (e.g., mepolizumab, reslizumab) used for severe eosinophilic asthma. - Omalizumab's mechanism is distinct, focusing on **IgE-mediated inflammation** rather than direct eosinophil control.

Question 519: A 34-year-old man was brought into the emergency room after he was found running in the streets. Upon arrival to the emergency room, he keeps screaming, “they are eating me alive," and swatting his hands. He reports that there are spiders crawling all over him. His girlfriend, who arrives shortly after, claims that he has been forgetful and would forget his keys from time to time. He denies weight loss, fever, shortness of breath, abdominal pain, or urinary changes but endorses chest pain. His temperature is 98.9°F (37.2°C), blood pressure is 160/110 mmHg, pulse is 112/min, respirations are 15/min, and oxygen saturation is 98%. He becomes increasingly agitated as he believes the healthcare providers are trying to sacrifice him to the “spider gods.” What is the most likely explanation for this patient’s symptoms?

• A. Schizophrenia
• B. Temporal lobe epilepsy
• C. Narcolepsy
• D. Pick disease
• E. Cocaine use (Correct Answer)

Explanation: ***Cocaine use*** - The patient's **agitation**, **paranoid delusions** ("they are eating me alive," "spider gods"), **tactile hallucinations** (spiders crawling), and **tachycardia** (pulse 112/min) and **hypertension** (160/110 mmHg) are classic signs of **acute cocaine intoxication**. - While forgetfulness can be a general neurological symptom, in this acute presentation with prominent psychotic and sympathomimetic features, cocaine use is the most probable cause. *Schizophrenia* - While schizophrenia involves **psychosis**, its onset is typically more gradual, and the presentation of acute, vivid tactile hallucinations and marked sympathetic overdrive is less characteristic of an acute schizophrenic exacerbation. - The sudden, florid presentation with severe agitation and physical signs like hypertension and tachycardia points away from an initial presentation of schizophrenia. *Temporal lobe epilepsy* - Temporal lobe seizures can cause **olfactory** or **gustatory hallucinations**, **déjà vu**, or **fear**, but **gross tactile hallucinations** of crawling spiders and prominent, sustained paranoia with agitation are less typical. - The patient's vital signs also indicate a systemic effect rather than purely a focal neurological event. *Narcolepsy* - Narcolepsy is a **sleep disorder** characterized by **excessive daytime sleepiness**, **cataplexy**, **sleep paralysis**, and **hypnagogic/hypnopompic hallucinations**. - It does not explain the patient's acute agitated, paranoid, and hyper-adrenergic state with tactile hallucinations. *Pick disease* - Pick disease, a type of **frontotemporal dementia**, is a **neurodegenerative disorder** characterized by **progressive changes in personality, behavior, and language**. - It typically presents with chronic, gradual cognitive decline and behavioral disinhibition, not an acute episode of florid psychosis with prominent sympathomimetic features and tactile hallucinations.

Question 520: A 53-year-old man presents with swelling of the right knee. He says that the pain began the previous night and was reduced by ibuprofen and an ice-pack. The pain persists but is tolerable. He denies any recent fever, chills, or joint pains in the past. Past medical history includes a coronary artery bypass graft (CABG) a year ago for which he takes aspirin, atorvastatin, captopril, and carvedilol. The patient reports a 20-pack-year history of smoking but quit 5 years ago. He also says he was a heavy drinker for the past 30 years but now drinks only a few drinks on the weekends. On physical examination, the right knee is erythematous, warm, swollen, and mildly tender to palpation. Cardiac exam is significant for a mild systolic ejection murmur. The remainder of the examination is unremarkable. Arthrocentesis of the right knee joint is performed, which reveals the presence of urate crystals. Which of the following medications is most likely responsible for this patient's symptoms?

• A. Aspirin (Correct Answer)
• B. Captopril
• C. Carvedilol
• D. Atorvastatin
• E. Hydrochlorothiazide

Explanation: ***Aspirin*** - **Low-dose aspirin** can inhibit renal tubular uric acid secretion, leading to an increase in serum uric acid levels and potentially precipitating a **gout attack**. - Given the patient's history of CABG, aspirin is prescribed for **platelet aggregation inhibition**, but this beneficial effect must be weighed against this side effect. *Captopril* - Captopril is an **ACE inhibitor** and is not typically associated with hyperuricemia or gout. - While some medications can affect uric acid levels, ACE inhibitors generally have a **neutral or mild uricosuric effect**. *Carvedilol* - Carvedilol is a non-selective **beta-blocker** with alpha-blocking activity. - It is not known to significantly impact **uric acid metabolism** or cause gout. *Atorvastatin* - Atorvastatin is an **HMG-CoA reductase inhibitor** (statin) used to lower cholesterol. - Statins are not associated with **hyperuricemia** or triggering gout attacks. *Hydrochlorothiazide* - Although **thiazide diuretics** like hydrochlorothiazide are well-known to cause hyperuricemia and gout by increasing uric acid reabsorption, the patient is not currently taking this medication. - This option is a distractor because the patient is on several other medications and a thorough medication reconciliation is key.

Question 521: A 42-year-old woman comes to the physician for evaluation of a 6-month history of irregular menstrual periods. Her last period was 3 months ago. Previously, her periods occurred at regular 28-day intervals and lasted 4–5 days with moderate flow. She has also noticed breast tenderness and scant nipple discharge. She has type 2 diabetes mellitus and refractory bipolar I disorder. Current medications include metformin, glipizide, lithium, and risperidone. Physical examination shows no abnormalities. A urine pregnancy test is negative. Which of the following is the most likely cause of the changes in her menstrual cycle?

• A. Dysregulation of theca and granulosa cell steroidogenesis
• B. Failure of ovaries to respond to gonadotropins
• C. Impaired production and release of thyroxine
• D. Blockade of pituitary dopamine receptors (Correct Answer)
• E. Reduced renal elimination of prolactin

Explanation: ***Blockade of pituitary dopamine receptors*** - The patient's symptoms of **irregular menstrual periods**, **breast tenderness**, and **scant nipple discharge** are classic for **drug-induced hyperprolactinemia**. - **Risperidone**, an atypical antipsychotic, blocks **dopamine D2 receptors** in the **tuberoinfundibular pathway** of the hypothalamus-pituitary axis. - Normally, dopamine from the hypothalamus **inhibits prolactin release** from lactotrophs in the anterior pituitary. When dopamine receptors are blocked, this tonic inhibition is removed, causing **elevated prolactin levels**. - Hyperprolactinemia suppresses **GnRH pulsatility**, leading to decreased FSH/LH, which causes **menstrual irregularities** and **hypogonadism**. Elevated prolactin also directly causes **galactorrhea** and **breast tenderness**. *Dysregulation of theca and granulosa cell steroidogenesis* - This describes the pathophysiology of **polycystic ovarian syndrome (PCOS)**, which presents with irregular periods, hyperandrogenism, and polycystic ovaries. - While PCOS causes menstrual irregularities, it does **not** cause nipple discharge or galactorrhea, making it less likely in this case. *Failure of ovaries to respond to gonadotropins* - This describes **premature ovarian insufficiency (POI)**, characterized by elevated FSH/LH and low estrogen, leading to irregular or absent menses. - POI typically presents with **hot flashes** and **vaginal dryness** due to estrogen deficiency, not galactorrhea or breast tenderness. *Impaired production and release of thyroxine* - **Primary hypothyroidism** can cause menstrual irregularities and, in severe cases, hyperprolactinemia due to elevated TRH (which stimulates both TSH and prolactin release). - However, hypothyroidism would typically present with **fatigue**, **weight gain**, **cold intolerance**, and **constipation**, none of which are mentioned in this case. *Reduced renal elimination of prolactin* - **Chronic kidney disease** can impair prolactin clearance, leading to hyperprolactinemia and similar symptoms. - However, there is **no evidence of renal dysfunction** in this patient (no mention of elevated creatinine, proteinuria, or CKD history), and the patient is on metformin (which requires dose adjustment in renal impairment), making drug-induced hyperprolactinemia the more likely cause.

Question 522: A 65-year-old gentleman presents to his primary care physician for difficulties with his gait and recent fatigue. The patient works in a health food store, follows a strict vegan diet, and takes an array of supplements. He noticed that his symptoms have progressed over the past year and decided to see a physician when he found himself feeling abnormally weak on a daily basis in conjunction with his trouble walking. The patient has a past medical history of Crohn's disease, diagnosed in his early 20's, as well as Celiac disease. He states that he has infrequent exacerbations of his Crohn's disease. Recently, the patient has been having worsening bouts of diarrhea that the patient claims is non-bloody. The patient is not currently taking any medications and is currently taking traditional Chinese medicine supplements. Physical exam is notable for 3/5 strength in the upper and lower extremities, absent upper and lower extremity reflexes, and a staggering, unbalanced gait. Laboratory values reveal the following: Serum: Na+: 135 mEq/L Cl-: 100 mEq/L K+: 5.6 mEq/L HCO3-: 22 mEq/L BUN: 27 mg/dL Glucose: 79 mg/dL Creatinine: 1.1 mg/dL Ca2+: 8.4 mg/dL Mg2+: 1.5 mEq/L Leukocyte count and differential: Leukocyte count: 4,522/mm^3 Hemoglobin: 9.2 g/dL Hematocrit: 29% Platelet count: 169,000/mm^3 Reticulocyte count: 2.5% Lactate dehydrogenase: 340 U/L Mean corpuscular volume: 97 fL Which of the following is most likely deficient in this patient?

• A. Vitamin D
• B. Iron
• C. Vitamin B9
• D. Vitamin E
• E. Vitamin B12 (Correct Answer)

Explanation: ***Vitamin B12*** - The patient's **vegan diet**, history of **Crohn's disease**, **Celiac disease**, and **diarrhea** all increase the risk of **vitamin B12 malabsorption**. - **Neurological symptoms** like gait difficulties, weakness, and absent reflexes are characteristic of **vitamin B12 deficiency**, which can also cause **anemia** with a **normal MCV** (masked by co-existing iron deficiency or thalassemia trait). *Vitamin D* - While common in patients with malabsorption conditions like Crohn's disease and Celiac disease, **vitamin D deficiency** primarily presents with **bone pain**, **muscle weakness**, and **osteoporosis**, not the prominent neurological findings seen here. - The patient's **calcium level (8.4 mg/dL)** is at the lower end of normal, but not overtly hypocalcemic, which would be expected with severe vitamin D deficiency. *Iron* - **Iron deficiency** is common in Crohn's and Celiac disease due to malabsorption and chronic blood loss, leading to **microcytic anemia** and **fatigue**. - However, the patient's **MCV is normal (97 fL)**, and iron deficiency does not typically explain the **neurological symptoms** (gait difficulties, absent reflexes) described. *Vitamin B9* - **Folate deficiency** can cause **megaloblastic anemia** and fatigue, similar to vitamin B12 deficiency, but it is less likely to cause the **severe neurological symptoms** seen here. - While malabsorption conditions can affect folate, the specific neurological presentation points more strongly towards B12. *Vitamin E* - **Vitamin E deficiency** can cause **neurological symptoms** such as ataxia, peripheral neuropathy, and muscle weakness due to its role as an antioxidant. - However, deficiency is rare in adults and usually severe malabsorption of fats from conditions like abetalipoproteinemia. While Crohn's and Celiac can cause fat malabsorption, the constellation of symptoms, including anemia and masked MCV, aligns more directly with B12.

Question 523: A 55-year-old woman comes to the clinic complaining of joint pain and stiffness for the past year. The pain is mainly concentrated in her hands and is usually worse towards the late afternoon. It is described with a burning quality that surrounds the joint with some numbness and tingling. The stiffness is especially worse in the morning and lasts approximately for 15-20 minutes. Her past medical history is significant for recurrent gastric ulcers. She reports that her mother struggled with lupus and is concerned that she might have the same thing. She denies fever, rashes, ulcers, genitourinary symptoms, weight loss, or bowel changes. Physical examination is significant for mild tenderness at the distal interphalangeal joints bilaterally. What is the best initial medication to prescribe to this patient?

• A. Methotrexate
• B. Hydroxychloroquine
• C. Infliximab
• D. Aspirin
• E. Acetaminophen (Correct Answer)

Explanation: ***Acetaminophen*** - Given the patient's symptoms of joint pain worse in the late afternoon, morning stiffness lasting 15-20 minutes, and tenderness at the **distal interphalangeal joints (DIPs)**, **osteoarthritis** is the most likely diagnosis. - As **acetaminophen** is an **analgesic** and a relatively safe medication, it is considered a first-line treatment for pain management in osteoarthritis, especially given her history of recurrent gastric ulcers which makes NSAIDs less favorable. *Methotrexate* - **Methotrexate** is a **disease-modifying antirheumatic drug (DMARD)** primarily used for inflammatory arthritis like **rheumatoid arthritis** or **psoriatic arthritis**. - Its side effects include **gastrointestinal upset** and **hepatic toxicity**, and it is not a first-line agent for osteoarthritis. *Hydroxychloroquine* - **Hydroxychloroquine** is an antimalarial drug used as a DMARD for conditions like **lupus** and **rheumatoid arthritis**. - While the patient's mother had lupus, her current symptoms are not consistent with lupus, and hydroxychloroquine is not indicated for osteoarthritis. *Infliximab* - **Infliximab** is a **biologic agent (TNF-alpha inhibitor)** used for severe inflammatory conditions like **rheumatoid arthritis**, **ankylosing spondylitis**, and inflammatory bowel disease. - It carries significant risks, including **immunosuppression** and **infusion reactions**, and is not appropriate for initial treatment of osteoarthritis. *Aspirin* - **Aspirin**, particularly in anti-inflammatory doses, can cause **gastric irritation** and is contraindicated or used with extreme caution in patients with a history of recurrent gastric ulcers. - Although it has analgesic properties, its anti-inflammatory effects are not specifically targeted at osteoarthritis as a first-line given her ulcer history, and other NSAIDs would be preferred if anti-inflammatory action was needed and gastric issues were not present.

Question 524: A 36-year-old woman comes to the physician because of multiple episodes of headache over the past 3 months. The headaches last the entire day and are unilateral and throbbing. During the headaches, she has severe nausea and is unable to work and perform her daily activities. She has noticed that she becomes unusually hungry prior to the onset of headache. She locks herself in a dark room, takes ibuprofen, and avoids going out until the headache subsides. However, over the past month, the headaches have increased to 2–3 times a week and become more intense. She has hypertension treated with amlodipine. Her temperature is 37°C (98.6°F), pulse is 80/min, and blood pressure is 128/76 mm Hg. Physical and neurologic examinations show no abnormalities. Which of the following is the most appropriate therapy for long-term prevention of headaches in this patient?

• A. Naproxen
• B. Sumatriptan
• C. Propranolol (Correct Answer)
• D. Fluoxetine
• E. Ergotamine

Explanation: ***Propranolol*** - This patient presents with **migraines** characterized by unilateral, throbbing headaches with severe nausea, photophobia (seeking dark room), and a prodrome (unusual hunger). Given the frequency (2-3 times/week) and intensity, **prophylactic treatment** is indicated. - **Propranolol** is a **beta-blocker** and a first-line agent for migraine prophylaxis, especially in patients who do not have contraindications like asthma or severe bradycardia. *Naproxen* - **Naproxen**, an **NSAID**, is primarily used for **acute migraine treatment**, not for long-term prevention. - While it can help alleviate pain during an attack, it does not reduce the frequency or intensity of future migraine episodes. *Sumatriptan* - **Sumatriptan** is a **triptan**, a class of drugs used for **acute migraine treatment**, acting as a 5-HT1B/1D receptor agonist. - It is effective in aborting an ongoing migraine but is not recommended for **prophylactic use** due to its mechanism and potential for medication overuse headache. *Fluoxetine* - **Fluoxetine** is an **SSRI** primarily used to treat **depression and anxiety disorders**, and sometimes for chronic pain syndromes. - While co-morbid depression can exacerbate migraines, SSRIs are not considered a first-line prophylactic treatment for migraines themselves. *Ergotamine* - **Ergotamine** is an older medication used for **acute migraine treatment**, but its use is limited due to significant side effects and a narrow therapeutic index. - It works by constricting blood vessels and is not recommended for **long-term prevention** of migraines.

Question 525: A 57-year-old man is brought to the emergency department 2 hours after the onset of severe nausea and vomiting. He also has cramping abdominal pain and feels fatigued. Two months ago, he injured his lumbar spine in a car accident and lost complete motor and sensory function below the level of injury. He has been bedridden ever since and is cared for at home. He has type 2 diabetes mellitus and renal insufficiency. Examination shows dry mucosal membranes and sensory impairment with flaccid paralysis in both lower limbs that is consistent with prior examinations. Laboratory studies show: Serum Calcium 12.8 mg/dL Parathyroid hormone, N-terminal 180 pg/mL Thyroid-stimulating hormone 2.5 μU/mL Thyroxine 8 μg/dL Calcitriol Decreased Creatinine 2.6 mg/dL Urine Calcium 550 mg/24 h In addition to administration of intravenous 0.9% saline and calcitonin, which of the following is the most appropriate next step in management?

• A. Thiazide diuretics
• B. Reduced calcium intake
• C. Bisphosphonates (Correct Answer)
• D. Hemodialysis
• E. Glucocorticoids

Explanation: ***Bisphosphonates*** - This patient presents with **severe hypercalcemia** (12.8 mg/dL) with symptoms of nausea, vomiting, and abdominal pain. Given his prolonged immobilization due to a spinal cord injury, **immobilization-induced hypercalcemia** is highly likely. - After initial rehydration with 0.9% saline and calcitonin to rapidly lower calcium, **bisphosphonates** (e.g., zoledronic acid) are the most appropriate next step to inhibit osteoclast activity and **reduce bone resorption**, which is the primary driver of hypercalcemia in immobilized patients. *Thiazide diuretics* - Thiazide diuretics **increase calcium reabsorption** in the renal tubules, which would worsen hypercalcemia. - These are typically used to treat hypercalciuria (and prevent kidney stones) in normocalcemic patients, not hypercalcemia. *Reduced calcium intake* - While reducing dietary calcium is a general recommendation for hypercalcemia, it is **insufficient** as the primary treatment for acute, severe hypercalcemia driven by **increased bone resorption**. - The main problem here is bone breakdown, not excessive intake. *Hemodialysis* - Hemodialysis is reserved for **severe, refractory hypercalcemia** that does not respond to intravenous fluids, calcitonin, and bisphosphonates, especially in patients with severe renal failure. - While this patient has renal insufficiency (Cr 2.6 mg/dL), other less invasive and highly effective treatments should be tried first. *Glucocorticoids* - Glucocorticoids are effective in treating hypercalcemia associated with certain conditions like **granulomatous diseases** (e.g., sarcoidosis) or **hematologic malignancies** (e.g., multiple myeloma). - They work by reducing intestinal calcium absorption and decreasing production of calcitriol. They are **not indicated** for immobilization-induced hypercalcemia.

Question 526: A 24-year-old graduate student is brought to the emergency department by her boyfriend because of chest pain that started 90 minutes ago. Her boyfriend says she has been taking medication to help her study for an important exam and has not slept in several days. On examination, she is diaphoretic, agitated, and attempts to remove her IV lines and ECG leads. Her temperature is 37.6°C (99.7°F), pulse is 128/min, and blood pressure is 163/97 mmHg. Her pupils are dilated. The most appropriate next step in management is the administration of which of the following?

• A. Lorazepam (Correct Answer)
• B. Ketamine
• C. Haloperidol
• D. Activated charcoal
• E. Dantrolene

Explanation: ***Lorazepam*** - This patient presents with symptoms highly suggestive of **sympathomimetic toxicity** (agitation, tachycardia, hypertension, dilated pupils, diaphoresis) likely due to stimulant abuse for studying. **Benzodiazepines** like lorazepam are the first-line treatment to manage agitation, tachycardia, and hypertension in this setting. - Lorazepam helps by **calming the central nervous system** and reducing the sympathetic overdrive, thereby mitigating the cardiovascular and neurological effects of stimulant toxicity. *Ketamine* - Ketamine is a **dissociative anesthetic** that typically increases heart rate and blood pressure, which would exacerbate the patient's existing sympathetic hyperactivity and cardiovascular instability. - It is not indicated for the management of stimulant-induced agitation or catecholamine surge. *Haloperidol* - Haloperidol is an **antipsychotic** that can prolong the **QT interval** and potentially lower the seizure threshold, effects that can be dangerous in stimulant toxicity. - It does not directly address the underlying sympathetic overdrive and can worsen hyperthermia with its anticholinergic properties. *Activated charcoal* - Activated charcoal is used to **prevent absorption** of toxins from the gastrointestinal tract, but it is typically only effective if given within 1-2 hours of ingestion. This patient's symptoms started 90 minutes ago, implying some absorption has already occurred, and her agitated state makes oral administration risky if airway protection is not ensured. - It is also contraindicated in patients with an unprotected airway due to the risk of aspiration, and benzodiazepines are needed first to control agitation and protect the airway. *Dantrolene* - Dantrolene is a **skeletal muscle relaxant** used primarily to treat **malignant hyperthermia** and **neuroleptic malignant syndrome**. - While this patient has some signs of hyperthermia, dantrolene is not the first-line treatment for stimulant-induced hyperthermia, which is primarily managed by controlling agitation and sympathetic overdrive with benzodiazepines and external cooling.

Question 527: A 71-year-old woman presents to her hematologist-oncologist for follow up after having begun doxorubicin and cyclophosphamide in addition to radiation therapy for the treatment of her stage 3 breast cancer. Her past medical history is significant for preeclampsia, hypertension, polycystic ovarian syndrome, and hypercholesterolemia. She currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and denies any illicit drug use. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 111/min, and respiratory rate 23/min. On physical examination, the pulses are strong and irregular, she has a grade 3/6 holosystolic murmur heard best at the left upper sternal border, clear bilateral breath sounds, and erythema over her site of radiation. Which of the following statements regarding doxorubicin is true?

• A. Doxorubicin has a maximum lifetime dose, due to the risk of cardiac toxicity (Correct Answer)
• B. Doxorubicin has a maximum lifetime dose, due to the risk of pulmonary toxicity
• C. Doxorubicin will increase her risk for deep vein thrombosis (DVT) and pulmonary embolism (PE)
• D. Doxorubicin frequently causes an acneiform rash
• E. Doxorubicin frequently causes cystitis

Explanation: ***Doxorubicin has a maximum lifetime dose, due to the risk of cardiac toxicity*** - **Doxorubicin** is a potent chemotherapy agent (anthracycline) with a well-known risk of **cardiotoxicity**, which can lead to **dilated cardiomyopathy** and heart failure. - To mitigate this severe side effect, a **cumulative lifetime dose limit** (usually 450-550 mg/m²) is established for doxorubicin. *Doxorubicin has a maximum lifetime dose, due to the risk of pulmonary toxicity* - While some chemotherapy agents can cause pulmonary toxicity, **doxorubicin** is not primarily associated with this as its main dose-limiting toxicity. - The most significant and common dose-limiting toxicity of doxorubicin is **cardiotoxicity**, not pulmonary. *Doxorubicin will increase her risk for deep vein thrombosis (DVT) and pulmonary embolism (PE)* - Chemotherapy in general can increase the risk of **thromboembolic events**, but this is not a specific dose-limiting toxicity of **doxorubicin** that dictates a lifetime maximum dose. - The concern for DVT/PE is a broader complication of cancer and its treatment, distinct from doxorubicin's specific cardiac risk. *Doxorubicin frequently causes an acneiform rash* - **Acneiform rash** is a common side effect of epidermal growth factor receptor (EGFR) inhibitors (e.g., cetuximab, erlotinib), not typically associated with **doxorubicin**. - Doxorubicin's dermatologic side effects usually involve **alopecia**, hand-foot syndrome, and radiation recall, but not a predominant acneiform rash. *Doxorubicin frequently causes cystitis* - **Cystitis**, particularly hemorrhagic cystitis, is a well-known side effect of **cyclophosphamide** (another drug the patient is receiving), not **doxorubicin**. - **Mesna** is often administered with cyclophosphamide to prevent this urological toxicity.

Question 528: A 70-year-old man comes to the physician for a follow-up examination of diffuse exertional chest pain which he has successfully been treating with sublingual nitroglycerin for the past year. The patient has been taking lisinopril daily for essential hypertension. His pulse is 75/min and regular, and blood pressure is 155/90 mm Hg. Cardiac and pulmonary examination show no abnormalities; there is no peripheral edema. A decrease of which of the following is the most likely explanation for the improvement of this patient's chest pain?

• A. Ventricular compliance
• B. Venous pooling
• C. End-diastolic pressure (Correct Answer)
• D. Peripheral arterial resistance
• E. Electrical conduction speed

Explanation: ***End-diastolic pressure*** - Sublingual nitroglycerin primarily works by causing **venodilation**, which leads to a decrease in **venous return** to the heart. - Reduced venous return results in a lower **end-diastolic volume** and consequently, a lower **end-diastolic pressure**, thereby decreasing **preload** and myocardial oxygen demand. *Ventricular compliance* - **Ventricular compliance** refers to the ventricle's ability to stretch and fill, and while nitroglycerin can slightly affect it through reduced pressure, it's not the primary mechanism for improving anginal symptoms. - A decrease in compliance would generally worsen performance, not improve chest pain, as it would make it harder for the ventricle to fill. *Venous pooling* - Nitroglycerin causes **vasodilation**, trapping blood in the peripheral veins, which is a mechanism leading to **decreased venous return**, not a descriptor of the improvement. - **Increased venous pooling** is the action of nitroglycerin, but the *decrease* in venous pooling would imply less blood trapped in veins, increasing cardiac preload. *Peripheral arterial resistance* - While nitroglycerin can cause some **arterial dilation**, leading to a decrease in **afterload**, its predominant effect in relieving angina is through venodilation and preload reduction. - **Lisinopril**, an ACE inhibitor, primarily reduces afterload by decreasing systemic vascular resistance, which is already being taken by the patient. *Electrical conduction speed* - Nitroglycerin has no significant direct effect on the **electrical conduction system** of the heart. - Changes in electrical conduction speed are related to conditions like **arrhythmias** or medications such as **beta-blockers** or **calcium channel blockers**, not a direct effect of nitrates for angina relief.

Question 529: A previously healthy 8-year-old boy is brought to the physician by his mother because of 6 months of progressive fatigue and weight loss. His mother reports that during this time, he has had decreased energy and has become a “picky eater.” He often has loose stools and complains of occasional abdominal pain and nausea. His family moved to a different house 7 months ago. He is at the 50th percentile for height and 25th percentile for weight. His temperature is 36.7°C (98°F), pulse is 116/min, and blood pressure is 85/46 mm Hg. Physical examination shows tanned skin and bluish-black gums. The abdomen is soft, nondistended, and nontender. Serum studies show: Na+ 134 mEq/L K+ 5.4 mEq/L Cl- 104 mEq/L Bicarbonate 21 mEq/L Urea nitrogen 16 mg/dL Creatinine 0.9 mg/dL Glucose 70 mg/dL Intravenous fluid resuscitation is begun. Which of the following is the most appropriate initial step in treatment?

• A. Fluoxetine
• B. Glucocorticoids (Correct Answer)
• C. Levothyroxine
• D. Deferoxamine
• E. Hyperbaric oxygen

Explanation: ***Glucocorticoids*** - This patient presents with symptoms highly suggestive of **adrenal insufficiency** (Addison's disease), including **fatigue**, weight loss, **hyperpigmentation** (tanned skin, bluish-black gums), **hypotension**, and electrolyte abnormalities like **hyponatremia** and **hyperkalemia**. - **Glucocorticoid replacement** (e.g., hydrocortisone) is the cornerstone of treatment for adrenal insufficiency and is immediately required, especially given the signs of adrenal crisis (hypotension, fatigue). *Fluoxetine* - **Fluoxetine** is a selective serotonin reuptake inhibitor (SSRI) used to treat **depression** and **anxiety disorders**. - While the patient has fatigue and "picky eating," these are symptoms of a systemic illness, not primary depression, and treating depression will not address the underlying adrenal pathology. *Levothyroxine* - **Levothyroxine** is a synthetic thyroid hormone used to treat **hypothyroidism**. - Symptoms of hypothyroidism (e.g., fatigue, weight gain, constipation) overlap somewhat with adrenal insufficiency, but the **hyperpigmentation** and electrolyte derangements (hyperkalemia, hyponatremia) are not characteristic of hypothyroidism. *Deferoxamine* - **Deferoxamine** is a **chelating agent** used to treat **iron toxicity** or iron overload, such as in hemochromatosis. - There are no clinical signs or laboratory findings in this patient to suggest iron overload or toxicity (e.g., no history of transfusions, no elevated ferritin). *Hyperbaric oxygen* - **Hyperbaric oxygen therapy** is used to treat conditions like **carbon monoxide poisoning**, decompression sickness, or refractory wounds. - None of these conditions are suggested by the patient's presentation; there is no indication for hyperbaric oxygen therapy.

Question 530: A 54-year-old man is brought to the emergency department 1 hour after the sudden onset of shortness of breath, severe chest pain, and sweating. He has hypertension and type 2 diabetes mellitus. He has smoked one pack and a half of cigarettes daily for 20 years. An ECG shows ST-segment elevations in leads II, III, and avF. The next hospital with a cardiac catheterization unit is more than 2 hours away. Reperfusion pharmacotherapy is initiated. Which of the following is the primary mechanism of action of this medication?

• A. Conversion of plasminogen to plasmin (Correct Answer)
• B. Inhibition of glutamic acid residue carboxylation
• C. Blocking of adenosine diphosphate receptors
• D. Direct inhibition of thrombin activity
• E. Prevention of thromboxane formation

Explanation: ***Conversion of plasminogen to plasmin*** - **Fibrinolytic** (thrombolytic) drugs, like **tissue plasminogen activator (tPA)**, work by converting plasminogen to plasmin, which then degrades the **fibrin mesh** of a **blood clot**. - This action helps to **restore blood flow** in cases of ST-segment elevation myocardial infarction (STEMI) where primary **percutaneous coronary intervention (PCI)** is not immediately available. *Inhibition of glutamic acid residue carboxylation* - This is the mechanism of action of **warfarin**, an anticoagulant that inhibits the synthesis of **vitamin K-dependent clotting factors** (II, VII, IX, X, protein C, and protein S). - While important for long-term anticoagulation, it does not provide immediate reperfusion in an acute STEMI. *Blocking of adenosine diphosphate receptors* - This describes the mechanism of action of **P2Y12 inhibitors** such as **clopidogrel**, **prasugrel**, and **ticagrelor**. - These drugs are **antiplatelet agents** that prevent platelet aggregation, but they do not directly dissolve an existing thrombus to restore blood flow in STEMI. *Direct inhibition of thrombin activity* - This is the mechanism of action of **direct thrombin inhibitors** like **dabigatran** and **bivalirudin**. - These drugs primarily prevent clot formation or extension and are not used as primary reperfusion agents for acute STEMI due to an existing occlusive thrombus. *Prevention of thromboxane formation* - This is the primary mechanism of action of **aspirin**, which irreversibly inhibits **cyclooxygenase-1 (COX-1)**, thereby reducing the production of thromboxane A2. - Aspirin is an important antiplatelet drug in STEMI management but does not provide reperfusion by dissolving the clot.

Question 531: A 24-year-old woman presents to the emergency department because she started experiencing dyspnea and urticaria after dinner. Her symptoms began approximately 15 minutes after eating a new type of shellfish that she has never had before. On physical exam her breathing is labored, and pulmonary auscultation reveals wheezing bilaterally. Given this presentation, she is immediately started on intramuscular epinephrine for treatment of her symptoms. If part of this patient's symptoms were related to the systemic release of certain complement components, which of the following is another function of the responsible component?

• A. Chemotaxis (Correct Answer)
• B. Direct cytolysis
• C. Inhibition of kallikrein activation
• D. Clearance of immune complexes
• E. Opsonization of pathogens

Explanation: **Chemotaxis** - The patient's symptoms are consistent with **anaphylaxis**, an IgE-mediated hypersensitivity reaction that causes mast cell degranulation. - During anaphylaxis, mast cells release mediators that can activate the **complement system**, producing anaphylatoxins like C3a and C5a. **C5a** is a potent **chemotactic factor** for neutrophils and macrophages, attracting them to the site of inflammation. *Direct cytolysis* - **Direct cytolysis** is primarily mediated by the **membrane attack complex (MAC)**, formed by C5b-C9. - While complement activation occurs in anaphylaxis, the immediate severe symptoms like urticaria and bronchospasm are predominantly due to mast cell degranulation and the release of histamine and other mediators, not direct cell lysis by MAC which occurs in later stages or different contexts. *Inhibition of kallikrein activation* - **Kallikrein activation** is inhibited by **C1 esterase inhibitor (C1-INH)**. - A deficiency in C1-INH leads to conditions like **hereditary angioedema**, which is distinct from the type I hypersensitivity reaction (anaphylaxis) described in the patient. *Clearance of immune complexes* - **Clearance of immune complexes** is a function primarily associated with **C3b** binding to immune complexes, allowing their uptake by phagocytes or transport to the liver and spleen. - While immune complexes are involved in other types of hypersensitivity reactions, they are not the primary mechanism or a direct complement component involved in the acute allergic reaction due to shellfish. *Opsonization of pathogens* - **Opsonization** is the process by which pathogens are tagged for phagocytosis, chiefly performed by **C3b** and antibodies. - While complement plays a role in host defense, opsonization is not the function of the complement components (C3a, C5a) primarily responsible for the anaphylactoid reactions seen in this patient's presentation.

Question 532: An 11-year-old boy with Burkitt lymphoma is brought to the emergency department because of nausea, vomiting, flank pain, and dark urine for 1 day. Two days ago, he began induction chemotherapy with cyclophosphamide, vincristine, prednisolone, and doxorubicin. Urinalysis shows 3+ blood and abundant amber-colored, rhomboid crystals. Which of the following is most likely to have been effective in preventing this patient’s symptoms?

• A. Administration of probenecid
• B. Alkalinization of the urine (Correct Answer)
• C. Administration of ceftriaxone
• D. Water restriction
• E. Administration of hydrochlorothiazide

Explanation: The patient is experiencing symptoms of **tumor lysis syndrome** (TLS) due to rapid cell breakdown from chemotherapy, leading to hyperuricemia and subsequent **uric acid crystal formation** in the kidneys [1], [3]. **Alkalinizing the urine (e.g., with sodium bicarbonate)** increases the solubility of uric acid, preventing its precipitation as crystals and subsequent renal damage [1], [2]. Probenecid works by inhibiting the renal tubular reabsorption of uric acid, thereby **increasing uric acid excretion**. In the setting of rapidly rising uric acid levels, as seen in TLS, this can paradoxically **worsen uric acid nephropathy** by increasing the amount of uric acid filtered and potentially precipitating in the renal tubules [4].

Question 533: A 65-year-old woman comes to the physician because of a 3-month history of progressive shortness of breath and a dry cough. She has also noticed gradual development of facial discoloration. She has coronary artery disease, hypertension, and atrial fibrillation. She does not remember which medications she takes. Her temperature is 37°C (98.6°F), pulse is 90/min, respirations are 18/min, and blood pressure is 150/85 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 95%. Examination shows blue-gray discoloration of the face and both hands. Diffuse inspiratory crackles are heard. An x-ray of the chest shows reticular opacities around the lung periphery and particularly around the lung bases. The most likely cause of this patient's findings is an adverse effect to which of the following medications?

• A. Warfarin
• B. Metoprolol
• C. Procainamide
• D. Amiodarone (Correct Answer)
• E. Lisinopril

Explanation: ***Amiodarone*** - The patient's **progressive shortness of breath**, **dry cough**, and **diffuse inspiratory crackles**, along with **reticular opacities** on chest X-ray, are classic signs of **amiodarone-induced pulmonary fibrosis**. - The distinctive **blue-gray facial and hand discoloration** is also a well-known side effect of chronic amiodarone use, due to **iodine accumulation in the skin** (amiodarone contains high iodine content). *Warfarin* - Warfarin is an anticoagulant used for conditions like atrial fibrillation, but its primary adverse effects include **bleeding** and **skin necrosis**, not pulmonary symptoms or blue-gray discoloration. - It does not cause interstitial lung disease or changes in skin pigmentation. *Metoprolol* - Metoprolol is a beta-blocker used for hypertension and coronary artery disease; common side effects include **bradycardia**, **fatigue**, and **bronchospasm** in susceptible individuals (asthmatics). - It does not typically cause pulmonary fibrosis or skin discoloration. *Procainamide* - Procainamide is an antiarrhythmic, but it is typically used for acute arrhythmias and not long-term management like amiodarone. Its major side effect is a **lupus-like syndrome** and **agranulocytosis**. - It is not associated with pulmonary fibrosis or skin discoloration as described. *Lisinopril* - Lisinopril is an ACE inhibitor used for hypertension and coronary artery disease; common side effects include a **dry cough** (due to bradykinin accumulation) and **angioedema**. - However, it does not cause pulmonary fibrosis (reticular opacities) or blue-gray skin discoloration.

Question 534: A 2-year-old boy is brought to the emergency department with an enlarged left knee. The patient’s parents state that his knee began to swell up a few hours ago while the family was indoors, watching TV. This has never happened before. The boy says his knee hurts when he puts weight on it. Past medical history is unremarkable. He was born at 39 weeks gestation via spontaneous vaginal delivery. He is up to date on all vaccines and is meeting all developmental milestones. Today, his vitals are normal for his age group with a blood pressure of 104/60 mm Hg, heart rate 90/min, respiratory rate 25/min, and temperature 37.1°C (98.8°F). On physical exam the child's left knee is indurated, erythematous, and painful to palpation. An ultrasound of the knee is consistent with hemarthrosis. A hematology workup is completed and the appropriate treatment was administered. Which of the following was the most likely treatment administered to this patient?

• A. Factor IX replacement injections
• B. vWF product
• C. Fresh frozen plasma (FFP)
• D. Desmopressin (Correct Answer)
• E. Cryoprecipitate

Explanation: ***Desmopressin*** - The sudden onset of **hemarthrosis** in a 2-year-old with an otherwise unremarkable history suggests a coagulation disorder, possibly **mild hemophilia A** or **von Willebrand disease (vWD)** due to the spontaneous nature of the bleeding and lack of trauma. - **Desmopressin (DDAVP)** is a synthetic analog of **vasopressin** that stimulates the release of **factor VIII** and **von Willebrand factor (vWF)** from endothelial cells, making it an effective treatment for mild hemophilia A and many types of vWD. *Factor IX replacement injections* - **Factor IX replacement** is the primary treatment for **hemophilia B**, which involves a deficiency in factor IX. - While hemarthrosis can occur in hemophilia B, the immediate and spontaneous nature described is more suggestive of hemophilia A or vWD, for which factor VIII or vWF-related treatments are more appropriate. *vWF product* - A **vWF product** is used for treating more severe forms of **von Willebrand disease** where desmopressin is insufficient or contraindicated. - While vWD is a possibility, desmopressin is often the first-line treatment for milder forms, fitting the current clinical picture. *Fresh frozen plasma (FFP)* - **FFP** contains all coagulation factors and is used in cases of **multiple factor deficiencies** or when specific factor concentrates are unavailable. - Given the focused nature of a potential hemophilia or vWD diagnosis suggested by hemarthrosis, administering specific factor concentrates or desmopressin is generally preferred over FFP, which carries risks of fluid overload and allergic reactions. *Cryoprecipitate* - **Cryoprecipitate** is rich in **fibrinogen, factor VIII, vWF, and factor XIII**. It is used primarily for **fibrinogen deficiency** or severe vWD when specific concentrates are not available or indicated. - While it contains vWF and factor VIII, more targeted therapies like desmopressin or specific factor concentrates are usually preferred if the patient's condition responds to them.

Question 535: A 31-year-old woman is brought to the emergency department for a severe throbbing headache, nausea, and photophobia for 3 hours. She has severe occipital pain and chest tightness. Prior to onset of symptoms, she had attended a networking event where she had red wine and, shortly after, a snack consisting of salami and some dried fruits. The patient has recurrent migraine headaches and depression, for which she takes medication daily. She is mildly distressed, diaphoretic, and her face is flushed. Her temperature is 37.0°C (98.6 F), pulse is 90/min, respirations are 20/min, and blood pressure is 195/130 mmHg. She is alert and oriented. Deep-tendon reflexes are 2+ bilaterally. This patient's symptoms are most likely caused by a side effect of which of the following medications?

• A. Phenelzine (Correct Answer)
• B. Topiramate
• C. Ibuprofen
• D. Valproic acid
• E. Verapamil

Explanation: ***Phenelzine*** - This patient is experiencing a **hypertensive crisis**, characterized by a severe headache, nausea, chest tightness, diaphoresis, and significantly elevated blood pressure (195/130 mmHg). This is a classic presentation of a **tyramine-induced hypertensive crisis**, which can occur in patients taking **monoamine oxidase inhibitors (MAOIs)** like phenelzine. - Phenelzine inhibits monoamine oxidase, which normally metabolizes **tyramine**. Ingestion of tyramine-rich foods (red wine, salami, dried fruits) leads to a buildup of tyramine, causing a massive release of **norepinephrine** and severe hypertension. *Topiramate* - Topiramate is an **anticonvulsant** commonly used for migraine prophylaxis. - Its side effects typically include **paresthesias**, cognitive slowing, and weight loss, not acute hypertensive crisis from dietary interactions. *Ibuprofen* - Ibuprofen is a **non-steroidal anti-inflammatory drug (NSAID)** used for pain relief. - While prolonged use can sometimes cause a mild increase in blood pressure or fluid retention, it does not typically lead to an acute, severe **hypertensive crisis** in response to specific food ingestion. *Valproic acid* - Valproic acid is an **anticonvulsant** and mood stabilizer, also used for migraine prophylaxis. - Common side effects include **gastrointestinal upset**, tremor, and hepatotoxicity; it is not associated with dietary-induced hypertensive crises. *Verapamil* - Verapamil is a **calcium channel blocker** often used for hypertension, angina, and migraine prophylaxis. - Its mechanism of action usually leads to a **decrease** in blood pressure, and it is not known to cause acute hypertensive reactions with specific food interactions.

Question 536: A 39-year-old female presents to the clinic with the complaints of dry skin for a few months. She adds that she also has constipation for which she started eating vegetables and fruits but with no improvement. She lives with her husband and children who often complain when she turns the air conditioning to high as she cannot tolerate low temperatures. She has gained 5 kgs (11.2 lb) since her last visit 2 months back although her diet has not changed much. Her past medical history is relevant for cardiac arrhythmias and diabetes. She is on several medications currently. Her temperature is 98.6° F (37° C), respirations are 15/min, pulse is 57/min and blood pressure is 132/98 mm Hg. A physical examination is within normal limits. Thyroid function test results are given below: Serum TSH: 13.0 μU/mL Thyroxine (T4): 3.0 μg/dL Triiodothyronine (T3): 100 ng/dL Which of the following medications is most likely to be responsible for her symptoms?

• A. Amiodarone (Correct Answer)
• B. Digoxin
• C. Metformin
• D. Theophylline
• E. Warfarin

Explanation: ***Amiodarone*** - Amiodarone is a known cause of both **hypothyroidism** and **hyperthyroidism** due to its iodine content and direct toxic effects on the thyroid gland. The patient's symptoms (dry skin, constipation, **cold intolerance**, **weight gain**, bradycardia) and thyroid function tests (high TSH, low T4, low T3) are highly consistent with drug-induced hypothyroidism. - The patient's history of **cardiac arrhythmias** makes amiodarone a plausible medication she would be taking, as it is a common antiarrhythmic drug. *Digoxin* - Digoxin is primarily used to treat **heart failure** and certain arrhythmias, but it does not typically cause thyroid dysfunction. - Its common side effects include gastrointestinal upset, visual disturbances, and various arrhythmias, which do not align with the patient's predominant symptoms of hypothyroidism. *Metformin* - Metformin is an oral hypoglycemic agent used to treat **Type 2 diabetes**, a condition the patient also has. - It does not have substantial effects on thyroid hormone synthesis or metabolism and is not associated with hypothyroidism or hyperthyroidism. *Theophylline* - Theophylline is a bronchodilator used in the treatment of **asthma** and **COPD**. - It is not known to cause thyroid dysfunction, and its side effects mainly involve the central nervous system, gastrointestinal tract, and cardiovascular system. *Warfarin* - Warfarin is an **anticoagulant** prescribed to prevent blood clots. - It has no direct known interaction with thyroid hormone synthesis or metabolism and is not associated with thyroid dysfunction.

Question 537: Three hours after undergoing a total right hip replacement, a 71-year-old woman has tingling around the lips and numbness in her fingertips. Her surgery was complicated by unintentional laceration of the right femoral artery that resulted in profuse bleeding. She appears uncomfortable. Examination shows an adducted thumb, extended fingers, and flexed metacarpophalangeal joints and wrists. Tapping on the cheeks leads to contraction of the facial muscles. Which of the following is the most likely cause of this patient's symptoms?

• A. Acute kidney injury
• B. Parathyroid ischemia
• C. Intravascular hemolysis
• D. Calcium chelation (Correct Answer)
• E. Metabolic acidosis

Explanation: ***Calcium chelation*** - The patient exhibits symptoms of **hypocalcemia**, including perioral tingling, fingertip numbness, **Trousseau sign** (adducted thumb, extended fingers, flexed metacarpophalangeal joints and wrists), and **Chvostek's sign** (facial muscle contraction upon tapping the cheek). - Her significant blood loss and subsequent transfusion likely involved large volumes of **citrated blood products** (e.g., packed red blood cells), where citrate acts as an **anticoagulant** by chelating calcium, leading to transient hypocalcemia. *Acute kidney injury* - While acute kidney injury can cause electrolyte imbalances, it typically leads to **hyperphosphatemia**, not necessarily acute symptomatic hypocalcemia presenting within hours of surgery in this manner. - The patient's immediate post-operative presentation points away from kidney injury being the primary cause of these acute neurological symptoms. *Parathyroid ischemia* - **Parathyroid ischemia** could cause hypocalcemia due to reduced parathyroid hormone production, but it is typically associated with **neck surgeries** (e.g., thyroidectomy) and not directly with hip replacement or arterial laceration. - The onset of symptoms within hours of surgery is too rapid for parathyroid ischemia to fully manifest, as the half-life of PTH is short, but the subsequent drop in calcium would take longer to become clinically significant. *Intravascular hemolysis* - **Intravascular hemolysis** can occur due to transfusion reactions or other causes, leading to symptoms like fever, chills, and hemoglobinuria. - It does not directly cause the specific neurological signs of hypocalcemia described (Trousseau's and Chvostek's signs). *Metabolic acidosis* - **Metabolic acidosis** can alter calcium binding to albumin, leading to an **increase in ionized calcium** (the physiologically active form), rather than a decrease. - While acidosis can occur after massive blood loss and shock, it would not explain the classic signs of hypocalcemia.

Question 538: A 16-year-old boy is brought to the emergency department following a car accident in which he suffered multiple injuries. He is accompanied by his mother. She reports that his medical history is notable only for recurrent sinusitis and otitis as a child. He lost a significant amount of blood from the accident, and he is transfused two units of O-negative blood on arrival at the emergency department. Shortly thereafter, he complains of itching and increasing shortness of breath. He develops stridor. Which of the following could have prevented this reaction?

• A. Administering IVIG with transfusion
• B. Pre-transfusion diphenhydramine
• C. Administering washed blood products (Correct Answer)
• D. Pre-transfusion acetaminophen
• E. Administering type-specific blood

Explanation: ***Administering washed blood products*** - The patient's history of recurrent sinusitis and otitis suggests **IgA deficiency**, making him susceptible to anaphylactic reactions from IgA in transfused blood. - **Washed blood products** remove plasma proteins, including IgA, preventing such reactions in IgA-deficient individuals. *Administering IVIG with transfusion* - **IVIG** contains IgA and could potentially worsen an IgA-mediated anaphylactic reaction in an IgA-deficient patient. - It is used to supplement antibodies in immunodeficiency, but not to prevent allergic reactions to blood products in this context. *Pre-transfusion diphenhydramine* - **Diphenhydramine**, an antihistamine, can alleviate mild allergic reactions but is insufficient to prevent or treat life-threatening anaphylaxis. - It does not remove the offending allergen (IgA) from the blood product. *Pre-transfusion acetaminophen* - **Acetaminophen** is an antipyretic and analgesic, used to manage fever or pain. - It has no role in preventing allergic or anaphylactic transfusion reactions mediated by IgA. *Administering type-specific blood* - While essential for preventing **hemolytic transfusion reactions** due to ABO incompatibility, type-specific blood does not address reactions to plasma proteins like IgA. - The patient's reaction is an **anaphylactic response**, not a hemolytic one.

Question 539: A 47-year-old woman presents to her physician for a routine checkup. She is in good health and has no complaints. Past medical history is significant for type 2 diabetes mellitus and obesity. She recently started metformin and is tolerating the mild side effects, but her fasting blood glucose levels range from 160–190 mg/dL. Today, her blood pressure is 125/82 mm Hg, the heart rate is 90/min, the respiratory rate is 17/min, and the temperature is 37.0°C (98.6°F). On physical exam, she appears well developed and obese. Her heart has a regular rate and rhythm and her lungs are clear to auscultation bilaterally. Her fasting glucose level is 175 mg/dL and her A1c is 7.1%. Her physician decides to add canagliflozin to her current treatment regimen. Which of the following should be evaluated before starting this medication?

• A. Atrial natriuretic peptide
• B. Alanine aminotransferase
• C. Serum creatinine (Correct Answer)
• D. β-hCG levels
• E. γ-glutamyltransferase

Explanation: ***Serum creatinine*** - Canagliflozin is an **SGLT2 inhibitor**, which acts by blocking glucose reabsorption in the **renal tubules**, leading to glucose excretion in the urine. - Due to its renal mechanism of action, it is crucial to assess **kidney function** via serum creatinine (and thus eGFR) before starting canagliflozin to ensure it can be safely and effectively used. - SGLT2 inhibitors are **less effective** when eGFR is reduced and carry increased risk of adverse effects including volume depletion and acute kidney injury. *Atrial natriuretic peptide* - This is a hormone primarily released from the atria in response to stretch, indicating **volume overload** or **heart failure**. - While heart failure can be a comorbidity in diabetes, ANP levels are **not a prerequisite screening test** for initiating SGLT2 inhibitors. *Alanine aminotransferase* - **ALT is a liver enzyme** used to assess liver function and detect liver injury. - While liver function is important for overall health, it is **not a primary consideration** for initiating SGLT2 inhibitors, as these drugs are primarily renally cleared and do not typically cause hepatotoxicity. *β-hCG levels* - **β-human chorionic gonadotropin** is a hormone measured to detect **pregnancy**. - While SGLT2 inhibitors should be avoided in pregnancy and β-hCG testing may be appropriate for women of childbearing age, it is **not the standard required pre-treatment test** for canagliflozin. - The **primary mandatory assessment** before initiating this drug class is **renal function**, not pregnancy testing. *γ-glutamyltransferase* - **GGT is an enzyme** found in the liver, bile ducts, and kidneys, often used as a marker for **cholestasis** or alcohol abuse. - It is **not a standard or necessary test** to evaluate before starting an SGLT2 inhibitor like canagliflozin.

Question 540: A 75-year-old male is diagnosed with advanced metastatic prostate cancer. After further evaluation and staging, the patient is started on flutamide therapy. Addition of which of the following medications to this patient’s medication regimen would be of greatest benefit in the treatment of this patient’s condition?

• A. Leuprolide (Correct Answer)
• B. Anastrozole
• C. Tamoxifen
• D. Clomiphene
• E. Cyproterone

Explanation: ***Leuprolide*** - **Leuprolide** is a **GnRH agonist** that initially stimulates but then downregulates GnRH receptors, leading to decreased LH and FSH secretion and thus reduced **testosterone production** by the testes. - Combining leuprolide with flutamide (an **androgen receptor blocker**) provides **maximal androgen blockade (MAB)**, which is the most effective initial hormonal therapy for advanced prostate cancer by blocking both testicular and adrenal androgen effects. *Anastrozole* - **Anastrozole** is an **aromatase inhibitor** used primarily in **postmenopausal women with estrogen-receptor-positive breast cancer** by blocking estrogen synthesis. - It is not indicated for prostate cancer, which is driven by androgens, not estrogens. *Tamoxifen* - **Tamoxifen** is a **selective estrogen receptor modulator (SERM)** used primarily in the treatment and prevention of **estrogen-receptor-positive breast cancer**. - It works by blocking estrogen's effects on breast tissue and has no direct role in the treatment of androgen-dependent prostate cancer. *Clomiphene* - **Clomiphene** is a **SERM** used to induce ovulation in women with **anovulatory infertility** by blocking estrogen receptors in the hypothalamus, leading to increased GnRH, FSH, and LH release. - It would actually increase testosterone levels in men by stimulating LH release, which is counterproductive in prostate cancer treatment. *Cyproterone* - **Cyproterone** is an **androgen receptor antagonist** and a progestin, which can reduce androgen production and block androgen receptors. - While it's an antiandrogen and could theoretically be used, flutamide is already an androgen receptor blocker, and the question asks for the "greatest benefit" addition, which points to **GnRH agonism** for maximal androgen blockade.

Question 541: A 27-year-old man is brought to the emergency department because of weakness, headache, and vomiting for 40 minutes. He is an amateur chef and his symptoms started 10 minutes after he ingested pufferfish that he had prepared. On arrival, he is lethargic. His temperature is 37°C (98.6°F), pulse is 120/min, respirations are 8/min, and blood pressure is 92/64 mm Hg. He is intubated and mechanical ventilation is begun. Intravenous fluid resuscitation is started. The cause of this patient's condition exerts its effect by which of the following mechanisms of action?

• A. Increase in cell membrane permeability to chloride ions
• B. Decrease in cell membrane permeability to potassium ions
• C. Increase in cell membrane permeability to calcium ions
• D. Decrease in cell membrane permeability to sodium ions (Correct Answer)
• E. Decrease in cell membrane permeability to calcium ions

Explanation: **Decrease in cell membrane permeability to sodium ions** - **Tetrodotoxin (TTX)**, found in pufferfish, is a potent neurotoxin that specifically blocks **voltage-gated sodium channels**, preventing sodium influx and inhibiting nerve impulse transmission. - This blockage leads to **paralysis of respiratory muscles**, hypotension, and loss of reflexes, explaining the patient's respiratory depression, weakness, and hypotension. *Increase in cell membrane permeability to chloride ions* - This mechanism is characteristic of neurotransmitters like **gamma-aminobutyric acid (GABA)**, which cause hyperpolarization and inhibition through chloride influx. - It does not explain the widespread neurological and muscular paralysis seen in tetrodotoxin poisoning. *Decrease in cell membrane permeability to potassium ions* - This effect would primarily lead to **prolonged repolarization** and increased excitability of nerve and muscle cells, which is not consistent with the symptoms of weakness and paralysis. - Toxins affecting potassium channels typically cause different clinical presentations, such as certain forms of cardiac arrhythmias or neurological hyperexcitability. *Increase in cell membrane permeability to calcium ions* - An increase in calcium permeability is usually associated with **muscle contraction** or **neurotransmitter release**, not the flaccid paralysis and respiratory depression observed. - Certain venom neurotoxins might target calcium channels, but their effects are distinct from those of tetrodotoxin. *Decrease in cell membrane permeability to calcium ions* - While some toxins can block calcium channels (e.g., conotoxins), a decrease in calcium permeability would generally lead to reduced neurotransmitter release and weakened muscle contraction. - However, the primary and most rapid mechanism explaining the acute, severe neurotoxicity of pufferfish poisoning is the blockage of sodium channels, leading to widespread nerve conduction failure.

Question 542: A 63-year-old woman comes to the physician for a follow-up examination. She has had numbness and burning sensation in her feet for 4 months. The pain is worse at rest and while sleeping. She has hypercholesterolemia and type 2 diabetes mellitus. Current medications include insulin, metformin, and atorvastatin. She has smoked one pack of cigarettes daily for 33 years. Her temperature is 37°C (98.6°F), pulse is 88/min, and blood pressure is 124/88 mm Hg. Examination shows full muscle strength and normal muscle tone in all extremities. Sensation to pinprick, light touch, and vibration is decreased over the soles of both feet. Ankle jerk is 1+ bilaterally. Biceps and triceps reflexes are 2+ bilaterally. Babinski sign is negative bilaterally. Laboratory studies show: Hemoglobin 11.2 g/dL Mean corpuscular volume 93 μm3 Hemoglobin A1C 8.2 % Serum Glucose 188 mg/dL Which of the following is the most appropriate next step in management?

• A. Vitamin B12 therapy
• B. Venlafaxine therapy
• C. Ankle-brachial index
• D. MRI with contrast of the spine
• E. Nerve conduction studies (Correct Answer)

Explanation: **Nerve conduction studies** - Given the patient's **numbness** and **burning sensation** in her feet, decreased sensation, and the chronicity of symptoms, **nerve conduction studies** are the most appropriate next step to assess for **peripheral neuropathy** and determine its type and severity. - This diagnostic test directly evaluates the function of peripheral nerves, helping to confirm the diagnosis of neuropathy and differentiate it from other conditions. *Vitamin B12 therapy* - While **vitamin B12 deficiency** can cause neuropathy and her hemoglobin is low, her **mean corpuscular volume (MCV)** is normal, making **macrocytic anemia** (typical for B12 deficiency) less likely. - Although B12 levels could be checked, starting therapy empirically without direct evidence is not the most appropriate immediate next step given the clear neuropathy symptoms. *Venlafaxine therapy* - **Venlafaxine** is an antidepressant that can be used to treat **neuropathic pain**; however, it is a treatment modality, not a diagnostic step. - An accurate diagnosis of the underlying cause and type of neuropathy should ideally precede the initiation of specific symptomatic treatment. *Ankle-brachial index* - An **ankle-brachial index** (ABI) is used to assess for **peripheral artery disease (PAD)**, which can also cause lower extremity symptoms. - While PAD is common in patients with diabetes and smoking history, the patient's primary symptoms of **numbness** and **burning sensation**, along with decreased sensation, are more indicative of neuropathy than ischemia. *MRI with contrast of the spine* - An **MRI of the spine** would be indicated if there were focal neurological deficits, signs of **radiculopathy**, or suspicion of a **spinal cord lesion** (e.g., myelopathy). - The patient's symptoms are distributed bilaterally in the feet, suggesting a diffuse peripheral process rather than a compressive spinal lesion.

Question 543: A 54-year-old woman comes to the emergency department because of sharp chest pain and shortness of breath for 1 day. Her temperature is 37.8°C (100°F), pulse is 110/min, respirations are 30/min, and blood pressure is 86/70 mm Hg. CT angiography of the chest shows a large embolus at the right pulmonary artery. Pharmacotherapy with a tissue plasminogen activator is administered. Six hours later, she develops right-sided weakness and slurred speech. Laboratory studies show elevated prothrombin and partial thromboplastin times and normal bleeding time. A CT scan of the head shows a large, left-sided intracranial hemorrhage. Administration of which of the following is most appropriate to reverse this patient's acquired coagulopathy?

• A. Vitamin K
• B. Desmopressin
• C. Aminocaproic acid (Correct Answer)
• D. Protamine sulfate
• E. Plasmin

Explanation: ***Aminocaproic acid*** - Aminocaproic acid is an **antifibrinolytic** agent that inhibits the activation of plasminogen to plasmin and directly inhibits plasmin, thereby stopping fibrinolysis. - It is the most appropriate drug to reverse the effects of **tissue plasminogen activator (tPA)**, which caused the intracranial hemorrhage, by blocking the breakdown of clots. *Vitamin K* - Vitamin K is essential for the synthesis of **coagulation factors II, VII, IX, and X** and proteins C and S. - It would be used to reverse the effects of **warfarin**, a vitamin K antagonist, which is not the cause of coagulopathy here. *Desmopressin* - Desmopressin (DDAVP) promotes the release of **von Willebrand factor** and factor VIII from endothelial cells, improving platelet aggregation and adhesion. - It is primarily used to treat **von Willebrand disease** and mild hemophilia A or to reverse the antiplatelet effects of certain drugs like aspirin. *Protamine sulfate* - Protamine sulfate is used to reverse the anticoagulant effects of **heparin** by forming a stable ion pair. - The patient's coagulopathy is due to tPA, not heparin, so protamine sulfate would not be effective. *Plasmin* - Plasmin is an enzyme that **breaks down fibrin clots**, leading to fibrinolysis. - Administering plasmin would exacerbate the patient's bleeding tendency and intracranial hemorrhage, as the issue is excessive fibrinolysis caused by tPA.

Question 544: A 6-year-old boy is presented to a pediatric clinic by his mother with complaints of fever, malaise, and cough for the past 2 days. He frequently complains of a sore throat and has difficulty eating solid foods. The mother mentions that, initially, the boy’s fever was low-grade and intermittent but later became high grade and continuous. The boy was born at 39 weeks gestation via spontaneous vaginal delivery. He is up to date on all vaccines and is meeting all developmental milestones. The past medical history is noncontributory. The boy takes a multivitamin every day. The mother reports that he does well in school and is helpful around the house. The boy’s vital signs include blood pressure 110/65 mm Hg, heart rate 110/min, respiratory rate 32/min, and temperature 38.3°C (101.0°F). On physical examination, the boy appears uncomfortable and has difficulty breathing. His heart is mildly tachycardic with a regular rhythm and his lungs are clear to auscultation bilaterally. Oropharyngeal examination shows that his palatine tonsils are covered with pus and that there is erythema of the surrounding mucosa. Which of the following mediators is responsible for this patient’s elevated temperature?

• A. Leukotriene D4
• B. Prostaglandin F2
• C. Prostaglandin E2 (Correct Answer)
• D. Thromboxane A2
• E. Prostaglandin I2

Explanation: ***Prostaglandin E2*** - **Prostaglandin E2 (PGE2)** is a key mediator of fever, acting directly on the **hypothalamus** to reset the body's thermoregulatory set point. - In response to infection and inflammation, immune cells release **pyrogens** (like IL-1, TNF-alpha), which stimulate PGE2 synthesis in the brain, leading to increased body temperature. *Leukotriene D4* - **Leukotriene D4 (LTD4)** is a potent mediator of **bronchoconstriction** and increased **vascular permeability**, particularly in allergic reactions and asthma. - While it plays a role in inflammation, it does not directly cause fever by altering the hypothalamic set point. *Prostaglandin F2* - **Prostaglandin F2 (PGF2)** has various physiological roles, including **uterine contraction** and **bronchoconstriction**, and is important for reproductive functions. - It is not primarily involved in mediating the febrile response to infection. *Thromboxane A2* - **Thromboxane A2 (TXA2)** is predominantly involved in **platelet aggregation** and **vasoconstriction**, playing a crucial role in hemostasis and thrombosis. - While it is a product of the arachidonic acid pathway, it does not directly contribute to fever. *Prostaglandin I2* - **Prostaglandin I2 (PGI2)**, also known as **prostacyclin**, is a potent **vasodilator** and inhibitor of **platelet aggregation**, protecting the vascular endothelium. - It typically counteracts the effects of TXA2 and is not a mediator of fever.

Question 545: A 55-year-old man presents after an episode of severe left ankle pain. The pain has resolved, but he decided to come in for evaluation as he has had pain like this before. He says he has experienced similar episodes of intense pain in the same ankle and his left knee in the past, which he associates with eating copious amounts of fatty food during parties. On one occasion the pain was so excruciating, he went to the emergency room, where an arthrocentesis was performed, revealing needle-shaped negatively birefringent crystals and a high neutrophil count in the synovial fluid. His past medical history is relevant for essential hypertension which is managed with hydrochlorothiazide 20 mg/day. His vital signs are stable, and his body temperature is 36.5°C (97.7°F). Physical examination shows a minimally tender left ankle with full range of motion. Which of the following is the most appropriate long-term treatment in this patient?

• A. Colchicine
• B. Intra-articular steroid injection
• C. Nonsteroidal antiinflammatory drugs (NSAIDs)
• D. Xanthine oxidase inhibitor (Correct Answer)
• E. Uricosuric drug

Explanation: ***Xanthine oxidase inhibitor*** - The patient's presentation with recurrent episodes of severe joint pain, association with fatty foods, and the finding of **negatively birefringent, needle-shaped crystals** in synovial fluid are classic for **gout**. Xanthine oxidase inhibitors like **allopurinol** or **febuxostat** are the most appropriate **long-term treatment** to reduce uric acid production and prevent future attacks. - His use of **hydrochlorothiazide**, a thiazide diuretic, further increases the risk of gout by increasing renal uric acid reabsorption, reinforcing the need for urate-lowering therapy. *Colchicine* - **Colchicine** is primarily used for the **acute treatment** or **prophylaxis of gout flares** during the initiation of urate-lowering therapy. It does not lower serum uric acid levels. - While effective in managing acute symptoms, it is not a long-term solution for preventing gout attacks in a patient with recurrent flares and confirmed crystal deposition. *Intra-articular steroid injection* - **Intra-articular steroid injections** can effectively treat **acute gout flares**, especially when systemic NSAIDs or colchicine are contraindicated or ineffective. - However, this is an acute treatment for symptom relief and does not address the underlying **hyperuricemia** or prevent future episodes, making it unsuitable as a long-term strategy for recurrent gout. *Nonsteroidal antiinflammatory drugs (NSAIDs)* - **NSAIDs** are effective in treating the **acute inflammation and pain** of a gout flare. The patient's current pain has resolved, so NSAIDs are not indicated at this time. - Similar to colchicine, NSAIDs treat the symptoms of an acute attack but do not lower uric acid levels or prevent future episodes. *Uricosuric drug* - **Uricosuric drugs** (e.g., probenecid) increase the excretion of uric acid via the kidneys. They are indicated for patients who **underexcrete uric acid** and have good renal function. - These drugs are contraindicated in patients with **renal impairment** or a history of **uric acid kidney stones**. Without knowing the patient's 24-hour uric acid excretion or renal function in detail, and considering his hypertension and potential renal impact of diuretics, a xanthine oxidase inhibitor is generally preferred as first-line long-term therapy.

Question 546: A 42-year-old woman comes to her primary care physician because of an irritating sensation in her nose. She noticed recently that there seems to be a lump in her nose. Her past medical history is significant for pain that seems to migrate around her body and is refractory to treatment. She has intermittently been taking a medication for the pain and recently increased the dose of the drug. Which of the following processes was most likely responsible for development of this patient's complaint?

• A. Decreased lipoxygenase pathway activity
• B. Increased mucous viscosity
• C. Increased lipoxygenase pathway activity (Correct Answer)
• D. Decreased prostaglandin activity
• E. Increased allergic reaction in mucosa

Explanation: ***Increased lipoxygenase pathway activity*** - This patient likely has **aspirin-exacerbated respiratory disease (AERD)**, characterized by a triad of **asthma, aspirin sensitivity, and chronic rhinosinusitis with nasal polyposis**. The history of "pain that seems to migrate around her body and is refractory to treatment" suggests a chronic pain condition, for which she is taking a medication that exacerbates her nasal symptoms. This medication is likely a **NSAID**. - **NSAIDs** inhibit **cyclooxygenase (COX) enzymes**, shunting arachidonic acid metabolism towards the **lipoxygenase pathway**. This leads to an overproduction of **leukotrienes**, which are potent bronchoconstrictors and promoters of inflammation and nasal polyp formation. *Decreased lipoxygenase pathway activity* - A decrease in lipoxygenase pathway activity would generally lead to **reduced leukotriene production**, which would typically *alleviate* symptoms like nasal irritation and polyp formation, not cause them. - This scenario would likely improve rather than worsen respiratory and allergic symptoms, making it inconsistent with the patient's presentation. *Increased mucous viscosity* - While increased mucous viscosity can contribute to nasal congestion and discomfort, it is a **symptom or consequence** of underlying inflammation, not the primary pathophysiological cause in AERD. - It does not explain the specific link to aspirin/NSAID use and the formation of **nasal polyps**. *Decreased prostaglandin activity* - **Decreased prostaglandin activity** is caused by **NSAID inhibition of COX enzymes**. While this is a crucial step in AERD, it is the *consequence* (shunting to lipoxygenase pathway) rather than the direct cause of the nasal polyps. - The direct cause of the patient's nasal obstruction and pain from the ASA is the **overproduction of leukotrienes**, not merely the absence of prostaglandins. *Increased allergic reaction in mucosa* - While AERD involves mast cell activation and eosinophilic inflammation, it is not primarily an **IgE-mediated allergic reaction** in the classical sense. - The trigger is **pharmacological (NSAIDs)**, not an environmental allergen, and the underlying mechanism is an imbalance in arachidonic acid metabolism rather than a specific antigen-antibody interaction.

Question 547: A 35-year-old man who works in a shipyard presents with a sharp pain in his left big toe for the past 5 hours. He says he has had this kind of pain before a few days ago after an evening of heavy drinking with his friends. He says he took acetaminophen and ibuprofen for the pain as before but, unlike the last time, it hasn't helped. The patient denies any recent history of trauma or fever. No significant past medical history and no other current medications. Family history is significant for his mother who has type 2 diabetes mellitus and his father who has hypertension. The patient reports regular drinking and the occasional binge on the weekends but denies any smoking history or recreational drug use. The vital signs include pulse 86/min, respiratory rate 14/min, and blood pressure 130/80 mm Hg. On physical examination, the patient is slightly overweight and in obvious distress. The 1st metatarsophalangeal joint of the left foot is erythematous, severely tender to touch, and swollen. No obvious deformity is seen. The remainder of the examination is unremarkable. Joint arthrocentesis of the 1st left metatarsophalangeal joint reveals sodium urate crystals. Which of the following drugs would be the next best therapeutic step in this patient?

• A. Probenecid
• B. Allopurinol
• C. Naproxen (Correct Answer)
• D. Aspirin
• E. Morphine

Explanation: ***Naproxen*** - This patient is experiencing an acute **gout flare**, characterized by sudden onset of severe pain, erythema, and swelling in the first metatarsophalangeal joint (podagra), confirmed by **sodium urate crystals** in joint fluid. - **NSAIDs** like naproxen are first-line treatment for acute gout attacks to reduce inflammation and pain, especially since acetaminophen and ibuprofen have been ineffective, and the patient has no contraindications. *Probenecid* - **Probenecid** is a **uricosuric agent** used for **long-term management of gout** by increasing uric acid excretion. - It is **not indicated for acute flares** as it does not provide immediate pain relief and can sometimes worsen an acute attack by mobilizing uric acid. *Allopurinol* - **Allopurinol** is a **xanthine oxidase inhibitor** used for **long-term prevention of gout flares** by reducing uric acid production. - Starting allopurinol during an acute flare can sometimes **exacerbate the attack** by causing rapid shifts in uric acid levels; it should typically be initiated after the acute flare has resolved. *Aspirin* - **Aspirin** can have **variable effects on uric acid levels** depending on the dose; low doses tend to reduce uric acid excretion and can precipitate gout, while high doses are uricosuric but are not typically used for gout treatment. - It is generally **not recommended for acute gout flares** due to its inconsistent effect on uric acid and the availability of more effective anti-inflammatory agents. *Morphine* - **Morphine** is a strong opioid analgesic used for severe pain, but it does **not address the underlying inflammation** of an acute gout flare. - While it could alleviate pain, the primary treatment strategy should target inflammation with NSAIDs, colchicine, or corticosteroids before considering opioids, especially given the side effect profile of opioids.

Question 548: A 60-year-old homeless man presents to the emergency department with an altered mental status. He is not answering questions. His past medical history is unknown. A venous blood gas is drawn demonstrating the following. Venous blood gas pH: 7.2 PaO2: 80 mmHg PaCO2: 80 mmHg HCO3-: 24 mEq/L Which of the following is the most likely etiology of this patient's presentation?

• A. Heroin overdose (Correct Answer)
• B. COPD
• C. Ethylene glycol intoxication
• D. Aspirin overdose
• E. Diabetic ketoacidosis

Explanation: ***Heroin overdose*** - The patient exhibits severe **respiratory depression** (high PaCO2 of 80 mmHg and altered mental status) leading to **respiratory acidosis** (pH 7.2) which is characteristic of opiate overdose. - The **normal bicarbonate (HCO3-) of 24 mEq/L** suggests an acute, uncompensated respiratory acidosis, consistent with an acute overdose event. *COPD* - While patients with COPD can have high PaCO2, they typically develop **chronic respiratory acidosis** and would have a **compensated metabolic alkalosis** with elevated bicarbonate levels. - The **normal bicarbonate** in this patient points away from a chronic respiratory condition. *Ethylene glycol intoxication* - Ethylene glycol intoxication causes a **high anion gap metabolic acidosis**, which would present with a **low bicarbonate level**. - This patient's bicarbonate is normal, ruling out this etiology. *Aspirin overdose* - Aspirin overdose commonly causes a **mixed acid-base disturbance**, initially a **respiratory alkalosis** (due to central nervous system stimulation) and subsequently a **metabolic acidosis**. - The patient's presentation of prominent respiratory acidosis and a normal bicarbonate level is inconsistent with aspirin overdose. *Diabetic ketoacidosis* - Diabetic ketoacidosis is characterized by a **high anion gap metabolic acidosis** with significantly **reduced bicarbonate levels**. - The patient's normal bicarbonate level effectively rules out diabetic ketoacidosis.

Question 549: A 38-year-old male is admitted to the hospital after a motor vehicle accident in which he sustained a right diaphyseal femur fracture. His medical history is significant for untreated hypertension. He reports smoking 1 pack of cigarettes per day and drinking 1 liter of bourbon daily. On hospital day 1, he undergoes open reduction internal fixation of his fracture with a femoral intramedullary nail. At what time after the patient's last drink is he at greatest risk for suffering from life-threatening effects of alcohol withdrawal?

• A. 24-48 hours
• B. 1 week
• C. Less than 24 hours
• D. 48-72 hours (Correct Answer)
• E. 5-6 days

Explanation: ***48-72 hours*** - The most severe and life-threatening symptoms of alcohol withdrawal, such as **delirium tremens (DTs)**, typically manifest within **48 to 72 hours** after the last drink. - This period is characterized by **autonomic hyperactivity**, profound confusion, hallucinations, and seizures. *24-48 hours* - This period may see the onset of more severe withdrawal symptoms like **hallucinations** (alcoholic hallucinosis) and **generalized tonic-clonic seizures**. - While serious, these symptoms are generally less life-threatening than the full-blown delirium tremens that follows. *1 week* - By one week, if left untreated, patients would likely already have experienced the peak severity of withdrawal. - While some mild symptoms might persist or resolve, the highest risk for acute, life-threatening events has usually passed. *Less than 24 hours* - Within this early timeframe, symptoms are usually milder, including **tremors, anxiety, nausea, vomiting, and insomnia**. - These are considered "minor withdrawal symptoms" and are not typically life-threatening. *5-6 days* - By 5-6 days, patients who are going to develop **delirium tremens** would generally have already experienced its onset. - The peak of severe withdrawal symptoms is usually within the 48-72 hour window, and by day 5-6, symptoms might be resolving or the patient would be in a critical state with established DTs.

Question 550: A 23-year-old woman is brought to the emergency department by her friend because of strange behavior. Two hours ago, she was at a night club where she got involved in a fight with the bartender. Her friend says that she was smoking a cigarette before she became irritable and combative. She repeatedly asked “Why are you pouring blood in my drink?” before hitting the bartender. She has no history of psychiatric illness. Her temperature is 38°C (100.4°F), pulse is 100/min, respirations are 19/min, and blood pressure is 158/95 mm Hg. Examination shows muscle rigidity. She has a reduced degree of facial expression. She has no recollection of her confrontation with the bartender. Which of the following is the most likely primary mechanism responsible for this patient's symptoms?

• A. Stimulation of cannabinoid receptors
• B. Inhibition of NMDA receptors (Correct Answer)
• C. Inhibition of norepinephrine, serotonin, and dopamine reuptake
• D. Stimulation of 5HT2A and dopamine D2 receptors
• E. Inhibition of dopamine D2 receptors

Explanation: ***Inhibition of NMDA receptors*** - The patient's symptoms, including **combativeness**, **erratic behavior**, **delusions** ("Why are you pouring blood in my drink?"), **hypertension**, **tachycardia**, and **muscle rigidity**, are characteristic of **PCP intoxication**. - **Phencyclidine (PCP)** acts primarily as an **NMDA receptor antagonist**, blocking calcium channels and leading to these neurotoxic effects. *Stimulation of cannabinoid receptors* - **Cannabis intoxication** typically involves **euphoria**, distorted perception, impaired memory, and increased appetite, which are not the primary features described here. - While agitation can occur, the severe combativeness, delusions, and specific vital sign changes point away from cannabinoid receptor stimulation as the primary mechanism for this presentation. *Inhibition of norepinephrine, serotonin, and dopamine reuptake* - This mechanism is characteristic of stimulants like **cocaine** or **amphetamines**. While these drugs can cause agitation, paranoia, hypertension, and tachycardia, they typically do not cause the prominent **muscle rigidity** and **delusional thought** content as described. - The "smoking a cigarette" context might suggest stimulants, but the overall clinical picture is more consistent with PCP. *Stimulation of 5HT2A and dopamine D2 receptors* - Stimulation of **5HT2A receptors** is associated with **hallucinogens** like LSD, causing perceptual distortions and altered consciousness, but typically not the intense combativeness, muscle rigidity, and specific delusions seen here. - While **dopamine D2 receptor stimulation** can contribute to psychosis, it's not the primary mechanism that brings together all the described symptoms in this acute, severe presentation. *Inhibition of dopamine D2 receptors* - **Dopamine D2 receptor inhibition** is the mechanism of action for antipsychotic medications and generally leads to a reduction in psychotic symptoms, not the intense agitation, combativeness, and psychotic features observed in this patient. - Such inhibition can lead to extrapyramidal symptoms, but not the acute, substance-induced presentation described.

Question 551: A 16-year-old girl is brought to the physician because of generalized fatigue and an inability to concentrate in school for the past 4 months. During this period, she has had excessive daytime sleepiness. While going to sleep, she sees cartoon characters playing in her room. She wakes up once or twice every night. While awakening, she feels stiff and cannot move for a couple of minutes. She goes to sleep by 9 pm every night and wakes up at 7 am. She takes two to three 15-minute naps during the day and wakes up feeling refreshed. During the past week while listening to a friend tell a joke, she had an episode in which her head tilted and jaw dropped for a few seconds; it resolved spontaneously. Her father has schizoaffective disorder and her parents are divorced. Vital signs are within normal limits. Physical examination is unremarkable. Which of the following is the most appropriate initial pharmacotherapy?

• A. Modafinil (Correct Answer)
• B. Venlafaxine
• C. Risperidone
• D. Oral contraceptive pill
• E. Citalopram

Explanation: ***Modafinil*** - This patient's symptoms (excessive daytime sleepiness, hypnagogic hallucinations, sleep paralysis, cataplexy, and refreshing naps) are highly suggestive of **narcolepsy**. - **Modafinil** is a wake-promoting agent and is a first-line treatment for excessive daytime sleepiness in narcolepsy. *Venlafaxine* - **Venlafaxine** is a serotonin-norepinephrine reuptake inhibitor (SNRI) that can be used to treat cataplexy in narcolepsy by suppressing REM sleep. - While cataplexy is present, the primary and most debilitating symptom is excessive daytime sleepiness, for which modafinil is the initial choice. *Risperidone* - **Risperidone** is an antipsychotic medication, primarily used to treat schizophrenia and bipolar disorder. - Although the patient experiences hypnagogic hallucinations, these are part of narcolepsy symptoms and not indicative of a primary psychotic disorder warranting antipsychotic treatment. *Oral contraceptive pill* - An **oral contraceptive pill** is used for contraception or managing hormonal-related conditions such as irregular menstruation, acne, or polycystic ovary syndrome. - There is no indication in the patient's presentation that would warrant treatment with oral contraceptives. *Citalopram* - **Citalopram** is a selective serotonin reuptake inhibitor (SSRI) and is typically used to treat depression or anxiety disorders. - While sometimes used off-label for cataplexy in narcolepsy due to its REM-suppressing effects, it is not the initial treatment for the primary symptom of excessive daytime sleepiness.

Question 552: A 24-year-old man is brought to the emergency department because of violent jerky movements of his arms and legs that began 30 minutes ago. His father reports that the patient has a history of epilepsy. He is not responsive. Physical examination shows alternating tonic jerks and clonic episodes. There is blood in the mouth. Administration of intravenous lorazepam is begun. In addition, treatment with a second drug is started that alters the flow of sodium ions across neuronal membranes. The second agent administered was most likely which of the following drugs?

• A. Lamotrigine
• B. Phenobarbital
• C. Topiramate
• D. Carbamazepine
• E. Fosphenytoin (Correct Answer)

Explanation: ***Fosphenytoin*** - This patient is experiencing **status epilepticus** as evidenced by prolonged tonic-clonic seizures. **Lorazepam** is the first-line short-acting benzodiazepine for acute seizure termination, but a second, longer-acting antiepileptic drug is needed for maintenance. - **Fosphenytoin** is a prodrug of **phenytoin** that can be administered intravenously; **phenytoin** works by blocking **voltage-sensitive sodium channels**, thereby altering the flow of sodium ions and stabilizing neuronal membranes. *Lamotrigine* - While **lamotrigine** does block voltage-gated sodium channels, it is primarily used for **partial seizures** and **generalized tonic-clonic seizures** as a maintenance therapy, not typically as an acute treatment for status epilepticus. - It requires **slow titration** due to the risk of severe skin reactions (e.g., Stevens-Johnson syndrome), making it unsuitable for immediate use in status epilepticus. *Phenobarbital* - **Phenobarbital** is an antiepileptic drug that enhances **GABAergic neurotransmission**, leading to neuronal hyperpolarization and reduced excitability. It is a very effective and older anticonvulsant. - Although it can be used for status epilepticus, it acts primarily on GABA receptors, not directly on **sodium ion channels** as described in the question. *Topiramate* - **Topiramate** has multiple mechanisms of action, including blocking voltage-gated sodium channels and enhancing GABA activity, but it is typically used as a **maintenance therapy** for various seizure types. - It is not a first-line agent for acute management of **status epilepticus** and its primary mechanism mentioned isn't restricted to sodium channel modulation as explicitly as phenytoin. *Carbamazepine* - **Carbamazepine** is a sodium channel blocker, similar to phenytoin, and is effective for **partial** and **tonic-clonic seizures**. - However, it is primarily an **oral medication** and its slow absorption makes it inappropriate for acute intravenous treatment of status epilepticus.

Question 553: A 44-year-old male is brought to the emergency department by fire and rescue after he was the unrestrained driver in a motor vehicle accident. His wife notes that the patient’s only past medical history is recent development of severe episodes of headache accompanied by sweating and palpitations. She says that these episodes were diagnosed as atypical panic attacks by the patient’s primary care provider, and the patient was started on sertraline and alprazolam. In the trauma bay, the patient’s temperature is 97.6°F (36.4°C), blood pressure is 81/56 mmHg, pulse is 127/min, and respirations are 14/min. He has a Glascow Coma Score (GCS) of 10. He is extremely tender to palpation in the abdomen with rebound and guarding. His skin is cool and clammy, and he has thready peripheral pulses. The patient's Focused Assessment with Sonography for Trauma (FAST) exam reveals bleeding in the perisplenic space, and he is taken for emergency laparotomy. He is found to have a ruptured spleen, and his spleen is removed. During manipulation of the bowel, the patient’s temperature is 97.8°F (36.6°C), blood pressure is 246/124 mmHg, and pulse is 104/min. The patient is administered intravenous labetalol, but his blood pressure continues to worsen. The patient dies during the surgery. Which of the following medications would most likely have prevented this outcome?

• A. Lorazepam
• B. Propylthiouracil
• C. Phenoxybenzamine (Correct Answer)
• D. Dantrolene
• E. Phentolamine

Explanation: ***Phenoxybenzamine*** - This patient likely had an undiagnosed **pheochromocytoma**, which is a **catecholamine-secreting tumor**. The severe labile hypertension during surgery, unresponsive to labetalol, is a classic sign of a catecholamine surge. - **Phenoxybenzamine** is an **irreversible alpha-adrenergic blocker** that would have been used pre-operatively to control blood pressure and prevent such a hypertensive crisis by blocking the effects of excess catecholamines. *Lorazepam* - **Lorazepam** is a **benzodiazepine** used for anxiety and seizure control. While it might have helped to calm the patient or manage panic, it would not address the underlying physiological cause of the hypertensive crisis associated with an endocrine tumor. - Its effects on blood pressure are generally mild and would not counteract the massive catecholamine release seen in a pheochromocytoma. *Propylthiouracil* - **Propylthiouracil** is an **antithyroid medication** used to treat **hyperthyroidism**. There is no indication of thyroid dysfunction in this patient's presentation. - The symptoms of palpitations and sweating are common to both pheochromocytoma and hyperthyroidism, but the rapid, extreme hypertensive crisis points away from thyroid storm and towards a catecholamine-secreting tumor. *Dantrolene* - **Dantrolene** is a **skeletal muscle relaxant** primarily used to treat and prevent **malignant hyperthermia**. - There is no evidence in the clinical presentation to suggest malignant hyperthermia as the cause of this patient's deterioration; the extreme hypertension is the primary issue. *Phentolamine* - **Phentolamine** is a **reversible alpha-adrenergic blocker** used to manage hypertensive crises, particularly those due to pheochromocytoma or monoamine oxidase inhibitor interactions. - While phentolamine could be used during a crisis, **phenoxybenzamine** is preferred for *pre-operative preparation* due to its longer-acting and irreversible blockade, preventing the crisis more effectively when surgery is anticipated for pheochromocytoma.

Question 554: A 72-year-old Caucasian female presents to the emergency department with complaints of a new-onset, right-sided throbbing headache which becomes markedly worse when eating. The daughter also reports that her mother has recently had difficulties with performing daily activities, such as climbing stairs or standing up. Past medical history is significant for a lower extremity deep vein thrombosis. The blood pressure is 124/78 mm Hg, the heart rate is 72/min, and the respiratory rate is 15/min. The physical examination is unremarkable except for the right visual field defect. Laboratory results are presented below: Hemoglobin 11.3 g/dL Hematocrit 37.7% Leukocyte count 6,200/mm3 Mean corpuscular volume 82.2 μm3 Platelet count 200,000/mm3 Erythrocyte sedimentation rate 75 mm/h C-reactive protein 50 mg/dL Which of the following medications would be most beneficial for this patient?

• A. Prednisolone (Correct Answer)
• B. Low-molecular-weight heparin
• C. Gabapentin
• D. Methotrexate
• E. Celecoxib

Explanation: ***Prednisolone*** - The patient's symptoms (new-onset headache, jaw claudication, visual field defect) and elevated inflammatory markers (**ESR, CRP**) are highly suggestive of **giant cell arteritis (GCA)**, which can lead to irreversible vision loss. - **High-dose corticosteroids** like prednisolone are the mainstay of treatment for GCA to prevent complications such as blindness and stroke. *Low-molecular-weight heparin* - This medication is primarily used for the **prevention and treatment of thromboembolic events**, such as deep vein thrombosis (DVT) or pulmonary embolism. - While the patient has a history of DVT, there are no current signs or symptoms indicating an acute thromboembolic event requiring immediate anticoagulation. *Gabapentin* - This drug is an **antiepileptic** and is commonly used to treat **neuropathic pain**, such as postherpetic neuralgia or diabetic neuropathy. - The patient's headache is characteristic of an inflammatory vascular process, not neuropathic pain. *Methotrexate* - Methotrexate is a **disease-modifying antirheumatic drug (DMARD)** primarily used in the treatment of various autoimmune conditions, including **rheumatoid arthritis** and **psoriasis**. - While it can be used as a steroid-sparing agent in some vasculitides, it is not the initial or most effective treatment for acute GCA and does not rapidly prevent acute ischemic complications. *Celecoxib* - Celecoxib is a **selective COX-2 inhibitor** (a type of NSAID) used for pain and inflammation, particularly in conditions like osteoarthritis and rheumatoid arthritis. - While it can reduce inflammation, it is **insufficient to rapidly control the systemic inflammation** and prevent the severe ischemic complications associated with GCA.

Question 555: A 66-year-old woman presents to the emergency department with a throbbing headache. She states that the pain is worse when eating and is localized over the right side of her head. Review of systems is only notable for some blurry vision in the right eye which is slightly worse currently. The patient's past medical history is notable only for chronic pain in her muscles and joints for which she has been taking ibuprofen. Her temperature is 99.1°F (37.3°C), blood pressure is 144/89 mmHg, pulse is 87/min, respirations are 14/min, and oxygen saturation is 98% on room air. Physical examination is significant for tenderness to palpation over the right temporal region. Which of the following is the best initial step in management?

• A. Methylprednisolone (Correct Answer)
• B. Ibuprofen and acetaminophen
• C. MRI head
• D. CT head
• E. 100% oxygen

Explanation: ***Methylprednisolone*** - The patient presents with classic symptoms of **giant cell arteritis (GCA)**, including a new-onset, unilateral, throbbing headache, jaw claudication (pain worse with eating), temporal artery tenderness, and new or acutely worsening **vision changes**. - Prompt initiation of **high-dose corticosteroids** (like methylprednisolone) is crucial to prevent irreversible vision loss and other ischemic complications. *Ibuprofen and acetaminophen* - These medications are **NSAIDs** and **analgesics** that primarily treat pain and inflammation, but they do not address the underlying acute vasculitis in GCA. - They will not prevent the progression of **ischemic damage** to the optic nerve or other affected arteries. *MRI head* - An **MRI head** is not the initial step in management for suspected GCA, as it is primarily used to evaluate for other intracranial pathologies like stroke or tumor, or for chronic changes. - While it can sometimes show **vessel wall edema** in GCA, it is not as urgent as starting steroids and does not replace the immediate need for treatment. *CT head* - A **CT head** is primarily used to rule out acute intracranial emergencies such as hemorrhage or large strokes. - It is generally **not useful** for diagnosing GCA or detecting inflammation of vessel walls, making it an inappropriate initial step given the patient's symptoms. *100% oxygen* - **100% oxygen** is a primary treatment for **cluster headaches**, which present with unilateral pain, but typically include autonomic symptoms like lacrimation, rhinorrhea, or ptosis, and are usually much shorter in duration. - It has **no role** in the management of GCA, which is an inflammatory vasculitis.

Question 556: A 45-year-old man comes to the physician because of intermittent lower back pain for 1 week. His symptoms began shortly after lifting heavy boxes at work. He has not had any fever, chills, or weight loss. He has a history of peptic ulcer disease. He does not smoke or drink alcohol. His vital signs are within normal limits. Examination shows mild paraspinal lumbar tenderness. Neurologic examination shows no focal findings. An x-ray of the spine shows no abnormalities. Which of the following is the most appropriate initial pharmacotherapy?

• A. Aspirin
• B. Ibuprofen
• C. Naproxen
• D. Oxycodone
• E. Acetaminophen (Correct Answer)

Explanation: ***Acetaminophen*** - Acetaminophen is the **initial pharmacotherapy of choice** for acute low back pain due to its efficacy and favorable side effect profile, especially in patients with a history of peptic ulcer disease who should avoid NSAIDs. - It provides **analgesia** by inhibiting prostaglandin synthesis in the central nervous system, helping to alleviate musculoskeletal pain without the gastrointestinal risks associated with NSAIDs. *Aspirin* - Aspirin is an **NSAID** and would be contraindicated in this patient due to his history of **peptic ulcer disease**, as it increases the risk of gastrointestinal bleeding and ulcer exacerbation. - While it has analgesic properties, its **antiplatelet effects** and gastrointestinal side effects make it unsuitable as a first-line treatment in this specific clinical context. *Ibuprofen* - Ibuprofen is another **NSAID** which, like aspirin, carries a significant risk of **gastrointestinal irritation** and ulceration. - Its use is **contraindicated** in patients with a history of peptic ulcer disease, making it an inappropriate initial choice for this patient's back pain. *Naproxen* - Naproxen is also an **NSAID** and shares the same contraindication as ibuprofen and aspirin in patients with a history of **peptic ulcer disease**. - Its mechanism of action involves inhibiting cyclooxygenase (COX-1 and COX-2) enzymes, which leads to reduced prostaglandin synthesis but also increased risk of **gastric mucosal damage**. *Oxycodone* - Oxycodone is an **opioid analgesic** and is generally reserved for severe pain that is not adequately controlled by non-opioid medications. Given the patient's presentation of **mild paraspinal tenderness** and no focal neurological deficits, it would be an excessive initial choice. - The use of opioids carries risks of **addiction**, constipation, and sedation, and it is not recommended as a first-line therapy for acute, non-severe low back pain.

Question 557: A 26-year-old gravida 4 para 1 presents to the emergency department with sudden severe abdominal pain and mild vaginal bleeding. Her last menstrual period was 12 weeks ago. She describes her pain as similar to uterine contractions. She has a history of 2 spontaneous abortions in the first trimester. She is not complaining of dizziness or dyspnea. On physical examination, the temperature is 36.9°C (98.4°F), the blood pressure is 120/85 mm Hg, the pulse is 95/min, and the respiratory rate is 17/min. The pelvic examination reveals mild active bleeding and an open cervical os. There are no clots. Transvaginal ultrasound reveals a fetus with no cardiac activity. She is counseled about the findings and the options are discussed. She requests to attempt medical management with mifepristone before progressing to surgical intervention. Which of the following describes the main mechanism of action for mifepristone?

• A. Interferes with cell growth in rapidly dividing cells
• B. Increase myometrial sensitivity to contractions and induce decidual breakdown (Correct Answer)
• C. Induce teratogenesis in the fetus
• D. Induce cervical dilation
• E. Interferes with placental blood supply to the fetus

Explanation: ***Increase myometrial sensitivity to contractions and induced decidual breakdown*** - **Mifepristone** acts primarily as a **progesterone receptor antagonist**, blocking progesterone's effects. - This blockade leads to **decidual breakdown**, increased uterine contractility, and increased sensitivity of the myometrium to prostaglandins, facilitating expulsion of uterine contents. *Interferes with cell growth in rapidly dividing cells* - This mechanism describes **chemotherapeutic agents** like methotrexate, which targets rapidly dividing cells. - **Mifepristone** does not interfere with cell growth in this manner; its action is receptor-mediated. *Induce teratogenesis in the fetus* - While mifepristone can affect fetal development by terminating a pregnancy, its primary mechanism of action is **not directly teratogenesis** (the induction of birth defects). - Its purpose is to induce abortion or miscarriage, not to cause malformations in a continuing pregnancy. *Induce cervical dilation* - While cervical dilation occurs as a consequence of the abortion process facilitated by mifepristone, it is not the **primary mechanism of action** of the drug itself. - Cervical dilation is often secondary to uterine contractions and the release of prostaglandins, which are downstream effects of mifepristone. *Interferes with placental blood supply to the fetus* - **Mifepristone's** main action is not directly on the placental blood supply; rather, it affects the **uterine lining and myometrial activity**. - The disruption of pregnancy by mifepristone leads to secondary effects on the placenta and fetal viability, but it doesn't primarily block blood flow.

Question 558: A 28-year-old man presents to the emergency department with vomiting. He states that he has experienced severe vomiting starting last night that has not been improving. He states that his symptoms improve with hot showers. The patient has presented to the emergency department with a similar complaint several times in the past as well as for intravenous drug abuse. His temperature is 99.5°F (37.5°C), blood pressure is 127/68 mmHg, pulse is 110/min, respirations are 22/min, and oxygen saturation is 98% on room air. Physical exam is deferred as the patient is actively vomiting. Which of the following is associated with the most likely diagnosis?

• A. Viral gastroenteritis
• B. Marijuana use (Correct Answer)
• C. Substance withdrawal
• D. Alcohol use
• E. Toxin ingestion

Explanation: ***Marijuana use*** - The patient's history of recurrent vomiting, improvement with hot showers, and a history of intravenous drug abuse are highly suggestive of **cannabinoid hyperemesis syndrome (CHS)**. **Marijuana use** is directly associated with CHS, which presents with cyclical vomiting in chronic cannabis users. - While the patient has a history of intravenous drug use, the specific pattern of recurrent vomiting relieved by hot showers points strongly towards **CHS**, which is caused by long-term cannabis use. *Viral gastroenteritis* - Although **viral gastroenteritis** can cause severe vomiting, it typically resolves within a few days and does not usually present as a recurrent issue relieved by hot showers. - This condition does not explain the patient's history of multiple similar presentations or the specific alleviating factor of hot showers. *Substance withdrawal* - While some **substance withdrawal syndromes** can cause nausea and vomiting, the characteristic relief with hot showers is not typical for withdrawal symptoms. - The patient's symptoms are more indicative of a syndrome directly linked to substance use rather than withdrawal. *Alcohol use* - **Alcohol use** can cause vomiting in episodes of acute intoxication or withdrawal; however, repeated episodes of severe vomiting relieved specifically by hot showers are not a classic presentation of alcohol-related vomiting. - There is no specific mention of alcohol abuse in the patient's history as a cause for these symptoms. *Toxin ingestion* - **Toxin ingestion** can indeed cause severe vomiting, but it would not typically be a recurring problem that improves with hot showers. - The recurrent nature and specific relieving factor point away from a one-time toxic exposure.

Question 559: A 12-year-old female presents to your office complaining of several brief episodes of shortness of breath of varying severity. Which of the following substances would lead to a decrease in FEV1 of 20% if the patient has asthma?

• A. Methacholine (Correct Answer)
• B. Epinephrine
• C. Albuterol
• D. Norepinephrine
• E. Ipratropium

Explanation: ***Methacholine*** - **Methacholine** is a **cholinergic agonist** that induces **bronchoconstriction**, and a 20% decrease in FEV1 is diagnostic for **asthma** in a methacholine challenge test. - This substance is used specifically to test for **airway hyperresponsiveness**, a hallmark of asthma. *Epinephrine* - **Epinephrine** is a **sympathomimetic** that causes **bronchodilation**, which would increase FEV1 rather than decrease it. - It acts on **beta-2 adrenergic receptors** in the lungs to relax airway smooth muscle. *Albuterol* - **Albuterol** is a **short-acting beta-2 agonist (SABA)** used as a rescue inhaler for asthma, leading to **bronchodilation**. - It would improve FEV1 by relaxing airway smooth muscle, not decrease it. *Norepinephrine* - **Norepinephrine** primarily acts on **alpha-adrenergic receptors** and has less potent beta-2 agonist effects compared to epinephrine. - While it can cause some bronchodilation, it is not used in asthma diagnosis or treatment in this context and would not cause a 20% FEV1 decrease. *Ipratropium* - **Ipratropium** is an **anticholinergic bronchodilator** that blocks muscarinic receptors, causing relaxation of airway smooth muscle. - It would lead to an increase in FEV1, not a decrease, and is primarily used in COPD and some asthma cases.

Question 560: While walking through a park with his wife, a 51-year-old man with type 2 diabetes mellitus develops nausea, sweating, pallor, and palpitations. For the past 3 weeks, he has been trying to lose weight and has adjusted his diet and activity level. He eats a low-carb diet and swims 3 times a week. The man returned home from a training session 2 hours ago. Current medications include basal insulin and metformin. Shortly before his wife returns from their car with his emergency medication kit, he becomes unconscious. Administration of which of the following is the most appropriate next step in management?

• A. Sublingual nitroglycerine
• B. Oral glucose
• C. Intramuscular glucagon (Correct Answer)
• D. Rectal lorazepam
• E. Intra-arterial dextrose

Explanation: ***Intramuscular glucagon*** - This patient is experiencing severe **hypoglycemia** (nausea, sweating, pallor, palpitations, unconsciousness) exacerbated by his weight loss efforts, diet, and recent exercise while on insulin and metformin. As he is unconscious and cannot take oral glucose, **intramuscular glucagon** is the most appropriate emergency treatment to raise blood glucose levels in this pre-hospital setting. - **Glucagon** mobilizes glucose from the liver by stimulating hepatic glycogenolysis, making it vital when oral intake is compromised due to altered consciousness and IV access is not immediately available. *Sublingual nitroglycerine* - **Nitroglycerine** is used for chest pain suspected to be angina or myocardial infarction, not for hypoglycemia. - Administering nitroglycerine in a hypoglycemic patient could cause **vasodilation** and further lower blood pressure, potentially worsening their condition. *Oral glucose* - While oral glucose is the primary treatment for mild to moderate hypoglycemia, this patient is **unconscious** and therefore cannot safely swallow. - Giving oral substances to an unconscious person risks **aspiration pneumonia** and choking. *Rectal lorazepam* - **Lorazepam** is an anxiolytic and anticonvulsant, used primarily to treat seizures or severe anxiety. - It does not address the underlying hypoglycemia and could further **depress the central nervous system**, worsening the patient's altered mental status. *Intra-arterial dextrose* - **Intra-arterial dextrose** is not a standard or safe route for treating hypoglycemia. While **intravenous dextrose** would be appropriate in a hospital setting, it is not available in this pre-hospital emergency scenario. - Administering substances intra-arterially can cause severe damage, including **arterial spasm**, thrombosis, and tissue necrosis.

Question 561: A 66-year-old man with coronary artery disease and hypertension comes to the emergency department because of intermittent retrosternal chest pain, lightheadedness, and palpitations. He has smoked one pack of cigarettes daily for 39 years. His pulse is 140/min and irregularly irregular, respirations are 20/min, and blood pressure is 108/60 mm Hg. An ECG shows an irregular, narrow-complex tachycardia with absent P waves. A drug with which of the following mechanisms of action is most likely to be effective in the long-term prevention of embolic stroke in this patient?

• A. Irreversible inhibition of cyclooxygenase
• B. Interference with carboxylation of glutamate residues (Correct Answer)
• C. Binding and activation of antithrombin III
• D. Irreversible blockade of adenosine diphosphate receptors
• E. Activation of the conversion of plasminogen to plasmin

Explanation: ***Interference with carboxylation of glutamate residues*** - The patient's presentation with **irregularly irregular pulse**, **narrow-complex tachycardia**, and **absent P waves** on ECG is highly suggestive of **atrial fibrillation**. - **Atrial fibrillation** increases the risk of **thromboembolic stroke**, and long-term prevention requires **anticoagulation**. - This mechanism describes **warfarin**, a vitamin K antagonist that inhibits the **carboxylation of glutamate residues** in clotting factors (II, VII, IX, X), preventing their activation. - While **direct oral anticoagulants (DOACs)** are now often preferred as first-line therapy, warfarin remains an effective and widely used option for stroke prevention in atrial fibrillation, particularly when DOACs are contraindicated or unavailable. *Irreversible inhibition of cyclooxygenase* - This mechanism describes **aspirin**, an **antiplatelet agent**. - While aspirin provides some cardiovascular protection, it is **significantly less effective than anticoagulants** like warfarin or DOACs for stroke prevention in patients with atrial fibrillation. - Antiplatelet agents alone are generally reserved for patients who cannot tolerate anticoagulation. *Binding and activation of antithrombin III* - This mechanism is characteristic of **unfractionated heparin** and **low molecular weight heparins (LMWH)**. - These agents are primarily used for **acute anticoagulation** (e.g., bridging therapy) and require parenteral administration. - They are not suitable for long-term oral stroke prevention in atrial fibrillation. *Irreversible blockade of adenosine diphosphate receptors* - This mechanism describes **P2Y12 inhibitors** like clopidogrel, prasugrel, and ticagrelor, which are **antiplatelet agents**. - Like aspirin, P2Y12 inhibitors are **not sufficient as monotherapy** for stroke prevention in atrial fibrillation. - They are more commonly used in acute coronary syndromes, after percutaneous coronary intervention, or in dual antiplatelet therapy. *Activation of the conversion of plasminogen to plasmin* - This mechanism describes **thrombolytic agents** (e.g., tissue plasminogen activator - tPA, alteplase), which are used to **dissolve existing clots** in acute scenarios like ischemic stroke or ST-elevation myocardial infarction. - They are not used for long-term prevention of embolic stroke due to their **significant bleeding risk** and lack of prophylactic benefit.

Question 562: A 67-year-old male presents to the emergency department with sudden onset shortness of breath and epigastric pain. The patient has a past medical history of GERD, obesity, diabetes mellitus type II, anxiety, glaucoma, and irritable bowel syndrome. His current medications include omeprazole, insulin, metformin, lisinopril, and clonazepam as needed. The patient's temperature is 99.5°F (37.5°C), pulse is 112/min, blood pressure is 90/70 mmHg, respirations are 18/min, and oxygen saturation is 95% on room air. On physical exam the patient's lungs are clear to auscultation bilaterally. JVD is notable and cardiac auscultation is not revealing. An EKG is obtained in the emergency department. The patient is given a bolus of fluids and his pulse becomes 80/min with a blood pressure of 105/75 mmHg. The patient is then started on beta-blockers, oxygen, nitroglycerin, morphine, IV fluids, and aspirin. Repeat vitals demonstrate a blood pressure of 80/65 mmHg. Which of the following is the best explanation of this patient's current vital signs?

• A. Increased cGMP (Correct Answer)
• B. Beta-adrenergic blockade
• C. Left ventricular failure
• D. Fluid overload
• E. Ventricular free wall rupture

Explanation: ***Increased cGMP*** - The administration of **nitroglycerin** leads to increased cGMP, which causes **vasodilation** and can result in **hypotension**, especially in patients with **preload-dependent conditions** like right ventricular infarction. - The patient's initial excellent response to fluids then subsequent hypotension after vasodilators suggests that the nitroglycerin exacerbated a **preload-dependent state**. *Beta-adrenergic blockade* - While beta-blockers can *decrease* **blood pressure** and **heart rate**, the dramatic drop in blood pressure here is more consistent with a strong **vasodilatory effect** from **nitroglycerin**, particularly in the context of the patient's presentation. - Beta-blockers primarily reduce **cardiac output** by decreasing myocardial contractility and heart rate but are less likely to cause such profound hypotension in this acute setting without significant underlying cardiac dysfunction. *Left ventricular failure* - **Left ventricular failure** would typically present with **pulmonary congestion** (e.g., crackles on auscultation), which is absent in this patient with clear lung sounds. - While heart failure can lead to hypotension, the patient's initial improvement with fluids and then hypotension *after* nitroglycerin points away from primary left ventricular failure as the cause of this specific vital sign change. *Fluid overload* - The patient's initial improvement with a fluid bolus and the presence of **JVD** suggest **hypovolemia** or **right ventricular dysfunction**, where cardiac output is preload-dependent. - **Fluid overload** itself would typically cause a *rise* in blood pressure (unless in cardiogenic shock), not a drop to 80/65 mmHg after therapeutic interventions. *Ventricular free wall rupture* - **Ventricular free wall rupture** is a catastrophic complication of myocardial infarction that typically presents with **sudden cardiogenic shock**, **cardiac tamponade**, and rapid clinical deterioration. - While possible in an MI setting, the patient's temporary improvement with fluids and subsequent hypotension after nitroglycerin make a free wall rupture less likely to be the *best* explanation for the specific vital sign changes observed.

Question 563: A 34-year-old woman presents to the physician because of fever and sore throat for 2 days. She also reports generalized body pain and fatigue over this period. She was diagnosed with Graves’ disease 6 months ago. Because of arthralgias and rash due to methimazole 3 months ago, her physician switched methimazole to PTU. She appears ill. The vital signs include: temperature 38.4℃ (101.1℉), pulse 88/min, respiratory rate 12/min, and blood pressure 120/80 mm Hg. A 1 × 1 cm ulcer is seen on the side of the tongue and is painful with surrounding erythema. Examination of the neck, lungs, heart, and abdomen shows no abnormalities. She had normal liver aminotransferases last week. Which of the following is the most important diagnostic study at this time?

• A. No further testing is indicated
• B. Complete blood count with differential (Correct Answer)
• C. Erythrocyte sedimentation rate
• D. Thyroid-stimulating hormone
• E. Alanine aminotransferase

Explanation: ***Complete blood count with differential*** - The patient's history of **Grave's disease** managed with **propylthiouracil (PTU)**, combined with symptoms of fever, sore throat, and oral ulcer, points to a high suspicion for **agranulocytosis**. - A **CBC with differential** is critical to assess the **neutrophil count**, which would be severely low in agranulocytosis. *No further testing is indicated* - This statement is incorrect because the patient's symptoms (fever, sore throat, oral ulcer) in the context of PTU use are highly concerning for **adverse drug reactions**, particularly **agranulocytosis**, which requires immediate investigation. - Delaying testing could lead to severe, potentially life-threatening complications due to **neutropenia** and increased susceptibility to infection. *Erythrocyte sedimentation rate* - While an **ESR** would likely be elevated due to the inflammatory response from fever and infection, it is a **non-specific marker** of inflammation. - It would not provide the crucial information about the **neutrophil count** needed to diagnose or rule out agranulocytosis. *Thyroid-stimulating hormone* - The patient's **Graves' disease** is already diagnosed, and she is undergoing treatment. Her current symptoms are acute and unlikely to be directly related to fluctuations in **TSH levels**. - A **TSH test** would not help diagnose the acute febrile illness or potential adverse drug reaction she is experiencing. *Alanine aminotransferase* - Although **PTU** can cause **hepatotoxicity**, the patient's **ALT** levels were normal last week, and her primary symptoms (fever, sore throat, oral ulcer) are not typical for acute liver injury. - While liver function might be monitored periodically in patients on PTU, it is not the most immediate or relevant diagnostic study for her current acute presentation.

Question 564: An 11-year-old girl is brought to the emergency department after she fell during a dance class. She was unable to stand after the accident and has a painful and swollen knee. On presentation she says that she has had 2 previous swollen joints as well as profuse bleeding after minor cuts. Based on her presentation, a panel of bleeding tests is obtained with the following results: Bleeding time: 11 minutes Prothrombin time: 12 seconds Partial thromboplastin time: 52 seconds Which of the following treatments would be most effective in treating this patient's condition?

• A. Vitamin K
• B. Factor VIII repletion
• C. Factor VII repletion
• D. Desmopressin (Correct Answer)
• E. Platelet infusion

Explanation: ***Desmopressin*** - The patient's history of **easy bruising and bleeding**, along with a **prolonged bleeding time** and **normal PT/prolonged PTT**, is highly suggestive of **von Willebrand disease (vWD)**, specifically type 1 given the bleeding time. - **Desmopressin (DDAVP)** is the treatment of choice for vWD, as it stimulates the release of **endogenous von Willebrand factor (vWF)** and factor VIII from endothelial cells, improving both primary hemostasis and the intrinsic coagulation pathway. *Vitamin K* - **Vitamin K** is essential for the synthesis of functioning **coagulation factors II, VII, IX, and X**, as well as proteins C and S. - This patient's **normal prothrombin time (PT)** suggests that the extrinsic and common pathways, which are dependent on adequate levels of vitamin K-dependent factors, are functioning adequately. *Factor VIII repletion* - Isolated **Factor VIII deficiency** (hemophilia A) would present with a **prolonged PTT** and **normal bleeding time**, as primary hemostasis (platelet plug formation) would be unaffected. - In this patient, the **prolonged bleeding time** indicates a primary hemostasis defect, which is not directly corrected by Factor VIII repletion alone. *Factor VII repletion* - **Factor VII deficiency** primarily affects the **extrinsic coagulation pathway**, which would result in a **prolonged prothrombin time (PT)**. - This patient has a **normal PT**, ruling out Factor VII deficiency as the primary cause of her bleeding disorder. *Platelet infusion* - A **prolonged bleeding time** can indicate a **quantitative (thrombocytopenia)** or **qualitative (platelet dysfunction)** defect in platelets. - While platelet dysfunction is characteristic of vWD due to impaired platelet adhesion, **platelet infusions are generally not indicated for vWD** unless other therapies fail or in severe, life-threatening bleeding with very low vWF levels, as the issue is typically not a lack of platelets themselves but rather a lack of functional vWF to mediate their adhesion.

Question 565: A 33-year-old man presents to the emergency department with agitation and combativeness. The paramedics who brought him in say that he was demonstrating violent, reckless behavior and was running into oncoming traffic. Chemical sedation is required to evaluate the patient. Physical examination reveals horizontal and vertical nystagmus, tachycardia, and profuse diaphoresis. Which of the following is the most likely causative agent in this patient?

• A. Cocaine
• B. Lysergic acid diethylamide (LSD)
• C. Gamma-hydroxybutyric acid (GHB)
• D. Phencyclidine (PCP) (Correct Answer)
• E. Cannabis

Explanation: ***Phencyclidine (PCP)*** - The combination of **agitation, combativeness, reckless behavior, nystagmus (both horizontal and vertical), tachycardia, and diaphoresis** is highly characteristic of PCP intoxication. - PCP is known to cause **dissociative anesthetic effects** leading to profound behavioral disturbances, psychotic symptoms, and a distinctive pattern of nystagmus. *Cocaine* - Cocaine intoxication presents with **agitation, tachycardia, and diaphoresis**, but typically does not cause **nystagmus**, especially not vertical nystagmus. - While it can cause psychosis and paranoia, the **dissociative and anesthetic features** seen with PCP are absent. *Lysergic acid diethylamide (LSD)* - LSD primarily causes **hallucinations, perceptual distortions, and altered thought processes**, without the prominent **psychomotor agitation, combativeness, and nystagmus** seen in this patient. - While it can cause some autonomic effects, the clinical picture is not consistent with an LSD "bad trip." *Gamma-hydroxybutyric acid (GHB)* - GHB is typically a **CNS depressant** that can cause sedation, coma, bradycardia, and respiratory depression, particularly at higher doses. - It does not cause the **agitation, combativeness, nystagmus, and sympathetic overactivity** described in the patient. *Cannabis* - Cannabis intoxication typically presents with **euphoria, relaxation, altered perception of time, and conjunctival injection**, with occasional mild anxiety or paranoia. - It does not cause the severe **agitation, combativeness, profound nystagmus, and sympathetic activation** observed in this patient.

Question 566: A 46-year-old male with a history of recurrent deep venous thromboses on warfarin presents to his hematologist for a follow-up visit. He reports that he feels well and has no complaints. His INR at his last visit was 2.5 while his current INR is 4.0. His past medical history is also notable for recent diagnoses of hypertension, hyperlipidemia, and gastroesophageal reflux disease. He also has severe seasonal allergies. He reports that since his last visit, he started multiple new medications at the recommendation of his primary care physician. Which of the following medications was this patient likely started on?

• A. Cetirizine
• B. Hydrochlorothiazide
• C. Omeprazole (Correct Answer)
• D. Lisinopril
• E. Atorvastatin

Explanation: ***Omeprazole*** - **Omeprazole** is a **proton pump inhibitor (PPI)** commonly prescribed for gastroesophageal reflux disease (GERD). - PPIs like omeprazole are known to **inhibit CYP2C19**, an enzyme responsible for metabolizing **warfarin**, leading to increased warfarin levels and a higher **INR**. *Cetirizine* - **Cetirizine** is an antihistamine used for allergies, and it generally has a **negligible interaction** with warfarin. - While it can cause some sedation, it does not significantly alter **warfarin metabolism** or INR. *Hydrochlorothiazide* - **Hydrochlorothiazide** is a diuretic used for hypertension, and its interaction with warfarin is typically **minimal** or can sometimes *decrease* INR due to fluid loss concentrating clotting factors. - It would not explain the observed **increase in INR** from 2.5 to 4.0. *Lisinopril* - **Lisinopril** is an ACE inhibitor used for hypertension and generally has **no significant interaction** with warfarin. - It does not inhibit or induce the **cytochrome P450 enzymes** involved in warfarin metabolism. *Atorvastatin* - **Atorvastatin** is a statin used for hyperlipidemia, and while some statins can slightly affect INR, **atorvastatin's effect is generally minor** and unpredictable, not typically causing such a significant jump. - Its metabolic pathway does not strongly inhibit the **CYP enzymes** critical for warfarin breakdown.

Question 567: A 35-year-old woman presents to her primary care physician for recurrent deep venous thrombosis (DVT) of her left lower extremity. She is a vegetarian and often struggles to maintain an adequate intake of non-animal based protein. She currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and currently denies any illicit drug use, although she endorses a history of heroin use (injection). Her past medical history is significant for 4 prior admissions for lower extremity swelling and pain that resulted in diagnoses of deep venous thrombosis. Her vital signs include: temperature, 36.7°C (98.0°F); blood pressure, 126/74 mm Hg; heart rate, 87/min; and respiratory rate, 16/min. On physical examination, her pulses are bounding, the patient's complexion is pale, breath sounds are clear, and heart sounds are normal. The spleen is mildly enlarged. She is admitted for DVT treatment and a full hypercoagulability workup. Which of the following is the best initial management for this patient?

• A. Begin heparin
• B. Begin warfarin, target INR 2.5–3.5
• C. Consult IR for IVC filter placement
• D. Begin heparin and warfarin (Correct Answer)
• E. Begin warfarin, target INR 2.0–3.0

Explanation: ***Begin heparin and warfarin*** - For **acute DVT**, immediate anticoagulation with **heparin** (or another direct thrombin inhibitor/factor Xa inhibitor) is crucial to prevent clot propagation and pulmonary embolism. - **Warfarin** is started concurrently, as it has a slower onset of action; heparin provides protection until warfarin reaches a therapeutic INR. *Begin heparin* - While **heparin** is the correct initial therapy for acute DVT, it is insufficient on its own for long-term management due to its short half-life and need for continuous infusion (unfractionated) or daily injections (low molecular weight). - A long-term oral anticoagulant like warfarin or a direct oral anticoagulant (DOAC) is necessary for extended prophylaxis, especially in a patient with recurrent DVT. *Begin warfarin, target INR 2.5–3.5* - **Warfarin** is appropriate for long-term anticoagulation, but it has a delayed onset of action and requires several days to reach therapeutic levels, during which time the patient would be unprotected from clot extension or embolization. - The initial target INR for most VTE is 2.0-3.0, though for recurrent events or certain conditions, a higher range might be considered later, but 2.5-3.5 is not the standard initial target. *Consult IR for IVC filter placement* - **IVC filters** are typically reserved for patients with an acute DVT who have a **contraindication to anticoagulation** or who experience recurrent PE despite adequate anticoagulation. - There is no mention of contraindications to anticoagulation in this patient, and filters are not a primary treatment for acute DVT but rather a preventative measure against pulmonary embolism in specific high-risk scenarios. *Begin warfarin, target INR 2.0–3.0* - While **warfarin** at an INR target of 2.0-3.0 is a standard long-term therapy for DVT, beginning it alone is inappropriate for acute DVT due to its **delayed therapeutic effect**. - Without concurrent rapid-acting anticoagulation (like heparin), the patient remains at high risk for complications while awaiting warfarin's full effect.

Question 568: A 67-year-old man presents to his physician with increased thirst and polyuria for the past 4 months. Patient also notes a decrease in his vision for the past 6 months and tingling in his feet. The medical history is significant for a chronic pyelonephritis and stage 2 chronic kidney disease. The current medications include losartan and atorvastatin. He reports a daily alcohol intake of 3 glasses of whiskey. The blood pressure is 140/90 mm Hg and the heart rate is 63/min. The BMI is 35.4 kg/m2. On physical examination, there is 2+ pitting edema of the lower legs and face. The pulmonary, cardiac, and abdominal examinations are within normal limits. There is no costovertebral angle tenderness noted. Ophthalmoscopy shows numerous microaneurysms and retinal hemorrhages concentrated in the fundus. The neurological examination reveals a symmetric decrease in vibration and 2 point discrimination in the patient’s feet and legs extending up to the lower third of the calves. The ankle-deep tendon reflexes are decreased bilaterally. The laboratory test results are as follows: Serum glucose (fasting) 140 mg/dL HbA1c 8.5% BUN 27 mg/dL Serum creatinine 1.3 mg/dL eGFR 55 mL/min The patient is prescribed the first-line drug recommended for his condition. Which of the following side effect is associated with this drug?

• A. Lactic acidosis (Correct Answer)
• B. Infections
• C. Hypoglycemia
• D. Iron deficiency anemia
• E. Hyperkalemia

Explanation: ***Lactic acidosis*** - The patient presents with classic **Type 2 Diabetes Mellitus** (polyuria, polydipsia, HbA1c 8.5%, fasting glucose 140 mg/dL, diabetic retinopathy, peripheral neuropathy). - **Metformin** is the first-line medication for Type 2 Diabetes according to all major guidelines (ADA, AACE). - While **lactic acidosis** is a rare side effect of metformin, it is the most **serious** adverse effect and the answer to this question. - This patient has multiple risk factors for lactic acidosis: **moderate renal impairment** (eGFR 55 mL/min), **chronic alcohol use** (3 glasses whiskey daily), and advanced age. - Note: Current guidelines allow metformin use at eGFR ≥30 mL/min with dose adjustment, so metformin is not contraindicated in this patient but requires careful monitoring. - The most common side effects of metformin are GI-related (diarrhea, nausea), but lactic acidosis is the most clinically significant. *Infections* - Increased risk of **genitourinary infections** is associated with **SGLT2 inhibitors** (canagliflozin, empagliflozin, dapagliflozin), not metformin. - While the patient has a history of chronic pyelonephritis, this is unrelated to metformin therapy. *Hypoglycemia* - **Metformin** decreases hepatic glucose production and improves insulin sensitivity without stimulating insulin secretion. - Metformin monotherapy **rarely causes hypoglycemia**, which is more common with sulfonylureas (glyburide, glipizide) or insulin. *Iron deficiency anemia* - Iron deficiency anemia is **not** a recognized side effect of metformin. - Note: Metformin is associated with **Vitamin B12 deficiency** (due to malabsorption) leading to megaloblastic anemia, but not iron deficiency anemia. *Hyperkalemia* - Hyperkalemia is **not** a side effect of metformin. - This patient's losartan (ARB) and chronic kidney disease could cause hyperkalemia, but this is unrelated to metformin therapy.

Question 569: A 50-year-old woman comes to the physician because of palpitations and irritability. Over the past 4 months, she has had several episodes of heart racing and skipping beats that lasted between 30 seconds and several hours. She has also been arguing with her husband more, often about the temperature being too warm. The patient has also lost 8.8-kg (19.4-lb) over the past 4 months, despite being less strict with her diet. She has mild asthma treated with inhaled bronchodilators. Her pulse is 102/min and blood pressure is 148/98 mm Hg. On physical examination, the skin is warm and moist. A mass is palpated in the anterior neck area. On laboratory studies, thyroid stimulating hormone is undetectable and there are antibodies against the thyrotropin-receptor. Thyroid scintigraphy shows diffusely increased iodine uptake. Two weeks later, a single oral dose of radioactive iodine is administered. This patient will most likely require which of the following in the long-term?

• A. Propranolol therapy
• B. Near-total thyroidectomy
• C. L-thyroxine therapy (Correct Answer)
• D. Methimazole therapy
• E. Estrogen replacement therapy

Explanation: * ***L-thyroxine therapy*** * Radioactive iodine ablation for **Graves' disease** often leads to **permanent hypothyroidism**, necessitating **lifelong thyroid hormone replacement** with levothyroxine. * The patient presents with classic **hyperthyroidism** symptoms (palpitations, irritability, weight loss, heat intolerance, warm/moist skin, goiter, undetectable TSH, positive **TSH receptor antibodies**, diffuse uptake on scintigraphy), treated with radioactive iodine. * *Propranolol therapy* * Propranolol is a **beta-blocker** used for symptomatic relief of hyperthyroidism, particularly palpitations and tremors. * It does **not treat the underlying cause** of hyperthyroidism or subsequent hypothyroidism, and therefore is not a long-term solution after successful radioactive iodine therapy. * *Near-total thyroidectomy* * A near-total thyroidectomy is a surgical option for hyperthyroidism, especially in cases of very large goiters, contraindications to radioactive iodine, or malignancy. * While it also often leads to **hypothyroidism** requiring long-term L-thyroxine, it was **not the chosen treatment modality** in this scenario (radioactive iodine was administered). * *Methimazole therapy* * Methimazole is an **antithyroid drug** used to decrease thyroid hormone synthesis in hyperthyroidism. * It is used as a **primary treatment for hyperthyroidism** or as preparation for definitive therapy like radioactive iodine or surgery; it is not a long-term treatment after successful radioactive iodine ablation has induced hypothyroidism. * *Estrogen replacement therapy* * Estrogen replacement therapy is used for symptoms of **menopause** or to prevent osteoporosis, but it has no direct role in the management of thyroid disorders. * The patient's symptoms are clearly indicative of a **thyroid pathology**, not primarily menopausal symptoms.

Question 570: A 22-year-old man is brought to the emergency department by his roommate 20 minutes after being discovered unconscious at home. On arrival, he is unresponsive to painful stimuli. His pulse is 65/min, respirations are 8/min, and blood pressure is 110/70 mm Hg. Pulse oximetry shows an oxygen saturation of 75%. Despite appropriate lifesaving measures, he dies. The physician suspects that he overdosed. If the suspicion is correct, statistically, the most likely cause of death is overdose with which of the following groups of drugs?

• A. Benzodiazepines
• B. Opioid analgesics (Correct Answer)
• C. Acetaminophen
• D. Antidepressants
• E. Amphetamines

Explanation: ***Opioid analgesics*** - The patient's presentation with **unresponsiveness**, **respiratory depression** (respirations 8/min, SpO2 75%), and **bradycardia** is highly characteristic of severe opioid overdose. - Opioids suppress the **respiratory drive** through their action on mu-opioid receptors in the brainstem, leading to hypoventilation, hypoxemia, and ultimately death if untreated. - **Statistically**, opioids are the leading cause of fatal drug overdoses in the United States. *Benzodiazepines* - While benzodiazepine overdose can cause significant **CNS depression** and unresponsiveness, it is less likely to cause such profound and rapid respiratory depression as the sole agent, particularly with a relatively preserved blood pressure. - Benzodiazepines primarily enhance the effect of **GABA**, leading to sedation and anxiolysis, but typically have a wider therapeutic index for respiratory depression compared to opioids. *Acetaminophen* - Acetaminophen overdose primarily causes **hepatotoxicity** (liver damage), which develops over 24-72 hours, not immediate death from respiratory depression. - Acute overdose symptoms may initially be mild or absent, with liver failure manifesting hours to days later, which does not fit the rapid demise in this case. *Antidepressants* - Overdoses with antidepressants, especially **tricyclic antidepressants (TCAs)**, can cause cardiac arrhythmias, seizures, and CNS depression. - However, the primary cause of death is typically from **cardiac toxicity** or intractable seizures, not the profound respiratory depression seen here. *Amphetamines* - Amphetamine overdose is characterized by **CNS stimulation**, including agitation, hyperthermia, tachycardia, hypertension, and seizures, with respiratory failure often secondary to status epilepticus or cardiovascular collapse. - This presentation is the opposite of the patient's severe CNS and respiratory depression.

Question 571: A 35-year-old male patient is brought into the emergency department by emergency medical services. The patient has a history of schizophrenia and is on medication per his mother. His mother also states that the dose of his medication was recently increased, though she is not sure of the specific medication he takes. His vitals are HR 110, BP 170/100, T 102.5, RR 22. On exam, he cannot respond to questions and has rigidity. His head is turned to the right and remains in that position during the exam. Labs are significant for a WBC count of 14,000 cells/mcL, with a creatine kinase (CK) level of 3,000 mcg/L. What is the best treatment for this patient?

• A. Valproate
• B. Morphine
• C. Dantrolene (Correct Answer)
• D. Diazepam
• E. Lamotrigine

Explanation: ***Dantrolene*** - This patient presents with symptoms highly suggestive of **neuroleptic malignant syndrome (NMS)**, including a history of schizophrenia, recent medication increase, fever, rigidity, autonomic instability (tachycardia, hypertension), elevated WBC, and elevated CK. - **Dantrolene** is a **direct-acting skeletal muscle relaxant** that reduces muscle rigidity and hyperthermia by inhibiting calcium release from the sarcoplasmic reticulum. - In **severe NMS** with marked hyperthermia (T 102.5°F), significant muscle rigidity, and elevated CK (indicating rhabdomyolysis risk), Dantrolene is the most appropriate pharmacologic intervention to directly address the life-threatening muscle rigidity and prevent further complications. *Valproate* - **Valproate** is an **anticonvulsant** and **mood stabilizer** used for seizures, bipolar disorder, and migraine prevention. - It does not directly address the pathophysiology of NMS, which involves central dopamine receptor blockade and muscle rigidity. *Morphine* - **Morphine** is an **opioid analgesic** primarily used for pain management. - It would not alleviate the underlying muscle rigidity, hyperthermia, or autonomic dysfunction associated with NMS and could potentially worsen respiratory depression. *Diazepam* - **Diazepam** is a **benzodiazepine** used for anxiety, seizures, and muscle spasms, and can be helpful for agitation or mild rigidity. - While it might provide some symptomatic relief and is used as adjunctive therapy in NMS, it is not the primary treatment for **severe NMS** with this degree of hyperthermia, marked rigidity, and elevated CK, and does not directly address the underlying muscle damage and rhabdomyolysis risk as effectively as Dantrolene. *Lamotrigine* - **Lamotrigine** is an **anticonvulsant** used for seizures and bipolar disorder, known for its risk of severe skin reactions. - It has no role in the treatment of NMS and would not impact the patient's severe symptoms.

Question 572: A 38-year-old man presents with a 1-year history of resting tremor and clumsiness in his right hand. He says his symptoms are progressively worsening and are starting to interfere with his work. He has no significant past medical history and is not currently taking any medications. The patient denies any smoking history, alcohol, or recreational drug use. Family history is significant for his grandfather, who had a tremor, and his father, who passed away at a young age. Neither his brother nor his sister have tremors. Vital signs include: pulse 70/min, respiratory rate 15/min, blood pressure 124/70 mm Hg, and temperature 36.7°C (98.1°F). Physical examination reveals decreased facial expression, hypophonia, resting tremor in the right hand, rigidity in the upper limbs, and normal deep tendon reflexes. No abnormalities of posture are seen and gait is normal except for decreased arm swing on the right. The remainder of the exam is unremarkable. Which of the following medications would be most effective in treating this patient's movement problems?

• A. Bromocriptine
• B. Selegiline
• C. Benztropine
• D. Levodopa/carbidopa (Correct Answer)
• E. Entacapone

Explanation: ***Levodopa/carbidopa*** - The patient's symptoms, including **resting tremor**, **rigidity**, **bradykinesia** (decreased facial expression, hypophonia, decreased arm swing), and progressive worsening, are classic for **Parkinson's disease**. - **Levodopa/carbidopa** is the **most effective treatment** for motor symptoms in Parkinson's disease, providing significant relief by replenishing dopamine levels in the brain. - While some clinicians may delay levodopa in younger patients (<65 years) to postpone long-term complications like dyskinesias, it remains the **most effective option** for symptom control when treatment is needed. *Bromocriptine* - This is a **dopamine agonist** that can be used for Parkinson's disease and may be considered as initial therapy in younger patients to delay levodopa exposure. - However, it is generally **less effective than levodopa/carbidopa** for motor symptom control and often causes more side effects, including impulse control disorders, hallucinations, and peripheral edema. - The question asks for the **most effective** medication, which is levodopa/carbidopa. *Selegiline* - **Selegiline** is a **MAO-B inhibitor** that helps prevent the breakdown of dopamine, offering mild symptomatic benefit in early Parkinson's disease or as an adjunct therapy. - It is not as potent as levodopa/carbidopa in addressing significant motor symptoms and would likely be insufficient for this patient's functionally impairing symptoms. *Benztropine* - **Benztropine** is an **anticholinergic medication** primarily used to treat tremors and dystonia, often in younger patients or for drug-induced parkinsonism. - It is less effective for **bradykinesia** and **rigidity** and carries a higher risk of side effects like cognitive impairment, dry mouth, constipation, and urinary retention. *Entacapone* - **Entacapone** is a **COMT inhibitor** that extends the half-life of levodopa by preventing its peripheral breakdown. - It is used only as an **adjunct therapy to levodopa/carbidopa** to improve its efficacy and reduce "wearing-off" symptoms, not as monotherapy for Parkinson's disease.

Question 573: A 42-year-old man is discovered unconscious by local police while patrolling in a park. He is unresponsive to stimulation. Syringes were found scattered around him. His heart rate is 70/min and respiratory rate is 6/min. Physical examination reveals a disheveled man with track marks on both arms. His glasgow coma scale is 8. Pupillary examination reveals miosis. An ambulance is called and a reversing agent is administered. Which of the following is most accurate regarding the reversal agent most likely administered to this patient?

• A. Works on dopamine receptors
• B. Has a short half-life
• C. Can be given per oral
• D. Results in acute withdrawal (Correct Answer)
• E. Is a non-competitive inhibitor

Explanation: ***Results in acute withdrawal*** - The patient's presentation (unconscious, track marks, miosis, bradypnea) is characteristic of **opioid overdose**. The reversal agent, **naloxone**, rapidly displaces opioids from their receptors, leading to an abrupt onset of withdrawal symptoms. - **Acute opioid withdrawal** can manifest with symptoms like nausea, vomiting, diarrhea, muscle cramps, and agitation, as the body suddenly lacks the opioid-induced suppression. - This is the **most clinically significant** characteristic of naloxone in the acute overdose setting, as it explains the immediate physiological response patients experience. *Works on dopamine receptors* - **Naloxone** primarily acts as an **opioid receptor antagonist**, particularly at the mu-opioid receptor. - It does not significantly interact with or exert its primary effects through **dopamine receptors**. *Has a short half-life* - While this statement is **factually true** (naloxone has a half-life of 30-81 minutes), it describes a **pharmacokinetic property** rather than a characteristic of its reversal mechanism. - The question asks about the reversal agent in the context of immediate administration, where the **acute precipitation of withdrawal** is the most defining and immediate clinical consequence. - The short half-life is clinically relevant for monitoring (patients may re-sedate), but it is not the most accurate statement regarding what happens when the reversal agent is administered. *Can be given per oral* - Although **naloxone** can be administered orally, its **bioavailability via the oral route is very low** (less than 3%) due to extensive first-pass metabolism. - For acute overdose reversal, it is typically administered via intravenous, intramuscular, subcutaneous, or intranasal routes for rapid and effective absorption. *Is a non-competitive inhibitor* - **Naloxone** is a **competitive antagonist** of opioid receptors, meaning it competes with opioids for binding sites. - It does not bind to an allosteric site to reduce the opioid's efficiency (non-competitive inhibition); rather, it directly blocks the receptor.

Question 574: A 40-year-old man with alcohol use disorder is brought to the emergency department because of sudden-onset blurry vision, severe upper abdominal pain, and vomiting that started one day after he drank a bottle of paint thinner. Physical examination shows epigastric tenderness without rebound or guarding. Ophthalmologic examination shows a visual acuity of 20/200 bilaterally despite corrective lenses. Arterial blood gas analysis on room air shows: pH 7.21 Sodium 135 mEq/L Chloride 103 mEq/L Bicarbonate 13 mEq/L An antidote with which of the following mechanisms of action is the most appropriate therapy for this patient's condition?

• A. Inhibition of acetyl-CoA synthetase
• B. Inhibition of acetaldehyde dehydrogenase
• C. Activation of acetaldehyde dehydrogenase
• D. Activation of acetyl-CoA synthetase
• E. Inhibition of alcohol dehydrogenase (Correct Answer)

Explanation: ***Inhibition of alcohol dehydrogenase*** - The patient's symptoms (sudden-onset blurry vision, severe abdominal pain, vomiting) and the history of drinking paint thinner (which contains **methanol**) point to **methanol poisoning**. - **Fomepizole** acts by **inhibiting alcohol dehydrogenase**, which is the enzyme responsible for metabolizing methanol into toxic metabolites like **formic acid**, thus preventing further damage. *Inhibition of acetyl-CoA synthetase* - This mechanism is not directly relevant to methanol poisoning treatment. - **Acetyl-CoA synthetase** is involved in fatty acid metabolism, and its inhibition would not counteract the toxic effects of methanol. *Inhibition of acetaldehyde dehydrogenase* - This is the mechanism of action of **disulfiram**, used to treat chronic alcoholism by causing an unpleasant reaction to alcohol consumption. - It would **increase acetaldehyde levels**, which are not the primary toxins in methanol poisoning. *Activation of acetaldehyde dehydrogenase* - While activation of acetaldehyde dehydrogenase would reduce acetaldehyde levels, this is not the therapeutic goal in methanol poisoning. - The primary toxic metabolites in methanol poisoning are **formic acid**, not acetaldehyde. *Activation of acetyl-CoA synthetase* - This mechanism is not involved in the treatment for methanol poisoning. - Activating this enzyme would not prevent the formation of toxic methanol metabolites.

Question 575: A 36-year-old man is brought to the emergency department by a neighbor with signs of altered mental status. He was found 6 hours ago stumbling through his neighbor's bushes and yelling obscenities. The neighbor helped him home, but found him again 1 hour later slumped over on his driveway in a puddle of vomit. He is oriented to self, but not to place or time. His vitals are as follows: temperature, 36.9°C (98.5°F); pulse, 82/min; respirations, 28/min; and blood pressure, 122/80 mm Hg. Cardiopulmonary examination indicates no abnormalities. He is unable to cooperate for a neurological examination. Physical examination reveals muscle spasms involving his arms and jaw. Laboratory studies show: Na+ 140 mEq/L K+ 5.5 mEq/L CI- 101 mEq/L HCO3- 9 mEq/L Urea nitrogen 28 mg/dL Creatinine 2.3 mg/dL Glucose 75 mg/dL Calcium 7.2 mg/dL Osmolality 320 mOsm/kg The calculated serum osmolality is 294 mOsm/kg. The arterial blood gas shows a pH of 7.25 and a lactate level of 3.2 mmol/L. Urine examination shows oxalate crystals and the absence of ketones. What is the most appropriate treatment indicated for this patient experiencing apparent substance toxicity?

• A. Ethanol
• B. Hydroxocobalamin
• C. Fomepizole (Correct Answer)
• D. N-acetyl cysteine
• E. Methylene blue

Explanation: ***Fomepizole*** - **Fomepizole** is indicated for **ethylene glycol** toxicity, which is strongly suggested by the patient's presentation: **high anion gap metabolic acidosis**, increased **osmolal gap**, elevated **creatinine**, and the presence of **oxalate crystals** in the urine. - It acts by **inhibiting alcohol dehydrogenase**, preventing the metabolism of ethylene glycol to toxic metabolites like glycolic acid and oxalic acid. *Ethanol* - **Ethanol** can be used as an antidote for ethylene glycol poisoning, but **fomepizole** is generally preferred due to its more favorable side effect profile and easier dosing. - It works by competitively inhibiting **alcohol dehydrogenase**, similar to fomepizole, but requires careful monitoring and often causes sedation. *Hydroxocobalamin* - **Hydroxocobalamin** is the antidote for **cyanide poisoning**, which typically presents with severe metabolic acidosis, but lacks the characteristic osmolal gap, renal failure, and oxalate crystals seen here. - It functions by binding to cyanide to form **cyanocobalamin**, which can then be safely excreted. *N-acetyl cysteine* - **N-acetyl cysteine (NAC)** is the antidote for **acetaminophen overdose**, which causes liver damage and a different metabolic profile, usually without an osmolal gap or oxalate crystals. - NAC replenishes **glutathione**, which is essential for detoxifying acetaminophen metabolites. *Methylene blue* - **Methylene blue** is used to treat **methemoglobinemia**, a condition typically caused by certain drugs or toxins that leads to impaired oxygen delivery and cyanosis, which is not suggested by the patient's current symptoms or lab results. - It acts as a **reducing agent** to convert methemoglobin back to hemoglobin.

Question 576: A 48-year-old woman presents to her family practitioner complaining of tremulousness of both hands for the past few years that have deteriorated over the past 7 months. She sometimes spills coffee while holding a full cup. She is a receptionist and her symptoms have led to difficulties with typing at work. She denies weight loss, diarrhea, fatigue, blurring of vision, walking difficulties, and heat intolerance. The past medical history is significant for well-controlled bronchial asthma. She does not smoke or use illicit drugs, but she drinks one cup of coffee daily. She drinks alcohol only socially and has noticed a decrease in her tremors afterward. She reports that her father had a head tremor, and her mother had hyperthyroidism. The patient is oriented to person, place, time and situation. On physical examination, the eye movements are normal and there is no nystagmus. She has a prominent rhythmic tremor of both hands that increase when hands are stretched with abducted fingers. The muscle strength, tone, and deep tendon reflexes are normal in all 4 limbs. The sensory examination and gait are normal. The laboratory test results are as follows: Hemoglobin 14.8 g/dL Leukocytes 5,500/mm3 Platelets 385,000/mm3 BUN 18 mg/dL Creatinine 0.9 mg/dL Na+ 143 mmol/L K+ 4.2 mmol/L Which of the following is the most appropriate management for this patient?

• A. Reassurance
• B. Primidone (Correct Answer)
• C. Levodopa/Carbidopa
• D. Clonazepam
• E. Propranolol

Explanation: ***Primidone*** - This patient's symptoms are highly suggestive of **essential tremor**, characterized by **bilateral action tremor** that improves with alcohol and has a family history. - **Primidone**, a **barbiturate derivative**, is a first-line treatment for essential tremor, especially when propranolol is contraindicated or ineffective, as it helps to reduce tremor amplitude. *Reassurance* - While reassurance might be appropriate for benign conditions without significant impact on daily life, this patient's tremors are causing **functional impairment** (spilling coffee, difficulty typing) and have progressive worsening. - A treatable cause has been identified, and therefore, medical management is warranted rather than just reassurance. *Levodopa/Carbidopa* - **Levodopa/carbidopa** is the primary treatment for **Parkinson's disease**, which typically presents with a **resting tremor**, bradykinesia, rigidity, and postural instability. - This patient exhibits an **action tremor**, not a resting tremor, and lacks other parkinsonian features, making levodopa/carbidopa an inappropriate choice for their condition. *Clonazepam* - **Clonazepam**, a benzodiazepine, can be used for various tremor disorders, but it is typically reserved for tremors associated with **anxiety** or as an **adjunct therapy** for essential tremor when other first-line agents fail. - It is not considered a first-line agent for essential tremor and carries risks of dependency and sedation, especially in patients with a history of asthma. *Propranolol* - **Propranolol** is generally considered a **first-line treatment** for essential tremor due to its efficacy in reducing tremor amplitude. - However, the patient has a history of **well-controlled bronchial asthma**, and propranolol, a non-selective beta-blocker, is **relatively contraindicated** in asthma due to the risk of bronchospasm.

Question 577: A 65-year-old male with a history of hypertension presents to his primary care physician complaining of multiple episodes of chest pain, palpitations, and syncope. Episodes have occurred twice daily for the last week, and he is asymptomatic between episodes. Electrocardiogram reveals a narrow-complex supraventricular tachycardia. He is treated with diltiazem. In addition to its effects on cardiac myocytes, on which of the following channels and tissues would diltiazem also block depolarization?

• A. L-type Ca channels in skeletal muscle
• B. T-type Ca channels in bone
• C. P-type Ca channels in Purkinje fibers
• D. N-type Ca channels in the peripheral nervous system
• E. L-type Ca channels in smooth muscle (Correct Answer)

Explanation: ***L-type Ca channels in smooth muscle*** - **Diltiazem** is a **calcium channel blocker** that acts on **L-type calcium channels**, which are extensively found in both cardiac muscle and vascular **smooth muscle**. - By blocking these channels in smooth muscle, diltiazem induces **vasodilation**, contributing to its use in hypertension, as seen in the patient's history. *L-type Ca channels in skeletal muscle* - While skeletal muscle does contain L-type calcium channels (also known as dihydropyridine receptors), their primary role is in **excitation-contraction coupling**, acting as voltage sensors rather than directly regulating calcium influx for contraction. - **Skeletal muscle contraction** is primarily triggered by calcium release from the sarcoplasmic reticulum, not direct calcium influx through L-type channels, making them largely **insensitive to calcium channel blockers** like diltiazem at therapeutic doses. *T-type Ca channels in bone* - **T-type calcium channels** are found in various tissues, including neurons and cardiac pacemaker cells, but they are generally **not the primary target of diltiazem**, which preferentially binds to L-type channels. - Furthermore, **bone tissue** is not known to have a significant physiological role mediated by T-type calcium channels that would be relevant to diltiazem's action or clinical effects. *P-type Ca channels in Purkinje fibers* - **Purkinje fibers** primarily rely on **L-type calcium channels** for phase 2 of their action potential and are sensitive to diltiazem, but **P-type calcium channels** are mainly found in neurons. - P-type calcium channels are involved in **neurotransmitter release** at the presynaptic terminal, and diltiazem does not typically block these channels clinically. *N-type Ca channels in the peripheral nervous system* - **N-type calcium channels** are predominantly located in the **peripheral and central nervous systems**, where they are crucial for **neurotransmitter release** at nerve terminals. - Diltiazem's primary mechanism of action is on **L-type calcium channels**, and it has **minimal to no clinically significant effect** on N-type calcium channels.

Question 578: A 29-year-old woman presents with low mood and tearfulness on most days for the past 4 weeks. She says that she has been struggling to cope with her life and feels that everything that is going wrong is her fault. She also says that there are nights when she cries herself to sleep as the burden of the whole day is too overwhelming for her. In the last 3 weeks, she cannot recall a day when she felt interested in going out and participating in her daily activities. She also says she doesn’t seem to have much energy and feels fatigued all day. She has lost her appetite and feels that she is losing weight. Over the past month, she also reports experiencing frequent and often unbearable migraine headaches. No significant past medical history. The patient has prescribed a drug for her symptoms which is known to be cardiotoxic and may result in ECG changes. Which of the following is the mechanism of action of the drug most likely prescribed to this patient?

• A. Acts as an antagonist at the dopamine and serotonin receptors
• B. Inhibits the uptake of serotonin and norepinephrine at the presynaptic terminal (Correct Answer)
• C. Blocks the reuptake of serotonin, increasing its concentration in the synaptic cleft
• D. Non-selectively inhibits monoamine oxidase A and B
• E. Stimulates the release of norepinephrine and dopamine in the presynaptic terminal

Explanation: ***Inhibits the uptake of serotonin and norepinephrine at the presynaptic terminal*** - The patient's symptoms are severely suggestive of **Major Depressive Disorder (MDD)**, which is often treated with **tricyclic antidepressants (TCAs)** in cases of severe depression or when other agents are ineffective. TCAs work by **inhibiting the reuptake of both serotonin and norepinephrine**. - TCAs are known for their potential **cardiotoxicity**, including **ECG changes** such as QT prolongation, due to their inhibition of fast sodium channels. The patient's severe Migraine headaches are also a specific indication for some TCAs, such as **amitriptyline**. *Acts as an antagonist at the dopamine and serotonin receptors* - Medications that act as antagonists at dopamine and serotonin receptors are typically **antipsychotics**, used to treat conditions like schizophrenia or bipolar disorder, which do not align with the patient's symptoms. - While some antipsychotics can have cardiac side effects, their primary mechanism is not for MDD with this symptom constellation and known cardiotoxicity profile. *Blocks the reuptake of serotonin, increasing its concentration in the synaptic cleft* - This describes the mechanism of **Selective Serotonin Reuptake Inhibitors (SSRIs)**. SSRIs are generally first-line for depression but are less likely to cause the severe cardiotoxicity and ECG changes mentioned. - While effective for depression, SSRIs are not typically associated with being "cardiotoxic and may result in ECG changes" to the same extent as TCAs. *Non-selectively inhibits monoamine oxidase A and B* - This describes the mechanism of **non-selective monoamine oxidase inhibitors (MAOIs)**. While MAOIs are effective antidepressants, they are typically reserved for **refractory depression** due to significant drug and food interactions. - Although MAOIs can have cardiovascular side effects (e.g., hypertensive crisis), their profile of cardiotoxicity is different from what is described, and they are usually not a first-line choice for general severe depression unless other options have failed. *Stimulates the release of norepinephrine and dopamine in the presynaptic terminal* - This mechanism is characteristic of **stimulants** (e.g., amphetamines) or some atypical antidepressants like **bupropion**, which also inhibit reuptake. Stimulants are used for conditions like ADHD and narcolepsy, not primary MDD with these specific features. - While some stimulants can have cardiovascular effects, they are not typically described as cardiotoxic with specific ECG changes in the context of treating severe depression.

Question 579: A 59-year-old man presents to a clinic with exertional chest pain for the past several months. He says the pain is central in his chest and relieved with rest. The physical examination is unremarkable. An electrocardiogram is normal, but an exercise tolerance test revealed ST-segment depression in chest leads V1-V4. He is prescribed nitroglycerin to be taken in the first half of the day. Which of the following statements best describes the reason behind the timing of this medication?

• A. To prevent methemoglobinemia
• B. More effective in patients with angina due to anemia
• C. To avoid nitrate tolerance (Correct Answer)
• D. To prevent collapse
• E. To avoid nitrate headache

Explanation: ***To avoid nitrate tolerance*** - Chronic or continuous exposure to nitrates leads to **nitrate tolerance**, where therapeutic effectiveness diminishes over time. - A **nitrate-free interval** (typically 10-14 hours, such as overnight or during the latter half of the day) allows restoration of nitrate sensitivity and maintains therapeutic efficacy. - This is the primary reason for timing nitrate administration to the first half of the day. *To prevent methemoglobinemia* - **Methemoglobinemia** is a rare, dose-related complication typically seen with nitrate overdose or very high doses, not standard therapeutic use. - The timing of nitroglycerin administration is not designed to prevent this rare adverse effect. *More effective in patients with angina due to anemia* - This statement is **not medically accurate**. Nitroglycerin timing is unrelated to whether angina is caused by anemia or coronary artery disease. - Anemia-related angina is managed by correcting the underlying anemia, and nitrate efficacy does not vary based on anemia status. *To prevent collapse* - While nitroglycerin can cause **hypotension** and potential syncope due to vasodilation, this is an acute effect managed by dose titration and patient education. - The nitrate-free interval strategy addresses **tolerance prevention**, not acute hemodynamic side effects. *To avoid nitrate headache* - **Nitrate-induced headache** is a common acute side effect caused by cerebral vasodilation, typically occurring shortly after administration. - The timing strategy (nitrate-free interval) is designed to prevent tolerance, not to avoid this acute side effect, which usually diminishes with continued use.

Question 580: A 58-year-old male presents to his primary care physician for a check-up. He reports that he visited an urgent care clinic last week for seasonal allergies; he was instructed at that encounter to follow-up with his primary care doctor because his blood pressure measured at that time was 162/88. He denies any bothersome symptoms and reports that he feels well overall. The patient denies any past history of medical problems other than cholecystitis that was surgically treated over 30 years ago. On further probing through review of symptoms, the patient reports that he often feels 'shaky' when performing tasks; he reports that his hands shake whenever he attempts to eat or drink something and also when he writes. Vital signs obtained at the visit are as follows: T 37.2 C, HR 88, BP 154/96, RR 20, SpO2 98%. A second blood pressure reading 10 minutes after the first set of vitals shows a blood pressure of 150/94. Physical examination is overall unremarkable and does not reveal a resting tremor in either hand; however, when the patient is asked to pick up a pen to fill out insurance paperwork, you note a fine shaking in his right hand. Which of the following is the next best step in the management of this patient?

• A. Referral to a neurologist
• B. Instruction to begin a diet and exercise regimen
• C. Initiate levodopa
• D. Start propranolol (Correct Answer)
• E. Prescribe losartan

Explanation: ***Start propranolol*** - This patient presents with an **action tremor** that is worsened with activity, consistent with **essential tremor**. Propranolol, a **beta-blocker**, is a first-line treatment for essential tremor, especially given the patient's concomitant **hypertension**. - The patient's blood pressure readings (154/96 and 150/94 mmHg) indicate **Stage 2 hypertension**, which also needs to be managed. Propranolol effectively treats both the tremor and helps in lowering blood pressure. *Referral to a neurologist* - While a neurologist might be consulted for complex or unclear tremor cases, initiating first-line treatment for a clear case of **essential tremor** with co-occurring **hypertension** is appropriate for a primary care physician. - Referral is usually considered if the tremor is **atypical**, refractory to initial treatment, or if there's suspicion of other neurological conditions. *Instruction to begin a diet and exercise regimen* - **Lifestyle modifications** are important for managing hypertension and overall health, but they specifically do not address the patient's bothersome **essential tremor**. - While beneficial as an adjunct, **diet and exercise** alone are insufficient to manage either the tremor or the blood pressure to target levels in this case. *Initiate levodopa* - **Levodopa** is the primary treatment for **Parkinson's disease**, which typically presents with a **resting tremor**, bradykinesia, rigidity, and postural instability. - This patient's tremor is an **action tremor**, not a resting tremor, making Parkinson's disease less likely and levodopa an inappropriate choice. *Prescribe losartan* - **Losartan** is an **ARB (angiotensin receptor blocker)** used for hypertension, which would effectively treat the patient's elevated blood pressure. - However, losartan would **not address the essential tremor**, and propranolol offers the advantage of treating both conditions simultaneously.

Question 581: A primary care physician who focuses on treating elderly patients is researching recommendations for secondary prevention. She is particularly interested in recommendations regarding aspirin, as she has several patients who ask her if they should take it. Of the following, which patient should be started on lifelong aspirin as monotherapy for secondary prevention of atherosclerotic cardiovascular disease?

• A. An 83-year-old female with a history of a hemorrhagic stroke 1 year ago without residual deficits
• B. A 75-year-old male who had a drug-eluting coronary stent placed 3 days ago
• C. A 67-year-old female who has diabetes mellitus and atrial fibrillation
• D. A 45-year-old female with no health problems
• E. A 63-year-old male with a history of a transient ischemic attack (Correct Answer)

Explanation: **A 63-year-old male with a history of a transient ischemic attack** - A patient with a history of **Transient Ischemic Attack (TIA)** has a high risk of subsequent stroke and should be on **lifelong aspirin monotherapy** for secondary prevention of **atherosclerotic cardiovascular disease (ASCVD)**. - Aspirin helps prevent further thrombotic events by inhibiting platelet aggregation, making it a cornerstone for secondary prevention after TIA or ischemic stroke. *An 83-year-old female with a history of a hemorrhagic stroke 1 year ago without residual deficits* - Aspirin is generally **contraindicated** in patients with a history of **hemorrhagic stroke** due to the increased risk of recurrent bleeding. - In such cases, the risks of aspirin therapy typically **outweigh the benefits** for cardiovascular prevention. *A 75-year-old male who had a drug-eluting coronary stent placed 3 days ago* - A patient with a recently placed **drug-eluting stent (DES)** requires **dual antiplatelet therapy (DAPT)**, typically aspirin plus a P2Y12 inhibitor, for a specific duration (e.g., 6-12 months), not aspirin monotherapy. - Monotherapy with aspirin alone would be **insufficient** to prevent stent thrombosis in the immediate post-stenting period. *A 67-year-old female who has diabetes mellitus and atrial fibrillation* - This patient has two significant risk factors requiring specific management: **diabetes mellitus** for cardiovascular risk and **atrial fibrillation** for stroke risk. - For atrial fibrillation, **anticoagulation with warfarin or a direct oral anticoagulant (DOAC)** is typically indicated, which makes aspirin monotherapy either unnecessary or potentially harmful if used alone. *A 45-year-old female with no health problems* - There is no indication for **aspirin primary prevention** in this patient, especially given the increased risk of bleeding without a clear cardiovascular benefit. - Guidelines currently recommend against routine aspirin use for primary prevention in healthy individuals due to the **unfavorable risk-benefit ratio**.

Question 582: A 34-year-old man comes to the physician because of palpitations, shortness of breath, diarrhea, and abdominal cramps for 2 months. Physical examination shows cutaneous flushing of the face. Auscultation of the chest shows bilateral wheezing. A 24-hour urine collection shows increased 5-hydroxyindoleacetic acid (5-HIAA) concentration. A contrast-enhanced CT scan of the abdomen shows an intestinal tumor with extensive metastasis to the liver. A diagnosis of an inoperable disease is made and the patient is started on treatment with octreotide. Six weeks later, the patient's symptoms have improved except for his abdominal pain and frequent loose stools. The physician suggests enrolling the patient in a trial to test additional treatment with a new drug that has been shown to improve symptoms in other patients with the same condition. The expected beneficial effect of this new drug is most likely caused by inhibition of which of the following?

• A. Histidine decarboxylase
• B. Plasma kallikrein
• C. Vasoactive intestinal peptide
• D. Tryptophan hydroxylase (Correct Answer)
• E. Dopamine β-hydroxylase

Explanation: ***Tryptophan hydroxylase*** - This patient presents with symptoms consistent with **carcinoid syndrome** from an intestinal neuroendocrine tumor with liver metastases. The increased urinary **5-HIAA** confirms serotonin overproduction. - While existing treatment with **octreotide** (a somatostatin analog) controls most symptoms, persistent abdominal pain and diarrhea suggest continued serotonin effects. A new drug targeting **tryptophan hydroxylase** would inhibit the rate-limiting step in serotonin synthesis, thus reducing serotonin levels. *Histidine decarboxylase* - This enzyme converts **histidine to histamine**. While histamine can contribute to flushing in some carcinoid tumors, it is not the primary mediator of the systemic symptoms in this case. - The main issue here is serotonin overproduction, not histamine. *Plasma kallikrein* - **Plasma kallikrein** is involved in the kinin-kallikrein system, which produces **bradykinin**, a potent vasodilator. While bradykinin can cause flushing, it is not primarily responsible for the GI symptoms or serotonin overproduction seen in carcinoid syndrome. - Inhibiting plasma kallikrein would not address the fundamental problem of excess serotonin. *Vasoactive intestinal peptide* - **VIP (Vasoactive Intestinal Peptide)** is a neuroendocrine peptide that can cause watery diarrhea and flushing, often associated with **VIPomas**. - However, the patient's elevated **5-HIAA** strongly points towards serotonin overproduction from a carcinoid tumor, not a VIPoma. *Dopamine β-hydroxylase* - This enzyme converts **dopamine to norepinephrine**. This pathway is relevant to catecholamine synthesis, not serotonin. - This enzyme would be targeted in conditions involving excess catecholamines (e.g., pheochromocytoma), which is not the case here.

Question 583: A 22-year-old woman is brought to the emergency department after being struck by a car while crossing the street. She has major depressive disorder with psychosis. Current medications include sertraline and haloperidol. Vital signs are within normal limits. X-ray of the lower extremity shows a mid-shaft femur fracture. The patient is taken to the operating room for surgical repair of the fracture. As the surgeon begins the internal fixation, the patient shows muscle rigidity and profuse diaphoresis. Her temperature is 39°C (102.2°F), pulse is 130/min, respirations are 24/min, and blood pressure is 146/70 mm Hg. The pupils are equal and reactive to light. The end tidal CO2 is 85 mm Hg. Which of the following is the most appropriate treatment for this patient's condition?

• A. Fat embolectomy
• B. Bromocriptine therapy
• C. Propranolol therapy
• D. Dantrolene therapy (Correct Answer)
• E. Cyproheptadine therapy

Explanation: ***Dantrolene therapy*** - The patient's presentation with **muscle rigidity**, **hyperthermia** (39°C), **tachycardia**, **tachypnea**, **hypertension**, and **markedly elevated end-tidal CO2 (85 mm Hg)** developing acutely **during surgery** is diagnostic of **malignant hyperthermia (MH)**. - MH is a life-threatening hypermetabolic crisis triggered by **volatile anesthetic agents** (e.g., sevoflurane, isoflurane) or **succinylcholine** in genetically susceptible individuals with mutations in the ryanodine receptor (RYR1). - **Dantrolene** is the specific antidote for MH, working by inhibiting calcium release from the sarcoplasmic reticulum, thereby reducing muscle contractility and heat production. - The **extremely elevated end-tidal CO2** reflects the hypermetabolic state and is a key diagnostic feature distinguishing MH from other conditions. *Fat embolectomy* - **Fat embolism syndrome** can occur 24-72 hours after long bone fractures and presents with **respiratory insufficiency**, **neurologic dysfunction** (confusion, altered mental status), and a **petechial rash** (classic triad). - While the patient has a femur fracture, the **acute intraoperative onset**, **muscle rigidity**, and **markedly elevated end-tidal CO2** are not consistent with fat embolism syndrome. *Bromocriptine therapy* - **Bromocriptine**, a dopamine agonist, is used in the treatment of **neuroleptic malignant syndrome (NMS)**, which shares features with MH (rigidity, hyperthermia, autonomic instability). - However, NMS typically develops over **days to weeks** after antipsychotic exposure or dose changes, not acutely during surgery. - The **intraoperative timing** and **extremely elevated end-tidal CO2** point to malignant hyperthermia triggered by anesthetic agents, not NMS. *Propranolol therapy* - **Propranolol**, a non-selective beta-blocker, may help manage **tachycardia** and **hypertension** symptomatically. - However, it does not address the underlying pathophysiology of MH (**uncontrolled calcium release** and **hypermetabolic crisis**) and is not a primary treatment. - Dantrolene is the specific and life-saving therapy for MH. *Cyproheptadine therapy* - **Cyproheptadine**, a serotonin antagonist, is the treatment for **serotonin syndrome**, which can present with hyperthermia, rigidity, and autonomic instability. - However, serotonin syndrome typically features **hyperreflexia** and **clonus** rather than the **lead-pipe rigidity** seen here, and develops after serotonergic drug exposure or interactions. - The **intraoperative timing**, **muscle rigidity**, and **markedly elevated end-tidal CO2** are pathognomonic for **malignant hyperthermia**, not serotonin syndrome.

Question 584: A 58-year-old man presents with an occasional tremor in his left hand. While the tremor disappears when he moves his hand, he finds it increasingly difficult to type and feels his handwriting has gotten much smaller. He finds the tremor is more pronounced when he is stressed out at work. He also complains of a decrease in his sense of smell, mild constipation, difficulty sleeping, and increased urinary frequency – all of which he feels is him ‘just getting older’. No significant past medical history and no current medications. Vital signs are a pulse of 74/min, a respiratory rate of 14/min, a blood pressure of 130/70 mm Hg, and a temperature of 36.7°C (98.0°F). On physical examination, a resting tremor in the left hand is noted with mild rigidity in the upper limbs and mask-like faces. While performing finger-to-nose and rapid alternating movements, he has some difficulty. All his movements are slow. The sensation is intact. Gait is normal except for a decreased arm swing. Which of the following drugs acts directly on the receptors responsible for this patient’s condition?

• A. Benztropine
• B. Selegiline
• C. Bromocriptine (Correct Answer)
• D. Entacapone
• E. Carbidopa

Explanation: ***Bromocriptine*** - This patient's symptoms (resting tremor, bradykinesia, rigidity, micrographia, decreased arm swing, mask-like facies, anosmia, constipation, sleep difficulties) are classic for **Parkinson's disease**. Bromocriptine is a **dopamine agonist** that directly stimulates dopamine receptors, mimicking the action of dopamine in the brain. - Dopamine agonists are often used to treat Parkinson's disease, particularly in early stages or to reduce the "off" periods associated with levodopa therapy. *Benztropine* - Benztropine is an **anticholinergic** medication used to treat Parkinson's disease, primarily for tremor and rigidity. - It acts by blocking muscarinic acetylcholine receptors, thereby restoring the balance between cholinergic and dopaminergic activity, but does not directly act on dopamine receptors. *Selegiline* - Selegiline is a **selective MAO-B inhibitor** that prevents the degradation of dopamine in the brain, thereby increasing its availability. - It does not directly act on dopamine receptors but rather prolongs the action of existing dopamine. *Entacapone* - Entacapone is a **catechol-O-methyltransferase (COMT) inhibitor** that is used as an adjunctive therapy to levodopa/carbidopa. - It works by preventing the peripheral breakdown of levodopa, thus increasing the amount of levodopa that reaches the brain and is converted to dopamine, but it does not directly stimulate dopamine receptors. *Carbidopa* - Carbidopa is a **peripheral DOPA decarboxylase inhibitor** that is always given in combination with levodopa. - It prevents the peripheral conversion of levodopa to dopamine, allowing more levodopa to cross the blood-brain barrier and be converted to dopamine, but it has no direct action on dopamine receptors itself.

Question 585: A 54-year-old woman is diagnosed with locally-advanced invasive ductal carcinoma of the breast. She undergoes surgical resection, radiation therapy, and is now being started on adjunctive chemotherapy with cyclophosphamide and doxorubicin. The patient is scheduled for follow up by her primary care provider. Which of the following tests should be performed regularly to monitor her current treatment regimen?

• A. No regular monitoring indicated
• B. Chest radiograph
• C. Cardiac MRI
• D. ECG
• E. Echocardiography (Correct Answer)

Explanation: ***Echocardiography*** - **Doxorubicin** is an anthracycline chemotherapy agent known for its dose-dependent **cardiotoxicity**, which can lead to **dilated cardiomyopathy** and heart failure. - Regular echocardiography is crucial to monitor **left ventricular ejection fraction (LVEF)** and detect early signs of cardiac dysfunction, allowing for timely intervention or adjustment of treatment. *No regular monitoring indicated* - This is incorrect as **doxorubicin**, a component of the chemotherapy regimen, has significant cardiotoxic effects that require close monitoring to prevent severe cardiac complications. - Neglecting monitoring could lead to irreversible cardiac damage. *Chest radiograph* - A chest radiograph primarily assesses lung fields and cardiac silhouette, but it is not sensitive enough to detect early-stage **doxorubicin-induced myocardial damage** or changes in **LVEF**. - While useful for detecting pulmonary complications or metastases, it is not the primary tool for monitoring cardiotoxicity. *Cardiac MRI* - Cardiac MRI is a highly sensitive and specific imaging modality for assessing cardiac function and structure, but it is typically reserved for cases where echocardiography findings are equivocal or more detailed assessment is needed. - It is not the routine or initial test for monitoring cardiotoxicity due to its higher cost and complexity. *ECG* - An ECG assesses the electrical activity of the heart and can detect arrhythmias or signs of ischemia, but it is generally not sufficient for monitoring **doxorubicin-induced cardiotoxicity**. - While it can show nonspecific changes, it does not directly measure changes in **LVEF** or structural heart damage, which are key indicators of cardiotoxicity.

Question 586: A 62-year-old man comes to the physician for hematemesis and progressive heartburn over the past 5 days. Ten days ago, he was started on a medication to treat a condition that causes hearing difficulties and pain of the lower legs. He has no other history of serious illness. He has smoked 1 pack of cigarettes daily for the past 20 years. Physical examination shows bowing of the tibias. Upper endoscopy shows inflammation of the mucosa and a 1-cm punched-out ulcer in the distal esophagus. Which of the following drugs is the most likely cause of the patient's current condition?

• A. Denosumab
• B. Risedronate (Correct Answer)
• C. Calcium citrate
• D. Acetaminophen
• E. Prednisolone

Explanation: ***Risedronate*** - The patient's history of hearing difficulties, lower leg pain, and bowing of the tibias suggests **Paget's disease of bone**. Bisphosphonates like **risedronate** are a common treatment for Paget's disease. - Bisphosphonates are well-known to cause **esophagitis, esophageal ulcers**, and inflammation of the mucosa, leading to symptoms like **heartburn** and **hematemesis**. *Denosumab* - **Denosumab** is also used to treat Paget's disease but is a **monoclonal antibody** that inhibits osteoclast formation and function. - It works differently from bisphosphonates and is not typically associated with **esophageal erosion** or **ulcers**. *Calcium citrate* - **Calcium citrate** is a calcium supplement often used to prevent or treat **osteoporosis**, not a primary treatment for Paget's disease. - It does not cause **esophageal ulcers** or inflammation. *Acetaminophen* - **Acetaminophen** is an analgesic and antipyretic, not used for Paget's disease, and its primary side effect is **hepatotoxicity** at high doses. - It **does not cause esophageal damage** or ulcers. *Prednisolone* - **Prednisolone** is a corticosteroid that can cause **gastric ulcers** but is not a first-line treatment for Paget's disease. - While it can cause gastrointestinal side effects, it is less directly implicated in **esophageal ulcers** in this context compared to bisphosphonates.

Question 587: A 58-year-old woman with breast cancer presents to her primary care physician for referral to a medical oncologist. She denies any personal history of blood clots in her past. Her past medical history is significant for preeclampsia, hypertension, polycystic ovarian syndrome, and hypercholesterolemia. She currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and she currently denies any illicit drug use, despite a history of cocaine use. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 111/min and irregular, and respiratory rate 17/min. On physical examination, she has a grade 2/6 holosystolic murmur heard best at the left upper sternal border, bilateral bibasilar crackles on the lungs, and a normal abdominal examination. At her follow-up with the oncologist, they subsequently plan to start the patient on a highly emetic chemotherapeutic regimen. Which of the following regimens for the treatment of chemotherapy-induced emesis is most appropriate for patients on the same day of treatment?

• A. Prochlorperazine + dexamethasone + dronabinol
• B. Dexamethasone + 5-HT3 receptor antagonist
• C. Dronabinol + dexamethasone
• D. Aprepitant + dronabinol
• E. Aprepitant + dexamethasone + 5-HT3 receptor antagonist (Correct Answer)

Explanation: ***Aprepitant + dexamethasone + 5-HT3 receptor antagonist*** - This combination is the recommended antiemetic regimen for patients receiving **highly emetogenic chemotherapy** (HEC), providing broad-spectrum coverage against acute and delayed nausea and vomiting. - **Aprepitant** is a neurokinin-1 (NK-1) receptor antagonist, **dexamethasone** is a corticosteroid, and **5-HT3 receptor antagonists** (e.g., ondansetron) block serotonin receptors, targeting multiple pathways involved in chemotherapy-induced nausea and vomiting (CINV). *Prochlorperazine + dexamethasone + dronabinol* - This combination is generally reserved for **breakthrough or refractory nausea and vomiting**, not for initial prophylaxis against HEC. - **Prochlorperazine** is a dopamine antagonist, and **dronabinol** is a cannabinoid, which are less potent as primary prophylactic agents compared to NK-1 and 5-HT3 antagonists for HEC. *Dexamethasone + 5-HT3 receptor antagonist* - While effective for moderately emetogenic chemotherapy, this two-drug regimen is **insufficient for highly emetogenic chemotherapy (HEC)** due to the high risk and severity of CINV. - It lacks the additional antiemetic action of an NK-1 receptor antagonist like aprepitant, which is crucial for HEC. *Dronabinol + dexamethasone* - This combination is not considered a first-line prophylactic regimen for HEC; **dronabinol** is typically used for **breakthrough CINV** or as an appetite stimulant. - It lacks the primary broad-spectrum coverage provided by 5-HT3 receptor antagonists and NK-1 antagonists for preventing acute and delayed emesis from HEC. *Aprepitant + dronabinol* - This combination is **incomplete** for optimal HEC prophylaxis, as it misses the critical component of a **5-HT3 receptor antagonist** and a corticosteroid (dexamethasone). - While aprepitant targets delayed emesis, and dronabinol can help with breakthrough, it's not the guideline-recommended multi-modal approach for strong initial prevention.

Question 588: A 65-year-old woman presents with memory problems for the past few weeks. Patient vividly describes how she forgot where she put her car keys this morning and did not remember to wish her grandson a happy birthday last week. Patient denies any cognitive problems, bowel/bladder incontinence, tremors, gait problems, or focal neurologic signs. Patient mentions she wants to take Ginkgo because her friend told her that it can help improve her brain function and prevent memory loss. Past medical history is significant for an acute cardiac event several years ago. Current medications are aspirin, carvedilol, and captopril. Patient denies any history of smoking, alcohol or recreational drug use. Patient is a widow, lives alone, and is able to perform all activities of daily living (ADLs) easily. No significant family history. Patient is afebrile and vital signs are within normal limits. Physical examination is unremarkable. Which of the following would be the most appropriate response to this patient’s request to take Ginkgo?

• A. "Yes, ginkgo is widely used for improving brain function and memory."
• B. “No, you have Alzheimer's disease and need to start donepezil.”
• C. “No, herbal preparations are unsafe because they are not regulated by the FDA.”
• D. "No, taking ginkgo will increase your risk for bleeding." (Correct Answer)
• E. Yes, ginkgo may not help with your memory, but there is no risk of adverse events so it is safe to take.

Explanation: ***"No, taking ginkgo will increase your risk for bleeding."*** - **Ginkgo biloba** has known antithrombotic effects due to its inhibition of platelet-activating factor, which can increase the risk of **bleeding**, especially when combined with other antithrombotic agents like **aspirin**, which this patient is taking. - Given her history of a cardiac event and current aspirin use, adding ginkgo would significantly raise her risk of hemorrhagic complications. *"Yes, ginkgo is widely used for improving brain function and memory."* - While ginkgo is popularly marketed for cognitive enhancement, there is **insufficient scientific evidence** to support its effectiveness in improving memory or preventing cognitive decline. - Recommending it based solely on popular belief disregards evidence-based medicine and potential patient risks. *"No, you have Alzheimer's disease and need to start donepezil.”* - This is an inappropriate response as a diagnosis of **Alzheimer's disease** cannot be made based solely on the patient's self-reported memory issues; a comprehensive workup is required. - Additionally, immediately prescribing **donepezil** without a confirmed diagnosis and without discussing potential risks or alternatives is premature and goes against diagnostic protocols. *"No, herbal preparations are unsafe because they are not regulated by the FDA."* - While it's true that **herbal preparations** are not regulated by the FDA in the same way as prescription drugs, labeling all such preparations as "unsafe" is an **overgeneralization**. - The primary concern here is not just the lack of FDA regulation, but the specific **pharmacological interaction** of ginkgo with her current medications. *"Yes, ginkgo may not help with your memory, but there is no risk of adverse events so it is safe to take."* - This statement is incorrect because, as explained, ginkgo carries a significant **risk of adverse events**, particularly **increased bleeding risk**, especially in this patient due to her concomitant aspirin use. - It is critical to acknowledge and address potential drug interactions and side effects, rather than dismissing them.

Question 589: A man is brought into the emergency department by police. The patient was found somnolent in the park and did not respond to questioning. The patient's past medical history is unknown, and he is poorly kempt. The patient's personal belongings include prescription medications and illicit substances such as alprazolam, diazepam, marijuana, cocaine, alcohol, acetaminophen, and a baggie containing an unknown powder. His temperature is 97.0°F (36.1°C), blood pressure is 117/58 mmHg, pulse is 80/min, respirations are 9/min, and oxygen saturation is 91% on room air. Physical exam reveals pupils that do not respond to light bilaterally, and a somnolent patient who only withdraws his limbs to pain. Which of the following is the best next step in management?

• A. N-acetylcysteine
• B. Supportive therapy, thiamine, and dextrose
• C. Naloxone (Correct Answer)
• D. Intubation
• E. Flumazenil

Explanation: ***Naloxone*** - The patient exhibits classic signs of **opioid overdose** including **respiratory depression** (bradypnea, SpO2 91%), **miosis** (though noted as non-reactive, pinpoint pupils are common in opioid overdose), and altered mental status (somnolence, withdrawal to pain). - Naloxone is an **opioid antagonist** that can rapidly reverse these effects and is indicated in suspected opioid overdose to improve breathing and consciousness. *N-acetylcysteine* - This is the antidote for **acetaminophen overdose**, which is possible given the presence of acetaminophen among the patient's belongings. - However, the patient's acute symptoms of **severe respiratory and CNS depression** are not typical of acute acetaminophen toxicity and require more immediate intervention. *Supportive therapy, thiamine, and dextrose* - **Supportive therapy** (e.g., airway management) is crucial, and **thiamine and dextrose** are often given empirically to patients with altered mental status to address potential **Wernicke's encephalopathy** or **hypoglycemia**. - While important general measures, these do not specifically target the immediate life-threatening respiratory depression and CNS depression so highly suggestive of opioid overdose. *Intubation* - While the patient has respiratory depression, **intubation** is an invasive procedure and should be considered if naloxone fails to improve respiratory status or if persistent airway compromise exists. - The first step in suspected opioid overdose is typically to administer naloxone, as it may avoid the need for intubation. *Flumazenil* - **Flumazenil** is an antagonist for **benzodiazepine overdose**, and alprazolam and diazepam were found in the patient's possession. - However, flumazenil can precipitate **withdrawal seizures** in chronic benzodiazepine users and is generally avoided in undifferentiated comatose patients, especially when mixed ingestions are suspected.

Question 590: A G1P0 mother gives birth to a male infant at 37 weeks gestation. She received adequate prenatal care and took all her prenatal vitamins. She is otherwise healthy and takes no medications. On the 1 month checkup, examination revealed a machine-like murmur heard at the left sternal border. Which of the following medications would be most appropriate to give the infant to address the murmur?

• A. Prostaglandin E1
• B. Prostaglandin E2
• C. Indomethacin (Correct Answer)
• D. Digoxin
• E. Bosentan

Explanation: ***Indomethacin*** - A **machine-like murmur** heard at the left sternal border in an infant is highly characteristic of a **patent ductus arteriosus (PDA)**. - **Indomethacin** is a **prostaglandin synthesis inhibitor** (NSAID) that promotes closure of a PDA by blocking prostaglandin production, which normally keeps the ductus arteriosus patent. - **Clinical note:** While indomethacin is most effective when given to premature infants in the first 10-14 days of life, it remains the **pharmacological agent** for PDA closure, making it the correct answer among the options provided from a pharmacology perspective. *Prostaglandin E1* - **Prostaglandin E1 (alprostadil)** is used to *maintain* patency of the ductus arteriosus in **ductal-dependent congenital heart lesions** (e.g., transposition of great arteries, severe coarctation, pulmonary atresia). - Administering PGE1 would worsen the PDA by preventing its closure, leading to increased left-to-right shunting and potential heart failure. *Prostaglandin E2* - Similar to PGE1, **prostaglandin E2** acts to *keep the ductus arteriosus open*, which is the opposite of the desired effect for a symptomatic PDA. - PGE2 would exacerbate the infant's condition by preventing closure of the PDA. *Digoxin* - **Digoxin** is a cardiac glycoside that increases myocardial contractility by inhibiting Na⁺/K⁺-ATPase and is used to treat **congestive heart failure** and control ventricular rate in **atrial fibrillation/flutter**. - While digoxin may be used for heart failure secondary to a large PDA, it does **not directly close the PDA** and does not address the underlying structural defect. *Bosentan* - **Bosentan** is an **endothelin receptor antagonist** used in the treatment of **pulmonary arterial hypertension**. - It has no role in PDA closure and does not affect the patency of the ductus arteriosus.

Question 591: A 45-year-old man presents to the physician with limb weakness over the last 24 hours. He is an otherwise healthy man with no significant past medical history. On physical examination, his vital signs are stable. On neurological examination, there is decreased strength in the muscles of all 4 extremities, and the deep tendon reflexes are depressed. A detailed laboratory evaluation shows that he has generalized decreased neuronal excitability due to an electrolyte imbalance. Which of the following electrolyte imbalances is most likely to be present in the man?

• A. Acute hypochloremia
• B. Acute hypernatremia
• C. Acute hyperkalemia
• D. Acute hypercalcemia (Correct Answer)
• E. Acute hypomagnesemia

Explanation: ***Acute hypercalcemia*** - **Hypercalcemia** causes decreased neuronal excitability by stabilizing nerve cell membranes, leading to **muscle weakness** and depressed deep tendon reflexes. - The generalized weakness and hyporeflexia described are classic neurological manifestations of elevated calcium levels. *Acute hypochloremia* - **Hypochloremia** is often associated with gastrointestinal losses and can lead to **metabolic alkalosis** and muscle cramps but not generalized muscle weakness with depressed reflexes. - Its direct effect on neuronal excitability to cause such profound weakness is not typical. *Acute hypernatremia* - **Hypernatremia** primarily causes neurological symptoms due to **cellular dehydration** and cerebral edema, leading to altered mental status, seizures, or coma. - It does not typically present with generalized muscle weakness and depressed deep tendon reflexes due to decreased neuronal excitability in the manner described. *Acute hyperkalemia* - **Hyperkalemia** can cause muscle weakness and paralysis, but it often progresses to **cardiac arrhythmias** and is typically associated with **increased neuronal excitability** initially, before paralyzing effects. - While it can lead to weakness, the generalized decreased excitability described is more characteristic of calcium imbalance. *Acute hypomagnesemia* - **Hypomagnesemia** typically increases neuronal excitability, leading to symptoms like **muscle cramps**, tremors, hyperreflexia, and even seizures. - It does not cause generalized muscle weakness with depressed deep tendon reflexes as a primary manifestation of decreased neuronal excitability.

Question 592: A 50-year-old man is brought to his neurologist by his wife for bizarre behavior. On several occasions over the last several days, he had started to complain about ‘bunnies, tigers, and emus’ in the living room. The patient has a history of multiple sclerosis and was last seen by his primary neurologist 2 weeks ago for complaints of new left upper extremity weakness. On physical exam, his temperature is 37.0°C (98.6°F), the heart rate is 70/min, the blood pressure is 126/78 mm Hg, the respiratory rate is 16/min, and the oxygen saturation is 98% on room air. The exam is disrupted by the patient’s repeated comments about various animals in the exam room. His neurologic exam is unchanged from his neurologist's last documented exam. The basic metabolic panel is as follows: Na+ 138 mEq/L K+ 3.9 mEq/L Cl- 101 mEq/L HCO3- 24 mEq/L BUN 10 mg/dL Cr 0.6 mg/dL Glucose 356 mg/dL Which of the following is the most likely etiology of this patient's presentation?

• A. Medication side effect
• B. Metabolic abnormality (Correct Answer)
• C. Recreational drug intoxication
• D. Progression of neurologic disease
• E. Primary psychiatric illness

Explanation: ***Metabolic abnormality*** - The patient's **blood glucose of 356 mg/dL** indicates significant hyperglycemia, a common cause of acute mental status changes, including **delirium** and **hallucinations**. - This **metabolic derangement** is the most likely driver of his "bizarre behavior" and visual hallucinations of animals, especially given the acuteness of the presentation. *Medication side effect* - While many medications, including those for MS symptoms, can cause mental status changes, there is **no specific medication mentioned** or recent change in regimen to support this as the primary cause. - The **elevated glucose** provides a more direct and evident cause for the observed symptoms compared to an unstated medication side effect. *Recreational drug intoxication* - There is **no information or clinical sign** in the vignette suggesting recreational drug use. - While drug intoxication can cause hallucinations, the presence of **severe hyperglycemia** points to a clear alternative etiology. *Progression of neurologic disease* - Although the patient has MS and new weakness, his **neurologic exam is noted as unchanged** from two weeks prior, and his bizarre behavior is not typical for an MS exacerbation or progression. - MS progression usually presents with **worsening focal neurological deficits** rather than isolated, acute psychiatric symptoms like visual hallucinations without other corresponding neurological changes. *Primary psychiatric illness* - The **acute onset** of symptoms, described as "bizarre behavior" and visual hallucinations, in a patient with no prior psychiatric history, makes a primary psychiatric illness less likely. - The presence of a significant **metabolic abnormality (hyperglycemia)** provides a more plausible organic cause for the symptoms.

Question 593: A 31-year-old woman is brought to the emergency room after an apparent suicide attempt. She is unable to provide a history, but her husband reports that he found her at home severely confused and agitated. She reportedly mentioned swallowing several of her pills but was unable to provide additional details. Her husband reports that she has a history of Crohn disease, major depressive disorder, social anxiety disorder, and prior heroin and alcohol abuse. She has not taken heroin or alcohol for 5 years and attends Alcoholics Anonymous and Narcotics Anonymous regularly. She takes multiple medications but he is unable to recount which medications she takes and they are not in the electronic medical record. Her temperature is 103.9°F (39.9°C), blood pressure is 160/95 mmHg, pulse is 125/min, and respirations are 28/min. On exam, she appears agitated, diaphoretic, and is responding to internal stimuli. She has clonus in her bilateral feet. Pupils are 3 mm and reactive to light. Patellar and Achilles reflexes are 3+ bilaterally. She is given alprazolam for her agitation but she remains severely agitated and confused. Which of the following medications should be given to this patient?

• A. Naloxone
• B. Ammonium chloride
• C. N-acetylcysteine
• D. Flumazenil
• E. Cyproheptadine (Correct Answer)

Explanation: ***Cyproheptadine*** - The patient's presentation with **agitation**, **confusion**, **diaphoresis**, **hyperthermia** (103.9°F), **tachycardia**, **hypertension**, **clonus**, and **hyperreflexia** is highly suggestive of **serotonin syndrome**. - **Cyproheptadine**, a **serotonin antagonist**, is the appropriate treatment for serotonin syndrome, especially when benzodiazepines like alprazolam have failed to control symptoms. *Naloxone* - **Naloxone** is an **opioid antagonist** used to reverse opioid overdose. - While the patient has a history of heroin abuse, her vital signs and neurological examination (e.g., hyperreflexia, clonus) are inconsistent with opioid overdose, which typically presents with **respiratory depression** and **miosis**. *Ammonium chloride* - **Ammonium chloride** is an **acidifying agent** used in some poisonings to promote renal excretion of basic drugs. - It is not indicated for the constellation of symptoms presented and can be dangerous if the specific toxin is unknown or if the patient has an acid-base disturbance. *N-acetylcysteine* - **N-acetylcysteine (NAC)** is the antidote for **acetaminophen overdose**. - There is no clinical evidence in the patient's presentation to suggest acetaminophen toxicity. *Flumazenil* - **Flumazenil** is a **benzodiazepine receptor antagonist** used to reverse the effects of benzodiazepine overdose. - While the patient was given alprazolam, her severe agitation and neurological findings (clonus, hyperreflexia) would not be indicative of benzodiazepine overdose; rather, benzodiazepines are used to *treat* the agitation seen in stimulant toxicity or serotonin syndrome.

Question 594: A 62-year-old man presents to the ED complaining of severe eye pain that started a few hours ago. The patient reports that he fell asleep while watching TV on the couch and woke up with right-sided eye pain and blurry vision. His wife drove him to the emergency room. His wife reports that since they arrived the patient has also been complaining of intense nausea. The patient denies fever, headache, or visual floaters. He has a history of hypertension, hyperlipidemia, type II diabetes mellitus, and osteoarthritis. He takes aspirin, lisinopril, metformin, atorvastatin, and over-the-counter ibuprofen. His temperature is 99°F (37.2°C), blood pressure is 135/82 mmHg, and pulse is 78/min. On physical examination, the right eye is firm with an injected conjunctiva and a mildly cloudy cornea. The pupil is dilated at 6 mm and is non-reactive to light. Ocular eye movements are intact. Vision is 20/200 in the right eye and 20/40 in the left eye. The left eye exam is unremarkable. Which of the following is the most appropriate initial treatment?

• A. Topical epinephrine
• B. Iridotomy
• C. Intravenous acetazolamide (Correct Answer)
• D. Topical prednisolone
• E. Retinal photocoagulation

Explanation: ***Intravenous acetazolamide*** - The patient's signs and symptoms, including **severe eye pain, blurry vision, dilated fixed pupil, firm eye, and injected conjunctiva**, are classic for **acute angle-closure glaucoma (AACG)**. - **Acetazolamide** (carbonic anhydrase inhibitor) reduces aqueous humor production and is a primary treatment to rapidly lower intraocular pressure in AACG. *Topical epinephrine* - **Epinephrine** can cause mydriasis (pupil dilation), which could further narrow the angle and worsen AACG. - While it has some role in open-angle glaucoma, it is generally **contraindicated in AACG**. *Iridotomy* - **Laser peripheral iridotomy** is a definitive treatment for AACG to create an alternate pathway for aqueous humor flow, but it is a **surgical procedure** performed after medical stabilization. - It is not the *initial* medical treatment for acute pressure reduction, but rather a subsequent intervention to prevent recurrence. *Topical prednisolone* - **Topical corticosteroids** like prednisolone are used to treat ocular inflammation but do not directly address the elevated intraocular pressure in AACG. - In some cases, steroids can even **increase intraocular pressure**, making them inappropriate for this acute presentation. *Retinal photocoagulation* - **Retinal photocoagulation** is a laser procedure used to treat retinal conditions such as **diabetic retinopathy** or **retinal tears**. - It is completely unrelated to the pathophysiology and treatment of acute angle-closure glaucoma.

Question 595: A 53-year-old man presents to a physician with repeated episodes of joint pain and fever for the last 3 months. The pain is present in the knee joints and small joints of the hands bilaterally. He recorded his temperature at home which never increased above 37.8°C (100.0°F). The medical history is significant for an acute myocardial infarction 1 year ago, with sustained ventricular tachycardia as a complication, for which he has been taking procainamide. The vital signs are as follows: pulse 88/min, blood pressure 134/88 mm Hg, respiratory rate 13/min, and temperature 37.2°C (99.0°F). On physical examination, he has mild joint swelling. A radiologic evaluation of the involved joints does not suggest osteoarthritis or rheumatoid arthritis. Based on the laboratory evaluation, the physician suspects that the joint pain and fever may be due to the use of procainamide. Which of the following serologic finding is most likely to be present in this patient?

• A. Decreased serum C4 level
• B. Presence of anti-dsDNA antibodies
• C. Presence of anti-histone antibodies (Correct Answer)
• D. Decreased serum C3 level
• E. Presence of anti-Sm antibodies

Explanation: ***Presence of anti-histone antibodies*** - The patient's history of taking **procainamide** along with symptoms of **joint pain** and **low-grade fever** strongly suggests **drug-induced lupus erythematosus (DILE)**. - **Anti-histone antibodies** are present in 95% of patients with DILE and are considered a hallmark of the condition. *Decreased serum C4 level* - **Decreased C4 levels** are more characteristic of **classic systemic lupus erythematosus (SLE)**, particularly in active disease. - In DILE, complement levels (C3 and C4) are typically **normal** or only mildly decreased. *Presence of anti-dsDNA antibodies* - **Anti-dsDNA antibodies** are highly specific for **classic SLE** and are rarely found in DILE. - Their presence would suggest a diagnosis of SLE rather than drug-induced disease. *Decreased serum C3 level* - Similar to decreased C4, **low C3 levels** are indicative of **classic SLE** due to immune complex deposition and complement consumption. - In DILE, complement levels are generally **preserved**. *Presence of anti-Sm antibodies* - **Anti-Smith (Sm) antibodies** are also highly specific for **classic SLE** and are considered a diagnostic criterion. - They are not typically found in patients with DILE.

Question 596: A 62-year-old Nigerian woman arrived 2 days ago to the US to visit her adult children from Nigeria. She is now brought to an urgent care center by her daughter for leg pain. Her right leg has been painful for 24 hours and is now causing her to limp. She denies any fevers, chills, or sweats and does not remember injuring her leg. She tells you she takes medications for hypertension and diabetes and occasionally for exertional chest pain. She has not had any recent chest pain. The right leg is swollen and tender. Flexion of the right ankle causes a worsening of the pain. Doppler ultrasonography reveals a large clot in a deep vein. Which of the following is the most appropriate course of action?

• A. Direct oral anticoagulant (DOAC) therapy (Correct Answer)
• B. Initiation of heparin followed by bridge to warfarin
• C. Initiation of heparin
• D. Initiation of warfarin
• E. Treatment with tissue plasminogen activator

Explanation: ***Direct oral anticoagulant (DOAC) therapy*** - **DOACs are the first-line treatment** for acute DVT in most patients according to current guidelines (ACCP, ASH, ESC 2023-2024). - Options include **rivaroxaban, apixaban, edoxaban, or dabigatran**, which provide rapid anticoagulation without the need for bridging therapy or routine INR monitoring. - This patient has **provoked DVT** (recent long-distance travel from Nigeria), standard cardiovascular risk factors, and no contraindications to DOACs. - DOACs offer **comparable efficacy** to warfarin with **lower risk of major bleeding** and greater convenience for patients. *Initiation of heparin followed by bridge to warfarin* - The **heparin-warfarin bridge** was standard therapy in the past but is now considered **second-line** for most patients. - This approach is now **reserved for specific situations**: severe renal impairment (CrCl <30 mL/min), antiphospholipid syndrome, mechanical heart valves, or when DOACs are contraindicated or unavailable. - The patient has **exertional chest pain** (angina), which is related to coronary artery disease and does **not** constitute a contraindication to DOACs or an indication for warfarin. - The heparin bridge adds complexity, requires hospitalization or close monitoring, and delays transition to oral therapy. *Initiation of heparin* - **Heparin monotherapy** is insufficient for long-term DVT management and is only used as a bridge to oral anticoagulation in specific scenarios. - While it provides immediate anticoagulation, discontinuing heparin without oral anticoagulant coverage leads to high recurrence risk. - Modern practice favors **direct initiation of DOACs**, eliminating the need for parenteral therapy in most cases. *Initiation of warfarin* - **Warfarin monotherapy** at initiation is contraindicated because warfarin has a **delayed onset of action** (5-7 days) due to its mechanism of depleting vitamin K-dependent clotting factors. - Starting warfarin alone creates a paradoxical **prothrombotic state** in the first 24-48 hours (due to rapid depletion of protein C) and leaves the patient unprotected from clot propagation. - Warfarin requires **bridging with heparin** if used, but DOACs are preferred in current practice. *Treatment with tissue plasminogen activator* - **Thrombolytic therapy** (tPA, catheter-directed thrombolysis) is reserved for **life- or limb-threatening DVT** such as phlegmasia cerulea dolens or massive pulmonary embolism with hemodynamic instability. - This patient has **uncomplicated DVT** without signs of limb-threatening ischemia, making anticoagulation the appropriate first-line therapy. - Thrombolysis carries significant **bleeding risk** and is not indicated for routine DVT management.

Question 597: A 58-year-old man comes to the physician because of a sore throat and painful lesions in his mouth for the past few days. Six weeks ago, he underwent cardiac catheterization and stent implantation of the left anterior descending artery for treatment of acute myocardial infarction. Pharmacotherapy with aspirin and ticlopidine was started. His temperature is 38.1°C (100.6°F). Oral examination shows several shallow ulcers on the buccal mucosa. Laboratory studies show: Hematocrit 41.5% Leukocyte count 1,050/mm3 Segmented neutrophils 35% Platelet count 175,000/mm3 Which of the following drugs is most likely responsible for this patient's current condition?

• A. Enoxaparin
• B. Aspirin
• C. Abciximab
• D. Apixaban
• E. Ticlopidine (Correct Answer)

Explanation: **Ticlopidine** * This patient presents with **neutropenia** (leukocyte count 1,050/mm3 with 35% segmented neutrophils) and **oral ulcers**, which signifies a severe adverse drug reaction. * **Ticlopidine** is a P2Y12 inhibitor that carries a known risk of severe adverse effects, including **neutropenia** and **thrombotic thrombocytopenic purpura (TTP).** *Enoxaparin* * Enoxaparin is a **low molecular weight heparin** used for anticoagulation. * It is associated with **heparin-induced thrombocytopenia (HIT)**, but not typically neutropenia or oral ulcers. *Aspirin* * Aspirin is a **COX inhibitor** and an antiplatelet agent. * Common side effects include **gastrointestinal upset** and bleeding, but it does not typically cause neutropenia or oral ulcers. *Abciximab* * Abciximab is a **glycoprotein IIb/IIIa inhibitor** used as an antiplatelet agent. * Its primary adverse effect is **bleeding** and **thrombocytopenia**, but not neutropenia or oral ulcers. *Apixaban* * Apixaban is a **direct oral anticoagulant (DOAC)**, specifically a Factor Xa inhibitor. * It is primarily associated with an increased risk of **bleeding** and does not typically cause neutropenia or oral ulcers.

Question 598: A 46-year-old man comes to the physician because of a 6-week history of fatigue and cramping abdominal pain. He works at a gun range. Examination shows pale conjunctivae and gingival hyperpigmentation. There is weakness when extending the left wrist against resistance. Further evaluation of this patient is most likely to show which of the following?

• A. Beta‑2 microglobulin in urine
• B. Septal thickening on chest x-ray
• C. Basophilic stippling of erythrocytes (Correct Answer)
• D. White bands across the nails
• E. Increased total iron binding capacity

Explanation: ***Basophilic stippling of erythrocytes*** - This patient's symptoms (fatigue, anemic conjunctivae, abdominal pain, gingival hyperpigmentation, wrist drop) and occupational exposure (gun range) are classic signs of **lead poisoning**. - **Basophilic stippling** is a characteristic finding on a peripheral blood smear in lead poisoning, resulting from the aggregation of ribosomal RNA due to impaired heme synthesis. *Beta‑2 microglobulin in urine* - **Beta-2 microglobulinuria** is typically associated with **renal tubular damage** or increased cell turnover (e.g., multiple myeloma), not directly with lead poisoning. - While lead toxicity can affect the kidneys in the long term, this is not the most direct or common initial diagnostic finding for acute or subacute lead poisoning. *Septal thickening on chest x-ray* - **Septal thickening** on a chest x-ray suggests conditions like **pulmonary fibrosis**, **interstitial lung disease**, or cardiac conditions causing fluid overload. - It is not a typical manifestation or diagnostic feature of lead poisoning. *White bands across the nails* - **White bands across the nails**, known as **Mees' lines**, are associated with **arsenic poisoning**, not lead poisoning. - The clinical picture presented strongly points away from arsenic toxicity. *Increased total iron binding capacity* - **Increased total iron binding capacity (TIBC)** is characteristic of **iron deficiency anemia**, as the body attempts to make more transferrin to capture what little iron is available. - In lead poisoning, TIBC is usually normal or decreased, as lead inhibits heme synthesis, leading to anemia but not necessarily iron deficiency.

Question 599: A 30-year-old woman presents to her physician for difficulty breathing. She states that this typically happens to her when she goes outside and improves with rest and staying indoors. Her symptoms are currently worse than usual. The patient has never seen a physician before and has no diagnosed past medical history. Her temperature is 99.5°F (37.5°C), blood pressure is 97/58 mmHg, pulse is 110/min, respirations are 25/min, and oxygen saturation is 88% on room air. Pulmonary function tests demonstrate a decreased inspiratory and expiratory flow rate. Which of the following is the best initial treatment for this patient?

• A. Epinephrine
• B. Albuterol (Correct Answer)
• C. Diphenhydramine
• D. Intubation
• E. Prednisone

Explanation: ***Albuterol*** - The patient presents with **acute respiratory distress** involving bronchoconstriction, indicated by difficulty breathing, low oxygen saturation (88%), and decreased inspiratory and expiratory flow rates, consistent with an **asthma exacerbation**. - **Albuterol**, a short-acting beta-2 agonist (SABA), is the first-line treatment for acute asthma bronchodilation due to its **rapid onset of action**. *Epinephrine* - While epinephrine can cause bronchodilation, its primary use is for severe allergic reactions or **anaphylaxis**, which is not directly indicated here. - Its use in asthma is typically reserved for cases where **anaphylaxis** is suspected to be contributing or in severe, refractory bronchospasm. *Diphenhydramine* - **Diphenhydramine** is an antihistamine used for allergic reactions, but it does not treat **bronchoconstriction** and is not indicated for acute respiratory distress. - It can cause sedation, which could further complicate respiratory management in an acutely breathless patient. *Intubation* - **Intubation** is a last resort management for respiratory failure, when medical therapies have failed to improve oxygenation or ventilation. - Although the patient's oxygen saturation is low, initial medical management should be attempted before considering invasive interventions like intubation. *Prednisone* - **Prednisone** is a corticosteroid used to reduce inflammation in asthma exacerbations, but its onset of action is slow (hours to days). - It is often used in conjunction with bronchodilators for moderate to severe exacerbations but is not the **best initial treatment** for immediate symptom relief.

Question 600: A 63-year-old man presents to his primary care provider with colicky pain radiating to his left groin. The pain has been intermittent for several days. He has also been experiencing occasional burning pain in his hands and feet and frequent headaches. His past medical history is significant for an NSTEMI last year. He is currently taking atorvastatin and low dose aspirin. Today his temperature is 36.8°C (98.2°F), the heart rate is 103/min, the respiratory rate is 15/min, the blood pressure 135/85 mm Hg, and the oxygen saturation is 100% on room air. On physical exam, he appears gaunt and anxious. His heart is tachycardia with a regular rhythm and his lungs are clear to auscultation bilaterally. On abdominal exam he has hepatomegaly. A thorough blood analysis reveals a hemoglobin of 22 mg/dL and a significantly reduced EPO. Renal function and serum electrolytes are within normal limits. A urinalysis is positive for blood. A non-contrast CT shows a large kidney stone obstructing the left ureter. The patient’s pain is managed with acetaminophen and the stone passes with adequate hydration. It is sent to pathology for analysis. Additionally, a bone marrow biopsy is performed which reveals trilineage hematopoiesis and hypercellularity with a JAK2 mutation. Which medication would help prevent future episodes of nephrolithiasis?

• A. Hydroxyurea
• B. Probenecid
• C. Thiazide
• D. Antihistamines
• E. Allopurinol (Correct Answer)

Explanation: ***Allopurinol*** - The patient's presentation, including **hypercellularity** with a **JAK2 mutation**, extremely high hemoglobin (22 mg/dL), and hepatomegaly, is consistent with **polycythemia vera**. This condition leads to increased cell turnover and elevated uric acid levels, predisposing to **uric acid nephrolithiasis**. - **Allopurinol** inhibits xanthine oxidase, reducing the production of uric acid and preventing the formation of uric acid stones, which is crucial in patients with myeloproliferative disorders like polycythemia vera. *Hydroxyurea* - **Hydroxyurea** is a cytoreductive agent used in polycythemia vera to lower blood cell counts, thereby reducing the risk of thrombotic events and controlling symptoms. - While it manages the underlying myeloproliferative disorder, it does not directly prevent **uric acid stone formation** and can sometimes increase uric acid levels during initial cytoreduction due to rapid cell lysis. *Probenecid* - **Probenecid** is a uricosuric agent that increases the excretion of uric acid in the urine. - It is used in patients with **gout** or hyperuricemia who are underexcretors of uric acid, but it can paradoxically increase the risk of uric acid nephrolithiasis due to higher urinary uric acid concentrations. *Thiazide* - **Thiazide diuretics** reduce urinary calcium excretion and are primarily used to prevent **calcium-containing kidney stones**, such as calcium oxalate or calcium phosphate stones. - They are not indicated for the prevention of **uric acid stones**, which are the likely type in this patient given his polycythemia vera. *Antihistamines* - **Antihistamines** block histamine receptors and are primarily used to treat allergic reactions, insomnia, or nausea. - They have no role in the prevention or treatment of **nephrolithiasis** or conditions like polycythemia vera.

Question 601: A 59-year-old woman is referred to a neurologist for a hand tremor. Her symptoms began a few months prior to presentation and has progressively worsened. She noticed she was having difficulty drinking her coffee and writing in her notebook. The patient reports that her father also had a tremor but is unsure what type of tremor it was. She drinks 2-3 glasses of wine per week and only takes a multivitamin. Laboratory studies prior to seeing the neurologist demonstrated a normal basic metabolic panel and thyroid studies. On physical exam, there is a mid-amplitude 8 Hz frequency postural tremor of the right hand. The tremor is notable when the right hand is outstretched to the very end of finger-to-nose testing. Neurologic exam is otherwise normal. Which of the following is the best treatment option for this patient?

• A. Levodopa-carbidopa
• B. Alprazolam
• C. Botulinum toxin injection
• D. Deep brain stimulation
• E. Primidone (Correct Answer)

Explanation: ***Primidone*** - This patient's symptoms are highly suggestive of **essential tremor**, characterized by a **postural or kinetic tremor**, often familial, and affecting daily activities like drinking and writing. **Primidone** is a first-line treatment for essential tremor. - The exam findings of a **mid-amplitude 8 Hz frequency postural tremor** and worsening during action like finger-to-nose testing, along with the absence of other neurological deficits and a normal workup, support this diagnosis. *Levodopa-carbidopa* - This combination therapy is the gold standard for treating **Parkinson's disease**, which is characterized by a **resting tremor**, bradykinesia, rigidity, and postural instability. - The patient's tremor is primarily **postural/kinetic**, not resting, and other parkinsonian symptoms are absent. *Alprazolam* - **Benzodiazepines** like alprazolam can sometimes be used to treat anxiety, which may exacerbate tremors, or for tremors associated with severe anxiety or alcohol withdrawal. - It is generally not considered a primary treatment for essential tremor due to its **sedative side effects** and potential for dependence. *Botulinum toxin injection* - **Botulinum toxin** can be effective for tremors that are focal and severe, especially when other medications have failed or are not tolerated. - It is typically used for specific, localized tremors and is not usually the first-line systemic treatment for generalized essential tremor. *Deep brain stimulation* - **Deep brain stimulation (DBS)** is a surgical option reserved for **severe, medication-refractory essential tremor** or Parkinson's disease. - It is an invasive procedure and is not considered a first-line treatment for a newly diagnosed tremor, especially before trying conservative medical management.

Question 602: A 51-year-old woman with a history of paroxysmal atrial fibrillation comes to the physician for a follow-up visit. She feels well and wants to discuss pausing her only current medication, flecainide. Her pulse is 75/min and regular, blood pressure is 125/75 mm Hg. Physical examination shows no abnormalities. An ECG shows a PR interval of 180 ms, QRS time of 120 ms, and corrected QT interval of 440 ms. Which of the following ECG changes is most likely to be seen on cardiac stress testing in this patient?

• A. Decreased maximal heart rate
• B. Prolonged QRS complex (Correct Answer)
• C. Shortened PR interval
• D. False-positive ST-segment depression
• E. Prolonged QTc interval

Explanation: ***Prolonged QRS complex*** - **Flecainide** is a class Ic antiarrhythmic that **blocks fast sodium channels** in myocardial cells, slowing conduction in the atria, ventricles, and His-Purkinje system. - Its effects are **use-dependent**, meaning the drug binds more effectively to channels that are frequently activated (i.e., at higher heart rates), leading to a **further widening of the QRS complex** during exercise. *Decreased maximal heart rate* - While some class II antiarrhythmics (beta-blockers) can decrease maximal heart rate, **flecainide** primarily affects cardiac conduction and does not significantly impact heart rate response to stress. - The ECG does not suggest sinus node dysfunction that would limit heart rate increase with activity. *Shortened PR interval* - Flecainide typically **prolongs the PR interval** by slowing conduction through the atrioventricular (AV) node. - Exercise would likely exacerbate this effect rather than shorten the PR interval. *False-positive ST-segment depression* - While wide QRS complexes (as may occur with flecainide-induced conduction slowing) can cause abnormal ST-segment morphology, the **most prominent and characteristic effect** of flecainide during stress testing is **progressive QRS widening** due to use-dependent sodium channel blockade. - False-positive ST changes are a nonspecific finding and not the hallmark ECG change expected with flecainide during exercise. *Prolonged QTc interval* - Flecainide is generally known to **not significantly prolong the QT interval**; in some cases, it may even shorten it due to its effect on action potential duration. - Other antiarrhythmics like Class III agents (e.g., amiodarone, sotalol) are more commonly associated with QTc prolongation.

Question 603: A 31-year-old male with bipolar disorder comes to the physician because of erectile dysfunction for the past month. He cannot maintain an erection during intercourse and rarely wakes up with an erection. He says he is happy in his current relationship, but admits to decreased desire for sex and feeling embarrassed about his sexual performance. He sustained a lumbar vertebral injury one year ago following a motor vehicle accident. He takes medication for his bipolar disorder but does not remember the name. Physical examination shows testicular atrophy with otherwise normal genitalia. Which of the following is the most likely cause of this patient's symptoms?

• A. Psychologic stressors
• B. Microvascular disease
• C. Peripheral nerve injury
• D. Peyronie disease
• E. Decreased testosterone levels (Correct Answer)

Explanation: ***Decreased testosterone levels*** - This patient's **testicular atrophy** is a strong indicator of primary testicular failure leading to **hypogonadism** and decreased testosterone. - Decreased testosterone causes **erectile dysfunction**, reduced libido and morning erections, all consistent with the patient's symptoms. - The most likely cause of testicular atrophy in this patient is **medication-induced hypogonadism** from his bipolar disorder treatment—particularly **valproate** (which causes testicular atrophy and suppresses spermatogenesis) or certain **antipsychotic medications**. - Regardless of the underlying etiology of testicular atrophy, the **proximate cause** of his erectile dysfunction is the resulting **decreased testosterone levels**. *Psychologic stressors* - While psychological factors can cause erectile dysfunction, the presence of **testicular atrophy** points to a clear organic cause. - His reported happiness in the relationship also makes primary psychological etiology less likely, though performance anxiety could be secondary. *Microvascular disease* - Microvascular disease, often associated with **diabetes** or **hypertension**, can cause erectile dysfunction due to impaired blood flow. - However, it does not explain the **testicular atrophy** observed in this patient. *Peripheral nerve injury* - A lumbar vertebral injury could potentially cause **neuropathic erectile dysfunction** if nerves innervating the penis were damaged. - This typically does not lead to **testicular atrophy**, making it a less likely primary cause given the physical exam findings. *Peyronie disease* - Peyronie disease involves the formation of **fibrous plaques** in the penile tunica albuginea, leading to penile curvature and painful erections. - It does not cause **testicular atrophy** or decreased libido, and no penile curvature is mentioned.

Question 604: A 23-year-old man comes to the emergency department because of a rash on his neck and back for the past 6 hours. He says that he first noticed some reddening of the skin on his back the previous evening, which turned into a blistering, red rash overnight. He went surfing the previous day and spent 5 hours at the beach. He reports having applied at least 1 oz of water-resistant SPF 30 sunscreen 30 minutes before leaving his home. His vitals are within normal limits. Physical examination shows erythema of the skin over the upper back and dorsum of the neck, with 3 vesicles filled with clear fluid. The affected area is edematous and tender to touch. Which of the following recommendations is most appropriate to prevent a recurrence of this patient's symptoms in the future?

• A. Use waterproof sunscreen
• B. Reapply sunscreen after water exposure (Correct Answer)
• C. Use SPF 50 sunscreen
• D. Apply at least 3 oz of sunscreen
• E. Apply sunscreen directly before getting into water

Explanation: ***Reapply sunscreen after water exposure*** - The patient spent 5 hours at the beach and went surfing, indicating significant **water exposure**. Even **water-resistant sunscreen** eventually loses its effectiveness, especially after prolonged water immersion, necessitating reapplication. - The presence of **blistering and erythema with vesicles** indicates a **second-degree sunburn**, which occurred despite initial sunscreen application, highlighting the need for reapplication after activities involving sweat or water. *Use waterproof sunscreen* - The patient already used **water-resistant sunscreen**, which provides some protection in water, but its effectiveness is not indefinite; "waterproof" implies even longer resistance (*80 minutes* vs. *40 minutes* for water-resistant), but still requires reapplication after certain time or activities. - Emphasizing "waterproof" over "reapplication" does not address the core issue of the sunscreen eventually washing off or degrading with prolonged water exposure and friction. *Use SPF 50 sunscreen* - While a higher **SPF (e.g., 50 vs. 30)** offers slightly more protection, the primary issue here is likely the **duration of protection and water exposure**, not merely the initial SPF factor. - SPF 30 blocks about 97% of UVB rays, while SPF 50 blocks 98%, a marginal difference that does not negate the need for reapplication. *Apply at least 3 oz of sunscreen* - The patient reported applying "at least 1 oz" of SPF 30 sunscreen, which is often considered adequate for a single full-body application for an average adult (the recommended amount is about 1 oz for the entire body). - While more sunscreen can provide better coverage, the problem is most likely related to the **duration of efficacy** and **water exposure**, not the initial quantity applied if it was sufficient. *Apply sunscreen directly before getting into water* - Sunscreen needs time to bind to the skin and become effective. Applying it "directly before" getting into water (as opposed to 15-30 minutes before exposure) can reduce its protective capacity, as it may wash off before it fully penetrates the skin. - The patient applied sunscreen 30 minutes before leaving home, which is the recommended time for optimal absorption and protection. His sunburn indicates an issue with **maintenance of protection**, not initial application timing.

Question 605: A 58-year-old woman presents to the office after receiving a bone mineral density screening test result with a T score of -4.1 and a Z score of -3.8. She is diagnosed with osteoporosis. A review of her medical history reveals that she has taken estrogen-containing oral contraceptive pills from the age of 20 to 30. She suffered from heartburn from the age of 45 and took lansoprazole and ranitidine often for her symptoms. She also was on lithium for 2 years after being diagnosed with bipolar disorder at the age of 54. Last year she was diagnosed with congestive heart failure and was started on low dose hydrochlorothiazide. Which of her medications most likely contributed to the development of her osteoporosis?

• A. Ranitidine
• B. Lansoprazole (Correct Answer)
• C. Hydrochlorothiazide
• D. Lithium
• E. Estrogen

Explanation: ***Lansoprazole*** - **Proton pump inhibitors (PPIs)** like lansoprazole reduce gastric acid production, which can impair the absorption of **calcium** and **magnesium**, leading to a negative impact on bone mineral density with long-term use. - Chronic use of PPIs has been associated with an increased risk of **osteoporosis** and **fractures**, especially in older adults. *Ranitidine* - Ranitidine is a **H2-receptor blocker**, which also reduces stomach acid but acts via a different mechanism than PPIs. It is generally not as strongly linked to osteoporosis as PPIs. - While decreased gastric acid can affect nutrient absorption, the evidence for ranitidine directly causing osteoporosis is significantly weaker compared to PPIs. *Hydrochlorothiazide* - **Thiazide diuretics** like hydrochlorothiazide are known to **decrease urinary calcium excretion**, which can actually have a protective effect on bone mineral density, or at least be neutral. - Therefore, hydrochlorothiazide is unlikely to contribute to or worsen osteoporosis; it may even be beneficial for bone health. *Lithium* - Lithium typically does not have a direct adverse effect on bone mineral density; its primary effects are on the **central nervous system**. - Some studies have suggested potential complex effects on bone metabolism, but it is not a recognized direct cause of osteoporosis. *Estrogen* - **Estrogen** generally has a **protective effect on bone health** by inhibiting bone resorption. - The past use of estrogen-containing oral contraceptive pills would have been protective during that period and does not contribute to current osteoporosis; rather, post-menopausal estrogen deficiency is a major risk factor for osteoporosis.

Question 606: A 56-year-old man comes to the physician because of a painless blistering rash on his hands, forearms, and face for 2 weeks. The rash is not itchy and seems to get worse in the sunlight. He has also noticed that his urine is darker than usual. His aunt and sister have a history of similar skin lesions. Examination of the skin shows multiple fluid-filled blisters and oozing erosions on the forearms, dorsal side of both hands, and forehead. There are areas of hyperpigmented scarring and patches of bald skin along the sides of the blisters. Which of the following is the most appropriate pharmacotherapy to treat this patient's condition?

• A. Phlebotomy
• B. Hemin
• C. Acyclovir
• D. Low-dose hydroxychloroquine (Correct Answer)
• E. Prednisone

Explanation: ***Low-dose hydroxychloroquine*** - This patient presents with symptoms highly suggestive of **porphyria cutanea tarda (PCT)**, including **painless blistering rash** on sun-exposed areas, worsening with sunlight, **hyperpigmented scarring**, and **dark urine**. - **Low-dose hydroxychloroquine** is the most appropriate **pharmacotherapy** for PCT. It works by forming a complex with excess porphyrins which facilitates their excretion and helps to alleviate cutaneous symptoms. - As an antimalarial and immunomodulatory agent, hydroxychloroquine provides effective symptomatic relief in PCT. *Phlebotomy* - **Phlebotomy** is actually a **primary treatment for PCT**, aiming to reduce elevated iron stores, which are often a contributing factor to the disease. - However, phlebotomy is a **procedure, not a pharmacotherapy**. Since the question specifically asks for pharmacotherapy (drug treatment), this is not the correct answer despite being an effective treatment modality for PCT. *Hemin* - **Hemin** is used to treat **acute hepatic porphyrias** (e.g., acute intermittent porphyria), not porphyria cutanea tarda. - It works by suppressing hepatic delta-aminolevulinic acid (ALA) synthase activity, thereby reducing the overproduction of neurotoxic heme precursors characteristic of acute porphyrias. - PCT is a **cutaneous porphyria**, not an acute hepatic porphyria, making hemin inappropriate. *Acyclovir* - **Acyclovir** is an **antiviral medication** used to treat herpes simplex virus or varicella-zoster virus infections. - The patient's symptoms (photosensitive blistering, dark urine, family history) are characteristic of PCT, not a viral infection, making acyclovir inappropriate. *Prednisone* - **Prednisone** is a **corticosteroid** with anti-inflammatory and immunosuppressive properties, often used for autoimmune blistering diseases. - It is **not indicated** for PCT and could potentially worsen the condition by affecting liver enzyme activity or exacerbating photosensitivity.

Question 607: A 57-year-old man presents to his family physician for a checkup. He has had type 2 diabetes mellitus for 13 years, for which he has been taking metformin and vildagliptin. He has smoked 10–15 cigarettes daily for 29 years. Family history is irrelevant. Vital signs include: temperature 36.6°C (97.8°F), blood pressure 152/87 mm Hg and pulse 88/min. Examination reveals moderate abdominal obesity with a body mass index of 32 kg/m². The remainder of the examination is unremarkable. His fasting lipid profile is shown: Total cholesterol (TC) 280 mg/dL Low-density lipoprotein (LDL)-cholesterol 210 mg/dL High-density lipoprotein (HDL)-cholesterol 40 mg/dL Triglycerides (TGs) 230 mg/dL Which of the following is the mechanism of action of the best initial therapy for this patient?

• A. Activation of PPAR-alpha
• B. Inhibition of cholesterol absorption
• C. Bile acid sequestration
• D. Inhibition of cholesterol synthesis (Correct Answer)
• E. Inhibition of adipose tissue lipolysis

Explanation: ***Inhibition of cholesterol synthesis*** - This patient has multiple risk factors for cardiovascular disease including **type 2 diabetes**, **hypertension**, **smoking**, and significantly **elevated LDL-cholesterol (210 mg/dL)**, making him a candidate for high-intensity statin therapy. - **Statins** (HMG-CoA reductase inhibitors) are the first-line therapy for such patients as they significantly reduce cardiovascular events by **inhibiting the rate-limiting step in cholesterol synthesis** in the liver. *Activation of PPAR-alpha* - This is the mechanism of action of **fibrates** (e.g., fenofibrate, gemfibrozil), which are primarily used to **lower triglycerides** and raise HDL-cholesterol. - While this patient has elevated triglycerides, his primary lipid abnormality and cardiovascular risk comes from his high LDL-cholesterol, making statins the better initial choice. *Inhibition of cholesterol absorption* - This describes the mechanism of action of **ezetimibe**, which selectively inhibits cholesterol absorption at the brush border of the small intestine. - Ezetimibe is typically used as an add-on therapy if statins alone are insufficient to reach LDL-C goals, or if a patient is statin-intolerant, not as a monotherapy for high-risk patients. *Bile acid sequestration* - This is the mechanism of **bile acid resins** (e.g., cholestyramine, colestipol, colesevelam), which bind bile acids in the intestine, preventing their reabsorption and increasing their excretion. - This leads to increased hepatic synthesis of bile acids from cholesterol, thereby upregulating LDL receptors and lowering LDL-cholesterol, but they are less potent than statins and can cause gastrointestinal side effects. *Inhibition of adipose tissue lipolysis* - This is the mechanism of action of **niacin (nicotinic acid)**, which reduces the synthesis of VLDL and LDL by inhibiting lipolysis in adipose tissue. - Niacin can improve all lipid parameters but is often associated with significant side effects (e.g., flushing, insulin resistance) and has not consistently shown cardiovascular benefit beyond statins in recent trials, making it a less preferred initial therapy.

Question 608: A 56-year-old man presents for a follow-up regarding his management for type 2 diabetes mellitus (DM). He was diagnosed with type 2 DM about 7 years ago and was recently started on insulin therapy because oral agents were insufficient to control his glucose levels. He is currently following a regimen combining insulin lispro and neutral protamine Hagedorn (NPH) insulin. He is taking insulin lispro 3 times a day before meals and NPH insulin once in the morning. He has been on this regimen for about 2 months. He says that his glucose reading at night averages around 200 mg/dL and remains close to 180 mg/dL before his shot of NPH in the morning. The readings during the rest of the day range between 100–120 mg/dL. The patient denies any changes in vision or tingling or numbness in his hands or feet. His latest HbA1C level was 6.2%. Which of the following adjustments to his insulin regimen would be most effective in helping this patient achieve better glycemic control?

• A. Add another dose of insulin lispro in the evening.
• B. Reduce a dose of insulin lispro.
• C. Replace lispro with insulin aspart.
• D. Add insulin glargine to the current regimen.
• E. Add another dose of NPH in the evening. (Correct Answer)

Explanation: ***Add another dose of NPH in the evening.*** - The patient has persistently elevated **nighttime** and **pre-morning glucose levels** (200 mg/dL and 180 mg/dL, respectively), while daytime levels are well-controlled. This indicates insufficient **basal insulin coverage** overnight. - Adding a dose of **intermediate-acting NPH insulin** in the evening would provide longer-acting basal insulin to cover the overnight period and address the high morning fasting glucose. *Add another dose of insulin lispro in the evening.* - Insulin lispro is a **rapid-acting insulin** primarily used to cover post-prandial glucose spikes. Adding another dose would primarily affect post-dinner glucose, not the sustained overnight hyperglycemia. - While it might slightly lower evening glucose, its short duration of action would not adequately address the **pre-morning hyperglycemia**. *Reduce a dose of insulin lispro.* - The patient's **daytime glucose levels (100–120 mg/dL)** are well-controlled, suggesting that the current lispro doses are appropriate for meal coverage. - Reducing lispro could lead to **post-prandial hyperglycemia** during the day, worsening overall control. *Replace lispro with insulin aspart.* - Both insulin lispro and insulin aspart are **rapid-acting insulins** with very similar pharmacokinetics and duration of action. - Replacing one with the other would likely not significantly alter the glycemic profile, as the problem lies with **basal insulin coverage**, not rapid-acting insulin. *Add insulin glargine to the current regimen.* - While **insulin glargine** is a **long-acting basal insulin** and could address the overnight hyperglycemia, the patient is already on NPH as his basal insulin. - The simpler and more direct adjustment would be to optimize the **existing NPH regimen** by adding an evening dose, rather than introducing a new type of basal insulin, which might complicate the regimen further or be less cost-effective.

Question 609: A 52-year-old man who was recently hospitalized with a pulmonary embolism is put on an unfractionated heparin drip as a bridge to chronic warfarin therapy. During morning rounds, he is found to have diffuse bruising despite minimal trauma, and his heparin infusion rate is found to be faster than prescribed. A coagulation panel is obtained, which shows a aPTT of 130 seconds (therapeutic 70-120 seconds), and the decision is made to reverse the effects of heparin. Which of the following would most likely be administered in order to do this?

• A. Vitamin K
• B. Fresh frozen plasma
• C. Protamine sulfate (Correct Answer)
• D. Platelets
• E. Aminocaproic acid

Explanation: ***Correct: Protamine sulfate*** - **Specific reversal agent for heparin** via ionic binding (positively charged protamine neutralizes negatively charged heparin) - Rapidly reverses anticoagulant effects within minutes - Dose: 1 mg protamine per 100 units of heparin (titrated based on time since last dose) - **Indicated for heparin overdose** with bleeding or need for urgent reversal *Incorrect: Vitamin K* - Reverses **warfarin**, not heparin - Warfarin inhibits vitamin K-dependent clotting factors (II, VII, IX, X) - Takes hours to work (requires synthesis of new clotting factors) *Incorrect: Fresh frozen plasma* - Contains clotting factors for **warfarin reversal** or coagulopathy from factor deficiency - Not specific for heparin overdose - Would be used if protamine fails or for complex coagulopathy *Incorrect: Platelets* - Used for thrombocytopenia or platelet dysfunction - Does not reverse anticoagulant effects of heparin - This patient has normal platelet function; issue is excessive anticoagulation *Incorrect: Aminocaproic acid* - Antifibrinolytic agent that inhibits plasminogen activation - Used for hyperfibrinolysis (e.g., after thrombolytic therapy) - Does not reverse heparin's effect on the coagulation cascade

Question 610: Background: Beta-blockers reduce mortality in patients who have chronic heart failure, systolic dysfunction, and are on background treatment with diuretics and angiotensin-converting enzyme inhibitors. We aimed to compare the effects of carvedilol and metoprolol on clinical outcome. Methods: In a multicenter, double-blind, and randomized parallel group trial, we assigned 1,511 patients with chronic heart failure to treatment with carvedilol (target dose 25 mg twice daily) and 1,518 to metoprolol (metoprolol tartrate, target dose 50 mg twice daily). Patients were required to have chronic heart failure (NYHA II-IV), previous admission for a cardiovascular reason, an ejection fraction of less than 0.35, and to have been treated optimally with diuretics and angiotensin-converting enzyme inhibitors unless not tolerated. The primary endpoints were all-cause mortality, the composite endpoint of all-cause mortality, or all-cause admission. Analysis was done by intention to treat Findings: The mean study duration was 58 months (SD 6). The mean ejection fraction was 0.26 (0.07) and the mean age was 62 years (11). The all-cause mortality was 34% (512 of 1,511) for carvedilol and 40% (600 of 1,518) for metoprolol (hazard ratio 0.83 [95% CI 0.74-0.93], p = 0.0017). The reduction of all-cause mortality was consistent across predefined subgroups. Incidence of side effects and drug withdrawals did not differ by much between the 2 study groups. Which of the following represents the number of patients needed to treat to save one life?

• A. 1/(34 - 40)
• B. 1/0.83
• C. 1/(0.40 - 0.34) (Correct Answer)
• D. 1/(0.34 - 0.40)
• E. 1/(40 - 34)

Explanation: ***1/(0.40 - 0.34)*** - The **number needed to treat (NNT)** is calculated as **1 / Absolute Risk Reduction (ARR)**. - In this study, the mortality rate for carvedilol was 34% (0.34) and for metoprolol was 40% (0.40), so ARR = 0.40 - 0.34. *1/(34 - 40)* - This calculation uses raw percentages rather than **proportions**, and the subtraction order would result in a negative number, which is incorrect for NNT. - The NNT is always a positive value, representing the number of patients to treat to prevent one adverse event. *1/0.83* - **0.83 represents the hazard ratio**, not the absolute risk reduction. - The hazard ratio indicates the relative risk of an event in one group compared to another, not the difference in event rates needed for NNT. *1/(0.34 - 0.40)* - While using proportions, the **order of subtraction is incorrect**, yielding a negative value. - The ARR should be the **risk in the control group minus the risk in the experimental group** to reflect the benefit of the intervention. *1/(40 - 34)* - This uses raw percentages instead of **proportions (decimal form)**, and while the result would be positive, it's conventional and more precise to use proportions in NNT calculations. - Though numerically similar to the correct answer for the difference, using percentages directly for risk calculation can be less accurate in other contexts.

Question 611: A 56-year-old man presents with sudden-onset severe eye pain and blurred vision. He says the symptoms onset an hour ago and his vision has progressively worsened. Physical examination reveals a cloudy cornea and decreased visual acuity. Timolol is administered into the eyes to treat this patient’s symptoms. Which of the following best describes the mechanism of action of this drug in the treatment of this patient’s condition?

• A. It decreases the production of aqueous humor by decreasing levels of bicarbonate through a cAMP-mediated pathway
• B. It leads to opening of the trabecular meshwork
• C. Increased outflow via dilatation of the uveoscleral veins
• D. It suppresses the ciliary epithelium from producing aqueous humor (Correct Answer)
• E. It increases the transit of aqueous humor into the vitreous humor for absorption into the choroid

Explanation: ***It suppresses the ciliary epithelium from producing aqueous humor*** - The patient's symptoms (sudden-onset severe **eye pain**, **blurred vision**, **cloudy cornea**, and **decreased visual acuity**) are classic for **acute angle-closure glaucoma**. - **Timolol** is a **beta-blocker** that reduces intraocular pressure by **decreasing the production of aqueous humor** by the **ciliary epithelium**. *It decreases the production of aqueous humor by decreasing levels of bicarbonate through a cAMP-mediated pathway* - This mechanism describes **carbonic anhydrase inhibitors** (e.g., dorzolamide, acetazolamide), which decrease aqueous humor production by inhibiting the enzyme responsible for bicarbonate formation in the ciliary body. - While carbonic anhydrase inhibitors can be used in glaucoma, this is not the mechanism of action for **timolol**. *It leads to opening of the trabecular meshwork* - Medications that increase outflow through the **trabecular meshwork** include **cholinergic agonists** (e.g., pilocarpine), which act by causing miosis and pulling on the scleral spur to open the meshwork. - This is not the primary mechanism of action of **timolol**. *Increased outflow via dilatation of the uveoscleral veins* - Medications like **prostaglandin analogs** (e.g., latanoprost) increase uveoscleral outflow, but they do so by mechanisms involving remodeling of the extracellular matrix of the ciliary body and not directly dilating uveoscleral veins. - **Timolol** primarily affects aqueous humor production, not outflow via this pathway. *It increases the transit of aqueous humor into the vitreous humor for absorption into the choroid* - The vitreous humor is a gel-like substance primarily for structural support and is not a major pathway for aqueous humor absorption or outflow. - The primary outflow pathways for aqueous humor are the **trabecular meshwork** and the **uveoscleral pathway**.

Question 612: A 48-year-old woman underwent a thyroidectomy with central neck dissection due to papillary thyroid carcinoma. On day 2 postoperatively, she developed irritability, dysphagia, difficulty breathing, and spasms in different muscle groups in her upper and lower extremities. The vital signs include blood pressure 102/65 mm Hg, heart rate 93/min, respiratory rate 17/min, and temperature 36.1℃ (97.0℉). Physical examination shows several petechiae on her forearms, muscle twitching in her upper and lower extremities, expiratory wheezes on lung auscultation, decreased S1 and S2 and the presence of an S3 on cardiac auscultation, and positive Trousseau and Chvostek signs. Laboratory studies show: Ca2+ 4.4 mg/dL Mg2+ 1.7 mEq/L Na+ 140 mEq/L K+ 4.3 mEq/L Cl- 107 mEq/L HCO3- 25 mEq/L Administration of which of the following agents could prevent the patient’s condition?

• A. Anticonvulsants prior to and for 1 week after the operation
• B. Vitamin D and ionic calcium prior to and 2 weeks after the operation (Correct Answer)
• C. Potassium supplementation prior to and 2 weeks after the operation
• D. Calcium gluconate intraoperatively
• E. Magnesium sulfate intraoperatively

Explanation: ***Vitamin D and ionic calcium prior to and 2 weeks after the operation*** - The patient's symptoms are consistent with **hypocalcemia** (low calcium), a common complication after thyroidectomy due to inadvertent parathyroid gland removal or damage. Prophylactic **calcium and vitamin D supplementation** can prevent severe postoperative hypocalcemia by helping maintain calcium homeostasis. - The patient's calcium level of 4.4 mg/dL (normal range 8.5-10.2 mg/dL) confirms severe hypocalcemia. The presence of **Trousseau and Chvostek signs**, muscle spasms, and dysphagia are classic signs of hypocalcemic tetany. *Anticonvulsants prior to and for 1 week after the operation* - This patient's symptoms are not indicative of an underlying seizure disorder, but rather **neuromuscular excitability** due to hypocalcemia. Anticonvulsants would not address the root cause. - While severe hypocalcemia can rarely lead to seizures, prophylactic anticonvulsant administration is not standard practice for preventing this specific post-thyroidectomy complication. *Potassium supplementation prior to and 2 weeks after the operation* - The patient's potassium level is 4.3 mEq/L, which is within the normal range (3.5-5.0 mEq/L). **Hyperkalemia or hypokalemia** is not the primary issue here. - Potassium supplementation would not address the hypocalcemia causing her symptoms and could potentially lead to **hyperkalemia**, which has its own set of dangers. *Calcium gluconate intraoperatively* - **Intraoperative calcium gluconate** is typically used for acute, severe hypocalcemia or cardiac arrest, not as a prophylactic measure. Administering it intraoperatively would not prevent the delayed onset of hypocalcemia seen on day 2. - The goal is to prevent hypocalcemia by supporting calcium levels proactively, rather than treating an acute drop during surgery, which is rare. *Magnesium sulfate intraoperatively* - The patient's magnesium level of 1.7 mEq/L is at the lower limit of normal (1.7-2.2 mEq/L). While **hypomagnesemia** can impair PTH secretion and cause refractory hypocalcemia, magnesium supplementation is not the primary prophylactic strategy for post-thyroidectomy hypocalcemia. - Intraoperative magnesium sulfate would not address the fundamental issue of parathyroid gland injury or removal causing the hypocalcemia. Calcium and vitamin D remain the cornerstone of prevention.

Question 613: A 25-year-old man presents to the emergency department after a motor vehicle accident. He was the unrestrained front seat driver in a head on collision. The patient is unresponsive and his medical history is unknown. His temperature is 99.5°F (37.5°C), blood pressure is 67/38 mmHg, pulse is 190/min, respirations are 33/min, and oxygen saturation is 98% on room air. The patient is started on IV fluids, blood products, and norepinephrine. A FAST exam is performed and a pelvic binder is placed. One hour later, his temperature is 98.3°F (36.8°C), blood pressure is 119/66 mmHg, pulse is 110/min, respirations are 15/min, and oxygen saturation is 97% on room air. The patient is currently responsive. Management of the patient's pelvic fracture is scheduled by the orthopedic service. While the patient is waiting in the emergency department he suddenly complains of feeling hot, aches, and a headache. The patient's temperature is currently 101°F (38.3°C). He has not been given any pain medications and his past medical history is still unknown. Which of the following is the most likely diagnosis?

• A. Acute hemolytic transfusion reaction
• B. Febrile non-hemolytic transfusion reaction (Correct Answer)
• C. Sympathetic response to pain
• D. Minor blood group incompatibility
• E. Leukoagglutination reaction

Explanation: ***Febrile non-hemolytic transfusion reaction*** - This reaction is characterized by a **fever** and other constitutional symptoms (chills, headache, malaise) developing **within 4 hours of transfusion**, without evidence of hemolysis. The patient's symptoms and temperature rise after blood product administration fit this description. - It is typically caused by antibodies in the recipient's plasma reacting with **leukocyte antigens** present on donor white blood cells or by **cytokines** released from donor leukocytes during storage. *Acute hemolytic transfusion reaction* - This reaction typically presents with more severe symptoms such as **hypotension**, **hemoglobinuria**, flank pain, and diffuse bleeding, indicating widespread intravascular hemolysis due to **ABO incompatibility**. - Although the patient received blood products, his symptoms (feeling hot, aches, headache, mild fever) are not indicative of the severe, life-threatening nature of an acute hemolytic reaction. *Sympathetic response to pain* - While pain can cause a sympathetic response (tachycardia, hypertension), it typically does **not cause a fever** as seen in this patient. - The patient's initial presentation included signs of shock, and after resuscitation, his vital signs normalized before the new symptoms appeared, suggesting a new process rather than ongoing pain alone. *Minor blood group incompatibility* - Reactions to minor blood group incompatibilities are usually **milder and delayed** compared to ABO incompatibilities. - They often involve **extravascular hemolysis**, which might not present with the acute febrile reaction seen here, and are less common a cause of immediate febrile reactions. *Leukoagglutination reaction* - This is an older term for what is now often considered a type of **febrile non-hemolytic transfusion reaction (FNHTR)** caused by recipient antibodies to donor leukocyte antigens leading to leukocyte clumping. - While related to FNHTR, the term "febrile non-hemolytic transfusion reaction" is the more encompassing and appropriate diagnosis given the typical symptom complex of fever, chills, and headache.

Question 614: A 16-year-old boy with history of seizure disorder is rushed to the Emergency Department with multiple generalized tonic-clonic seizures that have spanned more than 30 minutes in duration. He has not regained consciousness between these episodes. In addition to taking measures to ensure that he maintains adequate respiration, which of the following is appropriate for initial pharmacological therapy?

• A. Carbamazepine
• B. Gabapentin
• C. Lorazepam (Correct Answer)
• D. Valproic acid
• E. Phenytoin

Explanation: ***Lorazepam*** - This patient is experiencing **status epilepticus**, defined by continuous seizures lasting over 5 minutes or recurrent seizures without regaining consciousness. **Intravenous benzodiazepines**, like lorazepam, are the first-line treatment due to their rapid onset of action on GABA receptors. - **Lorazepam** is preferred over other benzodiazepines in this setting due to its relatively **longer duration of action** and availability as an intravenous formulation, effectively terminating the acute seizure. *Carbamazepine* - **Carbamazepine** is an oral **anti-epileptic drug** used for long-term control of focal seizures, but it is not suitable for acute management of status epilepticus due to its **slow onset of action** and lack of intravenous formulation for rapid effect. - It works by blocking **voltage-gated sodium channels**, which is not the primary mechanism for immediate seizure termination in an emergency. *Gabapentin* - **Gabapentin** is an anti-epileptic medication primarily used for focal seizures and neuropathic pain, and is **not effective** in treating acute generalized tonic-clonic seizures or status epilepticus. - Its mechanism of action involves modulation of **calcium channels** and GABA, but it has a **slow onset** and limited efficacy in acute seizure termination. *Valproic acid* - **Valproic acid** can be used in the long-term management of various seizure types, including generalized tonic-clonic seizures, and has an intravenous formulation, but it is **not the first-line choice for immediate termination** of status epilepticus. - Benzodiazepines are typically administered first, and if they fail, valproic acid can be considered as a **second-line agent** along with other antiepileptics. *Phenytoin* - **Phenytoin** is a classic anti-epileptic drug that can be used intravenously as a **second-line agent** for status epilepticus if benzodiazepines are unsuccessful. - It has a slower onset of action compared to benzodiazepines and carries risks such as **cardiac arrhythmias** and **hypotension** with rapid infusion, making it less ideal for initial therapy.

Question 615: A 60-year-old male presents to the emergency room complaining of substernal chest pain. He reports a three-hour history of dull substernal chest pain that radiates into his left arm and jaw. He had a similar incident two months ago after walking one mile, but this pain is more severe. His past medical history is notable for hypertension and hyperlipidemia. An EKG demonstrates non-specific changes. Serum troponins are normal. In addition to aspirin, oxygen, and morphine, he is started on a medication that releases nitric oxide. Which of the following is a downstream effect of this molecule?

• A. Guanylyl cyclase activation (Correct Answer)
• B. cAMP production
• C. L-type calcium channel inhibition
• D. ß1-adrenergic antagonism
• E. Prostaglandin synthesis inhibition

Explanation: ***Guanylyl cyclase activation*** - The medication releasing **nitric oxide (NO)** is **nitroglycerin**, an organic nitrate that undergoes bioconversion to release NO. - **Nitric oxide** activates **soluble guanylyl cyclase** in vascular smooth muscle, leading to increased production of **cGMP (cyclic guanosine monophosphate)**. - Increased cGMP causes **vascular smooth muscle relaxation**, resulting in **venodilation** (reducing preload) and **coronary vasodilation** (improving myocardial oxygen supply). *cAMP production* - **cAMP production** is mediated by **adenylyl cyclase**, typically activated by **beta-adrenergic receptors** or other G-protein coupled receptors. - This is not the primary mechanism of nitric oxide signaling, which works through the cGMP pathway. *L-type calcium channel inhibition* - **L-type calcium channel inhibition** is the mechanism of action for **calcium channel blockers** (e.g., amlodipine, diltiazem, verapamil). - These drugs directly block calcium channels, reducing cardiac contractility and vascular tone through a mechanism distinct from nitric oxide signaling. *ß1-adrenergic antagonism* - **ß1-adrenergic antagonism** is the primary mechanism of **beta-blockers** (e.g., metoprolol, atenolol), which reduce heart rate and myocardial contractility. - This is a distinct pharmacological action unrelated to nitric oxide's downstream effects. *Prostaglandin synthesis inhibition* - **Prostaglandin synthesis inhibition** is the mechanism of action for **NSAIDs** including **aspirin**, which irreversibly inhibits cyclooxygenase (COX) enzymes. - While aspirin is given to this patient for antiplatelet effects, it is not related to the nitric oxide-releasing medication.

Question 616: A 5-year-old boy undergoes MRI neuroimaging for the evaluation of worsening headaches and intermittent nausea upon awakening. He receives a bolus of intravenous thiopental for sedation during the procedure. Ten minutes after the MRI, the patient is awake and responsive. Which of the following pharmacological properties is most likely responsible for this patient's rapid recovery from this anesthetic agent?

• A. First-pass metabolism
• B. Redistribution (Correct Answer)
• C. Zero-order elimination
• D. Ion trapping
• E. Cytochrome P450 oxidation

Explanation: ***Redistribution*** - Thiopental is a highly **lipid-soluble** drug that rapidly crosses the **blood-brain barrier**, leading to quick onset of action. - The drug then rapidly **redistributes** from the brain to other highly perfused tissues (e.g., muscle, fat) and then less perfused tissues, causing a rapid decrease in drug concentration at the site of action and thus termination of the anesthetic effect. *First-pass metabolism* - This refers to the **metabolism of a drug** before it reaches systemic circulation, typically after oral administration, and does not explain the termination of action for an intravenously administered drug like thiopental. - While thiopental is ultimately metabolized by the liver, this process is slower than redistribution and does not account for the **rapid awakening**. *Zero-order elimination* - **Zero-order elimination** occurs when a constant amount of drug is eliminated per unit of time, regardless of the drug's concentration, often seen with drug saturation of elimination pathways. - Thiopental elimination follows **first-order kinetics** at therapeutic doses, meaning a constant fraction of the drug is eliminated per unit time, and this describes slower, overall elimination, not rapid recovery. *Ion trapping* - **Ion trapping** occurs when a drug accumulates in a compartment due to differences in pH across a membrane and the drug's pKa, leading to ionization and reduced ability to diffuse back. - This mechanism is important for drug excretion or distribution into specific compartments (e.g., accumulation of basic drugs in acidic urine) but does not explain the **rapid termination of CNS effects** via redistribution. *Cytochrome P450 oxidation* - **Cytochrome P450 (CYP450) oxidation** is a major pathway for drug metabolism in the liver, which is responsible for the eventual elimination of thiopental from the body. - While important for overall drug clearance, the rate of CYP450 oxidation is too slow to account for the **rapid awakening** seen after a single bolus dose of thiopental; redistribution is the primary factor for rapid recovery.

Question 617: A 66-year-old man is brought to the emergency department 1 hour after the abrupt onset of painless loss of vision in his left eye. Over the last several years, he has noticed increased blurring of vision; he says the blurring has made it difficult to read, but he can read better if he holds the book below or above eye level. He has smoked 1 pack of cigarettes daily for 40 years. Fundoscopic examination shows subretinal fluid and small hemorrhage with grayish-green discoloration in the macular area in the left eye, and multiple drusen in the right eye with retinal pigment epithelial changes. Which of the following is the most appropriate pharmacotherapy for this patient's eye condition?

• A. Ustekinumab
• B. Etanercept
• C. Cetuximab
• D. Ruxolitinib
• E. Ranibizumab (Correct Answer)

Explanation: ***Ranibizumab*** - The patient's presentation with **abrupt, painless vision loss**, **subretinal fluid**, hemorrhage, and grayish-green discoloration in the macula of the left eye, along with drusen and retinal pigment epithelial changes in the right, is highly suggestive of **wet age-related macular degeneration (AMD)**. - **Ranibizumab** is an anti-VEGF (vascular endothelial growth factor) agent that inhibits neovascularization and leakage, making it the **approved first-line treatment for wet AMD**. *Ustekinumab* - This is a monoclonal antibody targeting **IL-12 and IL-23**, primarily used in the treatment of **psoriasis** and **psoriatic arthritis**, not wet AMD. - It has no role in inhibiting VEGF pathways or treating retinal neovascularization. *Etanercept* - Etanercept is a **TNF-alpha inhibitor** used in conditions like **rheumatoid arthritis**, **psoriasis**, and **ankylosing spondylitis**. - It does not target pathways involved in the pathogenesis of wet AMD. *Cetuximab* - Cetuximab is an **epidermal growth factor receptor (EGFR) inhibitor** used in the treatment of certain **cancers**, such as colorectal and head and neck cancers. - It is not indicated for ophthalmological conditions like wet AMD. *Ruxolitinib* - Ruxolitinib is a **JAK (Janus kinase) inhibitor** primarily used for **myelofibrosis** and **polycythemia vera**. - Its mechanism of action is unrelated to the treatment of neovascular AMD.

Question 618: A 35-year-old woman presents to the clinic with a 2-week history of headaches. She was in her usual state of health until 2 weeks ago, when she started having headaches. The headaches are throughout her whole head and rated as a 7/10. They are worse in the mornings and when she bends over. She has some mild nausea, but no vomiting. The headaches are not throbbing and are not associated with photophobia or phonophobia. On further questioning, she has noticed more hair than usual on her pillow in the morning and coming out in her hands when she washes her hair. The past medical history is unremarkable; she takes no prescription medications, but for the past year she has been taking an oral 'health supplement' recommended by her sister, which she orders over the internet. She cannot recall the supplement's name and does not know its contents. The physical exam is notable for some mild hepatomegaly but is otherwise unremarkable. This patient's presentation is most likely related to which of the following micronutrients?

• A. Vitamin D
• B. Vitamin B12
• C. Vitamin C
• D. Vitamin K
• E. Vitamin A (Correct Answer)

Explanation: ***Vitamin A*** - The patient's symptoms, including **headaches worse in the mornings and with bending over**, **mild nausea**, and **diffuse hair loss**, along with **hepatomegaly**, are classic signs of **chronic vitamin A toxicity** (**hypervitaminosis A**). - The likely source is a high-dose oral "health supplement" of unknown content, as vitamin A is a fat-soluble vitamin stored in the liver, leading to toxicity with excessive intake. *Vitamin D* - **Vitamin D toxicity** (hypervitaminosis D) typically presents with **hypercalcemia**, leading to symptoms like polyuria, polydipsia, renal stones, and muscle weakness, which are not described here. - While headaches can occur, **hair loss** and **hepatomegaly** are not characteristic features of vitamin D toxicity. *Vitamin B12* - **Vitamin B12 toxicity** is extremely rare, as it is a water-soluble vitamin and excess is readily excreted. - There are no well-established adverse effects or toxicity syndromes associated with high doses of vitamin B12 that would explain these symptoms. *Vitamin C* - **Vitamin C** is a water-soluble vitamin, and acute toxicity is uncommon because excess is excreted in urine. - High doses can lead to **gastrointestinal upset** (diarrhea, nausea, abdominal cramps) and, rarely, kidney stones, but not the constellation of headache, hair loss, and hepatomegaly seen in this patient. *Vitamin K* - **Vitamin K toxicity** is generally rare and primarily associated with synthetic forms (menadione). - In infants, high doses can cause **hemolytic anemia** and **jaundice**, but these symptoms are not typical for adults, nor do they explain the described presentation of headache, hair loss, and hepatomegaly.

Question 619: A 22-year-old woman with type 1 diabetes mellitus and mild asthma comes to the physician for a follow-up examination. She has had several episodes of sweating, dizziness, and nausea in the past 2 months that occur during the day and always resolve after she drinks orange juice. She is compliant with her diet and insulin regimen. The physician recommends lowering her insulin dose in certain situations. This recommendation is most important in which of the following situations?

• A. After a stressful exam
• B. During a viral infection
• C. Before exercise (Correct Answer)
• D. After large meals
• E. During pregnancy

Explanation: ***Before exercise*** - Exercise increases **glucose utilization** by muscles, which can lead to **hypoglycemia** in individuals taking insulin if the dose isn't adjusted. - The patient's symptoms (sweating, dizziness, nausea) are classic for **hypoglycemia**, which resolves with sugar intake (orange juice). *After a stressful exam* - **Stress** typically elevates **counter-regulatory hormones** (e.g., cortisol, epinephrine), which can increase blood glucose levels rather than cause hypoglycemia. - An insulin dose reduction is usually not necessary and could lead to **hyperglycemia** in this situation. *During a viral infection* - Infections, even viral ones, often trigger the release of **stress hormones**, increasing glucose production and leading to **hyperglycemia** and increased insulin requirements. - Insulin doses usually need to be *increased*, not decreased, during illness to manage elevated blood sugar. *After large meals* - Large meals, especially those rich in carbohydrates, would necessitate an **increased or consistent insulin dose** to cover the glucose intake and prevent **postprandial hyperglycemia**. - Reducing insulin after a large meal would likely lead to uncontrolled high blood sugar rather than prevent hypoglycemia. *During pregnancy* - While insulin requirements can fluctuate throughout pregnancy, they generally **increase** in the second and third trimesters due to increased **insulin resistance**. - Reducing insulin during pregnancy without careful monitoring could lead to uncontrolled **hyperglycemia**, posing risks to both mother and fetus.

Question 620: A 25-year-old man presents to the emergency department with pain in his leg. He states that the pain was sudden and that his leg feels very tender. This has happened before, but symptoms resolved a few days later with acetaminophen. His temperature is 98.5°F (36.9°C), blood pressure is 129/88 mmHg, pulse is 90/min, respirations are 12/min, and oxygen saturation is 98% on room air. Physical exam reveals clear breath sounds bilaterally and a normal S1 and S2. The patient’s right leg is red, inflamed, and tender to palpation inferior to the popliteal fossa. Which of the following is the best treatment for this patient?

• A. Heparin (Correct Answer)
• B. Aspirin
• C. Ibuprofen and rest
• D. Clindamycin
• E. Warfarin

Explanation: ***Heparin*** - The sudden onset of leg pain, tenderness, and inflammation, especially with a history of recurrent episodes, is highly suggestive of a **deep vein thrombosis (DVT)**. The location inferior to the popliteal fossa is a common site for calf vein DVTs. - **Heparin** (either unfractionated or low molecular weight) is the first-line treatment for acute DVT to prevent clot propagation, pulmonary embolism, and post-thrombotic syndrome. *Aspirin* - **Aspirin** is an antiplatelet agent used for arterial thrombosis and cardiovascular event prevention, not effective for treating acute venous thromboembolism like DVT. - Its mechanism primarily involves inhibiting cyclooxygenase to reduce thromboxane A2, which is less relevant in the coagulation cascade implicated in DVT. *Ibuprofen and rest* - **Ibuprofen** is an NSAID that can reduce pain and inflammation but does not address the underlying **thrombotic process** and will not prevent complications like pulmonary embolism. - While rest might alleviate discomfort, it is not a primary treatment for DVT and prolonged immobility can actually worsen venous stasis. *Clindamycin* - **Clindamycin** is an antibiotic used to treat bacterial infections; it has no role in the management of DVT, which is a vascular condition. - There are no signs of infection in the patient's presentation that would warrant antibiotic therapy. *Warfarin* - **Warfarin** is an oral anticoagulant used for long-term management of DVT and other thrombotic conditions, but it has a **delayed onset of action** (several days) due to its mechanism of inhibiting vitamin K-dependent clotting factors. - It is typically initiated concurrently with a rapid-acting anticoagulant like heparin, which provides immediate anticoagulation until warfarin reaches therapeutic levels.

Question 621: A 42-year-old man is brought in to the emergency department by his daughter. She reports that her father drank heavily for the last 16 years, but he stopped 4 days ago after he decided to quit drinking on his birthday. She also reports that he has been talking about seeing cats running in his room since this morning, although there were no cats. There is no history of any known medical problems or any other substance use. On physical examination, his temperature is 38.4ºC (101.2ºF), heart rate is 116/min, blood pressure is 160/94 mm Hg, and respiratory rate is 22/min. He is severely agitated and is not oriented to his name, time, or place. On physical examination, profuse perspiration and tremors are present. Which of the following best describes the pathophysiologic mechanism underlying his condition?

• A. Increased influx of chloride ions
• B. Increased inhibition of norepinephrine
• C. Functional increase in GABA
• D. Increased activity of NMDA receptors (Correct Answer)
• E. Increased inhibition of glutamate

Explanation: ***Increased activity of NMDA receptors*** - Chronic alcohol use leads to **downregulation of GABA receptors** and **upregulation of NMDA receptors** to compensate for alcohol's inhibitory effects. - When alcohol is withdrawn, the unopposed upregulation of NMDA receptors (and decreased GABA activity) causes a state of **neuronal hyperexcitability**, leading to symptoms like agitation, hallucinations, and autonomic hyperactivity seen in **delirium tremens**. *Increased influx of chloride ions* - This describes the mechanism of action of **GABA-A agonists** (like benzodiazepines), which enhance GABA's inhibitory effects by increasing chloride influx and hyperpolarizing neurons. - In alcohol withdrawal, there is a **functional decrease in GABAergic activity**, not an increase in chloride ion influx. *Increased inhibition of norepinephrine* - **Norepinephrine** is a neurotransmitter associated with wakefulness, alertness, and autonomic responses; increased activity is seen in alcohol withdrawal, contributing to sympathetic overdrive. - Increased inhibition of norepinephrine would lead to sedation and reduced autonomic activity, which is the opposite of the patient's presentation. *Functional increase in GABA* - **GABA** (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in the brain; alcohol enhances GABAergic activity. - In alcohol withdrawal, there is a **functional decrease in GABAergic activity**, contributing to neuronal hyperexcitability and withdrawal symptoms. *Increased inhibition of glutamate* - **Glutamate** is the primary excitatory neurotransmitter, and its receptors (like NMDA) are implicated in alcohol withdrawal. - Alcohol withdrawal is characterized by **increased excitatory activity**, including increased glutamate release and NMDA receptor activation, not increased inhibition of glutamate.

Question 622: A 47-year-old African-American woman presents to her primary care physician for a general checkup appointment. She works as a middle school teacher and has a 25 pack-year smoking history. She has a body mass index (BMI) of 22 kg/m^2 and is a vegetarian. Her last menstrual period was 1 week ago. Her current medications include oral contraceptive pills. Which of the following is a risk factor for osteoporosis in this patient?

• A. Smoking history (Correct Answer)
• B. Race
• C. Estrogen therapy
• D. Age
• E. Body mass index

Explanation: ***Smoking history*** - **Smoking** is a well-established risk factor for osteoporosis due to its negative effects on bone density and **calcium absorption**. - Smokers have lower bone density and increased fracture risk due to direct toxic effects on osteoblasts and accelerated estrogen metabolism. *Race* - **African-American women** typically have higher bone mineral density and a lower risk of osteoporosis compared to Caucasians and Asians. - This patient's racial background is considered a protective factor, not a risk factor, for osteoporosis. *Estrogen therapy* - **Oral contraceptive pills** contain estrogen, which helps maintain bone density and is protective against osteoporosis. - Estrogen deficiency, not estrogen therapy, is a risk factor for osteoporosis, especially after menopause. *Age* - While **advancing age** is a significant risk factor for osteoporosis, this patient is 47 years old and still having regular menstrual periods, indicating pre-menopausal status. - The effects of age on bone density become more pronounced after menopause due to declining estrogen levels. *Body mass index* - A **BMI of 22 kg/m^2** is within the normal range, and higher BMI is generally associated with greater bone density due to increased weight bearing and higher estrogen levels in adipose tissue. - Being underweight (low BMI) is a risk factor for osteoporosis, as it often correlates with poorer nutritional status and lower bone mass.

Question 623: A 33-year-old man comes to the emergency department because of a pounding headache for the past 3 hours. The pain is 8 out of 10 in intensity, does not radiate, and is not relieved by ibuprofen. He also has associated dizziness, blurring of vision, and palpitations. He has had similar episodes over the last 6 months but none this severe. He has not had fever, weight change, or loss of appetite. He underwent an appendectomy at the age of 18. His father died of renal cancer. He is diaphoretic. His temperature is 36.8°C (98.4°F), pulse is 112/min, and blood pressure is 220/130 mm Hg. Physical examination shows no abnormalities. Laboratory studies show: Hemoglobin 14.8 g/dL Leukocyte count 9600/mm3 Platelet count 345,000/mm3 Serum Glucose 112 mg/dL Na+ 137 mEq/L K+ 4.2 mEq/L Cl- 105 mEq/L Creatinine 1.0 mg/dL Urine dipstick shows no abnormalities. Which of the following findings on imaging is the most likely explanation for this patient's symptoms?

• A. Paravertebral mass
• B. Adrenal medullary mass (Correct Answer)
• C. Intracranial hemorrhage
• D. Renal cortical mass
• E. Meningeal mass

Explanation: ***Adrenal medullary mass*** - The patient's symptoms (pounding headache, palpitations, diaphoresis, dizziness, blurred vision) along with severe **hypertension** (220/130 mmHg) and tachycardia (112/min) are classic for a **pheochromocytoma**, which is typically an adrenal medullary tumor. - The episodic nature of the symptoms over 6 months and the patient's father dying of **renal cancer** (suggesting a potential familial syndrome like VHL or MEN2, which can include pheochromocytoma) further support this diagnosis. *Paravertebral mass* - While pheochromocytomas can sometimes be **extra-adrenal** (paragangliomas) and located in the paravertebral regions, an "adrenal medullary mass" is the most common and direct explanation for these symptoms. - A paravertebral mass without the context of catecholamine excess would typically present with symptoms related to **compression** or local invasion, not systemic paroxysmal symptoms of hypertension, headache, and palpitations. *Intracranial hemorrhage* - An intracranial hemorrhage can cause severe headache and neurological symptoms, but it is less likely to cause a prolonged history of episodic symptoms with associated **palpitations and diaphoresis**. - While severe hypertension can be a cause or consequence of hemorrhage, the constellation of symptoms strongly points towards **catecholamine excess**. *Renal cortical mass* - A renal cortical mass, such as a **renal cell carcinoma**, typically presents with hematuria, flank pain, or an abdominal mass. - It usually does not cause paroxysmal headaches, palpitations, and severe, episodic hypertension unless it's an extremely rare instance of a renin-producing tumor, which wouldn't cause the other adrenergic symptoms. *Meningeal mass* - A meningeal mass (e.g., meningioma) typically causes symptoms related to **mass effect** on the brain or spinal cord, such as seizures, focal neurological deficits, or chronic headache. - It would not explain the prominent **adrenergic symptoms** like palpitations and diaphoresis, or the severe, episodic hypertension.

Question 624: A 25-year-old man presents to the clinic with a complaint of lightheadedness when standing up from his bed in the morning and then from his chair at work. He has had similar complaints for many months, and the symptoms have not improved despite drinking lots of fluids, eating regular meals, and taking daily multivitamin. His daily routine is disturbed as he finds himself getting up very slowly to avoid the problem. This has created some awkward situations at his workplace and in social settings. His blood pressure while seated is 120/80 mm Hg, and upon standing it falls to 100/68 mm Hg. The physical examination is unremarkable except for a strong odor suggestive of marijuana use. The patient denies drug use and insists the odor is due to his roommate who smokes marijuana for medical purposes. No pallor or signs of dehydration are seen. The lab results are as follows: Serum Glucose 90 mg/dL Sodium 140 mEq/L Potassium 4.1 mEq/L Chloride 100 mEq/L Serum Creatinine 0.8 mg/dL Blood Urea Nitrogen 9 mg/dL Hemoglobin (Hb) Concentration 15.3 g/dL Mean Corpuscular Volume (MCV) 83 fl Reticulocyte count 0.5% Erythrocyte count 5.3 million/mm3 Platelet count 200,000/mm3 The ECG shows no abnormal finding. Which of the following could alleviate this patient’s symptoms?

• A. Sodium chloride infusion
• B. Inhibition of the baroreceptor response
• C. Increased parasympathetic stimulation
• D. Carotid massage
• E. Alpha 1 receptor activation (Correct Answer)

Explanation: ***Alpha 1 receptor activation*** - Patients with **orthostatic hypotension** benefit from medications that increase **peripheral vasoconstriction**. - **Alpha-1 adrenergic agonists** (such as midodrine) stimulate vasoconstriction, leading to an increase in **mean arterial pressure** and ameliorating orthostatic symptoms. - This is the **most effective pharmacologic intervention** for this patient who has failed conservative measures. *Sodium chloride infusion* - While **increased sodium and fluid intake** can help orthostatic hypotension, this patient has already been **drinking lots of fluids** without improvement. - His normal **hemoglobin**, **electrolytes**, and absence of dehydration signs suggest euvolemia. - Although IV saline or increased salt intake may provide some benefit, it is less effective than targeted pharmacologic vasoconstriction, especially when conservative hydration measures have already failed. *Inhibition of the baroreceptor response* - The baroreceptors are crucial in maintaining blood pressure homeostasis by sensing changes in blood pressure and initiating reflex adjustments. - **Inhibiting the baroreceptor response** would remove an important compensatory mechanism, potentially worsening orthostatic hypotension rather than improving it. *Increased parasympathetic stimulation* - Increased **parasympathetic activity** generally leads to **vasodilation** and a decrease in heart rate, which would exacerbate rather than alleviate orthostatic hypotension. - The symptoms of orthostatic hypotension are primarily due to inadequate sympathetic response upon standing. *Carotid massage* - **Carotid massage** is a maneuver that stimulates the **baroreceptors** in the carotid sinus, leading to increased parasympathetic tone and decreased sympathetic output. - This typically results in a **reduction in heart rate and blood pressure**, which would worsen the patient's existing orthostatic hypotension.

Question 625: A 7-year-old boy with asthma is brought to the physician because of a 1-month history of worsening shortness of breath and cough. The mother reports that the shortness of breath usually occurs when he is exercising with his older brother. His only medication is an albuterol inhaler that is taken as needed. The physician considers adding zafirlukast to his drug regimen. Which of the following is the most likely mechanism of action of this drug?

• A. Antagonism at muscarinic receptors
• B. Blockade of 5-lipoxygenase pathway
• C. Inhibition of mast cell degranulation
• D. Inhibition of phosphodiesterase
• E. Antagonism at leukotriene receptors (Correct Answer)

Explanation: ***Antagonism at leukotriene receptors*** - **Zafirlukast** is a **leukotriene receptor antagonist** (LTRA) that blocks the action of leukotrienes at their CysLT1 receptors. - This action helps to reduce **bronchoconstriction**, airway edema, and inflammation, which are key features of asthma pathophysiology. *Antagonism at muscarinic receptors* - This is the mechanism of action for **anticholinergic bronchodilators** like **ipratropium** or **tiotropium**, which are not **zafirlukast**. - These drugs primarily prevent **acetylcholine-induced bronchoconstriction** but do not target the leukotriene pathway. *Blockade of 5-lipoxygenase pathway* - This is the mechanism of **zileuton**, a **leukotriene synthesis inhibitor**, which prevents the formation of all leukotrienes. - While it targets leukotrienes, it is distinct from **receptor antagonism**, which is how **zafirlukast** works. *Inhibition of mast cell degranulation* - This is the mechanism of **mast cell stabilizers** such as **cromolyn sodium** or **nedocromil**, which prevent the release of inflammatory mediators. - This action differs from the direct receptor blockade provided by **zafirlukast**. *Inhibition of phosphodiesterase* - This is the mechanism of **methylxanthines** like **theophylline**, which increase intracellular cAMP and lead to **bronchodilation**. - This is a distinct pharmacological class and mechanism from **zafirlukast**.

Question 626: A 38-year-old man comes to the physician because of a 2-year-history of cough and progressively worsening breathlessness. He has smoked 1 pack of cigarettes daily for the past 10 years. Physical examination shows contraction of the anterior scalene and sternocleidomastoid muscles during inspiration. An x-ray of the chest shows flattening of the diaphragm and increased radiolucency in the lower lung fields. Further analysis shows increased activity of an isoform of elastase that is normally inhibited by alpha-1-antitrypsin. The cells that produce this isoform of elastase were most likely stimulated to enter the site of inflammation by which of the following substances?

• A. Leukotriene B4 (Correct Answer)
• B. Thromboxane A2
• C. Lactoferrin
• D. Interferon gamma
• E. High-molecular-weight kininogen

Explanation: ***Leukotriene B4*** - The patient's symptoms and findings (cough, breathlessness, smoking history, increased elastase activity, flattened diaphragm, increased radiolucency) are consistent with **emphysema**, specifically **centrilobular emphysema** secondary to smoking. The increased elastase activity, normally inhibited by alpha-1-antitrypsin, points to **neutrophilic elastase**. - **Leukotriene B4 (LTB4)** is a potent **chemoattractant for neutrophils**, drawing them to the site of inflammation in the lungs where they release elastase, contributing to alveolar destruction. *Thromboxane A2* - **Thromboxane A2** is primarily involved in **platelet aggregation** and **vasoconstriction**. - It does not serve as a direct chemoattractant for neutrophils in the context of emphysema. *Lactoferrin* - **Lactoferrin** is an **iron-binding protein** found in various secretions and within neutrophil granules, acting as an antimicrobial agent and modulating immune responses. - While present in neutrophils, it is not a primary chemoattractant for these cells to the site of inflammation. *Interferon gamma* - **Interferon gamma (IFN-$\gamma$)** is a cytokine produced by T cells and NK cells, important for **antiviral and antitumor immunity** and macrophage activation. - It plays a role in chronic inflammation but is not a direct chemoattractant for neutrophils in the same manner as LTB4. *High-molecular-weight kininogen* - **High-molecular-weight kininogen (HMWK)** is a protein involved in the **coagulation cascade** and the **kallikrein-kinin system**, leading to the production of bradykinin. - Its primary role is not as a direct chemoattractant for neutrophils in the inflammatory process leading to emphysema.

Question 627: A 17-year-old high school student is brought to the emergency department because of irritability and rapid breathing. He appears agitated and is diaphoretic. His temperature is 38.3°C (101°F), pulse is 129/min, respirations are 28/min, and blood pressure is 158/95 mmHg. His pupils are dilated. An ECG shows sinus tachycardia. Which of the following substances is used to make the drug this patient has most likely taken?

• A. Ergotamine
• B. Codeine
• C. Sodium oxybate
• D. Homatropine
• E. Pseudoephedrine (Correct Answer)

Explanation: ***Pseudoephedrine*** - This patient's symptoms (irritability, agitation, rapid breathing, tachycardia, hypertension, dilated pupils, and diaphoresis) are consistent with **sympathomimetic toxicity**, often seen with stimulants like **methamphetamine**. - **Pseudoephedrine** is a common over-the-counter decongestant that can be chemically converted into methamphetamine through a process called **reduction**. *Ergotamine* - **Ergotamine** is an ergot alkaloid used to treat migraines; it causes vasoconstriction and can lead to symptoms like nausea, vomiting, and peripheral ischemia, which do not fully align with the patient's presentation. - While it can cause elevated blood pressure, the widespread stimulant effects and agitation are less typical, and it's not a common precursor for illicit stimulant synthesis. *Codeine* - **Codeine** is an opioid; overdose would present with central nervous system depression, respiratory depression, and miosis (pinpoint pupils), which is the opposite of this patient's dilated pupils and agitated state. - It is a precursor to certain other opioids (e.g., desomorphine or "krokodil"), but not to the type of stimulant producing these symptoms. *Sodium oxybate* - **Sodium oxybate** (GHB) is a central nervous system depressant and would cause sedation, bradycardia, and respiratory depression, not the stimulant toxidrome observed. - It is not commonly used as a precursor for illicit stimulants causing sympathomimetic effects. *Homatropine* - **Homatropine** is an anticholinergic agent, which can cause dilated pupils, tachycardia, and a dry mouth, but typically not severe diaphoresis with agitation to this degree; also less common for illicit drug manufacturing. - While it fits some anticholinergic toxidrome features, it is not a direct precursor for street drugs causing such profound sympathomimetic effects.

Question 628: A 60-year-old man is brought to the emergency department because of a 30-minute history of dizziness and shortness of breath. After establishing the diagnosis, treatment with a drug is administered. Shortly after administration, the patient develops severe left eye pain and decreased vision of the left eye, along with nausea and vomiting. Ophthalmologic examination shows a fixed, mid-dilated pupil and a narrowed anterior chamber of the left eye. The patient was most likely treated for which of the following conditions?

• A. Hypertensive crisis
• B. Atrioventricular block (Correct Answer)
• C. Viral pleuritis
• D. Pulmonary embolism
• E. Mitral regurgitation

Explanation: **Atrioventricular block** - The medication likely administered was **atropine**, a muscarinic antagonist used to treat symptomatic bradycardia from AV block. - Atropine can precipitate **acute angle-closure glaucoma** due to its mydriatic effect, causing eye pain, decreased vision, and a fixed, mid-dilated pupil. *Hypertensive crisis* - Treatment for hypertensive crisis typically involves antihypertensive medications like **labetalol or nitroglycerin**, which do not cause acute angle-closure glaucoma. - Symptoms of hypertensive crisis primarily relate to end-organ damage from high blood pressure, not acute ocular symptoms. *Viral pleuritis* - Viral pleuritis is an inflammatory condition of the pleura causing **pleuritic chest pain**, not cardiac symptoms, and is typically treated with NSAIDs. - The treatment for viral pleuritis would not involve atropine or lead to acute angle-closure glaucoma. *Pulmonary embolism* - Pulmonary embolism presents with **acute dyspnea and hypoxemia** and is treated with anticoagulants. - Such treatment would not cause the described ocular side effects or be mistaken for a condition requiring atropine. *Mitral regurgitation* - Mitral regurgitation is a valvular heart disease with symptoms often including **dyspnea on exertion** and fatigue, not acute dizziness and shortness of breath requiring immediate atropine. - Treatment for acute mitral regurgitation typically involves vasodilators or surgical intervention, not atropine, and does not cause acute angle-closure glaucoma.

Question 629: A 33-year-old woman comes to the physician because of a 3-day history of dry cough and low-grade fever. Four months ago, she was diagnosed with major depressive disorder and started treatment with fluoxetine. Physical examination shows no abnormalities. A diagnosis of upper respiratory infection is made and medication is prescribed to relieve her symptoms. A drug with which of the following mechanisms of action should be avoided in this patient?

• A. Inhibition of H1 receptors
• B. Inhibition of NMDA glutamate receptors (Correct Answer)
• C. Disruption of mucoid disulfide bonds
• D. Inhibition of cyclooxygenase enzymes
• E. Stimulation of α-adrenergic receptors

Explanation: ***Inhibition of NMDA glutamate receptors*** - This mechanism describes **dextromethorphan**, a commonly used antitussive (cough suppressant) for upper respiratory infections - Dextromethorphan has **serotonergic activity** and can precipitate **serotonin syndrome** when combined with SSRIs like fluoxetine - Serotonin syndrome presents with mental status changes, autonomic hyperactivity (hyperthermia, tachycardia, diaphoresis), and neuromuscular abnormalities (hyperreflexia, clonus, rigidity) - This is a **well-documented drug interaction** that should be avoided; alternative antitussives like benzonatate or guaifenesin should be used instead *Inhibition of H1 receptors* - This mechanism describes **first-generation antihistamines** (e.g., diphenhydramine, chlorpheniramine) used for cough and congestion - These are **generally safe** with fluoxetine, though may cause additive sedation - Do not pose a risk for serotonin syndrome *Disruption of mucoid disulfide bonds* - This mechanism describes **mucolytics** like N-acetylcysteine, which break down mucus to facilitate expectoration - No significant drug interaction with fluoxetine - Safe to use concurrently *Inhibition of cyclooxygenase enzymes* - This mechanism describes **NSAIDs** (e.g., ibuprofen, naproxen) used for fever and body aches - SSRIs can modestly increase risk of GI bleeding when combined with NSAIDs due to decreased platelet serotonin - However, NSAIDs are **not contraindicated** for short-term symptomatic relief and do not cause serotonin syndrome *Stimulation of α-adrenergic receptors* - This mechanism describes **nasal decongestants** (e.g., pseudoephedrine, phenylephrine) used for nasal congestion - Generally safe with SSRIs; no serotonin syndrome risk - May cause mild elevation in blood pressure but this is typically not clinically significant

Question 630: A 64-year-old man presents to his physician for a scheduled follow-up visit. He has chronic left-sided heart failure with systolic dysfunction. His current regular medications include captopril and digoxin, which were started after his last episode of symptomatic heart failure approximately 3 months ago. His last episode of heart failure was accompanied by atrial fibrillation, which followed an alcohol binge over a weekend. Since then he stopped drinking. He reports that he has no current symptoms at rest and is able to perform regular physical exercise without limitation. On physical examination, mild bipedal edema is noted. The physician suggested to him that he should discontinue digoxin and continue captopril and scheduled him for the next follow-up visit. Which of the following statements best justifies the suggestion made by the physician?

• A. Long-term digoxin therapy produces significant survival benefits in patients with heart failure, but at the cost of increased heart failure-related admissions.
• B. Both captopril and digoxin are likely to improve the long-term survival of the patient with heart failure, but digoxin has more severe side effects.
• C. Captopril is likely to improve the long-term survival of the patient with heart failure, unlike digoxin.
• D. Digoxin does not benefit patients with left-sided heart failure in the absence of atrial fibrillation.
• E. Digoxin is useful to treat atrial fibrillation, but does not benefit patients with systolic dysfunction who are in sinus rhythm. (Correct Answer)

Explanation: ***Digoxin is useful to treat atrial fibrillation, but does not benefit patients with systolic dysfunction who are in sinus rhythm.*** - The patient's **atrial fibrillation** was likely triggered by the alcohol binge and has since resolved, suggesting he is now in **sinus rhythm**. - Digoxin's primary benefit in heart failure with **systolic dysfunction** (HFrEF) is to control ventricular rate in patients with **atrial fibrillation**, but it does not offer survival benefit in HFrEF patients who are in **sinus rhythm** and well-managed with other therapies. *Long-term digoxin therapy produces significant survival benefits in patients with heart failure, but at the cost of increased heart failure-related admissions.* - This statement is incorrect; digoxin has been shown to **reduce hospital admissions** for heart failure, but it does **not provide a significant survival benefit** in patients with HFrEF in sinus rhythm. - The main benefit of digoxin in HFrEF is to improve symptoms and quality of life, alongside reducing hospitalizations, but not prolonging life. *Both captopril and digoxin are likely to improve the long-term survival of the patient with heart failure, but digoxin has more severe side effects.* - **Captopril (an ACE inhibitor)** does improve **long-term survival** in heart failure, but **digoxin does not** demonstrably improve survival. - While digoxin can have side effects, its lack of survival benefit for HFrEF in sinus rhythm is the primary reason for discontinuation, not just side effect severity. *Captopril is likely to improve the long-term survival of the patient with heart failure, unlike digoxin.* - This statement is partially correct that **captopril improves survival**, but it does not fully explain the physician's decision to discontinue digoxin. - The key missing piece is the patient's current **sinus rhythm** and the lack of benefit of digoxin in that specific context for HFrEF. *Digoxin does not benefit patients with left-sided heart failure in the absence of atrial fibrillation.* - This statement is nearly correct, but "left-sided heart failure" is broad. It is specifically in patients with **systolic dysfunction (HFrEF)** who are in **sinus rhythm** that digoxin lacks significant benefit beyond symptom control, and does not provide survival benefit.

Question 631: A 19-year-old G1P0 presents to the emergency department with severe abdominal pain. She states that the pain has been recurring every 3 to 5 minutes for the past 5 hours. She denies having regular prenatal care but recalls that her last menstrual period was about 9 months ago. She initially denies substance use but later admits to occasional prescription pain medication use during pregnancy. Her temperature is 98°F (37°C), blood pressure is 120/60 mmHg, pulse is 120/min, and respirations are 18/min. Tenderness is elicited in the lower abdominal quadrants. Clear fluid is seen in her vaginal vault with a fetal crown seen at 10 cm cervical dilation and +1 station. The patient is emergently taken into the labor and delivery suite, where she delivers a male infant with APGAR scores of 9 and 9 at 5 and 10 minutes, respectively. Several hours after delivery, the nurse notes that the infant is very irritable and crying in high pitches. The infant appears very diaphoretic with a runny nose and flailing limbs. What is the necessary pharmacological treatment for this patient?

• A. Morphine (Correct Answer)
• B. Phenobarbital
• C. Naloxone
• D. Diazepam
• E. Acetaminophen

Explanation: ***Morphine*** - The infant is presenting with symptoms consistent with **neonatal abstinence syndrome (NAS)** due to maternal opioid use, requiring opioid replacement therapy. - **Morphine** is the most appropriate pharmacological treatment to manage these withdrawal symptoms and gradually wean the infant. *Phenobarbital* - While **phenobarbital** can be used as a second-line agent for NAS, particularly if seizures are present or first-line opioids are ineffective, it is not the initial treatment of choice. - Its primary role is in controlling severe **irritability** and **seizures** associated with withdrawal. *Naloxone* - **Naloxone** is an opioid antagonist and would worsen the withdrawal symptoms in an infant with NAS by abruptly blocking opioid receptors. - It is used to reverse **acute opioid overdose** and respiratory depression, not for managing withdrawal. *Diazepam* - **Diazepam**, a benzodiazepine, might be considered in severe cases of NAS, especially if there are significant **seizures** or uncontrollable irritability. - However, it is not the first-line treatment and could cause sedation or respiratory depression. *Acetaminophen* - **Acetaminophen** is a pain reliever and antipyretic but does not address the underlying **opioid withdrawal** symptoms. - It would not alleviate the neurological symptoms, autonomic dysfunction, or gastrointestinal distress typical of NAS.

Question 632: A 25-year-old woman presents to the ED with nausea, vomiting, diarrhea, abdominal pain, and hematemesis after ingesting large quantities of a drug. Which of the following pairs a drug overdose with the correct antidote for this scenario?

• A. Iron; deferoxamine (Correct Answer)
• B. Organophosphate; physostigmine
• C. Atropine; fomepizole
• D. Aspirin; N-acetylcysteine
• E. Acetaminophen; naloxone

Explanation: ***Iron; deferoxamine*** - The symptoms of **nausea, vomiting, diarrhea, abdominal pain, and hematemesis** are classic signs of **iron overdose**, which causes direct corrosive injury to the GI mucosa. - **Deferoxamine** is a **chelating agent** specifically used to bind iron ions and facilitate their excretion, thus reversing iron toxicity. *Organophosphate; physostigmine* - **Organophosphate poisoning** presents with a **cholinergic crisis** (SLUDGE: salivation, lacrimation, urination, defecation, GI upset, emesis, miosis), but **hematemesis** is not a primary feature. - **Physostigmine** is an acetylcholinesterase inhibitor used for atropine overdose, not organophosphate poisoning; **atropine** and **pralidoxime** are the antidotes for organophosphate. *Atropine; fomepizole* - **Atropine overdose** causes **anticholinergic symptoms** (dry mouth, blurred vision, tachycardia, urinary retention, delirium), not GI irritation and hematemesis. - **Fomepizole** is an antidote for **methanol** or **ethylene glycol poisoning**, not atropine. *Aspirin; N-acetylcysteine* - **Aspirin overdose** (salicylate toxicity) results in **tinnitus, hyperventilation, metabolic acidosis, and altered mental status**, but **hematemesis** is less common than with iron. - **N-acetylcysteine** is the antidote for acetaminophen overdose, not aspirin; aspirin overdose is treated with **alkalinization of urine** and **hemodialysis**. *Acetaminophen; naloxone* - **Acetaminophen overdose** primarily causes **hepatic toxicity**, initially presenting with non-specific GI symptoms, but **hematemesis** is atypical, and the main concern is liver damage. - **Naloxone** is an opioid antagonist used to reverse opioid overdose, not acetaminophen.

Question 633: A 48-year-old woman comes to the physician for a follow-up examination. At her visit 1 month ago, her glomerular filtration rate (GFR) was 100 mL/min/1.73 m2 and her renal plasma flow (RPF) was 588 mL/min. Today, her RPF is 540 mL/min and her filtration fraction (FF) is 0.2. After her previous appointment, this patient was most likely started on a drug that has which of the following effects?

• A. Inhibition of the renal Na-K-Cl cotransporter
• B. Constriction of the afferent arteriole
• C. Relaxation of urinary smooth muscle
• D. Constriction of the efferent arteriole (Correct Answer)
• E. Inhibition of vasopressin

Explanation: ***Constriction of the efferent arteriole*** - The previous GFR was 100 mL/min and RPF was 588 mL/min. For the follow-up, RPF is 540 mL/min and FF is 0.2. The new GFR can be calculated as FF × RPF = 0.2 × 540 = **108 mL/min**. - The patient shows **increased GFR** (100→108 mL/min) with **decreased RPF** (588→540 mL/min), resulting in an **increased filtration fraction**. - Medications that **constrict the efferent arteriole**, such as **NSAIDs**, produce this pattern by blocking prostaglandin synthesis. Prostaglandins normally cause vasodilation (predominantly of the afferent arteriole). When blocked, there is relatively more **efferent arteriolar constriction**, which increases glomerular hydrostatic pressure, thereby **increasing GFR while reducing overall RPF**. *Inhibition of the renal Na-K-Cl cotransporter* - This effect describes **loop diuretics** (e.g., furosemide), which increase sodium excretion and water diuresis. - Loop diuretics typically cause a **decrease in GFR** due to reduced fluid volume and lower filtration pressure, which contradicts the slight increase in GFR observed. *Constriction of the afferent arteriole* - **Afferent arteriole constriction** (e.g., by NSAIDs in high doses or norepinephrine) would decrease blood flow into the glomerulus, leading to a **decrease in both RPF and GFR**. - While RPF decreased in this case, GFR actually increased, making this option incorrect. *Relaxation of urinary smooth muscle* - Relaxation of urinary smooth muscle is characteristic of drugs like **alpha-blockers** (e.g., tamsulosin) or antimuscarinics used for conditions like benign prostatic hyperplasia or overactive bladder. - This effect primarily impacts urine flow out of the bladder and does **not directly affect GFR or RPF** in the way described. *Inhibition of vasopressin* - Vasopressin (ADH) inhibition leads to **increased water excretion** and is seen with drugs like **vasopressin receptor antagonists** (vaptans) or ethanol. - While it affects fluid balance, it typically causes a **decrease in GFR** due to hypovolemia and has no direct mechanism to increase GFR with decreased RPF as observed.

Question 634: A 23-year-old male is brought into the emergency department by his girlfriend following an argument. The patient’s girlfriend claims that she threatened to break up with him. He then called her saying he was going to kill himself. When she arrived at the patient’s home, she found him lying on the couch with empty alcohol bottles and multiple pill containers. The patient reports he does not remember everything he took, but says he ingested many pills about four hours ago. The patient’s temperature is 99°F (37.2°C), blood pressure is 110/68 mmHg, pulse is 88/min, and respirations are 25/min with an oxygen saturation of 98% O2 on room air. An arterial blood gas (ABG) is obtained, with results shown below: pH: 7.47 pO2: 94 mmHg pCO2: 24 mmHg HCO3-: 22 mEq/L You check on him a couple hours later, and the patient appears agitated. His girlfriend says he keeps grabbing his head, yelling about non-stop ringing in his ears. Labs and a repeat ABG shows: pH: 7.30 pO2: 90 mmHg pCO2: 22 mmHg HCO3-: 9 mEq/L Na+: 144 mEq/L Cl-: 98 mEq/L K+: 3.6 mEq/L BUN: 18 mg/dL Glucose: 100 mg/dL Creatinine: 1.4 mg/dL Which of the following is the best next step in management?

• A. N-acetylcysteine
• B. IV sodium bicarbonate (Correct Answer)
• C. Acetazolamide
• D. Activated charcoal
• E. IV haloperidol

Explanation: ***IV sodium bicarbonate*** - The patient's condition, including **tinnitus**, agitation, and the ABG showing **mixed acid-base disturbance** (initially respiratory alkalosis, progressing to metabolic acidosis), is highly suggestive of **salicylate toxicity**. **IV sodium bicarbonate** is crucial here to **alkalinize the urine** and plasma, which promotes salicylate excretion and reduces its CNS penetration. - The calculated **anion gap** (Na - (Cl + HCO3) = 144 - (98 + 9) = 37) is significantly elevated, indicating a **high anion gap metabolic acidosis**, which is characteristic of salicylate poisoning during the later stages. *N-acetylcysteine* - This is the antidote for **acetaminophen overdose**, which presents differently. The patient's symptoms, especially **tinnitus** and the specific acid-base derangements, are not consistent with acetaminophen toxicity. - While it's important to consider co-ingestions, the dominant clinical picture points away from acetaminophen being the primary or most life-threatening agent here. *Acetazolamide* - **Acetazolamide** is a carbonic anhydrase inhibitor that **promotes renal bicarbonate wasting**, leading to **systemic metabolic acidosis** which would worsen the patient's existing acidosis. - Systemic acidosis increases salicylate penetration into the CNS, potentially worsening neurotoxicity and clinical outcomes. *Activated charcoal* - Activated charcoal is effective in **adsorbing toxins** in the gastrointestinal tract, but its efficacy is time-dependent and significantly reduced if administered several hours post-ingestion. - The patient ingested pills about four hours ago, and while it might be considered early on, it is not the most definitive treatment for established salicylate toxicity with severe acid-base derangements. *IV haloperidol* - **Haloperidol** is an antipsychotic used to treat agitation, but it does not address the underlying **toxidrome** or the severe metabolic derangements. - Treating agitation symptomatically without addressing the root cause, especially in the context of a drug overdose, is inappropriate and could mask critical clinical deterioration.

Question 635: A 45-year-old woman comes to the physician because of a 6-month history of worsening involuntary movement of the left hand. Her symptoms are worse when she feels stressed at work. She has no history of serious illness and takes no medications. Neurological examination shows difficulty initiating movement and a tremor in the left hand at rest. The tremor decreases when the patient is asked to draw a circle. Which of the following is the most appropriate pharmacotherapy?

• A. Trihexyphenidyl
• B. Pramipexole (Correct Answer)
• C. Clonazepam
• D. Donepezil
• E. Methimazole

Explanation: ***Pramipexole*** - This patient's symptoms of difficulty initiating movement, a **resting tremor** that improves with purposeful movement, and worsening with stress are characteristic of **Parkinson's disease**. - **Pramipexole** is a **dopamine agonist** that directly stimulates dopamine receptors, effectively treating motor symptoms in Parkinson's disease. *Trihexyphenidyl* - **Trihexyphenidyl** is an **anticholinergic** agent primarily used for Parkinson's disease symptoms like **tremor** and **dystonia**, especially in younger patients. - However, its side effects (e.g., dry mouth, blurred vision, confusion) are more pronounced in older patients, and **dopamine agonists** are generally preferred for initial treatment of motor symptoms in middle-aged adults. *Clonazepam* - **Clonazepam** is a **benzodiazepine** used to treat anxiety, seizures, and some movement disorders like essential tremor or restless legs syndrome. - It is not a primary treatment for **Parkinson's disease** and would not address the underlying dopaminergic deficit or difficulty initiating movement. *Donepezil* - **Donepezil** is an **acetylcholinesterase inhibitor** used to treat the cognitive symptoms of Alzheimer's disease. - It has no role in the treatment of the motor symptoms of **Parkinson's disease**. *Methimazole* - **Methimazole** is an **antithyroid medication** used to treat hyperthyroidism. - It has no relevance to the neurological symptoms presented by the patient, which are indicative of a movement disorder.

Question 636: A previously healthy 29-year-old man comes to the emergency department because of a 4-day history of abdominal pain and confusion. Prior to the onset of the abdominal pain, he visited a festival where he consumed large amounts of alcohol. Examination shows a distended abdomen, decreased bowel sounds, and diffuse tenderness to palpation. There is motor weakness in the upper extremities. Sensation is decreased over the upper and lower extremities. Laboratory studies show no abnormalities. Which of the following is the most appropriate therapy for this patient's condition?

• A. Chlordiazepoxide
• B. Ethylenediaminetetraacetic acid
• C. Intravenous immunoglobulin
• D. Chloroquine
• E. Hemin (Correct Answer)

Explanation: ***Hemin*** - The patient's presentation with **abdominal pain**, **confusion**, **motor weakness**, **sensory deficits**, and a recent history of **alcohol consumption** (a known trigger) is highly suggestive of **acute intermittent porphyria (AIP)**. - **Hemin** is the most appropriate therapy for acute porphyria attacks as it inhibits **aminolevulinate synthase (ALA synthase)**, the rate-limiting enzyme in heme synthesis, thereby reducing the harmful buildup of neurotoxic porphyrin precursors. *Chlordiazepoxide* - **Chlordiazepoxide** is a **benzodiazepine** used to treat alcohol withdrawal symptoms, anxiety, and insomnia. - While the patient consumed alcohol, the symptoms of abdominal pain, neurologic deficits, and confusion point away from typical alcohol withdrawal and more towards an underlying metabolic disorder. *Ethylenediaminetetraacetic acid* - **Ethylenediaminetetraacetic acid (EDTA)** is a chelating agent primarily used to treat **lead poisoning** by binding to heavy metals. - The symptoms described do not fit the typical presentation of lead poisoning, and there's no indication of heavy metal exposure. *Intravenous immunoglobulin* - **Intravenous immunoglobulin (IVIG)** is used to treat various autoimmune and inflammatory disorders, such as Guillain-Barré syndrome or myasthenia gravis. - While the patient has neurological symptoms, the constellation of abdominal pain and confusion triggered by alcohol is not characteristic of conditions for which IVIG is first-line therapy. *Chloroquine* - **Chloroquine** is an antimalarial drug also used in the treatment of some autoimmune conditions like lupus. - It is **contraindicated** in patients with **porphyrias** (especially porphyria cutanea tarda) as it can exacerbate the condition by interfering with porphyrin metabolism.

Question 637: A 45-year-old male presents to the emergency room for toe pain. He reports that his right great toe became acutely painful, red, and swollen approximately five hours prior. He has had one similar prior episode six months ago that resolved with indomethacin. His medical history is notable for obesity, hypertension, and alcohol abuse. He currently takes hydrochlorothiazide (HCTZ). On physical examination, his right great toe is swollen, erythematous, and exquisitely tender to light touch. The patient is started on a new medication that decreases leukocyte migration and mitosis, and his pain eventually resolves; however, he develops nausea and vomiting as a result of therapy. Which of the following underlying mechanisms of action is characteristic of this patient’s new medication?

• A. Inhibits microtubule polymerization (Correct Answer)
• B. Prevents conversion of xanthine to uric acid
• C. Decreases cyclooxygenase-induced production of prostaglandins
• D. Decreases phospholipase A2-induced production of arachidonic acid
• E. Metabolizes uric acid to water-soluble allantoin

Explanation: ***Inhibits microtubule polymerization*** - The patient's presentation with acute, exquisitely painful, red, and swollen great toe, history of similar episodes, and risk factors (obesity, hypertension, alcohol abuse, HCTZ use) are highly suggestive of **acute gout**. The medication's effect of decreasing **leukocyte migration and mitosis** with side effects of nausea and vomiting points to **colchicine**. - **Colchicine** exerts its anti-inflammatory effects by binding to **tubulin** and inhibiting its polymerization into microtubules, thereby disrupting leukocyte function, migration, and mitosis. *Prevents conversion of xanthine to uric acid* - This mechanism of action describes **allopurinol** and **febuxostat**, which are **xanthine oxidase inhibitors** used for chronic uric acid lowering to prevent future gout attacks, not for acute treatment. - These medications do not primarily decrease leukocyte migration or cause acute gastrointestinal distress like colchicine. *Decreases cyclooxygenase-induced production of prostaglandins* - This is the mechanism of action for **NSAIDs** (like indomethacin, which the patient previously used), which primarily reduce pain and inflammation by inhibiting the synthesis of prostaglandins. - While NSAIDs are effective for acute gout, they do not decrease leukocyte migration and mitosis directly in the way colchicine does. *Decreases phospholipase A2-induced production of arachidonic acid* - This mechanism describes **corticosteroids** (e.g., prednisone), which inhibit the entire pathway of arachidonic acid metabolism, leading to reduced production of inflammatory mediators. - Corticosteroids are used for acute gout, but their mechanism is broader than just affecting leukocyte migration and mitosis, and they don't exclusively cause the specific GI side effects described as the primary concern. *Metabolizes uric acid to water-soluble allantoin* - This describes the mechanism of action for **rasburicase** and **pegloticase**, which are **recombinant uricases** used to break down uric acid in severe cases (e.g., tumor lysis syndrome, refractory chronic gout). - These agents are not typically used for acute gout attacks and act to reduce uric acid levels, not by inhibiting leukocyte function directly as was described.

Question 638: A 40-year-old woman with a recent history of carcinoma of the breast status post mastectomy and adjuvant chemotherapy one week ago presents for follow-up. She reports adequate pain control managed with the analgesic drug she was prescribed. Past medical history is significant for hepatitis C and major depressive disorder. The patient denies any history of smoking or alcohol use but says she is currently using intravenous heroin and has been for the past 10 years. However, she reports that she has been using much less heroin since she started taking the pain medication, which is confirmed by the toxicology screen. Which of the following is the primary mechanism of action of the analgesic drug she was most likely prescribed?

• A. Pure antagonist at opioid receptors
• B. Pure agonist at the µ-opioid receptor (Correct Answer)
• C. Inhibits prostaglandin synthesis
• D. Mixed agonist-antagonist at opioid receptors
• E. Central action via blockade of serotonin reuptake

Explanation: ***Pure agonist at the µ-opioid receptor*** - Opioid analgesics, commonly prescribed for **post-mastectomy pain** and cancer-related pain, primarily exert their effects by acting as **pure agonists at the µ-opioid receptor**. - This activation leads to profound **analgesia** by modulating pain perception and emotional response to pain in the central nervous system. *Pure antagonist at opioid receptors* - A **pure antagonist** would block opioid receptors and **reverse** the effects of opioid agonists, not provide analgesia. - Such drugs are used to treat **opioid overdose** (e.g., naloxone) or to manage addiction by preventing opioid effects. *Inhibits prostaglandin synthesis* - This is the mechanism of action for **NSAIDs** (non-steroidal anti-inflammatory drugs), which primarily treat **mild to moderate pain** and inflammation. - NSAIDs are generally insufficient for severe **post-surgical** or **cancer pain** of the magnitude experienced by this patient. *Mixed agonist-antagonist at opioid receptors* - Mixed agonist-antagonists provide analgesia by acting as agonists at some opioid receptors while acting as antagonists at others (e.g., **buprenorphine**). - While they can provide pain relief, their use in acute severe pain is often limited, and they can sometimes **precipitate withdrawal** in patients chronically using full opioid agonists. *Central action via blockade of serotonin reuptake* - This is the primary mechanism of action for **antidepressants** (SSRIs) and some drugs used for **neuropathic pain** (e.g., tramadol with additional opioid action). - While some antidepressants have analgesic properties, this mechanism alone is not typically the primary one for the potent pain relief needed post-mastectomy, which usually requires an **opioid**.

Question 639: A 52-year-old man presents to his primary care physician complaining of a blistering rash in his inguinal region. Upon further questioning, he also endorses an unintended weight loss, diarrhea, polydipsia, and polyuria. A fingerstick glucose test shows elevated glucose even though this patient has no previous history of diabetes. After referral to an endocrinologist, the patient is found to have elevated serum glucagon and is diagnosed with glucagonoma. Which of the following is a function of glucagon?

• A. Inhibition of insulin release
• B. Increased glycolysis
• C. Increased lipolysis (Correct Answer)
• D. Decreased glycogenolysis
• E. Decreased ketone body production

Explanation: ***Increased lipolysis*** - **Glucagon** promotes the breakdown of **triglycerides** in adipose tissue into **fatty acids** and glycerol, which can then be used for energy. - This metabolic effect contributes to **gluconeogenesis** by providing substrates, helping to raise blood glucose levels. *Inhibition of insulin release* - **Glucagon** generally **stimulates insulin release** in the presence of high blood glucose or certain amino acids, aiming to maintain glucose homeostasis. - Its primary role is to counteract insulin's effects, not inhibit its secretion directly. *Increased glycolysis* - **Glucagon's** main function is to **increase blood glucose**, so it **inhibits glycolysis**, which is the breakdown of glucose for energy, to preserve glucose for other tissues. - Instead, it promotes processes like **gluconeogenesis** and **glycogenolysis** to release glucose. *Decreased glycogenolysis* - **Glucagon** is a key hormone that **stimulates glycogenolysis**, the breakdown of stored **glycogen** in the liver, to release glucose into the bloodstream. - This action helps to rapidly raise blood glucose levels, particularly during periods of fasting or low blood sugar. *Decreased ketone body production* - **Glucagon** generally **promotes ketone body production** (ketogenesis) in the liver by increasing the availability of fatty acids through lipolysis and shifting metabolism towards **fat oxidation**. - This occurs when glucose is scarce, providing an alternative fuel source for the brain and other tissues.

Question 640: A 6-year-old boy is brought to the pediatrician by his foster father because he is concerned about the boy's health. He states that at seemingly random times he will have episodes of severe difficulty breathing and wheezing. Upon questioning, the pediatrician learns that these episodes do not appear to be associated with exercise, irritants, or infection. The pediatrician suspects the child has a type of asthma that is associated with eosinophils. In this type of asthma, what is released by the eosinophils to cause bronchial epithelial damage?

• A. Major basic protein (Correct Answer)
• B. IL-8
• C. Interferon-gamma
• D. IgM
• E. IL-5

Explanation: ***Major basic protein*** - **Eosinophils** release several cytotoxic granule proteins, including **major basic protein (MBP)**, which directly damages bronchial epithelial cells, contributing to airway remodeling and hyperresponsiveness in eosinophilic asthma. - MBP, along with **eosinophil cationic protein (ECP)**, **eosinophil peroxidase (EPO)**, and **eosinophil-derived neurotoxin (EDN)**, are key mediators of eosinophil-induced tissue injury. *IL-8* - **IL-8** (interleukin-8) is a **chemokine** primarily produced by macrophages and endothelial cells, which plays a crucial role in recruiting **neutrophils** to sites of inflammation. - While important in inflammation, IL-8 is not directly released by eosinophils to cause bronchial epithelial damage. *Interferon-gamma* - **Interferon-gamma (IFN-γ)** is a cytokine predominantly produced by **T lymphocytes** and **natural killer (NK) cells**, playing a central role in antiviral and antitumor immunity. - It is a key mediator of **Th1 immune responses** and is not released by eosinophils as a primary effector in bronchial damage. *IgM* - **IgM** is an **antibody** class, primarily involved in the primary immune response and activation of the complement system. - Antibodies are produced by **B lymphocytes** and plasma cells, not by eosinophils, and their primary function is immune recognition rather than direct cytotoxic damage to epithelial cells. *IL-5* - **IL-5** (interleukin-5) is a cytokine that is critical for the **growth, differentiation, and activation of eosinophils** themselves; it is not released *by* eosinophils to cause damage. - It is primarily produced by **Th2 lymphocytes** and mast cells, and is a key driver of eosinophilic inflammation, but it acts *on* eosinophils, rather than being an eosinophil-secreted damaging agent.

Question 641: A 22-year-old woman is brought to the emergency department by her roommate for unusual behavior. They were at a party where alcohol and recreational drugs were consumed, but her roommate is unsure of what she may have taken or had to drink. She is otherwise healthy and does not take any medications. The patient appears anxious. Her temperature is 37.5°C (99.5°F), pulse is 110/min, respiratory rate is 16/min, and blood pressure is 145/82 mmHg. Examination shows dry mucous membranes and bilateral conjunctival injection. Breath sounds are normal. The abdomen is soft and nontender. Further evaluation will most likely reveal which of the following?

• A. Decreased appetite
• B. Impaired reaction time (Correct Answer)
• C. Respiratory depression
• D. Pupillary constriction
• E. Increased libido

Explanation: ***Impaired reaction time*** - The patient's presentation with **anxiety**, **tachycardia**, **hypertension**, **dry mucous membranes**, and **conjunctival injection** are consistent with acute **cannabis intoxication**. - **Cannabis use** is known to cause dose-dependent **psychomotor impairment** including **slowed reaction time**, impaired judgment, and decreased coordination, making tasks like driving dangerous. - This is the most clinically significant finding that would be revealed upon further evaluation (e.g., through psychomotor testing or assessment). *Decreased appetite* - While chronic cannabis use can increase appetite (the "munchies"), acute intoxication does not typically lead to decreased appetite. - Cannabis is more commonly associated with increased appetite rather than decreased appetite, making this option incorrect. *Respiratory depression* - **Opioid overdose** or severe sedative intoxication would typically present with **respiratory depression**, which is not seen in this patient (respiratory rate is normal at 16/min). - Cannabis intoxication generally causes either no significant change in respiratory rate or, less commonly, slight bronchodilation, not respiratory depression. *Pupillary constriction* - **Pupillary constriction** (miosis) is a classic sign of **opioid intoxication** or organophosphate poisoning. - Cannabis intoxication more commonly causes **pupillary dilation** (mydriasis) or no significant change, not constriction. *Increased libido* - While some individuals may report altered sexual experiences under the influence of cannabis, it is not a consistent or clinically significant feature of acute intoxication in an emergency setting. - This is not an objective finding that would likely be revealed upon further evaluation in the emergency department.

Question 642: A 40-year-old woman presents to her primary care physician with a 2-month history of joint pain and morning stiffness that improves through the course of the day. Her left knee also sometimes bothers her. She has taken ibuprofen and Tylenol without relief, and the pain is starting to upset her daily routine. On physical examination, the joints of her fingers and wrists are swollen and tender to touch. Her left knee also feels warm. The strength in both hands is reduced but the sensation is intact. On auscultation, the heart sounds are regular and the lungs are clear. Laboratory findings are presented below: Hemoglobin 12.7 g/dL Hematocrit 37.5% Leukocyte count 5,500/mm3 Mean corpuscular volume 82.2 μm3 Platelet count 190,000/mm3 Erythrocyte sedimentation rate 45 mm/h C-reactive protein 14 mg/dL Anti-citrullinated protein antibody 43 (normal reference values: < 20) Which of the following is the most appropriate treatment for this patient?

• A. Methotrexate (Correct Answer)
• B. Hydroxychloroquine
• C. Infliximab
• D. Etanercept
• E. Ibuprofen

Explanation: ***Methotrexate*** - This patient presents with **symmetrical polyarthritis** (fingers, wrists, knee), **morning stiffness**, elevated **ESR and CRP**, and a **positive anti-citrullinated protein antibody**, all highly suggestive of **rheumatoid arthritis (RA)**. - **Methotrexate** is considered the **first-line disease-modifying antirheumatic drug (DMARD)** for RA due to its efficacy in reducing joint inflammation and preventing joint damage. *Hydroxychloroquine* - While used in RA, **hydroxychloroquine** is generally reserved for **mild RA** or for patients who cannot tolerate methotrexate, and it is less effective for moderate to severe disease. - This patient's symptoms are beginning to upset her daily routine, indicating more than mild disease, and she has **high inflammatory markers** (ESR 45, CRP 14) and a **positive anti-CCP antibody**, suggesting a more aggressive course. *Infliximab* - **Infliximab** is a biologic DMARD (TNF-alpha inhibitor) used for RA, but it is typically reserved for patients with a **suboptimal response to methotrexate** or other conventional DMARDs. - It is not usually prescribed as a first-line treatment due to its higher cost and potential side effects compared to methotrexate. *Etanercept* - **Etanercept** is another biologic DMARD (TNF-alpha inhibitor) used for RA that is also typically reserved for patients who have had an **inadequate response to methotrexate** or other non-biologic DMARDs. - Like infliximab, it is not a first-line agent, and initial management begins with conventional DMARDs. *Ibuprofen* - **Ibuprofen** is a **nonsteroidal anti-inflammatory drug (NSAID)** that provides symptomatic relief from pain and inflammation but does **not modify the disease course** or prevent joint damage in RA. - The patient has already tried ibuprofen without relief, and NSAIDs are used as adjuncts to DMARDs, not as monotherapy for chronic inflammatory conditions like RA.

Question 643: A 62-year-old woman presents to her primary care physician for her annual check-up. She has no current complaints and says that she has been healthy over the last year. Her past medical history is significant for obesity and diabetes that is well controlled on metformin. She does not smoke and drinks socially. Selected lab results are shown below: High-density lipoprotein: 48 mg/dL Low-density lipoprotein: 192 mg/dL Triglycerides: 138 mg/dL Given these results, the patient is placed on the drug that will be the best therapy for these findings. Which of the following is a potential side effect of this treatment?

• A. Gallstones
• B. Pruritus
• C. Gastrointestinal upset
• D. Malabsorption
• E. Hepatotoxicity (Correct Answer)

Explanation: ***Hepatotoxicity*** - This patient has significantly elevated **LDL cholesterol**, necessitating treatment with a **statin drug** (HMG-CoA reductase inhibitor). - A known, though rare, side effect of statin therapy is **hepatotoxicity**, which requires monitoring of **liver enzymes**. *Gallstones* - **Fibrates** are a class of lipid-lowering drugs that can increase the risk of **gallstone formation** by increasing cholesterol secretion into bile. - While fibrates lower triglycerides, they are not the primary treatment for significantly elevated LDL as seen in this patient. *Pruritus* - **Niacin** (vitamin B3) is a lipid-lowering agent known for causing significant **cutaneous flushing and pruritus** due to prostaglandin release. - Niacin is not the first-line treatment for high LDL, especially given the side effect burden. *Gastrointestinal upset* - **Bile acid sequestrants** (e.g., cholestyramine, colestipol) often cause gastrointestinal side effects such as **constipation, bloating, and nausea**. - These drugs are typically used in combination with statins or as an alternative in statin-intolerant patients, but statins are the initial choice for high LDL. *Malabsorption* - **Ezetimibe**, a cholesterol absorption inhibitor, can rarely cause gastrointestinal discomfort, but it is not typically associated with widespread **malabsorption of nutrients**. - Its primary role is to block cholesterol absorption in the small intestine, leading to a modest reduction in LDL, often as an add-on therapy.

Question 644: A 19-year-old woman presents to the ED after multiple episodes of vomiting in the last 6 hours. The vomitus is non-bloody and non-bilious. The vomiting started shortly after she began having a throbbing, unilateral headache and associated photophobia. She has had several similar headaches in the past. Her vital signs are unremarkable. Which of the following is an appropriate therapy for this patient's vomiting?

• A. Ergonovine
• B. Propranolol
• C. Chlorpromazine (Correct Answer)
• D. Amitriptyline
• E. Calcium channel blockers

Explanation: ***Chlorpromazine*** - Patients experiencing **acute migraine attacks with severe nausea and vomiting** can benefit from antiemetics, particularly those with additional dopamine antagonist properties like chlorpromazine. - This medication helps in reducing both the **headache severity** and the associated emesis due to its broader neurological effects on **dopaminergic pathways**. *Ergonovine* - **Ergonovine is an ergot alkaloid** primarily used to prevent or treat **postpartum hemorrhage** by inducing uterine contractions. - It is not indicated for the treatment of migraine-associated nausea and vomiting and could potentially worsen symptoms or cause **vasospasm**. *Propranolol* - **Propranolol is a beta-blocker primarily used for migraine prophylaxis**, meaning it helps prevent migraines from occurring. - It is not effective for **acute treatment of active migraine headaches** or for the immediate relief of associated vomiting. *Amitriptyline* - **Amitriptyline is a tricyclic antidepressant** commonly prescribed for **migraine prophylaxis** in patients with frequent attacks. - Like propranolol, it is a **preventive medication** and is not suitable for the acute management of migraine symptoms, including vomiting. *Calcium channel blockers* - **Calcium channel blockers** like verapamil are sometimes used for **migraine prophylaxis**, particularly in patients who do not respond to or tolerate other preventive therapies. - They are not considered a first-line treatment for **acute migraine attacks or associated vomiting**.

Question 645: A 56 year old female comes to the ED complaining of moderate right eye pain, headache, and acute onset of blurry vision, which she describes as colored halos around lights. She was watching a movie at home with her husband about an hour ago when the pain began. On physical exam of her right eye, her pupil is mid-dilated and unresponsive to light. Her right eyeball is firm to pressure. Intraocular pressure (IOP) measured with tonometer is elevated at 36mmHg. Which of the following is the most appropriate emergency treatment?

• A. Laser peripheral iridotomy
• B. Epinephrine ophthalmic solution
• C. Anti-cholinergic ophthalmic solution
• D. NSAID ophthalmic solution
• E. Timolol ophthalmic solution (Correct Answer)

Explanation: ***Timolol ophthalmic solution*** - The patient presents with symptoms and signs consistent with **acute angle-closure glaucoma** (AAGC), including acute eye pain, headache, colored halos, mid-dilated non-reactive pupil, firm eyeball, and elevated IOP. **Timolol** is a **beta-blocker** that reduces aqueous humor production, thereby lowering intraocular pressure. - Emergency treatment for AAGC focuses on rapidly lowering IOP to prevent permanent vision loss, often involving a combination of topical medications like beta-blockers (e.g., timolol), **alpha-agonists**, and **carbonic anhydrase inhibitors**, along with systemic agents if needed. *Laser peripheral iridotomy* - This is a definitive treatment for AAGC, creating an opening in the iris to equalize pressure between the anterior and posterior chambers; however, it is typically performed **after initial medical management** has reduced the IOP. - While it addresses the underlying anatomical cause, it is not the immediate first-line emergency treatment to acutely lower a critically high IOP. *Epinephrine ophthalmic solution* - Epinephrine can cause **pupil dilation (mydriasis)**, which can further exacerbate angle closure in AAGC by pushing the iris into the angle. - Therefore, it is **contraindicated** in acute angle-closure glaucoma. *Anti-cholinergic ophthalmic solution* - Anti-cholinergic agents like atropine cause **pupil dilation (mydriasis)** and relaxation of the ciliary muscle, pulling the iris posteriorly and potentially worsening angle closure. - These are **contraindicated** in acute angle-closure glaucoma as they can worsen the condition by further narrowing the anterior chamber angle. *NSAID ophthalmic solution* - NSAID ophthalmic solutions are primarily used to treat **ocular inflammation** and **pain** in conditions such as postoperative inflammation or allergic conjunctivitis. - They do not directly lower intraocular pressure and are therefore not an appropriate emergency treatment for acute angle-closure glaucoma.

Question 646: A 59-year-old woman comes to the clinic complaining of an intermittent, gnawing epigastric pain for the past 2 months. The pain is exacerbated with food and has been getting progressively worse. The patient denies any weight changes, nausea, vomiting, cough, or dyspepsia. Medical history is significant for chronic back pain for which she takes ibuprofen. Her father passed at the age of 55 due to pancreatic cancer. Labs were unremarkable except for a mild decrease in hemoglobin. What medication is most appropriate to be switched to from the current medication at this time?

• A. Naproxen
• B. Ranitidine
• C. Aspirin
• D. Acetaminophen
• E. Omeprazole (Correct Answer)

Explanation: ***Omeprazole*** - The patient's symptoms of **gnawing epigastric pain** exacerbated by food, along with a history of chronic ibuprofen use and mild anemia, strongly suggest a **peptic ulcer**. - **Omeprazole**, a proton pump inhibitor (PPI), is the most effective medication for healing ulcers and preventing their recurrence by reducing gastric acid production. *Naproxen* - **Naproxen** is a non-steroidal anti-inflammatory drug (NSAID), similar to ibuprofen, and would likely worsen the patient's symptoms by further inhibiting prostaglandin synthesis necessary for gastric mucosal protection. - Continuing an NSAID without gastroprotection would increase the risk of ulcer complications, such as bleeding. *Ranitidine* - **Ranitidine** is an H2-receptor antagonist, which reduces stomach acid, but it is generally less potent than PPIs like omeprazole for treating and healing ulcers, especially in cases of NSAID-induced gastropathy. - Its efficacy for advanced or severe peptic ulcer disease is inferior to that of PPIs. - Note: Ranitidine was withdrawn from the US market in 2020 due to NDMA contamination; alternative H2 blockers include famotidine. *Aspirin* - **Aspirin** is an NSAID with significant antiplatelet effects and is well-known to cause and exacerbate peptic ulcers and gastrointestinal bleeding. - Switching to aspirin would be contraindicated in the presence of strong evidence suggesting active peptic ulcer disease. *Acetaminophen* - **Acetaminophen** (paracetamol) is an analgesic that does not have significant anti-inflammatory properties and is not associated with gastric irritation or ulcer formation. - While it could be used for pain relief, it does not address the underlying issue of peptic ulcer disease or provide gastroprotection, making it an inadequate switch for effective management.

Question 647: An investigator is studying the metabolism of an experimental drug that is known to have first order kinetics. Immediately after administering an intravenous dose of the drug to a patient, the serum concentration is 60 U/L. 3 hours later, the serum concentration of the drug is 30 U/L. 9 hours after administration, the serum concentration of the drug is most likely to be which of the following?

• A. 5 U/L
• B. 0 U/L
• C. 15 U/L
• D. 7.5 U/L (Correct Answer)
• E. 3.75 U/L

Explanation: ***7.5 U/L*** - The drug follows **first-order kinetics**, meaning a constant fraction of the drug is eliminated per unit time, resulting in a constant **half-life**. - The concentration halved from 60 U/L to 30 U/L in 3 hours, indicating a **half-life of 3 hours**. Thus, after another 3 hours (total 6 hours), the concentration would be 15 U/L, and after yet another 3 hours (total 9 hours), it would be **7.5 U/L**. *5 U/L* - This answer suggests a slower rate of elimination than calculated for first-order kinetics with a 3-hour half-life. - If the half-life were longer than 3 hours, then 5 U/L might be a plausible concentration at 9 hours. *0 U/L* - For drugs following **first-order kinetics**, the concentration approaches zero asymptotically and never truly reaches zero within a finite timeframe, unless the total elimination has significantly exceeded multiple half-lives. - This answer indicates complete elimination, which is incorrect for a drug still undergoing elimination after 9 hours. *15 U/L* - This would be the concentration at 6 hours (two half-lives) after administration, not 9 hours (three half-lives). - It would occur if only two half-life periods had passed instead of three. *3.75 U/L* - This value represents the concentration after a fourth half-life (12 hours), not three half-lives (9 hours). - This would be the concentration after 12 hours had passed from the initial administration.

Question 648: A 15-year-old adolescent boy presents to his pediatrician for his scheduled follow-up after he was prescribed low-dose methylphenidate for treatment of attention-deficit/hyperactivity disorder 4 weeks ago. On follow-up, his mother reports mild improvement in his symptoms, but she also notes that his appetite has decreased significantly after starting the medication. This has led to a 1.6 kg (3.5 lb) weight loss over the last 4 weeks. His mother also reports that she no longer wants to continue the drug. Which of the following is the next drug of choice for pharmacological management of the condition?

• A. Imipramine
• B. Dextroamphetamine
• C. Clonidine
• D. Atomoxetine (Correct Answer)
• E. Dexmethylphenidate

Explanation: ***Atomoxetine*** - This patient is experiencing significant **appetite suppression and weight loss** with methylphenidate, a common side effect of stimulants. Atomoxetine is a **non-stimulant** medication that can effectively treat ADHD without significantly affecting appetite. - Atomoxetine is a **norepinephrine reuptake inhibitor** and is considered a second-line option for ADHD, especially when stimulants are not tolerated or are contraindicated. *Imipramine* - **Imipramine** is a **tricyclic antidepressant (TCA)** that can be used off-label for ADHD, but it is not typically considered a second-line drug of choice due to its potential for more significant side effects, including **cardiac abnormalities**. - Its use for ADHD would generally be reserved for cases where other approved medications, including non-stimulants, have failed or are not tolerated. *Dextroamphetamine* - **Dextroamphetamine** is another **stimulant medication** with a mechanism of action similar to methylphenidate, and it carries the same risk profile for **appetite suppression and weight loss**. - Switching to another stimulant like dextroamphetamine would likely lead to similar undesirable side effects and is therefore not the next drug of choice in this scenario. *Clonidine* - **Clonidine** is an **alpha-2 adrenergic agonist** that can be used to treat ADHD, particularly in cases with prominent **hyperactivity, impulsivity, or co-morbid tic disorders**. - While it is a non-stimulant, it is generally considered a third-line option or an adjunct therapy, not typically the next monotherapy choice after a stimulant fails due to side effects. *Dexmethylphenidate* - **Dexmethylphenidate** is the **d-isomer of methylphenidate**, and it also works as a **stimulant**. - It has a similar efficacy and side-effect profile to methylphenidate, including **appetite suppression and weight loss**, making it an inappropriate substitute in this situation.

Question 649: A 58-year-old man presents to his primary care physician with a 3-week history of increasing pain in his legs and feet. Specifically, he says that he has been getting electric shock sensations that started in his feet, but have progressed up his leg. In addition, the pain is accompanied by numbness and tingling in his hands and feet bilaterally. His past medical history is significant for poorly controlled type 2 diabetes mellitus. Given these symptoms, his physician prescribes a new drug to help him cope with these symptoms. Which of the following is the mechanism of action for the medication that was most likely prescribed in this case?

• A. Serotonin norepinephrine reuptake inhibitor (Correct Answer)
• B. Selective serotonin reuptake inhibitor
• C. Binding to mu opioid receptors
• D. Increased duration of GABA channel opening
• E. Increased frequency of GABA channel opening

Explanation: ***Serotonin norepinephrine reuptake inhibitor*** - The patient's symptoms of **electric shock sensations** and **neuropathic pain** (numbness, tingling) in a diabetic patient suggest **diabetic neuropathy**. - **SNRIs** such as Duloxetine and Venlafaxine are first-line agents for treating **neuropathic pain**, including diabetic neuropathy, by modulating pain pathways in the central nervous system. *Selective serotonin reuptake inhibitor* - While SSRIs can be used to treat depression, they are generally **not effective** for the treatment of **neuropathic pain**. - Their primary mechanism is to increase serotonin levels, which is less impactful on neuropathic pain than the combined serotonin and norepinephrine effects of SNRIs. *Binding to mu opioid receptors* - Opioids work by binding to **mu opioid receptors** and are effective analgesics, but they are generally **reserved for severe pain** and are associated with significant side effects and risk of dependence. - They are not considered a first-line treatment for chronic neuropathic pain due to concerns about addiction and limited long-term efficacy. *Increased duration of GABA channel opening* - This is the mechanism of action for **barbiturates**, which act by increasing the **duration of chloride channel opening** through GABA-A receptors. - Barbiturates are potent sedatives and anticonvulsants but are **not used for neuropathic pain** due to their narrow therapeutic index and significant side effects. *Increased frequency of GABA channel opening* - This is the mechanism for **benzodiazepines**, which act on GABA-A receptors to increase the **frequency of chloride channel opening**. - Benzodiazepines are primarily used as anxiolytics, sedatives, and anticonvulsants, and are **not indicated** for the treatment of neuropathic pain due to their sedative effects and lack of direct analgesic efficacy in this context.

Question 650: A 69-year-old man with history of coronary artery disease necessitating angioplasty and stent placement presents to the ED due to fever, chills, and productive cough for one day. He is started on levofloxacin and admitted because of his comorbidity and observed tachypnea of 35 breaths per minute. He is continued on his home medications including aspirin, clopidogrel, metoprolol, and lisinopril. He cannot ambulate as frequently as he would like due to his immediate dependence on oxygen. What intervention should be provided for deep venous thrombosis prophylaxis in this patient while hospitalized?

• A. Aspirin and clopidogrel are sufficient
• B. Warfarin
• C. Aspirin is sufficient; hold clopidogrel
• D. Clopidogrel is sufficient; hold aspirin
• E. Low molecular weight heparin (Correct Answer)

Explanation: ***Low molecular weight heparin*** - This patient has multiple risk factors for DVT, including **immobility**, **acute illness (pneumonia)**, and **advanced age**. **Low molecular weight heparin (LMWH)** is the preferred pharmacological agent for DVT prophylaxis in hospitalized medical patients due to its efficacy and predictable pharmacokinetics. - While the patient is on **antiplatelet agents**, these are not sufficient for DVT prophylaxis, which requires anticoagulation focusing on the clotting cascade, not platelet aggregation. *Aspirin and clopidogrel are sufficient* - **Aspirin** and **clopidogrel** are **antiplatelet agents** that prevent arterial thrombosis, primarily by inhibiting platelet aggregation. - They do not adequately prevent **venous thromboembolism (VTE)**, which primarily involves fibrin clot formation and requires anticoagulants targeting the clotting cascade. *Warfarin* - **Warfarin** is an effective anticoagulant but has a **slow onset of action** (several days to therapeutic effect) and requires **frequent monitoring (INR)**. - It is not suitable for **immediate DVT prophylaxis** in an acutely ill, hospitalized patient where rapid and predictable anticoagulation is needed. *Aspirin is sufficient; hold clopidogrel* - As an **antiplatelet agent**, **aspirin** alone is insufficient for DVT prophylaxis, which mechanisms differ from arterial thrombosis. - Holding **clopidogrel** in a patient with a recent coronary stent could increase the risk of **stent thrombosis**, which is a significant and potentially life-threatening complication. *Clopidogrel is sufficient; hold aspirin* - Similar to aspirin, **clopidogrel** is an antiplatelet agent and therefore **insufficient for DVT prophylaxis** alone. - Holding **aspirin** in a patient with a recent coronary stent could also increase the risk of **stent thrombosis**, which is critically important to prevent.

Question 651: A 64-year-old male presents to the emergency room with difficulty breathing. He recently returned to the USA following a trip to Singapore. He reports that he developed pleuritic chest pain, shortness of breath, and a cough. His temperature is 99°F (37.2°C), blood pressure is 140/85 mmHg, pulse is 110/min, and respirations are 24/min. A spiral CT reveals a pulmonary embolus in the right segmental pulmonary artery. Results from a complete blood count are all within normal limits. He is admitted and started on unfractionated heparin. Four days later, the patient develops unprovoked epistaxis. A complete blood count reveals the following: Leukocyte count: 7,000/mm^3 Hemoglobin: 14 g/dl Hematocrit: 44% Platelet count 40,000/mm^3 What is the underlying pathogenesis of this patient’s condition?

• A. ADAMTS13 deficiency
• B. Loss of vitamin K-dependent clotting factors
• C. Autoantibodies directed against platelet factor 4 (Correct Answer)
• D. Medication-mediated platelet aggregation
• E. Autoantibodies directed against GPIIb/IIIa

Explanation: ***Autoantibodies directed against platelet factor 4*** - The patient developed **thrombocytopenia** (platelet count 40,000/mm^3) and bleeding (epistaxis) after starting **unfractionated heparin**, which is highly suggestive of **heparin-induced thrombocytopenia (HIT)**. - HIT is characterized by the formation of **autoantibodies against the heparin-platelet factor 4 (PF4) complex**, leading to platelet activation and consumption, paradoxically increasing the risk of both bleeding and thrombosis. *ADAMTS13 deficiency* - **ADAMTS13 deficiency** causes **thrombotic thrombocytopenic purpura (TTP)**, characterized by microangiopathic hemolytic anemia, acute kidney injury, neurologic symptoms, fever, and severe thrombocytopenia. - While TTP presents with thrombocytopenia, it is not typically associated with heparin use and lacks the specific clinical context of HIT. *Loss of vitamin K-dependent clotting factors* - **Loss of vitamin K-dependent clotting factors** (factors II, VII, IX, X, and proteins C and S) typically occurs with **warfarin overdose** or severe vitamin K deficiency, leading to prolongation of PT/INR and increased bleeding risk. - This condition primarily affects coagulation factor synthesis rather than platelet count, which would not explain the observed thrombocytopenia. *Medication-mediated platelet aggregation* - **Medication-mediated platelet aggregation** can occur with certain drugs like **NSAIDs** or **COX-2 inhibitors**, leading to reduced platelet function and increased bleeding. - This mechanism inhibits platelet function but does not cause the severe thrombocytopenia seen in this patient, which is characteristic of HIT. *Autoantibodies directed against GPIIb/IIIa* - **Autoantibodies directed against GPIIb/IIIa** cause **immune thrombocytopenia (ITP)**, characterized by isolated thrombocytopenia, often without an inciting drug like heparin. - While ITP presents with low platelet counts, the specific trigger of heparin in this patient points away from primary ITP towards drug-induced thrombocytopenia.

Question 652: A 52-year-old tow truck driver presents to the emergency room in the middle of the night complaining of sudden onset right ankle pain. He states that the pain came on suddenly and woke him up from sleep. It was so severe that he had to call an ambulance to bring him to the hospital since he was unable to drive. He has a history of hypertension and type 2 diabetes mellitus, for which he takes lisinopril and metformin. He has no other medical problems. The family history is notable for hypertension on his father's side. The vital signs include: blood pressure 126/86 mm Hg, heart rate 84/min, respiratory rate 14/min, and temperature 37.2°C (99.0°F). On physical exam, the patient's right ankle is swollen, erythematous, exquisitely painful, and warm to the touch. An arthrocentesis is performed and shows negatively birefringent crystals on polarized light. Which of the following is the best choice for treating this patient's pain?

• A. Administer colchicine (Correct Answer)
• B. Administer febuxostat
• C. Administer indomethacin
• D. Administer allopurinol
• E. Administer probenecid

Explanation: ***Administer colchicine*** - The patient's presentation with **sudden onset, severe right ankle pain**, **swelling**, **erythema**, and **warmth** strongly suggests an acute gout attack, confirmed by **negatively birefringent crystals** (monosodium urate) on arthrocentesis. - **Colchicine** is a **first-line treatment for acute gout** and is particularly appropriate for this patient given his comorbidities (**type 2 diabetes** and **hypertension**) and concomitant use of **lisinopril** (ACE inhibitor). - Colchicine is **most effective when started within 36 hours** of symptom onset and has a **favorable safety profile** compared to NSAIDs in patients with cardiovascular and renal risk factors. - It works by inhibiting microtubule polymerization, thereby reducing neutrophil migration and inflammatory response in the affected joint. *Administer indomethacin* - **Indomethacin** and other **NSAIDs** are also first-line options for acute gout in healthy individuals due to their potent anti-inflammatory effects. - However, NSAIDs are **relatively contraindicated** in this patient because they can: - **Worsen renal function**, especially concerning in patients taking ACE inhibitors like lisinopril - Cause **fluid retention** and exacerbate hypertension - Increase **cardiovascular risk** in patients with diabetes - While effective for gout, NSAIDs are not the best choice given this patient's specific comorbidities. *Administer febuxostat* - **Febuxostat** is a **xanthine oxidase inhibitor** used for the prophylactic management of chronic gout by lowering uric acid levels. - It is **not indicated for treating acute gout attacks** as it does not provide immediate pain relief and can worsen an acute flare if initiated during the attack. - Febuxostat should be started only after the acute attack has resolved. *Administer allopurinol* - **Allopurinol** is another **xanthine oxidase inhibitor** used for the long-term management of chronic gout by reducing uric acid production. - It is **contraindicated during an acute gout flare** because initiating or changing the dose can precipitate or prolong the attack due to rapid changes in serum uric acid levels. - Like febuxostat, it should be started after the acute episode resolves. *Administer probenecid* - **Probenecid** is a **uricosuric agent** that increases renal uric acid excretion and is used for the long-term management of chronic gout in patients who underexcrete uric acid. - It is **not effective for acute gout attacks** and should not be initiated during a flare as it can worsen symptoms. - Probenecid is also contraindicated in patients with renal impairment.

Question 653: A 34-year-old woman presents to the emergency department with sudden onset of painful vision loss in her left eye. The patient is otherwise healthy with a history only notable for a few emergency department presentations for numbness and tingling in her extremities with no clear etiology of her symptoms. Her temperature is 100°F (37.8°C), blood pressure is 122/83 mmHg, pulse is 100/min, respirations are 15/min, and oxygen saturation is 98% on room air. Examination of the patient's cranial nerves reveals an inability to adduct the left eye when the patient is asked to look right. Which of the following is the most appropriate treatment?

• A. Methylprednisolone (Correct Answer)
• B. Rituximab
• C. Glatiramer acetate
• D. Estriol
• E. Interferon-beta

Explanation: ***Methylprednisolone*** - This patient presents with symptoms highly suggestive of an acute **multiple sclerosis (MS) exacerbation**, including painful vision loss (optic neuritis), prior neurological symptoms (numbness and tingling), and internuclear ophthalmoplegia (inability to adduct one eye while the other abducts, indicating a lesion in the **medial longitudinal fasciculus**). - High-dose intravenous **methylprednisolone** is the first-line treatment for acute MS relapses to reduce inflammation and shorten the duration of the exacerbation. *Rituximab* - **Rituximab** is an anti-CD20 monoclonal antibody used as a disease-modifying therapy for MS, particularly for **relapsing-remitting MS (RRMS)** and **primary progressive MS (PPMS)**. - It is not used for the acute treatment of an MS exacerbation, but rather for long-term disease management. *Glatiramer acetate* - **Glatiramer acetate** is an immunomodulatory drug used as a disease-modifying therapy for **relapsing forms of MS**. - It helps reduce the frequency of relapses and slow disease progression but is not indicated for the immediate treatment of an acute flare-up. *Estriol* - **Estriol** is a weak estrogen that has shown some promise in clinical trials for MS, particularly in reducing relapse rates during pregnancy and in postpartum women. - However, it is **not an approved treatment** for MS and certainly not for an acute exacerbation. *Interferon-beta* - **Interferon-beta** is a common **disease-modifying therapy** for relapsing forms of MS, reducing the frequency and severity of relapses. - Like glatiramer acetate and rituximab, it is used for chronic management rather than for treating an acute MS exacerbation.

Question 654: A 24-year-old woman in graduate school comes to the physician for recurrent headaches. The headaches are unilateral, throbbing, and usually preceded by blurring of vision. The symptoms last between 12 and 48 hours and are only relieved by lying down in a dark room. She has approximately two headaches per month and has missed several days of class because of the symptoms. Physical examination is unremarkable. The patient is prescribed an abortive therapy that acts by inducing cerebral vasoconstriction. Which of the following is the most likely mechanism of action of this drug?

• A. Activation of 5-HT1 receptors (Correct Answer)
• B. Inhibition of 5-HT and NE reuptake
• C. Inhibition of β1- and β2-adrenergic receptors
• D. Inhibition of voltage-dependent Na+ channels
• E. Inactivation of GABA degradation

Explanation: ***Activation of 5-HT1 receptors*** - The patient's symptoms are consistent with **migraine headaches**, which are characterized by unilateral, throbbing pain, visual aura (blurring of vision), and relief by lying down in a dark room. - Triptan medications, commonly used as **abortive therapy** for migraines, act as **5-HT1B/1D receptor agonists**, leading to **cerebral vasoconstriction** and inhibition of neuropeptide release. *Inhibition of 5-HT and NE reuptake* - This mechanism describes the action of **serotonin-norepinephrine reuptake inhibitors (SNRIs)**, which are primarily used as antidepressants and sometimes for neuropathic pain. - While some antidepressants can be used for **migraine prophylaxis**, they do not act as acute abortive therapy to induce cerebral vasoconstriction. *Inhibition of β1- and β2-adrenergic receptors* - This mechanism describes the action of **beta-blockers**, which are commonly used for conditions like hypertension, angina pectoris, and sometimes as **migraine prophylaxis**. - Beta-blockers reduce heart rate and blood pressure and do not induce acute cerebral vasoconstriction for migraine abortion. *Inhibition of voltage-dependent Na+ channels* - This mechanism describes the action of certain **antiepileptic drugs** (e.g., carbamazepine, lamotrigine) and **local anesthetics**, which are used to stabilize neuronal membranes and prevent excessive firing. - Some antiepileptics (e.g., topiramate, valproate) can be used for **migraine prophylaxis**, but they do not mediate acute vasoconstriction for abortive treatment. *Inactivation of GABA degradation* - This mechanism describes the action of drugs like **valproic acid** or **vigabatrin**, which increase GABA levels in the brain to inhibit neuronal activity, commonly used for seizure disorders. - While valproic acid can be used for **migraine prophylaxis**, it does not achieve acute migraine relief through cerebral vasoconstriction.

Question 655: A 38-year-old woman comes to the physician because of a 4-month history of crampy abdominal pain, recurrent watery diarrhea, and a 2.5-kg (5.5-lb) weight loss. Her husband has noticed that after meals, her face and neck sometimes become red, and she develops shortness of breath and starts wheezing. Examination shows a grade 3/6 systolic murmur heard best at the left lower sternal border. The abdomen is soft, and there is mild tenderness to palpation with no guarding or rebound. Without treatment, this patient is at greatest risk of developing which of the following conditions?

• A. T-cell lymphoma
• B. Achlorhydria
• C. Pigmented dermatitis (Correct Answer)
• D. Megaloblastic anemia
• E. Laryngeal edema

Explanation: ***Pigmented dermatitis*** - This patient has **carcinoid syndrome** (flushing, diarrhea, wheezing, heart murmur from right-sided valvular disease). - Without treatment, patients are at risk of developing **pellagra** (pigmented dermatitis, diarrhea, dementia). - **Pellagra** results from **niacin (vitamin B3) deficiency** because tryptophan is diverted away from niacin synthesis to produce excessive **serotonin** by the carcinoid tumor. - The classic triad of pellagra is the "3 Ds": **Dermatitis** (photosensitive, pigmented skin changes), **Diarrhea**, and **Dementia**. *T-cell lymphoma* - There is **no established association** between carcinoid syndrome and T-cell lymphoma. - While neuroendocrine tumors can metastasize, they do not predispose to lymphoid malignancies. *Achlorhydria* - **Achlorhydria** can be associated with **gastric type 1 carcinoid tumors** that occur in the setting of chronic atrophic gastritis and pernicious anemia. - However, this patient has **metastatic carcinoid syndrome** (requires liver metastases for systemic symptoms), not a localized gastric carcinoid. - Achlorhydria would precede the gastric carcinoid, not develop as a complication of systemic carcinoid syndrome. *Laryngeal edema* - **Laryngeal edema** is not a recognized complication of carcinoid syndrome. - While carcinoid crisis can cause severe bronchospasm and flushing, laryngeal edema is more typical of **angioedema** from ACE inhibitor use or C1 esterase inhibitor deficiency. *Megaloblastic anemia* - **Megaloblastic anemia** results from **vitamin B12 or folate deficiency**. - This is not a typical complication of carcinoid syndrome, which primarily affects tryptophan/niacin metabolism, not B12 or folate.

Question 656: A 20-year-old man is found lying unconscious on the floor of his room by his roommate. The paramedics arrive at the site and find him unresponsive with cold, clammy extremities and constricted, non-reactive pupils. He smells of alcohol and his vital signs show the following: blood pressure 110/80 mm Hg, pulse 100/min, and respiratory rate 8/min. Intravenous access is established and dextrose is administered. The roommate suggests the possibility of drug abuse by the patient. He says he has seen the patient sniff a powdery substance, and he sees the patient inject himself often but has never confronted him about it. After the initial assessment, the patient is given medication and, within 5–10 minutes of administration, the patient regains consciousness and his breathing improves. He is alert and cooperative within the next few minutes. Which of the following drugs was given to this patient to help alleviate his symptoms?

• A. Ethanol
• B. Naloxone (Correct Answer)
• C. Dextrose
• D. Atropine
• E. Methadone

Explanation: ***Naloxone*** - The patient's presentation with **unconsciousness**, **respiratory depression** (8 breaths/min), **constricted pupils**, and rapid improvement after medication strongly suggests an **opioid overdose**. - **Naloxone** is an **opioid antagonist** that rapidly reverses the effects of opioid overdose by competing for opioid receptors. *Ethanol* - While the patient smells of alcohol, **ethanol** intoxication typically presents with a different constellation of symptoms and does not usually cause such profound and rapid respiratory depression with pinpoint pupils that are instantly reversible by naloxone. - Furthermore, administering more ethanol would worsen his condition, not improve it. *Dextrose* - **Dextrose** was already administered and did not lead to improvement, ruling out **hypoglycemia** as the primary cause of unconsciousness. - While hypoglycemia can cause unconsciousness, it does not typically lead to **respiratory depression** or **pinpoint pupils**. *Atropine* - **Atropine** is an **anticholinergic** agent used to treat bradycardia or organophosphate poisoning, which would present with different symptoms such as excessive salivation, lacrimation, and bronchorrhea. - It would worsen constricted pupils rather than being beneficial in this scenario because it causes pupillary dilation (mydriasis). *Methadone* - **Methadone** is a **long-acting opioid agonist** used for opioid addiction treatment or severe pain. Administering methadone to someone suffering from an opioid overdose would worsen their condition due to its opioid effects. - It has a slow onset of action and is not used as an acute rescue medication for overdose.

Question 657: A 65-year-old man presents to the physician with pain in his right calf over the last 3 months. He mentions that the pain typically occurs after he walks approximately 100 meters and subsides after resting for 5 minutes. His medical history is significant for hypercholesterolemia, ischemic heart disease, and bilateral knee osteoarthritis. His current daily medications include aspirin and simvastatin, which he has taken for the last 2 years. The physical examination reveals diminished popliteal artery pulses on the right side. Which of the following drugs is most likely to improve this patient's symptoms?

• A. Cilostazol (Correct Answer)
• B. Acetaminophen
• C. Isosorbide dinitrate
• D. Ranolazine
• E. Amlodipine

Explanation: ***Cilostazol*** - This patient presents with symptoms highly suggestive of **peripheral artery disease (PAD)**, characterized by **intermittent claudication** (calf pain with exertion, relieved by rest) and diminished peripheral pulses, exacerbated by risk factors like hypercholesterolemia and ischemic heart disease. - **Cilostazol** is a **phosphodiesterase-3 inhibitor** that increases **cAMP** in platelets and vascular smooth muscle, leading to **vasodilation** and **inhibition of platelet aggregation**, effectively improving claudication symptoms and increasing walking distance in patients with PAD. *Acetaminophen* - **Acetaminophen** is an **analgesic** and **antipyretic** but does not address the underlying pathophysiology of peripheral artery disease or directly improve blood flow. - While it could help with pain management, it would not improve the patient's **walking distance** or the fundamental issue of **ischemia**. *Isosorbide dinitrate* - **Isosorbide dinitrate** is a **nitrate** primarily used to treat **angina pectoris** by causing **venodilation** and reducing cardiac preload, and arterial dilation at higher doses. - It would not specifically address the **intermittent claudication** caused by atherosclerotic peripheral artery disease in the lower extremities. *Ranolazine* - **Ranolazine** is an anti-anginal agent that **inhibits the late sodium current** in cardiac myocytes, improving myocardial oxygen supply/demand balance. - It is used for **chronic stable angina** but does not have a role in treating peripheral artery disease or improving symptoms of claudication. *Amlodipine* - **Amlodipine** is a **dihydropyridine calcium channel blocker** used primarily for **hypertension** and **angina**. - While it causes vasodilation, it does not specifically improve the symptoms of **intermittent claudication** in PAD and is not a first-line treatment for this condition.

Question 658: A 32-year-old woman brought to the emergency department because of a 1-week history of palpitations and shortness of breath. She has congestive heart failure. Current medications include furosemide, lisinopril, and atenolol. Her pulse is 124/min and irregularly irregular, and blood pressure is 110/70 mm Hg. Examination shows coarse crackles over the lower lung fields bilaterally. Treatment with digoxin is started. Five days later, an ECG shows prolongation of the PR interval. Which of the following is the most likely explanation for the observed effect of this drug?

• A. Activation of Na+/Ca2+ exchanger
• B. Increase in vagal tone (Correct Answer)
• C. Inhibition of myocardial Na+/K+ ATPase
• D. Decrease in intracellular cAMP
• E. Inhibition of AV node L-type Ca2+ channels

Explanation: ***Increase in vagal tone*** - Digoxin enhances **vagal tone**, which slows conduction through the **AV node** and prolongs the **PR interval**. - This effect is mediated by increased **acetylcholine** release and sensitivity at the AV node. *Activation of Na+/Ca2+ exchanger* - Digoxin indirectly increases the activity of the **Na+/Ca2+ exchanger** by raising intracellular calcium, but this primarily affects **myocardial contractility**, not AV nodal conduction. - While increased intracellular calcium is a part of digoxin's mechanism, direct activation of the exchanger is not the primary reason for **PR interval prolongation**. *Inhibition of myocardial Na+/K+ ATPase* - Digoxin primarily acts by **inhibiting the Na+/K+ ATPase**, leading to increased intracellular sodium and subsequently increased calcium. - This action is responsible for its **positive inotropic effect** on contractility, but not the direct cause of increased PR interval. *Decrease in intracellular cAMP* - A decrease in intracellular **cAMP** is typically associated with drugs like **beta-blockers**, which directly reduce sympathetic stimulation. - Digoxin's effect on AV nodal conduction is primarily through increased **vagal tone**, not reduced cAMP. *Inhibition of AV node L-type Ca2+ channels* - Inhibition of **L-type Ca2+ channels** in the AV node is characteristic of **calcium channel blockers** (e.g., verapamil, diltiazem), which would also prolong the PR interval. - Digoxin does not directly block these channels; its effect is mediated by **vagal stimulation**.

Question 659: A 2-year-old boy is brought to the physician for evaluation of delayed onset of speech. Over the past year, he has also had recurrent dizziness and three episodes of syncope. Examination of the ears shows clear auditory canals and intact tympanic membranes with normal light reflexes. Visual reinforcement audiometry shows bilateral sensorineural deafness. Genetic analysis reveals a mutation in the KCNQ1 gene causing a defect in slow voltage-gated potassium channels. An electrocardiogram of this patient is most likely to show which of the following?

• A. Prolongation of the QT interval (Correct Answer)
• B. Epsilon wave following the QRS complex
• C. Slurred upstroke of the QRS complex
• D. Absence of P waves
• E. Pseudo-right bundle branch block

Explanation: **Prolongation of the QT interval** - The constellation of **congenital sensorineural deafness**, **recurrent syncope**, and **dizziness** points to **Jervell and Lange-Nielsen syndrome (JLNS)**, a form of **long QT syndrome (LQTS)**. - JLNS is caused by mutations, often in the **KCNQ1 gene**, which encodes a subunit of the **slow delayed rectifier potassium channel (Iks)**, leading to a **prolonged QT interval** on EKG. *Epsilon wave following the QRS complex* - An **epsilon wave** is characteristic of **arrhythmogenic right ventricular cardiomyopathy (ARVC)** and represents delayed ventricular depolarization. - ARVC is not associated with congenital deafness or mutations in the KCNQ1 gene. *Slurred upstroke of the QRS complex* - A **slurred upstroke of the QRS complex** (delta wave) is typical of **Wolff-Parkinson-White syndrome (WPW)**, indicating pre-excitation via an accessory pathway. - While WPW can cause syncope, it is not linked to congenital deafness or KCNQ1 mutations. *Absence of P waves* - The **absence of P waves** is seen in conditions like **atrial fibrillation** or **sinus arrest with a junctional escape rhythm**. - These conditions do not typically present with congenital sensorineural deafness in a 2-year-old child and are not caused by KCNQ1 gene mutations. *Pseudo-right bundle branch block* - A **pseudo-right bundle branch block pattern** (Brugada pattern) is seen in **Brugada syndrome**, a channelopathy associated with sudden cardiac death. - Brugada syndrome is not associated with congenital deafness and involves different genetic mutations (e.g., SCN5A).

Question 660: A 45-year-old Caucasian male presents complaining of inability to open his mouth. Patient history reveals that he recently injured his foot from an exposed floor nail in his house. This patient's symptoms are likely the result of:

• A. Increased production of gas in his soft tissues
• B. Impaired motor neuron release of ACh
• C. Bacterial infiltration of the central nervous system
• D. Cross-reactivity of bacterial antigens
• E. Impaired motor neuron release of GABA (Correct Answer)

Explanation: ***Impaired motor neuron release of GABA*** - The patient's inability to open his mouth (**trismus** or lockjaw) following a contaminated wound (exposed nail) is highly suggestive of **tetanus**. - Tetanus toxin (tetanospasmin) produced by *Clostridioides tetani* inhibits the release of **inhibitory neurotransmitters** like **GABA** (gamma-aminobutyric acid) and glycine from presynaptic terminals in the spinal cord, leading to uncontrolled muscle spasms. *Increased production of gas in his soft tissues* - This symptom is characteristic of **gas gangrene**, caused by *Clostridium perfringens*, which leads to tissue necrosis and gas formation, but not typically lockjaw. - While *Clostridium* species are involved, the clinical picture of gas gangrene differs significantly from the described symptoms. *Impaired motor neuron release of ACh* - Impaired release of **acetylcholine (ACh)** at the neuromuscular junction leads to **flaccid paralysis**, as seen in **botulism**, not the spastic paralysis and muscle rigidity of tetanus. - Botulism typically causes generalized muscle weakness and cranial nerve palsies, not trismus where muscles are rigidly contracted. *Bacterial infiltration of the central nervous system* - While some bacteria can directly invade the CNS (e.g., in bacterial meningitis), tetanus toxin acts by **retrograde transport** to the CNS, where it inhibits neurotransmitter release; it does not involve direct bacterial infiltration of the CNS. - Bacterial meningitis would present with fever, headache, and nuchal rigidity, not specifically trismus as the primary symptom. *Cross-reactivity of bacterial antigens* - Cross-reactivity of bacterial antigens is the mechanism for conditions like **post-streptococcal glomerulonephritis** or **rheumatic fever**, where the immune system mistakenly attacks host tissues. - This mechanism does not explain the acute muscle spasm and rigidity seen in tetanus, which is a direct effect of a neurotoxin.

Question 661: An 18-year-old college student presents to the ED straight from chemistry lab where he ingested an unknown compound. He complains of a headache, and is flushed, tachypneic and tachycardic. Suspecting cyanide poisoning, you administer amyl nitrite which causes which of the following?

• A. Formation of thiocyanate
• B. Increase in intracellular NADH/NAD+ ratio
• C. A decrease in serum methemoglobin levels
• D. Chelation of the residue
• E. Oxidation of ferrous iron in hemoglobin to ferric iron (Correct Answer)

Explanation: ***Oxidation of ferrous iron in hemoglobin to ferric iron*** - Amyl nitrite induces **methemoglobinemia**, converting the **ferrous iron (Fe2+)** in hemoglobin to **ferric iron (Fe3+)**, forming methemoglobin. - Methemoglobin competes with **cytochrome c oxidase** for cyanide, forming **cyanmethemoglobin**, thereby reducing cyanide's toxic effect on cellular respiration. *Formation of thiocyanate* - The formation of **thiocyanate** is the result of cyanide detoxification by the enzyme **rhodanase**, which is a slower process and not directly caused by amyl nitrite. - This process requires a **sulfur donor**, typically provided by **sodium thiosulfate**, and is not the immediate mechanism of action of nitrites. *Increase in intracellular NADH/NAD+ ratio* - An **increase in the intracellular NADH/NAD+ ratio** indicates metabolic dysfunction, which is a consequence of cyanide poisoning inhibiting oxidative phosphorylation. - Amyl nitrite therapy aims to mitigate these effects rather than directly causing this ratio change. *A decrease in serum methemoglobin levels* - Amyl nitrite works by **increasing serum methemoglobin levels**, as its therapeutic effect relies on creating methemoglobin to bind cyanide. - A decrease in methemoglobin would counteract the desired effect, as methemoglobin is crucial for cyanide sequestration. *Chelation of the residue* - **Chelation** typically refers to the binding of a metal ion, often facilitated by agents like **EDTA** or **deferoxamine**, to detoxify heavy metal poisoning. - While cyanide binds metals in enzymes, amyl nitrite's action is specifically to convert hemoglobin to **methemoglobin** to bind free cyanide, not through a general chelation of the cyanide molecule itself.

Question 662: A pharmaceutical company has created an experimental medication, Drug Z, for patients with relapsing-remitting multiple sclerosis. Drug Z has been deemed to be safe in rats and is nearly ready for human trials. Before initiating a Phase I clinical trial, the company would like to study the medication’s pharmacokinetic properties in humans. The drug was found to have a half-life of 2.5 hours and is eliminated by first-order kinetics. The volume of distribution of the drug is determined to be 0.5 L/kg. The drug is administered intravenously and sublingually and plasma drug concentration vs. time plots are obtained. Intravenous administration of 10 mg of Drug Z yields an area under the curve (AUC) of 15 mg hr/L. Sublingual administration of 25 mg of Drug Z yields an area under the curve of 20 mg hr/L. What is the absolute bioavailability of this medication?

• A. 48%
• B. 59%
• C. 67%
• D. 71%
• E. 53% (Correct Answer)

Explanation: ***53%*** - Absolute bioavailability (F) is calculated as the ratio of the AUC of the extravascular dose to the AUC of the intravenous dose, adjusted for the respective doses: **F = (AUC_sublingual / Dose_sublingual) / (AUC_intravenous / Dose_intravenous)**. - Substituting the given values: F = (20 mg·hr/L / 25 mg) / (15 mg·hr/L / 10 mg) = (0.8 hr/L) / (1.5 hr/L) = 0.5333, or approximately **53%**. *48%* - This value would be obtained if the calculation were incorrect, possibly by reversing the doses or AUC values, leading to an underestimation of bioavailability. - It does not align with the correct application of the formula for absolute bioavailability. *59%* - This result might arise from a calculation error, such as transposing values or an arithmetic mistake in the division or multiplication steps. - It is not consistent with the correct formula for absolute bioavailability given the provided data. *67%* - This would be the result if there was a significant overestimation in the bioavailability calculation, possibly due to incorrectly assigning AUCs or doses. - A value of 67% would imply a much higher absorption rate than the given data actually supports. *71%* - This outcome would suggest a calculation error that significantly inflates the bioavailability, potentially from an incorrect manipulation of the AUC or dose ratios. - It is not derivable from the provided information using the correct formula for absolute bioavailability.

Question 663: A goalkeeper of a famous soccer team gives an interview with a health agency regarding his childhood. He describes how when he was a child, he would constantly clear his throat in class and the teachers would write a note to his mother with advice to go see an ENT doctor. He complained of being restless, fidgety, and sometimes hyperactive in class, disrupting the environment and causing him many social problems. He would blurt out the answer at times and keep repeating it without any control, leading to some embarrassing timeouts. But he was always nice to his teachers, so he calls it a “benign frustration” rather than aggressively causing distress. He also talked about how his symptoms were dramatically improved with medication. Which of the following is an FDA approved drug for this patient’s most likely condition?

• A. Lithium
• B. Clonazepam
• C. Haloperidol (Correct Answer)
• D. Clonidine
• E. Guanfacine

Explanation: ***Haloperidol*** - The patient's presentation of constant throat clearing (**motor tics**), blurting out answers and repeating words (**vocal tics**), along with restlessness and hyperactivity, is highly suggestive of **Tourette syndrome**. - **Haloperidol** is one of the **FDA-approved medications** specifically for Tourette syndrome, along with pimozide and aripiprazole. - It is a **typical antipsychotic** that effectively treats severe tics through **dopamine D2 receptor blockade**, particularly in the nigrostriatal pathway. - It remains a gold standard treatment despite potential extrapyramidal side effects. *Lithium* - **Lithium** is a **mood stabilizer** used primarily for **bipolar disorder** through its effects on intracellular signaling pathways. - It has no role in treating Tourette syndrome or tic disorders and is not FDA-approved for this indication. *Clonazepam* - **Clonazepam** is a **benzodiazepine** with **GABAergic effects** used for **anxiety disorders**, **panic disorder**, and certain seizure disorders. - While it may help with comorbid anxiety, it is not a primary treatment for tics and is **not FDA-approved** for Tourette syndrome. *Clonidine* - **Clonidine** is an **alpha-2 adrenergic agonist** that can reduce tics, particularly in children with mild to moderate symptoms or comorbid ADHD. - However, it is **off-label** for Tourette syndrome and not FDA-approved for this indication, though commonly used as a second-line agent. *Guanfacine* - **Guanfacine** is also an **alpha-2 adrenergic agonist** similar to clonidine, used primarily for ADHD. - It may help with tics in an **off-label capacity**, especially when ADHD is comorbid, but it is **not FDA-approved** specifically for Tourette syndrome.

Question 664: A 32-year-old man presents to the emergency department with vomiting, diarrhea, and abdominal pain 2 hours after eating seafood in a restaurant. He also mentions that immediately after ingestion of the food, he experienced tingling and numbness over the lips and face. On physical examination, his vital signs are stable. On neurological examination, he has reduced strength in the lower extremities, but deep tendon reflexes are present and normal. Laboratory evaluation of the seafood from the restaurant confirms the presence of a toxin which is known to block voltage-gated fast sodium channels. Which of the following toxins is the most likely cause of the patient’s symptoms?

• A. Tetrodotoxin (Correct Answer)
• B. Domoic acid
• C. Scombrotoxin
• D. Okadaic acid
• E. Saxitoxin

Explanation: ***Tetrodotoxin*** - The symptoms of **tingling, numbness (paresthesias) of the lips and face**, followed by **gastrointestinal symptoms** and **progressive weakness**, are classic for **tetrodotoxin poisoning**. - **Tetrodotoxin** blocks voltage-gated fast **sodium channels**, preventing neuronal depolarization and leading to paralysis without affecting deep tendon reflexes until severe stages. *Domoic acid* - **Domoic acid** poisoning (Amnesic Shellfish Poisoning) typically presents with **gastrointestinal symptoms** and **neurological symptoms** like confusion, memory loss, and seizures, not paresthesias and weakness as prominently. - It acts as an **excitotoxin** by overstimulating **glutamate receptors**, leading to neuronal damage. *Scombrotoxin* - **Scombrotoxin** (histamine poisoning) causes symptoms resembling an **allergic reaction**, including flushing, headache, palpitations, and gastrointestinal distress, usually without neurological deficits. - It results from the bacterial breakdown of histidine into **histamine** in improperly stored fish like tuna and mackerel. *Okadaic acid* - **Okadaic acid** (Diarrhetic Shellfish Poisoning) primarily causes **gastrointestinal symptoms** such as nausea, vomiting, diarrhea, and abdominal pain. - It acts as a **toxin** that inhibits **protein phosphatases**, leading to increased phosphorylation and altered cellular signaling. *Saxitoxin* - **Saxitoxin** (Paralytic Shellfish Poisoning) also blocks **voltage-gated sodium channels** like tetrodotoxin but is produced by different organisms (dinoflagellates). - While it causes similar neurological symptoms, the key distinguishing feature in this case is the **specific clinical presentation and timing** that is most consistent with tetrodotoxin from pufferfish or certain shellfish. - Saxitoxin poisoning can progress to respiratory paralysis more rapidly in severe cases.

Question 665: A 44-year-old man presents to the clinic with recurrent epigastric pain following meals for a month. He adds that the pain radiates up his neck and throat. Over the counter antacids have not helped. On further questioning, he endorses foul breath upon waking in the morning and worsening of pain when lying down. He denies any recent weight loss. His temperature is 37°C (98.6°F), respirations are 15/min, pulse is 70/min, and blood pressure is 100/84 mm Hg. A physical examination is performed which is within normal limits except for mild tenderness on deep palpation of the epigastrium. An ECG performed in the clinic shows no abnormalities. What is the next best step in the management of this patient?

• A. Liquid antacid
• B. Lansoprazole (Correct Answer)
• C. Endoscopy
• D. Barium swallow
• E. Ranitidine

Explanation: ***Correct Option: Lansoprazole*** - The patient's symptoms, including **postprandial epigastric pain that radiates up the neck and throat**, **foul breath**, and **worsening pain when lying down**, are highly suggestive of **gastroesophageal reflux disease (GERD)**. - **Proton pump inhibitors (PPIs)** such as lansoprazole are the most effective medications for symptom relief and healing in GERD due to their potent and sustained acid suppression. - PPIs are first-line therapy for patients with **moderate-to-severe GERD symptoms** or those who have failed antacid therapy. *Incorrect Option: Liquid antacid* - While antacids can provide **temporary relief** for heartburn, they do not address the underlying pathology of GERD and are generally **insufficient for chronic or severe symptoms**. - The patient has already tried **over-the-counter antacids without relief**, indicating that a stronger medication is needed. *Incorrect Option: Endoscopy* - **Endoscopy** is typically reserved for patients with **alarm symptoms** (e.g., dysphagia, odynophagia, weight loss, GI bleeding, anemia) or those who **fail to respond to an empiric trial of PPIs**. - This patient does not have alarm symptoms, and a trial of PPIs is the appropriate initial step. *Incorrect Option: Barium swallow* - A **barium swallow** (esophagogram) can be useful for evaluating **structural abnormalities** of the esophagus, such as strictures, rings, or motility disorders. - However, it has **limited sensitivity for diagnosing GERD** itself and is not typically the first-line diagnostic or therapeutic step in uncomplicated GERD. *Incorrect Option: Ranitidine* - **Ranitidine** is an **H2 receptor antagonist** that reduces stomach acid production, but it is generally **less potent and less effective than PPIs** for controlling GERD symptoms and healing erosions. - It might be considered for milder cases or as an add-on therapy, but a PPI like lansoprazole is preferred for initial empiric treatment given the persistent symptoms.

Question 666: A 57-year-old man comes to the emergency department because of shortness of breath and palpitations for 3 hours. He has had similar episodes intermittently for 4 months. His pulse is 140/min and blood pressure is 90/60 mm Hg. An ECG shows irregular narrow-complex tachycardia with no discernable P waves. Emergent electrical cardioversion is performed and the patient reverts to normal sinus rhythm. Pharmacotherapy with sotalol is begun. Which of the following is the most likely physiologic effect of this drug?

• A. Increased ventricular repolarization rate
• B. Increased myocyte inotropy
• C. Increased K+ efflux from myocytes
• D. Decreased Purkinje fiber conduction
• E. Decreased AV nodal conduction (Correct Answer)

Explanation: ***Decreased AV nodal conduction*** - **Sotalol** is a **beta-blocker** (Class II antiarrhythmic) and a **potassium channel blocker** (Class III antiarrhythmic). Its beta-blocking effect **slows AV nodal conduction**, increasing the refractory period and thereby reducing ventricular response in atrial fibrillation or flutter. - This action helps to **control the ventricular rate** and prevent rapid conduction from the atria to the ventricles, which is crucial in managing tachyarrhythmias. *Increased ventricular repolarization rate* - Sotalol is a **Class III antiarrhythmic** drug, which primarily works by **blocking potassium channels** and **prolonging the action potential duration** (and thus repolarization time) in ventricular myocytes. - Therefore, it **decreases** (rather than increases) the ventricular repolarization rate. *Increased myocyte inotropy* - As a **beta-blocker**, sotalol typically acts to **decrease myocardial contractility** (negative inotropy) by blocking beta-adrenergic receptors. - This effect is generally not desired in patients with heart failure but contributes to its antiarrhythmic properties by reducing myocardial oxygen demand. *Increased K+ efflux from myocytes* - Sotalol is a **potassium channel blocker**, meaning it **inhibits K+ efflux** from myocytes during phase 3 of the action potential. - This inhibition leads to a **prolongation of repolarization** and the refractory period, which is a key mechanism of its Class III antiarrhythmic effect. *Decreased Purkinje fiber conduction* - While sotalol can have some effect on Purkinje fibers due to its Class III activity (prolonging action potential), its direct and most significant effect as a beta-blocker on conduction is primarily on the **AV node**. - Other antiarrhythmics like **Class IC drugs** (e.g., flecainide, propafenone) are known for marked conduction velocity reduction in Purkinje fibers and ventricular myocardium.

Question 667: A 54-year-old man electively underwent an open cholecystectomy for cholelithiasis. The procedure was performed under general anesthesia with inhaled anesthetic agents, including nitrous oxide, after induction with an intravenous agent. The surgeon operated quickly, and the procedure was uncomplicated. As the surgery ended, the anesthesia resident stopped the anesthesia and noticed the oxygen saturation gradually decreasing to 84%. He quickly administers 100% oxygen, and the hypoxia improves. Which of the following most likely accounts for the decreased oxygen saturation seen after the anesthesia was stopped in this patient?

• A. Diffusion hypoxia (Correct Answer)
• B. Cardiotoxicity
• C. Laryngospasm
• D. Second gas effect
• E. Pneumothorax

Explanation: ***Diffusion hypoxia*** - Following the cessation of **nitrous oxide** administration, a large volume of N2O rapidly diffuses from the blood into the alveoli, diluting the partial pressures of oxygen and carbon dioxide. - This dilution can lead to a transient decrease in the partial pressure of alveolar oxygen, resulting in **hypoxia**, which resolves with 100% oxygen administration. *Cardiotoxicity* - While some anesthetic agents can be cardiotoxic, the rapid onset and resolution of hypoxia with oxygen administration in this scenario are not typical presentations of **anesthetic-induced cardiotoxicity**, which usually manifests with arrhythmias or myocardial dysfunction. *Laryngospasm* - **Laryngospasm** would cause sudden and severe airway obstruction, often accompanied by stridor and difficulty ventilating, which is a more acute and dramatic event than the described gradual decrease in oxygen saturation. - While it can cause hypoxia, the prompt improvement with 100% oxygen without specific maneuvers to relieve airway obstruction makes it less likely. *Second gas effect* - The **second gas effect** refers to the phenomenon where the rapid uptake of a highly soluble gas (like nitrous oxide) increases the alveolar concentration and thus the rate of uptake of a co-administered less soluble gas. - This effect occurs during the *induction* phase, not upon the *cessation* of anesthesia, and it enhances rather than diminishes oxygen uptake. *Pneumothorax* - A **pneumothorax** would typically present with a sudden drop in oxygen saturation, often accompanied by respiratory distress, unilateral breath sounds, and potentially hemodynamic instability. - It would not usually resolve simply by administering 100% oxygen without addressing the underlying lung collapse.

Question 668: A previously healthy 32-year-old man comes to the physician because of a 2-month history of fatigue and daytime sleepiness. He works as an accountant and cannot concentrate at work anymore. He also has depressed mood and no longer takes pleasure in activities he used to enjoy, such as playing tennis with his friends. He has decreased appetite and has had a 4-kg (8.8-lb) weight loss of over the past 2 months. He does not have suicidal ideation. He is diagnosed with major depressive disorder and treatment with paroxetine is begun. The patient is at greatest risk for which of the following adverse effects?

• A. Priapism
• B. Decreased libido (Correct Answer)
• C. Increased suicidality
• D. Postural hypotension
• E. Urinary retention

Explanation: ***Decreased libido*** - **Paroxetine** is a **selective serotonin reuptake inhibitor (SSRI)**, and sexual dysfunction, including **decreased libido**, **anorgasmia**, and **erectile dysfunction**, is the **most common adverse effect** impacting 40-70% of individuals. - This adverse effect is often a reason for **non-adherence** to antidepressant treatment and represents the **greatest risk** among the listed options. *Priapism* - **Priapism** (a prolonged, painful erection) is a rare but serious side effect more commonly associated with **trazodone**, an antidepressant with **α1-adrenergic receptor blockade** properties. - It is not a typical adverse effect of SSRIs like paroxetine. *Increased suicidality* - While there is a **black box warning** for increased suicidality in children, adolescents, and young adults (**up to age 24**) when starting antidepressants, this patient is **32 years old**. - The risk of increased suicidality **decreases with age** and is **lowest in adults over 25**, making this a less likely adverse effect than sexual dysfunction in this patient. *Postural hypotension* - **Postural hypotension** is more common with antidepressants that have **alpha-1 adrenergic blocking effects**, such as tricyclic antidepressants (TCAs) and some atypical antidepressants like trazodone. - SSRIs like paroxetine generally have a **much lower incidence** of alpha-adrenergic side effects. *Urinary retention* - **Urinary retention** is primarily an **anticholinergic side effect**, commonly seen with tricyclic antidepressants (TCAs). - While paroxetine has the **highest anticholinergic activity among SSRIs**, it is still **significantly lower than TCAs**, making urinary retention an **uncommon adverse effect** and far less likely than sexual dysfunction.

Question 669: A 60-year-old man is brought to the emergency room because of fever and increasing confusion for the past 2 days. He has paranoid schizophrenia and hypertension. His current medications are chlorpromazine and amlodipine. He appears ill. He is not oriented to time, place, or person. His temperature is 40°C (104°F), pulse is 130/min, respirations are 29/min and blood pressure is 155/100 mm Hg. Examination shows diaphoresis. Muscle tone is increased bilaterally. Deep tendon reflexes are 1+ bilaterally. Neurologic examination shows psychomotor agitation. His speech is incoherent. Lungs are clear to auscultation. His neck is supple. The abdomen is soft and nontender. Serum laboratory analysis shows a leukocyte count of 11,300/mm3 and serum creatine kinase concentration of 833 U/L. Which of the following is the most appropriate initial pharmacotherapy?

• A. Cyproheptadine
• B. Dantrolene (Correct Answer)
• C. Physostigmine
• D. Propranolol
• E. Clozapine

Explanation: ***Dantrolene*** - The patient's presentation with **fever (40°C), muscle rigidity, altered mental status, and elevated creatine kinase** while on **chlorpromazine** is highly suggestive of **neuroleptic malignant syndrome (NMS)**. - **Dantrolene** is a direct-acting skeletal muscle relaxant used to treat the muscle rigidity, hyperthermia, and rhabdomyolysis associated with NMS. *Cyproheptadine* - **Cyproheptadine** is a serotonin antagonist used to treat **serotonin syndrome**, which shares some features with NMS but is typically associated with serotonergic agents. - While there's some overlap, NMS is primarily due to dopamine blockade, and cyproheptadine is not the first-line treatment. *Physostigmine* - **Physostigmine** is an acetylcholinesterase inhibitor used to reverse **anticholinergic toxicity**. - The patient's symptoms are not indicative of anticholinergic toxicity; rather, they point to a dopaminergic blockade. *Propranolol* - **Propranolol** is a non-selective beta-blocker that can be used to manage some of the **autonomic instability** (e.g., tachycardia, hypertension) in NMS. - However, it does not address the underlying muscle rigidity or hyperthermia, which are critical components requiring specific treatment like dantrolene. *Clozapine* - **Clozapine** is an atypical antipsychotic often used for refractory schizophrenia, but it is not a treatment for NMS. - In fact, antipsychotics are the causative agents of NMS, and continuing or initiating another antipsychotic would be contraindicated.

Question 670: A 42-year-old man is brought to the emergency department after having a seizure. His wife states that the patient has been struggling with alcohol abuse and has recently decided to "quit once and for all". Physical exam is notable for a malnourished patient responsive to verbal stimuli. He has moderate extremity weakness, occasional palpitations, and brisk deep tendon reflexes (DTRs). EKG demonstrates normal sinus rhythm and a prolonged QT interval. What nutritional deficiency most likely contributed to these findings?

• A. Vitamin D
• B. Magnesium (Correct Answer)
• C. Potassium
• D. Calcium
• E. Folate

Explanation: ***Magnesium*** - **Hypomagnesemia** is common in chronic alcoholics due to poor nutrition and increased renal loss, leading to neuromuscular excitability (seizures, hyperreflexia, weakness) and cardiac abnormalities (prolonged QT interval, palpitations). - Magnesium is a crucial cofactor for many enzymes and plays a vital role in nerve impulse transmission, muscle contraction, and maintaining cardiac rhythm. *Vitamin D* - **Vitamin D deficiency** is associated with bone demineralization (osteomalacia) and weakness, but it does not typically cause acute seizures, prolonged QT interval, or brisk deep tendon reflexes. - While chronic alcohol abuse can impair vitamin D metabolism, the acute presentation here points more strongly to electrolyte imbalances. *Potassium* - **Hypokalemia** can cause muscle weakness, fatigue, and cardiac arrhythmias, including a prolonged QT interval, but it usually leads to **diminished** or absent DTRs, not brisk DTRs. - Seizures are also not a primary manifestation of hypokalemia. *Calcium* - **Hypocalcemia** can cause muscle cramps, spasms, and seizures due to increased neuromuscular excitability, and it can also lead to a prolonged QT interval. - However, brisk deep tendon reflexes (hyperreflexia) are more characteristic of **hypomagnesemia** that often coexists with hypocalcemia because magnesium is required for **parathyroid hormone (PTH)** secretion and action. *Folate* - **Folate deficiency** in alcoholics primarily causes **macrocytic anemia** and can lead to neurological symptoms like peripheral neuropathy or cognitive impairment. - It does not explain the acute seizure, prolonged QT, brisk DTRs, or palpitations seen in this patient.

Question 671: A 65-year-old woman with COPD comes to the emergency department with 2-day history of worsening shortness of breath and cough. She often has a mild productive cough, but she noticed that her sputum is more yellow than usual. She has not had any recent fevers, chills, sore throat, or a runny nose. Her only medication is a salmeterol inhaler that she uses twice daily. Her temperature is 36.7°C (98°F), pulse is 104/min, blood pressure is 134/73 mm Hg, respiratory rate is 22/min, and oxygen saturation is 85%. She appears uncomfortable and shows labored breathing. Lung auscultation reveals coarse bibasilar inspiratory crackles. A plain film of the chest shows mild hyperinflation and flattening of the diaphragm but no consolidation. She is started on supplemental oxygen via nasal cannula. Which of the following is the most appropriate initial pharmacotherapy?

• A. Albuterol and montelukast
• B. Albuterol and theophylline
• C. Prednisone and albuterol (Correct Answer)
• D. Roflumilast and prednisone
• E. Prednisone and salmeterol

Explanation: ***Prednisone and albuterol*** - This patient is experiencing an **acute exacerbation of COPD** (AECOPD) characterized by worsening dyspnea, increased sputum purulence (yellow sputum), and elevated respiratory rate, despite no fever or chills. AECOPD is managed with **systemic corticosteroids** (like prednisone) and **short-acting bronchodilators** (like albuterol). - Prednisone reduces **airway inflammation**, while albuterol provides rapid **bronchodilation** to relieve bronchospasm and improve airflow. *Albuterol and montelukast* - **Montelukast** is a leukotriene receptor antagonist used for chronic asthma management and sometimes for COPD patients with an asthmatic component, but it is not a first-line agent for acute exacerbations. - While **albuterol** is appropriate, montelukast works too slowly to be the primary acute anti-inflammatory agent needed for an AECOPD. *Albuterol and theophylline* - **Theophylline** is a phosphodiesterase inhibitor that can improve lung function but has a narrow therapeutic index and significant side effects, making it a less preferred option, especially in acute settings. - While **albuterol** is appropriate, theophylline is not generally used as an initial agent for AECOPD given safer and more effective alternatives like corticosteroids. *Roflumilast and prednisone* - **Roflumilast** is a phosphodiesterase-4 inhibitor used to reduce exacerbations in patients with severe COPD and chronic bronchitis, but it is a chronic medication and not indicated for acute management. - While **prednisone** is appropriate, roflumilast is not an acute bronchodilator for immediate relief. *Prednisone and salmeterol* - **Salmeterol** is a **long-acting beta-agonist (LABA)**, which is part of the patient's maintenance therapy for COPD. In an acute exacerbation, **short-acting bronchodilators** like albuterol are preferred for rapid relief. - While **prednisone** is appropriate, continuing salmeterol alone as the bronchodilator in an acute setting is insufficient without a short-acting agent.

Question 672: A 48-year-old man with a long history of mild persistent asthma on daily fluticasone therapy has been using his albuterol inhaler every day for the past month and presents requesting a refill. He denies any recent upper respiratory infections, but he says he has felt much more short of breath throughout this time frame. He works as a landscaper, and he informs you that he has been taking longer to complete some of his daily activities on the job. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 74/min, and respiratory rate 14/min. His physical exam reveals mild bilateral wheezes and normal heart sounds. What changes should be made to his current regimen?

• A. Add ciclesonide to current regimen
• B. Discontinue fluticasone and instead use salmeterol
• C. Add salmeterol to current regimen (Correct Answer)
• D. Add cromolyn to current regimen
• E. Discontinue fluticasone and add ipratropium to current regimen

Explanation: ***Add salmeterol to current regimen*** - The patient's increased albuterol use and worsening symptoms despite daily **fluticasone** indicate an escalation in his asthma severity, moving him from mild persistent to moderate persistent asthma. - Adding a **long-acting beta-agonist (LABA)** like **salmeterol** to his inhaled corticosteroid (fluticasone) is the next step in therapy for moderate persistent asthma to achieve better symptom control. *Add ciclesonide to current regimen* - **Ciclesonide** is another **inhaled corticosteroid (ICS)**. Adding it would either replace or supplement **fluticasone**, which would not address the need for an additional class of medication to improve bronchodilation and reduce rescue inhaler use. - The primary issue is insufficient disease control with current ICS, not a preference for a different steroid. *Discontinue fluticasone and instead use salmeterol* - **Discontinuing fluticasone** (an ICS) would remove the foundational anti-inflammatory therapy for asthma, which is critical for long-term control. - While **salmeterol** (a LABA) helps with bronchodilation, using it as monotherapy without an ICS is associated with an increased risk of severe asthma exacerbations and is not recommended. *Add cromolyn to current regimen* - **Cromolyn sodium** is a mast cell stabilizer used to prevent asthma symptoms, often in mild cases or for exercise-induced asthma. - It is generally less potent than ICS and LABA combinations and would not be sufficient for a patient whose asthma is worsening despite daily ICS therapy. *Discontinue fluticasone and add ipratropium to current regimen* - **Discontinuing fluticasone** would remove necessary anti-inflammatory control. - **Ipratropium** is a short-acting anticholinergic often used in acute asthma exacerbations or in patients who cannot tolerate beta-agonists, but it is not a first-line daily maintenance therapy for moderate persistent asthma.

Question 673: A 28-year-old man visits his physician complaining of hematochezia over the last several days. He also has tenesmus and bowel urgency without any abdominal pain. He has had several milder episodes over the past several years that resolved on their own. He has no history of a serious illness and takes no medications. His blood pressure is 129/85 mm Hg; temperature, 37.4°C (99.3°F); and pulse, 75/min. On physical exam, his abdominal examination shows mild tenderness on deep palpation of the left lower quadrant. Digital rectal examination reveals anal tenderness and fresh blood. Stool examination is negative for pathogenic bacteria and an ova and parasite test is negative. Erythrocyte sedimentation rate is 28 mm/h. Colonoscopy shows diffuse erythema involving the rectum and extending to the distal sigmoid. The mucosa also shows a decreased vascular pattern with fine granularity. The remaining colon and distal ileum are normal. Biopsy of the inflamed mucosa of the sigmoid colon shows distorted crypt architecture. The most appropriate next step is to administer which of the following?

• A. Ciprofloxacin
• B. Mesalamine (Correct Answer)
• C. Azathioprine
• D. Metronidazole
• E. Total parenteral nutrition

Explanation: ***Mesalamine*** - This patient presents with symptoms and endoscopic findings consistent with **ulcerative colitis**, specifically **proctosigmoiditis** (inflammation limited to the rectum and distal sigmoid). - **Mesalamine** (an aminosalicylate) is the first-line treatment for inducing and maintaining remission in mild-to-moderate ulcerative colitis, especially when it is localized to the distal colon. *Ciprofloxacin* - **Ciprofloxacin** is an antibiotic and would be considered if there was suspicion of **bacterial infection** or severe, complicated inflammatory bowel disease with signs of infection. - The stool tests were negative for pathogenic bacteria, making an antibiotic unlikely as a primary treatment for this presentation. *Azathioprine* - **Azathioprine** is an immunosuppressant used for **moderate-to-severe ulcerative colitis** or when patients are refractory to conventional therapy like mesalamine or corticosteroids. - This patient has a milder presentation, with localized disease and current treatment not yet initiated, meaning azathioprine is a step too far. *Metronidazole* - **Metronidazole** is an antibiotic often used for anaerobic infections or in certain cases of Crohn's disease (e.g., peri-anal disease), but not typically as first-line for ulcerative colitis. - No clear indication of bacterial overgrowth or abscess is present, and stool tests were negative. *Total parenteral nutrition* - **Total parenteral nutrition (TPN)** is reserved for patients with severe malnutrition, intractable vomiting, or conditions preventing enteral feeding. - This patient does not exhibit signs of severe malnutrition or an inability to tolerate oral intake, making TPN unnecessary and overly aggressive.

Question 674: A 73-year-old man presents to his primary care physician with chest pain. He noticed the pain after walking several blocks, and the pain is relieved by sitting. On exam, he has a BP 155/89 mmHg, HR 79 bpm, and T 98.9 F. The physician refers the patient to a cardiologist and offers prescriptions for carvedilol and nitroglycerin. Which of the following describes the mechanism or effects of each of these medications, respectively?

• A. Increased contractility; Decreased endothelial nitric oxide
• B. Decreased cAMP; Increased cGMP (Correct Answer)
• C. Increased cAMP; Increased cAMP
• D. Decreased cGMP; Increased venous resistance
• E. Increased heart rate; Decreased arterial resistance

Explanation: ***Decreased cAMP; Increased cGMP*** - **Carvedilol** is a beta-blocker that *blocks β1 and β2 adrenergic receptors*, leading to a **decrease in intracellular cAMP**, which in turn reduces heart rate, contractility, and blood pressure. - **Nitroglycerin** acts by releasing **nitric oxide**, which activates **guanylate cyclase** to convert GTP to **cGMP**, leading to smooth muscle relaxation and vasodilation. *Increased contractility; Decreased endothelial nitric oxide* - **Carvedilol** (a beta-blocker) causes a **decrease in contractility**, not an increase, by blocking beta-adrenergic receptors. - **Nitroglycerin** works by **increasing** the production of nitric oxide, not decreasing it. *Increased cAMP; Increased cAMP* - **Carvedilol** (a beta-blocker) functions by **decreasing** cAMP, not increasing it. - While other agents might increase cAMP, this is not the mechanism for nitroglycerin. *Decreased cGMP; Increased venous resistance* - **Nitroglycerin** works by **increasing cGMP**, which promotes vasodilation, rather than decreasing it. - Nitroglycerin causes **decreased venous resistance** (venous dilation) to reduce preload, not increased resistance. *Increased heart rate; Decreased arterial resistance* - **Carvedilol** (a beta-blocker) primarily **decreases heart rate**, not increases it. - While nitroglycerin does cause some arterial dilation, its primary effect at therapeutic doses is **venous dilation** to reduce preload, not just decreased arterial resistance.

Question 675: A 33-year-old woman comes to the physician for a follow-up examination. She has a history of Crohn disease, for which she takes methotrexate. She and her husband would like to start trying to have a child. Because of the teratogenicity of methotrexate, the physician switches the patient from methotrexate to a purine analog drug that inhibits lymphocyte proliferation by blocking nucleotide synthesis. Toxicity of the newly prescribed purine analog would most likely increase if the patient was also being treated with which of the following medications?

• A. Hydroxyurea
• B. Febuxostat (Correct Answer)
• C. Pemetrexed
• D. Cyclosporine
• E. Rasburicase

Explanation: ***Febuxostat*** - Febuxostat is a **xanthine oxidase inhibitor**, which will therefore increase the levels of the purine analog, as the purine analog is metabolized by **xanthine oxidase**. - Elevated levels of purine analogs can lead to increased toxicity, particularly **myelosuppression**. *Hydroxyurea* - Hydroxyurea inhibits **ribonucleotide reductase**, affecting DNA synthesis and repair. - Its mechanism of action is distinct from purine analog metabolism via xanthine oxidase, thus it is unlikely to directly increase purine analog toxicity through altered metabolism. *Pemetrexed* - Pemetrexed is an **antifolate agent** that inhibits several folate-dependent enzymes involved in pyrimidine and purine synthesis. - While it affects nucleotide synthesis, it is not primarily metabolized by xanthine oxidase, nor does it inhibit xanthine oxidase to alter purine analog levels. *Cyclosporine* - Cyclosporine is a **calcineurin inhibitor** used as an immunosuppressant, primarily by inhibiting T-lymphocyte activation. - It does not directly interact with the metabolic pathways of purine analogs in a way that would significantly increase their toxicity. *Rasburicase* - Rasburicase is a recombinant **urate oxidase** enzyme that converts uric acid to allantoin, used to manage tumor lysis syndrome. - It works on uric acid metabolism and does not inhibit xanthine oxidase, so it would not increase the toxicity of the purine analog.

Question 676: A 27-year-old man presents to the outpatient clinic with a swollen and painful toe. The pain intensity increased further after he went to a party last night. Which of the following is the drug of choice for the treatment of this patient's condition?

• A. Aspirin
• B. Rasburicase
• C. Indomethacin (Correct Answer)
• D. Probenecid
• E. Allopurinol

Explanation: ***Indomethacin*** - This patient's presentation with a **swollen and painful toe** (likely the first metatarsophalangeal joint) after a party is highly suggestive of **acute gout**, an inflammatory arthritis caused by **monosodium urate crystal deposition**. - **Indomethacin** is a potent **NSAID** traditionally considered the "classic" treatment for acute gout flares, though **current guidelines recommend any NSAID at anti-inflammatory doses** (indomethacin, naproxen, ibuprofen) as equally effective first-line options. - Other first-line options include **colchicine** and **corticosteroids** when NSAIDs are contraindicated. *Aspirin* - While aspirin is an NSAID, **low-dose aspirin** (<2 g/day) can actually **decrease renal uric acid excretion**, potentially worsening hyperuricemia and gout. - At high doses (>3 g/day), aspirin has uricosuric effects, but it is generally **avoided in acute gout** due to unpredictable effects on uric acid levels. *Rasburicase* - This is a **recombinant urate oxidase** enzyme that rapidly converts uric acid to allantoin, primarily used for **tumor lysis syndrome** with severe hyperuricemia in oncology patients. - It is **not used for acute gout** in otherwise healthy individuals and is administered intravenously in hospital settings. *Probenecid* - **Probenecid** is a **uricosuric agent** that increases renal uric acid excretion by blocking the URAT1 transporter in the proximal tubule, used for **chronic management** of gout. - It is **contraindicated during acute attacks** as it can mobilize urate deposits and worsen the flare; initiation should occur after the acute episode has resolved. *Allopurinol* - **Allopurinol** is a **xanthine oxidase inhibitor** that reduces uric acid production and is the most common agent for **long-term prophylaxis** of recurrent gout. - It should **not be initiated during an acute attack** as sudden changes in serum uric acid can precipitate or prolong the flare; if already taking allopurinol, continue it during acute attacks.

Question 677: A 43-year-old man presents to the emergency department with nausea and vomiting. He says symptoms onset 4 hours ago and is progressively worsening. He denies any hematemesis. Past medical history is significant for a recent negative screening colonoscopy that was performed due to a family history of colon cancer. His vital signs are significant for a temperature of 39.5°C (103.1°F). Physical examination is unremarkable. A contrast CT of the abdomen reveals a colonic perforation. Laboratory findings are significant for an elevated WBC count with a predominant left shift, a decreased platelet count, increased PT and PTT, slightly decreased hemoglobin/hematocrit, and prolonged bleeding time. Which of the following is most closely related to this patient's prolonged PT and PTT?

• A. Vitamin K
• B. Giant platelets
• C. COX-1 and COX-2
• D. GpIIb/IIIa
• E. Fibrinogen (Correct Answer)

Explanation: ***Fibrinogen*** - This patient has **disseminated intravascular coagulation (DIC)** secondary to sepsis from colonic perforation, evidenced by **elevated PT/PTT**, **thrombocytopenia**, **prolonged bleeding time**, and **decreased hemoglobin** - In DIC, there is widespread activation of coagulation leading to **consumption of clotting factors**, particularly **fibrinogen (Factor I)**, which is the substrate for fibrin clot formation in the **common pathway** - **Low fibrinogen directly prolongs PT, PTT, and thrombin time** because fibrinogen is essential for the final step of clot formation measured by these tests - Fibrinogen consumption is a hallmark of DIC and directly explains the coagulation factor deficiency causing PT/PTT prolongation *Vitamin K* - Vitamin K deficiency causes deficiency of factors II, VII, IX, and X, leading to prolonged PT and PTT - However, the acute presentation with **sepsis**, **thrombocytopenia**, and **prolonged bleeding time** indicates **DIC with factor consumption**, not vitamin K deficiency - Vitamin K deficiency would not explain the low platelet count or the acute septic picture *Giant platelets* - Giant platelets (megathrombocytes) indicate **increased platelet turnover** and bone marrow attempting to compensate for peripheral platelet destruction in DIC - While they explain the **thrombocytopenia** and contribute to **prolonged bleeding time**, they **do not prolong PT or PTT** - **PT and PTT measure coagulation factors in platelet-poor plasma**, not platelet function *COX-1 and COX-2* - COX-1 inhibitors (aspirin) block thromboxane A2, impairing platelet aggregation and prolonging **bleeding time** but not PT/PTT - COX-2 inhibitors primarily reduce inflammation with minimal platelet effects - Neither directly affect the coagulation cascade factors measured by PT/PTT *GpIIb/IIIa* - Glycoprotein IIb/IIIa receptor inhibitors (abciximab, eptifibatide, tirofiban) prevent platelet aggregation - They prolong **bleeding time** and can cause thrombocytopenia, but **do not prolong PT or PTT** - PT/PTT measure coagulation factors, not platelet function

Question 678: A 37-year-old previously healthy woman presents to the emergency room with right leg pain and difficulty breathing. She recently returned from a trip to Alaska and noticed her leg started to swell when she got home. Her medications include a multivitamin and oral contraceptives. She is diagnosed with a deep venous thrombosis complicated by a pulmonary embolism and started on anticoagulation. She remains stable and is discharged on the third hospital day with long-term anticoagulation. During the 2 month follow-up visit, the patient's lab results are as follows: Hemoglobin: 14 g/dL Hematocrit: 44% Leukocyte count: 5,000/mm^3 with normal differential Platelet count: 300,000/mm^3 Prothrombin time: 23 seconds Partial thromboplastin time (activated): 20 seconds Bleeding time: 4 minutes Which of the following factors is initially inhibited in the target pathway for her long-term treatment?

• A. VII (Correct Answer)
• B. IX
• C. V
• D. X
• E. II

Explanation: ***VII*** - The patient is taking long-term anticoagulation, specifically noted by the **prolonged prothrombin time (PT)** of 23 seconds (normal 11-13.5 seconds) while the **aPTT is shortened** (normal 25-35 seconds), indicating the target pathway is the **extrinsic pathway** of coagulation. - **Warfarin**, a common long-term oral anticoagulant, targets **Vitamin K-dependent factors** (II, VII, IX, X), and Factor VII has the **shortest half-life**, leading to its inhibition (and prolongation of PT) earliest. *IX* - **Factor IX** is part of the **intrinsic pathway** and is also a Vitamin K-dependent factor, but its inhibition would primarily prolong the **aPTT**, which is shortened in this case. - While warfarin eventually inhibits Factor IX, Factor VII inhibition and PT prolongation occur more rapidly. *V* - **Factor V** is a non-Vitamin K-dependent factor involved in both the intrinsic and common pathways; its inhibition is not the primary mechanism of action for common long-term oral anticoagulants like warfarin. - Inhibition of Factor V would likely affect both PT and aPTT, not selectively prolonging PT as seen here. *X* - **Factor X** is a Vitamin K-dependent factor in the **common pathway**, and its inhibition would prolong both PT and aPTT. - While warfarin inhibits Factor X, Factor VII has a shorter half-life and its inhibition is primarily responsible for the initial prolongation of PT. *II* - **Factor II (prothrombin)** is a **Vitamin K-dependent factor** in the **common pathway**, and its inhibition would prolong both PT and aPTT. - It has a longer half-life than Factor VII, so Factor VII's inhibition and PT prolongation would be seen first with warfarin therapy.

Question 679: A 50-year-old woman, gravida 5, para 5, comes to the physician for the evaluation of decreased sexual desire for approximately 6 months. She has been sexually active with her husband but reports that she has no desire in having sexual intercourse anymore. She states that she feels guilty and is worried about losing her husband if this problem goes on for a longer period of time. She also reports that they have had several fights recently due to financial problems. She has problems going to sleep and wakes up often, and is tired throughout the day. One year ago, the patient underwent hysterectomy with bilateral salpingo-oophorectomy due to uterine prolapse. Her last menstrual period was 2 years ago. She does not smoke. She drinks 3–4 glasses of wine daily. Vital signs are within normal limits. Physical examination shows no abnormalities except for an enlarged liver. Which of the following most likely explains this patient's loss of libido?

• A. Chronic alcohol intake (Correct Answer)
• B. Stress
• C. Decreased testosterone
• D. Major depressive disorder
• E. Elevated prolactin

Explanation: ***Chronic alcohol intake*** - The patient consumes **3-4 glasses of wine daily**, which is considered heavy drinking for women and can significantly **reduce libido** and cause hepatic dysfunction. - The presence of an **enlarged liver on physical exam** further supports chronic alcohol use as a likely cause for her symptoms, including decreased sexual desire. *Stress* - While the patient is experiencing stress due to financial problems and marital issues, **stress** alone is less likely to cause a **physical finding like an enlarged liver**. - Although stress can contribute to decreased libido, it does not fully explain the entire clinical picture observed. *Decreased testosterone* - The patient's hysterectomy with bilateral salpingo-oophorectomy 1 year prior would lead to a **decrease in ovarian hormone production**, including testosterone. - However, while **decreased testosterone** can cause low libido, this explanation does not account for the **enlarged liver**, which points more strongly towards chronic alcohol consumption. *Major depressive disorder* - Symptoms like **decreased sleep**, feeling tired, guilt, and reduced sexual desire are consistent with **major depressive disorder**. - However, an **enlarged liver** is not a typical symptom of major depressive disorder, making chronic alcohol intake a more unifying diagnosis for the presented symptoms. *Elevated prolactin* - **Elevated prolactin** can cause decreased libido, amenorrhea (which is not relevant here as she had a hysterectomy), and sometimes galactorrhea. - However, there is **no direct evidence or symptoms** presented to suggest elevated prolactin, and it would not explain the enlarged liver.

Question 680: A 73-year-old woman presents to the emergency department with diffuse abdominal pain, nausea, and vomiting. Her daughter who accompanies her says she was in her usual state of health until two days ago when she started to complain of abdominal pain and was unable to tolerate oral intake. She has hypertension, congestive heart failure, atrial fibrillation, and osteoarthritis. She underwent an exploratory laparotomy for an ovarian mass a year ago where a mucinous cystadenoma was excised. Her medications include aspirin, nifedipine, lisinopril, metoprolol, warfarin, and Tylenol as needed for pain. She does not drink alcohol or smoke cigarettes. She appears ill and disoriented. Her temperature is 37.9°C (100.3°F), blood pressure is 102/60 mm Hg, pulse is 110/min and irregular, and respirations are 16/min. Examination shows diffuse tenderness to palpation of the abdomen. The abdomen is tympanitic on percussion. Bowel sounds are hyperactive. The lungs are clear to auscultation bilaterally. There is a soft crescendo-decrescendo murmur best auscultated in the right second intercostal space. Laboratory studies show: Hemoglobin 10.2 g/dL Leukocyte count 14,000/mm3 Platelet count 130,000/mm3 Prothrombin time 38 seconds INR 3.2 Serum Na+ 132 mEq/dL K+ 3.6 mEq/dL Cl- 102 mEq/dL HCO3- 19 mEq/dL Urea nitrogen 36 mg/dl Creatinine 2.3 mg/dL Lactate 2.8 mEq/dL (N= 0.5-2.2 mEq/dL) An x-ray of the abdomen shows multiple centrally located dilated loops of gas filled bowel. There is no free air under the diaphragm. A nasogastric tube is inserted and IV fluids and empiric antibiotic therapy are started. Emergent exploratory laparotomy is planned. Which of the following is the next best step in management?

• A. Administer unfractionated heparin
• B. Administer protamine sulfate
• C. Administer recombinant activated factor VII
• D. Administer platelet concentrate
• E. Administer fresh frozen plasma and Vitamin K (Correct Answer)

Explanation: ***Administer fresh frozen plasma and Vitamin K*** - This patient presents with suspected **bowel ischemia** requiring emergent surgery, exacerbated by an **elevated INR (3.2)** due to warfarin use. **Fresh frozen plasma (FFP)** provides immediate replacement of clotting factors, while **Vitamin K** helps to restore endogenous factor synthesis over a longer period. - Reversing the anticoagulation rapidly is crucial to minimize the risk of severe **intraoperative and postoperative bleeding**, which would complicate an already critical condition. *Administer unfractionated heparin* - **Unfractionated heparin** is an anticoagulant and would worsen the patient's bleeding risk, making emergent surgery extremely dangerous. - It would further increase the risk of hemorrhage in a patient already coagulopathic from warfarin. *Administer protamine sulfate* - **Protamine sulfate** is used to reverse the effects of **heparin**, not warfarin. - Administering protamine would have no effect on the **INR elevation** caused by warfarin and would not correct the patient's coagulopathy. *Administer recombinant activated factor VII* - **Recombinant activated factor VII (rFVIIa)** is a potent procoagulant, but its use is typically reserved for severe, life-threatening bleeding not responsive to conventional therapy in patients with specific coagulation factor deficiencies. - While it can help improve coagulation, it carries a significant risk of **thromboembolic events**, which could be particularly dangerous in this patient with a history of **atrial fibrillation** and suspected ischemia, and it is not the first-line treatment for warfarin reversal. *Administer platelet concentrate* - The patient's **platelet count (130,000/mm3)** is within the acceptable range for most surgeries and her coagulopathy is primarily due to **warfarin-induced factor deficiencies (elevated INR)**. - Administering platelet concentrate would not address the underlying **coagulopathy** caused by warfarin and would be unnecessary in this situation.

Question 681: A 60-year-old man is brought to the emergency room because of fever and increasing confusion for the past 2 days. He has paranoid schizophrenia treated with chlorpromazine. He appears diaphoretic. His temperature is 40°C (104°F), pulse is 130/min, respirations are 29/min, and blood pressure is 155/100 mm Hg. Neurologic examination shows psychomotor agitation and incoherent speech. There is generalized muscle rigidity. His deep tendon reflexes are decreased bilaterally. Serum laboratory analysis shows a leukocyte count of 11,300/mm3 and serum creatine kinase concentration of 833 U/L. The most appropriate drug for this patient acts by inhibiting which of the following?

• A. Ryanodine receptor on the sarcoplasmic reticulum (Correct Answer)
• B. Cholinesterase
• C. Postsynaptic dopamine D2 receptors and serotonin 2A receptors
• D. Beta adrenergic receptors
• E. Histamine H1 receptor and serotonin 2 receptors

Explanation: ***Ryanodine receptor on the sarcoplasmic reticulum*** - The patient exhibits symptoms of **neuroleptic malignant syndrome (NMS)**, characterized by fever, muscle rigidity, altered mental status, and autonomic instability, likely induced by **chlorpromazine** (an antipsychotic). - The most appropriate treatment for NMS is often **dantrolene**, which acts by inhibiting the **ryanodine receptor** on the sarcoplasmic reticulum, thereby reducing intracellular calcium release and muscle contraction. *Cholinesterase* - Inhibiting cholinesterase would lead to increased acetylcholine, which is the treatment strategy for conditions like **myasthenia gravis** or **Alzheimer's disease**. - This mechanism is not relevant for treating NMS, which involves dopaminergic blockade and muscle rigidity. *Postsynaptic dopamine D2 receptors and serotonin 2A receptors* - **Chlorpromazine**, the causative agent for NMS in this patient, is a dopamine D2 receptor antagonist (and to a lesser extent, a serotonin 2A receptor antagonist). - Further inhibition of these receptors would worsen, not improve, NMS symptoms. *Beta adrenergic receptors* - **Beta-blockers** are used to treat conditions like hypertension, angina, and anxiety by reducing sympathetic nervous system activity. - While the patient has **tachycardia** and **hypertension**, these are symptoms of NMS, and beta-blockers would not address the underlying pathophysiology of muscle rigidity and hyperthermia. *Histamine H1 receptor and serotonin 2 receptors* - Antagonist effects on histamine H1 and serotonin 2 receptors are common side effects of many antipsychotics. - While antihistamine effects can cause sedation, targeting these receptors would not resolve the critical features of NMS such as profound muscle rigidity and hyperthermia.

Question 682: A 49-year-old man comes to the physician because of a 5-month history of progressive fatigue and exertional dyspnea. Cardiac examination shows a loud S2 in the 2nd left intercostal space. Right heart catheterization shows a pulmonary artery pressure of 32 mm Hg. Treatment with bosentan is initiated. The beneficial effect of this drug is due to binding to which of the following?

• A. L-type voltage-gated calcium channels
• B. Adenosine receptors
• C. Prostacyclin receptor
• D. Phosphodiesterase-5
• E. Endothelin receptors (Correct Answer)

Explanation: ***Endothelin receptors*** - **Bosentan** is an **endothelin receptor antagonist** that blocks the binding of **endothelin-1** to ETA and ETB receptors. - This action leads to **vasodilation** in pulmonary arteries, reducing pulmonary vascular resistance and benefiting patients with pulmonary hypertension. *L-type voltage-gated calcium channels* - These channels are blocked by **calcium channel blockers** such as amlodipine or diltiazem, which are not bosentan. - While some calcium channel blockers can be used in specific subgroups of pulmonary hypertension, their mechanism of action is distinct from bosentan. *Adenosine receptors* - **Adenosine receptor agonists** like adenosine itself cause vasodilation, particularly in the coronary circulation, and are used diagnostically for stress testing. - Bosentan does not act on adenosine receptors; its mechanism is focused on the endothelin pathway. *Prostacyclin receptor* - **Prostacyclin analogs** (e.g., epoprostenol, treprostinil) act on prostacyclin receptors, stimulating adenylate cyclase to increase cAMP and cause vasodilation. - Bosentan's mechanism is entirely separate from the prostacyclin pathway. *Phosphodiesterase-5* - **Phosphodiesterase-5 (PDE5) inhibitors** (e.g., sildenafil, tadalafil) increase cGMP levels, leading to vasodilation. - This is a common treatment for pulmonary hypertension, but bosentan belongs to a different class of drugs.

Question 683: A 69-year-old woman with type 2 diabetes mellitus has an HbA1c of 7.9% and has been using basal-bolus insulin to manage her diabetes for the past 5 years. She has been maintaining a healthy diet, taking her insulin as scheduled but her records show morning hyperglycemia before eating breakfast. To determine the cause of this hyperglycemia, you ask her to set an alarm and take her blood glucose at 3 am. At 3 am her blood glucose is 49 mg/dL. Which of the following statements best describes the management of this patient's current condition?

• A. She is experiencing Somogyi effect so her nighttime insulin should be increased
• B. She is experiencing dawn phenomenon so her nighttime insulin should be decreased
• C. Hyperosmolar hyperglycemic state; increase nighttime insulin
• D. She is experiencing Somogyi effect so her nighttime insulin should be decreased (Correct Answer)
• E. She is experiencing dawn phenomenon so her nighttime insulin should be kept the same

Explanation: ***She is experiencing Somogyi effect so her nighttime insulin should be decreased*** - The **Somogyi effect** (rebound hyperglycemia) occurs when a drop in blood glucose during the night (49 mg/dL at 3 am indicates **hypoglycemia**) triggers a release of counter-regulatory hormones, leading to **hyperglycemia** in the morning. - To prevent nocturnal hypoglycemia and subsequent rebound hyperglycemia, the **nighttime insulin dose should be decreased**. *She is experiencing Somogyi effect so her nighttime insulin should be increased* - While the patient is experiencing the **Somogyi effect**, increasing nighttime insulin would worsen the nocturnal hypoglycemia, further exacerbating the rebound hyperglycemia. - The core issue is **nocturnal hypoglycemia**, which is addressed by reducing, not increasing, the insulin dose. *She is experiencing dawn phenomenon so her nighttime insulin should be decreased* - The **dawn phenomenon** involves a natural rise in blood glucose in the early morning due to hormonal surges, without preceding hypoglycemia, and would typically necessitate an *increase* in nighttime insulin. - Since the patient exhibited **hypoglycemia at 3 am**, the dawn phenomenon is not the cause of her morning hyperglycemia. *Hyperosmolar hyperglycemic state; increase nighttime insulin* - **Hyperosmolar hyperglycemic state (HHS)** is a severe complication characterized by extreme hyperglycemia, dehydration, and altered consciousness, usually in type 2 diabetes with very high glucose levels (>600 mg/dL), which is not indicated by the HbA1c or 3 am glucose reading. - Increasing insulin might be part of acute HHS management, but it's not the underlying condition or appropriate treatment for this specific presentation of overnight hypoglycemia followed by morning hyperglycemia. *She is experiencing dawn phenomenon so her nighttime insulin should be kept the same* - If it were the **dawn phenomenon**, the 3 am blood glucose would likely be normal or slightly elevated, not hypoglycemic. - Keeping the insulin dose the same would not address the underlying nocturnal hypoglycemia, nor the subsequent morning hyperglycemia seen in the Somogyi effect.

Question 684: A 48-year-old homeless man is brought to the emergency department 2 hours after his right arm was burned by a fire. He is diagnosed with extensive third-degree burns of the right forearm and upper arm and is admitted to the hospital for debridement and grafting. During his stay in the hospital, he suddenly develops confusion and agitation. Neurologic examination shows horizontal nystagmus and a broad-based gait. Laboratory studies show decreased erythrocyte transketolase activity. Administration of which of the following most likely caused this patient's current condition?

• A. Cobalamin
• B. Glucose (Correct Answer)
• C. Aspirin
• D. Hypertonic saline
• E. Haloperidol

Explanation: **Glucose** - The patient's symptoms (confusion, agitation, nystagmus, broad-based gait) and decreased **erythrocyte transketolase activity** are classic signs of **Wernicke-Korsakoff syndrome**, caused by **thiamine (vitamin B1) deficiency**. - *Administering glucose without prior thiamine supplementation* can precipitate or worsen Wernicke-Korsakoff syndrome because glucose metabolism requires thiamine as a cofactor, further depleting already low stores. *Cobalamin* - **Cobalamin (vitamin B12) deficiency** typically causes **megaloblastic anemia** and **neurological symptoms** like peripheral neuropathy, subacute combined degeneration, and cognitive impairment, but not the acute presentation of confusion, agitation, nystagmus, and ataxia seen here. - It is not directly linked to transketolase activity. *Aspirin* - **Aspirin** is an antiplatelet and anti-inflammatory drug. Overdose can cause **salicylate toxicity**, leading to metabolic acidosis, tinnitus, and hyperthermia, but not the specific neurological symptoms or biochemical changes described. - It is not associated with Wernicke-Korsakoff syndrome. *Hypertonic saline* - **Hypertonic saline** is used to treat severe hyponatremia. Rapid correction can lead to **osmotic demyelination syndrome (central pontine myelinolysis)**, causing severe neurological deficits and locked-in syndrome. - This condition presents differently from the patient's symptoms and is not related to thiamine metabolism. *Haloperidol* - **Haloperidol** is an antipsychotic medication. Side effects can include **extrapyramidal symptoms** (dystonia, akathisia, parkinsonism), sedation, and QT prolongation. - It does not cause Wernicke-Korsakoff syndrome or affect erythrocyte transketolase activity.

Question 685: A 7-year-old boy is brought to the physician by his mother because of a 2-week history of intermittent shortness of breath and a dry cough that is worse at night. He had an upper respiratory tract infection 3 weeks ago. Lungs are clear to auscultation. Spirometry shows normal forced vital capacity and peak expiratory flow rate. The physician administers a drug, after which repeat spirometry shows a reduced peak expiratory flow rate. Which of the following drugs was most likely administered?

• A. Ipratropium bromide
• B. Epinephrine
• C. Methacholine (Correct Answer)
• D. Methoxyflurane
• E. Atenolol

Explanation: ***Methacholine*** - The patient's symptoms (intermittent shortness of breath, dry cough worse at night, history of URI) are suggestive of **asthma**. A methacholine challenge test is used to diagnose **asthma** when baseline spirometry is normal. - **Methacholine** is a **muscarinic agonist** that causes **bronchoconstriction** in hyperreactive airways, leading to a decrease in lung function parameters like **peak expiratory flow rate** in asthmatic patients. *Ipratropium bromide* - **Ipratropium bromide** is an **anticholinergic bronchodilator** that would cause **bronchodilation**, leading to an increase in peak expiratory flow rate, not a decrease. - It works by blocking muscarinic receptors in the airways, preventing acetylcholine-induced bronchoconstriction. *Epinephrine* - **Epinephrine** is a **sympathomimetic** drug that acts on both alpha and beta-adrenergic receptors, causing significant **bronchodilation** by stimulating beta-2 receptors in the airways. - This would result in an **increase** in peak expiratory flow rate, not a reduction. *Methoxyflurane* - **Methoxyflurane** is a volatile halogenated anesthetic and is not used in the diagnosis or management of asthma. - It primarily affects the central nervous system and can cause kidney toxicity. *Atenolol* - **Atenolol** is a **beta-1 selective blocker** used primarily for cardiovascular conditions like hypertension and angina. - While non-selective beta-blockers can cause bronchoconstriction in asthmatics by blocking beta-2 receptors, atenolol's beta-1 selectivity makes this less likely, and it is **not used as a diagnostic bronchoprovocation agent** for asthma. - **Methacholine challenge** is the standard diagnostic test for airway hyperreactivity.

Question 686: A 27-year-old woman presents to the clinic with a runny nose and productive cough for the past two weeks. She also complains of headaches and lethargy. She was started on sertraline after she was diagnosed with major depressive disorder 2 months ago and had the dosage periodically increased to achieve symptom control. She is afraid of starting any other medication because of possible side-effects or life-threatening drug interactions. What advice is most accurate regarding possible complications to her current pharmacotherapy?

• A. Treat life-threatening complication with gradual drug withdrawal.
• B. Migraine medication can trigger a life-threatening complication. (Correct Answer)
• C. Over-the-counter (OTC) medications are safe for her to use.
• D. Sertraline cannot be used concurrently with neuroleptics
• E. Monoamine-oxidase-inhibitors are safe for concurrent use.

Explanation: ***Migraine medication can trigger a life-threatening complication.*** - Certain **migraine medications**, particularly **triptans** (e.g., sumatriptan), significantly increase the risk of **serotonin syndrome** when co-administered with **SSRIs** like sertraline due to additive serotonergic effects. - **Serotonin syndrome** is a potentially life-threatening condition characterized by mental status changes, autonomic instability, and neuromuscular hyperactivity. *Treat life-threatening complication with gradual drug withdrawal.* - Treating a **life-threatening complication** often requires immediate medical intervention and possibly abrupt cessation of the offending drug, rather than gradual withdrawal, especially in cases like severe **serotonin syndrome**. - Gradual withdrawal is typically for avoiding **discontinuation syndrome** (withdrawal symptoms) when ceasing SSRIs, not for managing acute, severe adverse drug reactions. *Over-the-counter (OTC) medications are safe for her to use.* - No, many **OTC medications** can interact with sertraline, such as **NSAIDs** (increased bleeding risk), or **cold/flu remedies** containing **dextromethorphan** or **pseudoephedrine** (potential for serotonin syndrome or increased BP). - Patients on sertraline should always consult their physician before taking any OTC medications due to potential **drug interactions**. *Sertraline cannot be used concurrently with neuroleptics* - While interactions can occur, sertraline (an SSRI) can be and often is used concurrently with **neuroleptics** (antipsychotics) to manage comorbid conditions like psychosis or severe mood disorders, sometimes to augment antidepressant effects. - The combination requires careful monitoring for side effects, but it is not an absolute contraindication like with MAOIs or some triptans. *Monoamine-oxidase-inhibitors are safe for concurrent use.* - This statement is incorrect; **Monoamine Oxidase Inhibitors (MAOIs)**, such as phenelzine or selegiline, are **absolutely contraindicated** with SSRIs like sertraline. - Concurrent use of MAOIs and SSRIs can precipitate severe and potentially fatal **serotonin syndrome** due to excessive serotonin levels.

Question 687: A 28-year-old woman presents with severe diarrhea and abdominal pain. She says she has had 10 watery stools since the previous morning and is experiencing severe cramping in her abdomen. She reports similar past episodes of diarrhea with excruciating abdominal pain and mentions that she has taken diphenoxylate and atropine before which had helped her diarrhea and pain but resulted in severe constipation for a week. Which of the following receptors does diphenoxylate activate to cause the effects mentioned by this patient?

• A. 5-HT3 receptor
• B. NK1 receptor
• C. D2 receptor
• D. µ receptor (Correct Answer)
• E. H2 receptor

Explanation: ***µ receptor*** - Diphenoxylate is an **opioid agonist** that primarily acts on the **µ-opioid receptors** in the GI tract. - Activation of these receptors **inhibits GI motility**, increases fluid absorption, and reduces intestinal secretions, leading to its antidiarrheal effects and a common side effect of constipation. *5-HT3 receptor* - The 5-HT3 receptor is a **serotonin receptor** involved in the **vomiting reflex** and visceral pain sensation. - Antagonists like ondansetron block this receptor to treat nausea and vomiting, not diarrhea. *NK1 receptor* - The NK1 receptor (Neurokinin 1 receptor) binds **substance P** and is primarily involved in mediating **nausea, vomiting**, and pain. - Antagonists like aprepitant are used to prevent chemotherapy-induced nausea and vomiting. *D2 receptor* - The D2 receptor is a **dopamine receptor** involved in motor control, reward, and **nausea/vomiting**. - Antagonists like metoclopramide block this receptor, leading to prokinetic effects and antiemesis, but are not the primary target for diphenoxylate. *H2 receptor* - H2 receptors are **histamine receptors** found in the **gastric parietal cells** and are responsible for stimulating gastric acid secretion. - Antagonists like famotidine are used to reduce stomach acid and treat conditions like GERD and ulcers.

Question 688: A 28-year-old man presents to his primary care physician because he has been experiencing constipation for the last 6 days. He says that the constipation started 1 day after he started taking an over the counter medication for sinus congestion and a chronic cough. He has no other findings associated with the constipation. His past medical history is significant for seasonal allergies but he is not currently taking any other medications besides the one he reported. Which of the following drugs was most likely responsible for this patient's symptoms?

• A. Guaifenesin
• B. Dextromethorphan
• C. Loratadine
• D. N-acetylcysteine
• E. Diphenhydramine (Correct Answer)

Explanation: ***Diphenhydramine*** - Diphenhydramine is a **first-generation antihistamine** with significant **anticholinergic effects**, which commonly include constipation due to reduced gastrointestinal motility. - The patient's presentation of constipation after starting an over-the-counter medication for sinus congestion and cough strongly suggests a drug with antimuscarinic properties. *Guaifenesin* - Guaifenesin is an **expectorant** that helps thin mucus, making it easier to clear from the airways. - It does not typically cause constipation; its common side effects are usually mild, such as nausea or dizziness. *Dextromethorphan* - Dextromethorphan is a **cough suppressant** that acts on the cough center in the medulla. - While it can cause some gastrointestinal upset or drowsiness, constipation is not a common side effect. *Loratadine* - Loratadine is a **second-generation antihistamine** that is less sedating and has minimal anticholinergic effects compared to first-generation antihistamines. - Therefore, it is unlikely to cause constipation. *N-acetylcysteine* - N-acetylcysteine is a **mucolytic agent** that breaks down disulfide bonds in mucus, used to help clear thick secretions. - It is not associated with constipation as a side effect and is sometimes used as a treatment for acetaminophen overdose.

Question 689: A 30-year-old man presents with a 1-month history of frequent intermittent headaches. He says the headaches typically occur between 3–4 times/day, mostly at night, each lasting minutes to 1–2 hours. He describes the pain as severe, stabbing, unilateral, and localized to the left periorbital region. He says he frequently notes increased tear production and conjunctival injection in the left eye and rhinorrhea during these headaches. He mentions that he had a similar 3-week episode of these same, frequent intermittent headaches 3 months ago which stopped completely until 1 month ago. He denies any seizures, loss of consciousness, nausea, vomiting, photophobia, or phonophobia. His past medical history is significant for stable angina secondary to coronary artery disease diagnosed on a stress echocardiogram 1 year ago. He reports occasional alcohol use, which he says precipitates the headaches, but denies any smoking or recreational drug use. The patient is afebrile, and his vital signs are within normal limits. A physical examination is unremarkable. A noncontrast computed tomography (CT) scan of the head is normal. Which of the following is the best abortive treatment for this patient?

• A. Intranasal lidocaine
• B. Hydrocodone
• C. Sumatriptan
• D. High-flow 100% oxygen (Correct Answer)
• E. Dihydroergotamine

Explanation: ***High-flow 100% oxygen*** - This patient presents with classic symptoms of **cluster headaches**: frequent, severe, unilateral periorbital pain along with **autonomic symptoms** (tearing, conjunctival injection, rhinorrhea), episodic pattern, and alcohol as a trigger. - **High-flow 100% oxygen** via a non-rebreather mask is a highly effective and generally safe abortive treatment for cluster headaches. *Intranasal lidocaine* - While intranasal lidocaine can be used as an abortive treatment for cluster headaches, its efficacy is generally **lower** compared to high-flow oxygen or triptans. - It might be considered for patients who cannot tolerate or respond to first-line treatments, but it is not the **best** initial abortive option. *Hydrocodone* - **Opioids like hydrocodone** are generally **contraindicated** for the treatment of cluster headaches due to their limited efficacy in acute attacks and significant risk of dependence, abuse, and medication overuse headache. - Cluster headaches are characterized by short, severe attacks that require rapid-acting specific treatments, which opioids do not provide. *Sumatriptan* - **Sumatriptan** (specifically subcutaneous sumatriptan) is another **first-line abortive treatment** for cluster headaches and works rapidly and effectively. - However, this patient has a history of **stable angina secondary to coronary artery disease**. Triptans are **contraindicated** in patients with ischemic heart disease due to their vasoconstrictive properties, which can exacerbate myocardial ischemia. *Dihydroergotamine* - **Dihydroergotamine** is an ergot derivative that can be effective for acute migraine and, to some extent, cluster headaches, acting as a vasoconstrictor. - Similar to triptans, **dihydroergotamine is contraindicated** in patients with coronary artery disease or other cardiovascular conditions due to the risk of vasoconstriction and potential for cardiac events.

Question 690: A 55-year-old obese woman is referred to the cardiology clinic for progressive dyspnea. She has had no recent travel or sick contacts. Besides a multivitamin, she has only tried online weight-loss medications for the past five years, including fenfluramine-phentermine. An echocardiogram reveals a dilated right ventricle with systolic pressure of 60 mmHg as well as both tricuspid and pulmonary regurgitation. A right heart catheterization shows a mean pulmonary artery pressure of 40 mmHg. What disease process is most analogous to this patient's presentation?

• A. Chronic obstructive pulmonary disease
• B. Subacute endocarditis
• C. Chronic thromboembolic disease
• D. Left heart failure
• E. Carcinoid syndrome (Correct Answer)

Explanation: ***Carcinoid syndrome*** - Carcinoid syndrome is well-known to cause **pulmonary hypertension** and **right-sided valvular heart disease**, particularly **tricuspid and pulmonary regurgitation**, which is analogous to the patient's presentation following fenfluramine-phentermine use. - Both fenfluramine-phentermine and carcinoid syndrome cause valvular disease through **serotonin-mediated mechanisms**. Fenfluramine increases serotonin release and blocks reuptake, leading to **endocardial fibrosis** and valvular damage that mimics carcinoid heart disease. - The right-sided predominance occurs because the lungs metabolize serotonin, protecting the left heart. *Chronic obstructive pulmonary disease* - While **COPD** can lead to pulmonary hypertension and right heart failure (**cor pulmonale**), there is no mention of a smoking history or respiratory symptoms like chronic cough or wheezing that are typical of COPD. - The patient's primary risk factor is obesity and prior medication use, not factors directly implicating COPD. *Subacute endocarditis* - **Subacute endocarditis** typically involves bacterial infection of heart valves, presenting with fever, malaise, and new murmurs, which are not described in this patient's presentation. - While it can cause valvular disease, it doesn't typically cause primary pulmonary hypertension or isolated right-sided disease in this manner. *Chronic thromboembolic disease* - **Chronic thromboembolic pulmonary hypertension (CTEPH)** results from organized blood clots in the pulmonary arteries, leading to right ventricular strain and pulmonary hypertension. - There is no mention of prior **pulmonary emboli** or other risk factors for chronic thromboembolism in the patient's history. *Left heart failure* - **Left heart failure** can cause **pulmonary hypertension** due to backward pressure from the left side of the heart, but the echocardiogram specifically highlights isolated right ventricle dilation and right-sided valvular issues. - While the patient has dyspnea, there are no findings suggestive of primary left ventricular dysfunction, such as reduced ejection fraction or left atrial enlargement.

Question 691: A 21-year-old woman with type 1 diabetes mellitus suddenly develops tremors, cold sweats, and confusion while on a backpacking trip with friends. She is only oriented to person and is unable to follow commands. Her fingerstick blood glucose concentration is 28 mg/dL. Her friend administers an intramuscular injection with a substance that reverses her symptoms. Which of the following is the most likely mechanism of action of this drug?

• A. Activation of glucokinase
• B. Inhibition of glucose-6-phosphatase
• C. Inhibition of glycogen phosphorylase
• D. Activation of adenylyl cyclase (Correct Answer)
• E. Inhibition of α-glucosidase

Explanation: ***Activation of adenylyl cyclase*** - The patient is experiencing **hypoglycemia** (blood glucose 28 mg/dL) with severe symptoms (confusion, unable to follow commands), indicating a need for rapid glucose elevation. The drug administered is likely **glucagon**. - **Glucagon** primarily acts on hepatic cells by binding to G-protein coupled receptors, leading to the activation of **adenylyl cyclase**. This increases intracellular **cAMP**, which then activates protein kinase A, ultimately leading to increased **glycogenolysis** and **gluconeogenesis** to raise blood glucose. *Activation of glucokinase* - **Glucokinase** is an enzyme involved in the **phosphorylation of glucose** to glucose-6-phosphate, primarily in the liver and pancreatic beta cells. Its activation would promote glucose utilization and storage, thereby **lowering blood glucose**, which is contrary to the desired effect in hypoglycemia. - This enzyme is crucial for sensing glucose levels and initiating insulin secretion or glucose storage, not for rapid glucose elevation during hypoglycemia. *Inhibition of glucose-6-phosphatase* - **Glucose-6-phosphatase** is a key enzyme in the final step of both **gluconeogenesis** and **glycogenolysis**, converting glucose-6-phosphate to free glucose in the liver. Inhibition of this enzyme would **prevent glucose release** into the bloodstream and worsen hypoglycemia. - This enzyme's activity is crucial for maintaining blood glucose homeostasis, especially during fasting, by allowing the liver to export glucose. *Inhibition of glycogen phosphorylase* - **Glycogen phosphorylase** is the enzyme responsible for initiating **glycogenolysis**, the breakdown of glycogen into glucose-1-phosphate. Inhibition of this enzyme would **prevent the breakdown of glycogen**, thereby hindering the body's ability to release stored glucose and exacerbating hypoglycemia. - Glucagon, in contrast, *activates* glycogen phosphorylase to increase glucose output. *Inhibition of α-glucosidase* - **α-glucosidase inhibitors** (e.g., acarbose, miglitol) are oral hypoglycemic drugs that **slow down the digestion and absorption of carbohydrates** in the small intestine. - These drugs are used to **lower postprandial blood glucose** in type 2 diabetes and would worsen hypoglycemia if given to this patient, not reverse it.

Question 692: A 49-year-old man with alcohol use disorder is brought to the emergency department immediately after two episodes of coffee-ground emesis. His pulse is 116/min and blood pressure is 92/54 mm Hg. Physical examination shows a distended abdomen with shifting dullness. Skin examination shows jaundice, erythematous palms, and dilated veins in the anterior abdominal wall. After fluid resuscitation, he is given a drug that decreases portal venous pressure. The drug works by inhibiting the secretion of splanchnic vasodilatory hormones as well as blocking glucagon and insulin release. This drug is a synthetic analog of a substance normally produced in which of the following cells?

• A. G cells
• B. D cells (Correct Answer)
• C. K cells
• D. S cells
• E. I cells

Explanation: ***D cells*** - The patient's presentation with **coffee-ground emesis**, **hypotension**, and signs of **chronic liver disease** (jaundice, erythematous palms, dilated abdominal veins, ascites) suggests **gastrointestinal bleeding** due to **portal hypertension**, likely from **esophageal varices**. - The drug described, which reduces portal venous pressure by inhibiting splanchnic vasodilatory hormones and blocking glucagon/insulin release, is **octreotide**. Octreotide is a synthetic analog of **somatostatin**, which is primarily produced by **D cells** in the pancreatic islets and gastrointestinal mucosa. *G cells* - **G cells** primarily secrete **gastrin**, which stimulates gastric acid secretion. - Gastrin does not directly inhibit splanchnic vasodilatory hormones or affect portal venous pressure in this manner. *K cells* - **K cells** secrete **gastric inhibitory polypeptide (GIP)**, a hormone that stimulates insulin release and inhibits gastric acid secretion. - GIP is not involved in reducing portal hypertension or inhibiting splanchnic vasodilatory hormones. *S cells* - **S cells** secrete **secretin**, which stimulates bicarbonate secretion from the pancreas and liver. - Secretin's primary action is not to decrease portal venous pressure or inhibit splanchnic vasodilatory hormones. *I cells* - **I cells** secrete **cholecystokinin (CCK)**, which stimulates gallbladder contraction and pancreatic enzyme release. - CCK does not play a role in managing portal hypertension or inhibiting splanchnic vasodilatory hormones.

Question 693: A 24-year-old man presents to his family practitioner for routine follow-up of asthma. He is currently on albuterol, corticosteroids, and salmeterol, all via inhalation. The patient is compliant with his medications, but he still complains of episodic shortness of breath and wheezing. The peak expiratory flow (PEF) has improved since the last visit, but it is still less than the ideal predicted values based on age, gender, and height. Montelukast is added to his treatment regimen. What is the mechanism of action of this drug?

• A. Montelukast inhibits the release of inflammatory substances from mast cells.
• B. Montelukast activates adrenergic receptors on the bronchial smooth muscles.
• C. Montelukast inhibits lipoxygenase, thus decreasing the production of inflammatory leukotrienes.
• D. Montelukast binds to IgE.
• E. Montelukast blocks receptors of some arachidonic acid metabolites. (Correct Answer)

Explanation: ***Montelukast blocks receptors of some arachidonic acid metabolites.*** - Montelukast is a **leukotriene receptor antagonist** that specifically blocks the **cysteinyl leukotriene 1 (CysLT1) receptor**. - By blocking these receptors, montelukast prevents the inflammatory effects primarily mediated by **leukotrienes C4, D4, and E4**, which are metabolites of arachidonic acid and potent bronchoconstrictors and promoters of inflammation in asthma. *Montelukast inhibits the release of inflammatory substances from mast cells.* - This mechanism describes **mast cell stabilizers** like **cromolyn sodium** or **nedocromil**, which prevent the degranulation of mast cells and the subsequent release of inflammatory mediators. - Montelukast does not directly prevent the release of these substances; rather, it blocks the receptors for some of them. *Montelukast activates adrenergic receptors on the bronchial smooth muscles.* - The activation of **adrenergic receptors** (specifically **beta-2 adrenergic receptors**) on bronchial smooth muscles by drugs like **albuterol** and **salmeterol** leads to bronchodilation. - Montelukast is not an adrenergic agonist; it targets leukotriene pathways. *Montelukast inhibits lipoxygenase, thus decreasing the production of inflammatory leukotrienes.* - This mechanism describes **5-lipoxygenase inhibitors**, such as **zileuton**, which prevent the synthesis of leukotrienes from arachidonic acid. - Montelukast does not inhibit lipoxygenase; instead, it blocks the receptors where leukotrienes would normally bind. *Montelukast binds to IgE.* - This mechanism describes **omalizumab**, a **monoclonal antibody** that binds to circulating **IgE antibodies**, preventing them from binding to mast cells and basophils. - Omalizumab thereby reduces the allergic response; montelukast works on a different pathway.

Question 694: A 24-year-old woman, gravida 2, para 1, at 33 weeks’ gestation, is admitted to the hospital for treatment of preterm labor. She has no history of serious illness and her only medication is a multivitamin. Her temperature is 37.2°C (99.0°F), pulse is 100/min, respirations are 20/min, and blood pressure is 100/75 mm Hg. Therapy with nifedipine and betamethasone is begun. The patient continues to have contractions; nifedipine is discontinued and treatment with high-dose terbutaline is initiated. Her contractions resolve. Three hours later, the patient reports fatigue and weakness. Neurologic examination shows proximal muscle weakness of the lower extremities. Deep tendon reflexes are 1+ bilaterally. Which of the following is most likely to confirm the diagnosis?

• A. Serum electrolytes (Correct Answer)
• B. Thyroid function tests
• C. Complete blood count
• D. Amniotic fluid culture
• E. Serologic antibody testing

Explanation: ***Serum electrolytes*** - **High-dose terbutaline**, a **beta-2 agonist**, can cause a significant shift of potassium intracellularly, leading to **hypokalemia**. - Symptoms of hypokalemia include **muscle weakness**, fatigue, and diminished deep tendon reflexes, which matches the patient's presentation. *Thyroid function tests* - While **hyperthyroidism** can cause muscle weakness, it's less likely to manifest acutely after terbutaline administration. - The patient's vital signs and lack of other classic features (e.g., tremors, heat intolerance) do not strongly suggest thyroid dysfunction. *Complete blood count* - A CBC is useful for assessing for **anemia** or **infection**, but these conditions do not typically explain acute proximal muscle weakness and diminished reflexes in this context. - While anemia can cause fatigue, it wouldn't directly cause the specific neurological findings observed. *Amniotic fluid culture* - An amniotic fluid culture is primarily used to detect **intra-amniotic infection**, which could be a cause of preterm labor. - It would not explain the patient's acute muscle weakness and neurological symptoms occurring specifically after terbutaline administration. *Serologic antibody testing* - **Autoimmune disorders** that cause muscle weakness, such as **myasthenia gravis** or **Guillain-Barré syndrome**, are generally chronic or subacute in onset. - The acute timing of the symptoms following terbutaline makes these less likely; instead, the drug's known side effects are a more direct explanation.

Question 695: A 48-year-old male with a history of rhinitis presents to the emergency department with complaints of shortness of breath and wheezing over the past 2 days. He reports bilateral knee pain over the past month for which he recently began taking naproxen 1 week ago. Physical examination is significant for a nasal polyp and disappearance of bilateral radial pulses on deep inspiration. Which of the following is the most likely cause of this patient's physical examination findings?

• A. Pulmonary hypertension
• B. Cardiac tamponade
• C. Pulmonary embolism
• D. Asthma
• E. AERD (Aspirin-Exacerbated Respiratory Disease) (Correct Answer)

Explanation: ***AERD (Aspirin-Exacerbated Respiratory Disease)*** - The patient's presentation with **rhinitis, nasal polyps, asthma-like symptoms (shortness of breath, wheezing), and worsening after initiating naproxen (an NSAID)** is highly characteristic of AERD. - **The pulsus paradoxus (disappearance of radial pulses on deep inspiration)** is caused by **severe bronchospasm and airway obstruction** from the AERD exacerbation, which increases negative intrathoracic pressure during inspiration, reducing left ventricular stroke volume and systolic blood pressure. - **Aspirin and other NSAIDs** trigger respiratory distress and bronchospasm in AERD by inhibiting COX-1 enzyme, leading to increased leukotriene production and mast cell activation. - AERD is a distinct clinical syndrome (also called Samter's triad) involving the classic triad of **asthma, nasal polyps, and NSAID sensitivity**. *Pulmonary hypertension* - While pulmonary hypertension can cause shortness of breath, it typically does not present with **nasal polyps, rhinitis, or an acute exacerbation linked to NSAID use**. - Physical exam findings more commonly include **jugular venous distension, peripheral edema, and a prominent P2 heart sound**, which are not described here. *Cardiac tamponade* - While **pulsus paradoxus** is a classic sign of cardiac tamponade, the overall clinical picture—especially the **rhinitis, nasal polyp, and NSAID-induced respiratory exacerbation**—clearly points to a respiratory cause of the pulsus paradoxus, not cardiac tamponade. - Other features of tamponade include **Beck's triad (hypotension, muffled heart sounds, elevated JVP)**, which are absent in this case. - The pulsus paradoxus here is due to **severe airway obstruction**, not pericardial constriction. *Pulmonary embolism* - Pulmonary embolism typically presents with **acute onset dyspnea, pleuritic chest pain, and sometimes hemoptysis**. - It is not associated with a history of **rhinitis, nasal polyps, or a clear link to NSAID ingestion** exacerbating respiratory symptoms. - PE does not typically cause pulsus paradoxus. *Asthma* - While severe asthma can cause **wheezing, shortness of breath, and even pulsus paradoxus**, the presence of **nasal polyps** and the specific exacerbation with an **NSAID (naproxen)** point more directly to AERD, a distinct subset of asthma. - AERD is a unique clinical syndrome involving overproduction of leukotrienes, specifically triggered by COX-1 inhibitors, which differentiates it from typical allergic or non-allergic asthma.

Question 696: A 58-year-old female presents to her primary care physician with a 1-month history of facial and chest flushing, as well as intermittent diarrhea and occasional difficulty breathing. On physical exam, a new-onset systolic ejection murmur is auscultated and is loudest at the left second intercostal space. Subsequent echocardiography reveals leaflet thickening secondary to fibrous plaque deposition on both the pulmonic and tricuspid valves. Which of the following laboratory abnormalities would most likely be found in this patient?

• A. Elevated urinary 5-hydroxyindoleacetic acid (Correct Answer)
• B. Elevated serum bicarbonate
• C. Elevated serum potassium
• D. Decreased serum chromogranin A
• E. Elevated urinary vanillylmandelic acid

Explanation: **Elevated urinary 5-hydroxyindoleacetic acid** * This patient's symptoms (flushing, diarrhea, dyspnea, and cardiac valve abnormalities, especially right-sided with fibrous plaque deposition) are classic for **carcinoid syndrome**. This syndrome is caused by neuroendocrine tumors, often in the gastrointestinal tract, that secrete large amounts of serotonin. * **5-hydroxyindoleacetic acid (5-HIAA)** is the main metabolite of **serotonin**, and its elevated levels in urine are a key diagnostic marker for carcinoid syndrome. *Elevated serum bicarbonate* * **Elevated serum bicarbonate** is typically associated with **metabolic alkalosis**, which is not a direct or expected finding in carcinoid syndrome. * Carcinoid syndrome can lead to electrolyte imbalances due to diarrhea, but metabolic alkalosis through elevated bicarbonate is not a primary or characteristic feature. *Elevated serum potassium* * **Elevated serum potassium** (hyperkalemia) is not a common or direct consequence of carcinoid syndrome. * While severe diarrhea can sometimes lead to electrolyte disturbances, it more typically causes **hypokalemia** due to potassium loss, not hyperkalemia. *Decreased serum chromogranin A* * **Chromogranin A** is a general marker for neuroendocrine tumors; however, in actively secreting tumors like those causing carcinoid syndrome, **serum chromogranin A** levels would most likely be **elevated**, not decreased. * It serves as a useful diagnostic and prognostic marker for neuroendocrine tumors, indicating tumor burden and activity. *Elevated urinary vanillylmandelic acid* * **Elevated urinary vanillylmandelic acid (VMA)** is a diagnostic marker for **pheochromocytoma** and **paraganglioma**, tumors that secrete catecholamines (epinephrine and norepinephrine). * While some symptoms like flushing can overlap, the specific cardiac and gastrointestinal symptoms described, along with the right-sided valvular lesions, are characteristic of carcinoid syndrome, not pheochromocytoma.

Question 697: One month after undergoing surgical spinal fusion because of a traumatic spinal cord injury, a 68-year-old man comes to the physician because of lower abdominal pain. He last voided yesterday. Physical examination shows a suprapubic mass and decreased sensation below the umbilicus. Urodynamic studies show simultaneous contractions of the detrusor muscle and the internal urethral sphincter. Urinary catheterization drains 900 mL of urine from the bladder. Which of the following is the most appropriate pharmacotherapy for this patient’s urinary symptoms?

• A. Prazosin (Correct Answer)
• B. Phenylephrine
• C. Finasteride
• D. Neostigmine
• E. Bethanechol

Explanation: ***Prazosin*** - This patient is experiencing **detrusor-sphincter dyssynergia (DSD)** secondary to a spinal cord injury, leading to bladder outlet obstruction and urinary retention. **Prazosin** is an **alpha-1 antagonist** that relaxes the internal urethral sphincter, improving urine flow and reducing functional obstruction. - Relaxing the internal urethral sphincter helps to reduce the high bladder pressures during voiding, preventing complications like hydronephrosis and improving bladder emptying in patients with DSD. *Phenylephrine* - **Phenylephrine** is an **alpha-1 adrenergic agonist** that causes vasoconstriction and contraction of smooth muscles, including the internal urethral sphincter. - This would worsen the patient's condition by increasing urethral resistance and exacerbating urinary retention. *Finasteride* - **Finasteride** is a **5-alpha reductase inhibitor** used to treat benign prostatic hyperplasia (BPH) by reducing prostate size. - This patient's urinary symptoms are due to neurogenic bladder and DSD, not BPH; therefore, finasteride would not address the underlying pathology. *Neostigmine* - **Neostigmine** is an **acetylcholinesterase inhibitor** that increases acetylcholine levels at the neuromuscular junction, used for conditions like myasthenia gravis or to reverse neuromuscular blockade. - While it can increase detrusor contractility, it would not address the spastic contraction of the internal urethral sphincter (DSD), and could potentially worsen the symptoms by increasing detrusor pressure against an obstructed outlet. *Bethanechol* - **Bethanechol** is a **muscarinic agonist** that directly stimulates detrusor muscle contraction, used to promote bladder emptying in cases of hypotonic or atonic bladder. - Although it enhances detrusor contraction, it does not relax the internal urethral sphincter and could lead to even higher bladder pressures in the presence of detrusor-sphincter dyssynergia, increasing the risk of upper urinary tract damage.

Question 698: A 24-year-old African American male with sickle cell disease has been followed by a hematologist since infancy. Two years ago, he was started on hydroxyurea for frequent pain crises but has not achieved good control. The addition of a Gardos channel blocking agent is being considered. What is the mechanism of action of this class of medications?

• A. Increases water diffusion by increasing activity of aquaporin-1 receptors
• B. Increases production of hemoglobin F
• C. Encourages alkalinization of the blood by facilitating H+/K+ antiporter activity
• D. Prevents dehydration of RBCs by inhibiting Ca2+ efflux
• E. Prevents RBC dehydration by inhibiting K+ efflux (Correct Answer)

Explanation: ***Prevents RBC dehydration by inhibiting K+ efflux*** - Gardos channel blockers, like **voxelotor**, inhibit the **Gardos channel (KCCN4)** in red blood cells, which is a calcium-activated potassium channel. - By blocking **K+ efflu**x, these agents prevent the **dehydration** and sickling of red blood cells, thereby reducing the frequency of vaso-occlusive crises in sickle cell disease. *Increases water diffusion by increasing activity of aquaporin-1 receptors* - **Aquaporins** are water channels, but their modulation is not the primary mechanism of action for Gardos channel blockers in **sickle cell disease**. - The focus of Gardos channel blockers is on maintaining **RBC volume** by preventing K+ loss, not by directly increasing water diffusion across aquaporins. *Increases production of hemoglobin F* - **Hydroxyurea** is the medication that primarily works by increasing the production of **fetal hemoglobin (HbF)**, which is known to inhibit HbS polymerization. - Gardos channel blockers operate through a distinct mechanism, focusing on **red blood cell hydration**, rather than HbF induction. *Encourages alkalinization of the blood by facilitating H+/K+ antiporter activity* - The **H+/K+ antiporter** is more relevant in gastric acid secretion and kidney physiology, not as a primary target for preventing red blood cell sickling in sickle cell disease. - Gardos channel blockers specifically target potassium channels in RBCs to prevent **dehydration** and sickling, unconnected to H+/K+ antiporter activity. *Prevents dehydration of RBCs by inhibiting Ca2+ efflux* - While Gardos channels are **calcium-activated**, the Gardos channel blockers work by inhibiting the **potassium efflux** *through* the channel, rather than directly inhibiting calcium efflux. - The primary problem in sickle cell dehydration is the loss of **potassium**, which draws water out of the cell, leading to sickling.

Question 699: A 60-year-old woman presents to you with vision problems. Objects appear clear, but she just can't see as well as before. She says she first noticed this when she went to the movies with her grandkids, and she could not see the whole screen. She denies any complaints of redness, itchiness, or excessive tearing of her eyes. Current medications are captopril for her hypertension, acetaminophen for occasional headaches, and a daily multivitamin. Her vital signs are a blood pressure 130/80 mm Hg, pulse 80/min and regular, respiratory rate 14/min, and a temperature of 36.7°C (98.0°F). Eye examination reveals that her visual acuity is normal but the visual field is reduced with enlarged blind spots. Tonometry reveals mildly increased IOP. The patient is started on brimonidine. Which of the following statements best describes the therapeutic mechanism of action of this medication in this patient?

• A. Brimonidine blocks the beta-receptors on the ciliary body to reduce aqueous humor production.
• B. Brimonidine causes an increase in cAMP, leading to increased aqueous humor formation by the ciliary body.
• C. Peripheral vasoconstriction by brimonidine leads to better control of her hypertension.
• D. Brimonidine causes immediate contraction of the ciliary body, leading to decreased uveoscleral outflow.
• E. Brimonidine acts as an alpha-2 adrenergic agonist to reduce aqueous humor production and increase uveoscleral outflow. (Correct Answer)

Explanation: ***Brimonidine acts as an alpha-2 adrenergic agonist to reduce aqueous humor production and increase uveoscleral outflow.*** - **Brimonidine** is an **alpha-2 adrenergic agonist** that reduces **aqueous humor production** and increases **uveoscleral outflow**, thereby lowering intraocular pressure (IOP) in glaucoma. - This mechanism is crucial for treating conditions like **open-angle glaucoma**, which presents with visual field defects and increased IOP. *Brimonidine blocks the beta-receptors on the ciliary body to reduce aqueous humor production.* - **Brimonidine** is an **alpha-2 agonist**, not a **beta-blocker**. **Beta-blockers** (e.g., timolol) block beta-receptors on the ciliary body to reduce aqueous humor production. - The medication's primary action is not through beta-receptor antagonism. *Brimonidine causes an increase in cAMP, leading to increased aqueous humor formation by the ciliary body.* - **Alpha-2 adrenergic agonists** typically decrease **cAMP** levels, which leads to reduced aqueous humor production. - An increase in cAMP would generally lead to **increased aqueous humor formation**, which is counterproductive in treating glaucoma. *Peripheral vasoconstriction by brimonidine leads to better control of her hypertension.* - While **alpha-2 agonists** can affect blood pressure, **brimonidine** is primarily a topical agent for the eye, and its systemic effects on **hypertension** are not its primary therapeutic mechanism for glaucoma. - Its main role is to lower **intraocular pressure**, not to treat systemic hypertension. *Brimonidine causes immediate contraction of the ciliary body, leading to decreased uveoscleral outflow.* - **Brimonidine** primarily works by **reducing aqueous humor production** and **increasing uveoscleral outflow**, not by causing ciliary body contraction leading to decreased outflow. - **Miotics** (e.g., pilocarpine) cause ciliary body contraction to increase trabecular outflow, which is a different mechanism.

Question 700: A 47-year-old woman comes to the physician because of a 5-month history of insomnia. She frequently experiences leg discomfort when trying to fall asleep that is relieved temporarily by movement. Her husband tells her that she frequently flexes her ankles upward when she sleeps. She appears fatigued and anxious. Physical examination shows no abnormalities. Laboratory studies including a complete blood count and iron studies are within the reference range. Which of the following is the most appropriate pharmacotherapy?

• A. Ropinirole (Correct Answer)
• B. Atenolol
• C. Zolpidem
• D. Nortriptyline
• E. Sertraline

Explanation: ***Ropinirole*** - This patient's symptoms of **leg discomfort** at rest, relief with movement, and presence of **periodic limb movements in sleep** (flexing ankles upward) are classic for **Restless Legs Syndrome (RLS)**. - **Dopamine agonists** like ropinirole are first-line pharmacotherapy for RLS as they alleviate the primary motor and sensory symptoms. *Atenolol* - **Atenolol** is a **beta-blocker** primarily used for hypertension, angina, and certain arrhythmias. - It has no role in the treatment of RLS and would not address the patient's specific symptoms. *Zolpidem* - **Zolpidem** is a **sedative-hypnotic** (Z-drug) used for insomnia, helping initiate and maintain sleep. - While the patient has insomnia, zolpidem would only mask the sleep disturbance without treating the underlying RLS symptoms. *Nortriptyline* - **Nortriptyline** is a **tricyclic antidepressant (TCA)** used for depression, neuropathic pain, and occasionally insomnia. - TCAs can sometimes worsen RLS symptoms and are generally avoided in these patients. *Sertraline* - **Sertraline** is a **selective serotonin reuptake inhibitor (SSRI)** used for depression, anxiety disorders, and other psychiatric conditions. - Like TCAs, SSRIs can sometimes exacerbate RLS symptoms and are not appropriate first-line treatment for RLS-related insomnia.

Question 701: A 51-year-old man is undergoing chemotherapy treatment for a rapidly progressive newly-diagnosed acute myelogenous leukemia. On day 4 of his hospitalization, the patient is noted to be obtunded. Other than the chemotherapy, he is receiving lansoprazole, acetaminophen, and an infusion of D5–0.9% normal saline at 50 mL/h. On examination, the patient’s blood pressure is 94/50 mm Hg, heart rate is 52/min, and respiratory rate is 14/min. The patient appears weak but is in no acute distress. Chest auscultation reveals bibasilar crackles and scattered wheezing. His abdomen is soft, non-distended, and with a palpable liver and spleen. His ECG shows peaked T waves and widened QRS complexes. What is the best next step in the management of this patient?

• A. Glucagon
• B. Calcium chloride (Correct Answer)
• C. Polystyrene sulfonate
• D. Subcutaneous regular insulin
• E. Atropine

Explanation: ***Calcium chloride*** - This patient's presentation with **obtundation**, **bradycardia** (HR 52/min), **hypotension** (BP 94/50), widened QRS complexes, and peaked T waves on ECG, along with recent chemotherapy for AML, strongly suggests severe **hyperkalemia** secondary to **tumor lysis syndrome**. - **Calcium chloride** (or calcium gluconate) is the first-line treatment for hyperkalemia with ECG changes because it **stabilizes the cardiac membrane**, protecting against life-threatening arrhythmias, without directly lowering serum potassium levels. *Glucagon* - **Glucagon** is primarily used in cases of **hypoglycemia** or as an antidote for **beta-blocker overdose**, which is not indicated by the patient's symptoms or ECG findings. - There is no evidence suggesting its utility in treating severe hyperkalemia or its associated cardiac manifestations. *Polystyrene sulfonate* - **Polystyrene sulfonate** (e.g., Kayexalate) works by **exchanging potassium for sodium in the gastrointestinal tract**, thus reducing overall body potassium. - While effective in lowering potassium, its onset of action is slow (hours), making it inappropriate for acute, life-threatening hyperkalemia with ECG changes where immediate cardiac stabilization is required. *Subcutaneous regular insulin* - **Insulin**, often given with dextrose, helps shift potassium from the extracellular to the intracellular space, effectively lowering serum potassium levels. - However, its action is not immediate enough to protect the heart during acute hyperkalemia with ECG changes; therefore, it follows calcium in the management sequence. *Atropine* - **Atropine** is used to treat **bradycardia**, but its role is limited to vagally mediated bradycardia and would not address the underlying hyperkalemia or its direct cardiac effects like widened QRS and peaked T waves. - Treating bradycardia without addressing the cause (hyperkalemia) would not stabilize the patient in this scenario.

Question 702: A 59-year-old man is brought to the emergency department because of a 2-hour history of abdominal pain and severe vomiting after ingesting an unknown medication in a suicide attempt. On the way to the hospital, he had a generalized tonic-clonic seizure. He has chronic obstructive pulmonary disease, coronary artery disease, and chronic back pain. His pulse is 130/min, respirations are 16/min, and blood pressure is 110/60 mm Hg. Serum studies show a glucose concentration of 180 mg/dL and a potassium concentration of 2.8 mEq/L. An ECG shows ventricular tachycardia. This patient's current findings are most likely caused by an overdose of which of the following drugs?

• A. Theophylline (Correct Answer)
• B. Metoprolol
• C. Albuterol
• D. Acetaminophen
• E. Amitriptyline

Explanation: ***Theophylline*** - **Theophylline toxicity** presents with GI symptoms (vomiting), neurological symptoms (seizures), and cardiac arrhythmias like **ventricular tachycardia**. - Its narrow therapeutic index makes overdose particularly dangerous; the patient's history of **COPD** (for which theophylline might be prescribed) further supports this. *Metoprolol* - **Beta-blocker overdose** typically leads to **bradycardia**, hypotension, and potentially bronchospasm. - The patient's presentation with tachycardia and seizures is inconsistent with metoprolol overdose. *Albuterol* - **Albuterol overdose** (a beta-2 agonist) can cause tachycardia, palpitations, and hypokalemia. - However, it is less likely to induce **seizures** or severe, life-threatening arrhythmias like recurrent ventricular tachycardia as seen in this case. *Acetaminophen* - **Acetaminophen overdose** primarily causes **hepatotoxicity**, which would develop over days, not within 2 hours. - Initial symptoms might be vague (nausea, vomiting), but it would not typically cause acute seizures or ventricular tachycardia. *Amitriptyline* - **Tricyclic antidepressant (TCA) overdose** can cause cardiovascular (QT prolongation, arrhythmias) and neurological (seizures, coma) symptoms. - While it causes **wide QRS complex tachycardia** rather than ventricular tachycardia and **anticholinergic effects** (e.g., dry mouth, blurred vision) are common, the symptom profile here points more strongly to theophylline.

Question 703: A 78-year-old female presents to her primary care provider complaining of shaking of her hands. She reports that her hands shake when she is pouring her coffee in the morning and when she is buttoning her shirt. She has noticed that her tremor improves with the several beers she has every night with dinner. She has a past medical history of hypertension, atrial fibrillation, moderate persistent asthma, acute intermittent porphyria, and urinary retention. Her home medications include hydrochlorothiazide, warfarin, bethanechol, low-dose inhaled fluticasone, and an albuterol inhaler as needed. On physical exam, she has an irregularly irregular heart rhythm without S3/S4. She has mild wheezing on pulmonary exam. She has no tremor when her hands are in her lap. A low-amplitude tremor is present during finger-to-nose testing. Her neurological exam is otherwise unremarkable. Which of the following is a contraindication to the first-line treatment of this condition?

• A. Heavy alcohol use
• B. Asthma (Correct Answer)
• C. Urinary retention
• D. Acute intermittent porphyria
• E. Warfarin use

Explanation: ***Asthma*** - The patient's presentation of an **action tremor** that improves with alcohol is classic for **essential tremor**. First-line treatment is often a **beta-blocker** like propranolol. - Beta-blockers are contraindicated in patients with pulmonary conditions such as asthma, as they can cause **bronchoconstriction** and worsen respiratory symptoms. *Heavy alcohol use* - While the tremor briefly improves with alcohol, **heavy alcohol use** is not a contraindication to pharmacological treatment for essential tremor. In fact, it often indicates self-medication for the tremor. - Chronic heavy alcohol use can have its own adverse effects and interactions but typically does not preclude the use of first-line pharmacotherapy for essential tremor. *Urinary retention* - **Urinary retention** is primarily a concern with anticholinergic medications like oxybutynin, which are not first-line treatments for essential tremor. - Beta-blockers, the first-line treatment, generally do not exacerbate urinary retention. *Acute intermittent porphyria* - **Acute intermittent porphyria** is a rare genetic disorder where certain medications can trigger attacks. While some drugs are contraindicated, beta-blockers like propranolol are generally considered safe. - This condition does not directly contraindicate the use of beta-blockers for essential tremor. *Warfarin use* - **Warfarin** is an anticoagulant, and while drug interactions are a concern, there is generally no absolute contraindication to using beta-blockers with warfarin. - Close monitoring of **INR** may be needed as some beta-blockers can affect warfarin metabolism, but this is typically a management consideration, not a contraindication.

Question 704: A 27-year-old woman, primigravida, gave birth to a boy 3 months ago and now presents the newborn to your clinic for evaluation. She did not receive prenatal care. She reports that she was taking a medication for her mood swings, but cannot remember the medication’s name. The baby was born cyanotic, with a congenital malformation of the heart that is characterized by apical displacement of the septa and posterior tricuspid valve leaflets. A chest radiograph is shown in the image. Which of the following medications was the mother most likely taking?

• A. Buspirone
• B. Clozapine
• C. Enalapril
• D. Losartan
• E. Lithium (Correct Answer)

Explanation: ***Lithium*** - Lithium exposure during pregnancy is associated with a specific cardiac anomaly known as **Ebstein's anomaly**, characterized by apical displacement of the **tricuspid valve leaflets** and septa, leading to atrialization of the right ventricle. - The medication's use for "mood swings" (suggesting **bipolar disorder**) combined with the characteristic heart defect in the newborn strongly points to lithium as the causative agent. *Buspirone* - Buspirone is an anxiolytic medication generally considered to have a **low risk of teratogenicity** (Category B) and is not associated with specific congenital heart defects like Ebstein's anomaly. - It is used for anxiety disorders, not typically for mood swings in the context of bipolar disorder, which lithium treats. *Clozapine* - Clozapine is an antipsychotic medication, and while some antipsychotics have been investigated for teratogenicity, it is **not specifically linked to Ebstein's anomaly**. - Its primary use is for refractory schizophrenia, not typically for mood swings in the same context as lithium. *Enalapril* - Enalapril is an ACE inhibitor and is known to be **teratogenic in the second and third trimesters**, causing renal dysfunction, oligohydramnios, and skeletal defects, but not Ebstein's anomaly. - It treats hypertension and heart failure, not mood swings. *Losartan* - Losartan is an ARB (angiotensin receptor blocker), which, like ACE inhibitors, is **teratogenic in the second and third trimesters**, causing renal and skeletal malformations. - Its use is for hypertension and heart failure, not mood swings.

Question 705: Two 19-year-old men are referred by their professor and mentor to a psychiatrist for substance abuse management. The two friends have both used different stimulants for 3 years—Drug A and Drug B, respectively. Both use these substances cyclically. Use of Drug A usually lasts for about 12 hours. The cycle for Drug B lasts several days. A month ago, both men visited the emergency room (ER) due to acute intoxication. Clinical features in the emergency department included hypotension, bradycardia, sweating, chills, mydriasis, nausea, and psychomotor agitation. After a urine drug screen, the psychiatrist identifies both the drugs and informs the professor that although both Drug A and Drug B are stimulants, their mechanisms of action are different. Drug A is an alkaloid that is naturally present in the leaves of the coca plant, while it is possible to make Drug B from over-the-counter nasal decongestant products. Which of the following options best describes the mechanism of action of both drugs?

• A. Drug A increases norepinephrine activity, while Drug B does not.
• B. Drug A increases serotonin activity, while Drug B does not.
• C. Drug A predominantly acts by increasing the release of monoamine neurotransmitters (dopamine, serotonin, and norepinephrine) into the synapse, while Drug B does not.
• D. Drug A transiently increases the extracellular concentration of dopamine in the reward circuit, while Drug B does not.
• E. Drug A predominantly acts by inhibiting the reuptake of monoamine neurotransmitters (dopamine, serotonin, and norepinephrine) at the synapse, while Drug B predominantly acts by promoting their release from presynaptic terminals. (Correct Answer)

Explanation: ***Drug A predominantly acts by inhibiting the reuptake of monoamine neurotransmitters (dopamine, serotonin, and norepinephrine) at the synapse, while Drug B predominantly acts by promoting their release from presynaptic terminals.*** - Drug A is **cocaine**, an alkaloid from the coca plant, which primarily acts by **blocking the reuptake of dopamine, norepinephrine, and serotonin**, leading to their accumulation in the synaptic cleft. - Drug B is likely **methamphetamine**, derivable from nasal decongestants, which primarily works by **promoting the release of monoamines** from presynaptic terminals, particularly dopamine and norepinephrine. *Drug A increases norepinephrine activity, while Drug B does not.* - While Drug A (cocaine) does increase norepinephrine activity by inhibiting its reuptake, Drug B (methamphetamine) also significantly increases norepinephrine activity by promoting its release. - This option incorrectly states that Drug B does not increase norepinephrine activity. *Drug A increases serotonin activity, while Drug B does not.* - Both Drug A (cocaine) and Drug B (methamphetamine) increase serotonin activity, albeit through different mechanisms. Cocaine inhibits serotonin reuptake, while methamphetamine promotes its release. - The premise that Drug B does not affect serotonin activity is incorrect. *Drug A predominantly acts by increasing the release of monoamine neurotransmitters (dopamine, serotonin, and norepinephrine) into the synapse, while Drug B does not.* - This statement misrepresents the primary mechanism of Drug A (cocaine), which is to **inhibit reuptake**, not primarily increase release. - It also incorrectly implies that Drug B does not significantly affect the monoamine neurotransmitter release. *Drug A transiently increases the extracellular concentration of dopamine in the reward circuit, while Drug B does not.* - Both cocaine (Drug A) and methamphetamine (Drug B) **increase extracellular dopamine** in the reward circuit, which is central to their addictive properties. - This option is incorrect because Drug B also significantly increases dopamine concentrations.

Question 706: A 51-year-old man presents to his primary care provider for recurrent epigastric pain. He reports a 3-month history of gnawing epigastric and chest pain that is worse after meals and after lying down. His past medical history is notable for obesity, hypertension, and hyperlipidemia. He takes lisinopril and rosuvastatin. He has a 30 pack-year smoking history and drinks 4-5 beers per day. On exam, he is well-appearing and in no acute distress. He has no epigastric tenderness. He is prescribed an appropriate medication for his symptoms and is told to follow up in 2 weeks. He returns 2 weeks later with improvement in his symptoms, and a decision is made to continue the medication. However, he returns to clinic 3 months later complaining of decreased libido and enlarged breast tissue. Which of the following medications was this patient most likely taking?

• A. Nizatidine
• B. Cimetidine (Correct Answer)
• C. Famotidine
• D. Lansoprazole
• E. Calcium carbonate

Explanation: ***Cimetidine*** - **Cimetidine** is an H2-receptor antagonist known to cause **antiandrogenic side effects** like gynecomastia and decreased libido, matching the patient's symptoms. - It works by blocking **histamine H2 receptors** in the stomach, reducing acid production, which would improve relief of epigastric pain. *Nizatidine* - **Nizatidine** is an H2-receptor antagonist that does not commonly cause **gynecomastia** or **decreased libido** as side effects. - While effective for acid reduction, it lacks the specific adverse effect profile seen in this patient. *Famotidine* - **Famotidine** is another H2-receptor antagonist with a similar mechanism of action but is not typically associated with **antiandrogenic effects**. - Its side effect profile is generally mild and does not include gynecomastia or sexual dysfunction. *Lansoprazole* - **Lansoprazole** is a proton pump inhibitor (PPI), which works by irreversibly blocking the **H+/K+-ATPase pump** in parietal cells. - PPIs are not known to cause **gynecomastia** or **decreased libido** as side effects. *Calcium carbonate* - **Calcium carbonate** is an antacid that neutralizes stomach acid directly and is used for symptomatic relief. - It can cause **constipation** or **acid rebound** but is not associated with gynecomastia or decreased libido.

Question 707: A 24-year-old female medical student presents to the emergency department after she develops sudden difficulty breathing and vague chest pain while preparing for exams. The chest pain is non-pleuritic without radiation. She denies any recent travel. She denies any hemoptysis, nausea, vomiting, or leg pain. She only takes oral contraceptives; she denies smoking or alcohol use. Her vitals reveal a heart rate of 120 beats per minute, blood pressure of 100/80 mm Hg, and respiratory rate of 30 per minute. She is afebrile. Otherwise, her physical exam is unremarkable. A CT scan of her chest with IV contrast reveals filling defects along her left pulmonary artery. Which of the following is the most likely mechanism of this finding?

• A. Anxiety
• B. Endothelial injury
• C. Venous stasis
• D. Dehydration
• E. Hypercoagulability (Correct Answer)

Explanation: ***Hypercoagulability*** - The patient's use of **oral contraceptives** is a known risk factor for developing a **hypercoagulable state**, increasing the likelihood of thrombus formation. - The imaging finding of **filling defects in the pulmonary artery** confirms a **pulmonary embolism (PE)**, a condition directly caused by hypercoagulability leading to clot formation. *Anxiety* - While exam stress can cause symptoms like **dyspnea** and **chest pain**, it does not explain the objective finding of **filling defects in the pulmonary artery** on CT scan. - Pulmonary embolism can induce anxiety, but anxiety itself does not cause the anatomical changes seen on imaging. *Endothelial injury* - **Endothelial injury** is a component of Virchow's triad, but there are no clinical indications like **trauma**, **surgery**, or **vasculitis** to suggest significant endothelial damage in this patient. - Oral contraceptive use primarily affects coagulation factors rather than directly causing widespread vascular injury. *Venous stasis* - **Venous stasis** is another component of Virchow's triad, often seen with **prolonged immobility** (e.g., long flights, bed rest), which is not described in this active patient. - While studying could involve prolonged sitting, it's less likely to be the primary cause of a PE compared to a strong prothrombotic risk factor. *Dehydration* - **Dehydration** can lead to **increased blood viscosity**, potentially contributing to clot formation, but it is not as direct or significant a risk factor for PE as **oral contraceptive use** leading to hypercoagulability. - There are no specific clinical signs of major dehydration in this patient to make it a primary mechanism.

Question 708: A 59-year-old man comes to the emergency department because of progressively worsening chest pain and nausea that started while visiting a local bar 30 minutes ago. The pain radiates to the epigastric area. He has a 10-year history of untreated hypertension. He has smoked 1 pack of cigarettes daily for 35 years. The patient is diaphoretic and in marked distress. His pulse is 94/min, respirations are 28/min, and blood pressure is 161/92 mm Hg. Pulse oximetry on 2 L/min of oxygen via nasal cannula shows an oxygen saturation of 97%. Cardiac examination shows a regular heartbeat and a systolic ejection murmur heard best over the upper right sternal border. The lungs are clear to auscultation bilaterally. Pedal pulses are intact. An ECG shows inverted T waves in leads I, avL, and V5-6. Urine toxicology screening is positive for cocaine. Which of the following drugs is contraindicated in the management of this patient's condition?

• A. Prasugrel
• B. Diazepam
• C. Diltiazem
• D. Propranolol (Correct Answer)
• E. Aspirin

Explanation: ***Propranolol*** - The patient's cocaine use and presenting symptoms (chest pain, elevated blood pressure, tachycardia) indicate a likely **cocaine-induced myocardial ischemia or infarction**. Beta-blockers like propranolol are **contraindicated** in acute cocaine intoxication because they can cause **unopposed alpha-adrenergic vasoconstriction**, worsening coronary vasoconstriction and increasing blood pressure. - This unopposed alpha stimulation can exacerbate myocardial ischemia and increase the risk of adverse cardiovascular events such as **hypertensive crisis** or **myocardial infarction extension**. *Prasugrel* - Prasugrel is an **antiplatelet agent** (P2Y12 inhibitor) used in acute coronary syndromes to prevent platelet aggregation and thrombosis. - While typically indicated in managing myocardial infarction, its use is not immediately contraindicated in the presence of cocaine; rather, its administration may be delayed until the acute cocaine effects are managed. *Diazepam* - Diazepam, a **benzodiazepine**, is often used to manage agitation, anxiety, and hypertension associated with **cocaine intoxication** due to its sedative and anxiolytic effects. - It can help to reduce sympathetic overdrive, which is beneficial in this clinical scenario. *Diltiazem* - Diltiazem is a **calcium channel blocker** that can be used to treat cocaine-induced chest pain, hypertension, and tachycardia. - It works by causing **vasodilation** and reducing myocardial oxygen demand, making it a safer alternative to beta-blockers in this setting. *Aspirin* - Aspirin is an **antiplatelet agent** indicated for acute coronary syndromes, including myocardial infarction, to prevent further thrombus formation. - Its use is standard practice and **not contraindicated** in patients with cocaine-induced chest pain, as it helps to inhibit platelet aggregation and improve coronary blood flow.

Question 709: A 28-year-old female patient with a history of schizophrenia, type 2 diabetes mellitus, and hypothyroidism comes to clinic stating she would like to be put back on a medication. She recently stopped taking her haloperidol as it made it hard for her to "sit still." She requests to be put on olanzapine as a friend from a support group said it was helpful. Why should this medication be avoided in this patient?

• A. The patient has type 2 diabetes (Correct Answer)
• B. The patient may develop galactorrhea
• C. Tardive dyskinesia will likely result from the prolonged use of olanzapine
• D. There is a high risk for retinopathy
• E. The patient is at a high risk for torsades de pointes

Explanation: **The patient has type 2 diabetes** - Olanzapine is associated with a high risk of **metabolic side effects**, including **weight gain**, **hyperglycemia**, and **dyslipidemia**, which would exacerbate her pre-existing type 2 diabetes. - Given her history of diabetes, choosing a different antipsychotic with a lower metabolic risk profile would be more appropriate to prevent further metabolic complications. *The patient may develop galactorrhea* - **First-generation antipsychotics** and some **second-generation antipsychotics** like **risperidone** or **paliperidone** are more commonly associated with hyperprolactinemia, which can lead to galactorrhea. - Olanzapine has a relatively **lower propensity** to cause significant elevations in prolactin compared to other antipsychotics. *Tardive dyskinesia will likely result from the prolonged use of olanzapine* - While all antipsychotics carry some risk of **tardive dyskinesia**, **second-generation antipsychotics** like olanzapine have a **lower risk** compared to first-generation antipsychotics such as haloperidol. - The patient stopped haloperidol due to **akathisia**, an acute extrapyramidal symptom, not tardive dyskinesia, and olanzapine is generally associated with a lower incidence of extrapyramidal symptoms. *There is a high risk for retinopathy* - **Retinopathy** is not a common or significant adverse effect associated with olanzapine. - **Thioridazine**, a first-generation antipsychotic, is uniquely associated with **pigmentary retinopathy** at high doses. *The patient is at a high risk for torsades de pointes* - Olanzapine carries a **low risk** for QTc prolongation and **torsades de pointes** compared to some other antipsychotics like **ziprasidone** or **thioridazine**. - There is no indication from the patient's history that she is at an increased risk for QT prolongation, such as pre-existing cardiac conditions or electrolyte imbalances.

Question 710: A 4-year-old boy presents to the ED with a one day history of severe right eye pain accompanied by nausea, vomiting, and headache. He is afebrile and he appears to be alert despite being irritable. Three days ago an ophthalmologist prescribed eye drops for his right eye but his parents do not know the name of the medication. On exam, his right eye is hard to palpation and moderately dilated. His left eye is unremarkable. What is the mechanism of action of the medication that most likely provoked this acute presentation?

• A. M3 agonist causing ciliary muscle contraction
• B. Alpha-adrenergic agonist increasing aqueous fluid production
• C. Muscarinic antagonist inhibiting pupillary sphincter muscle contraction (Correct Answer)
• D. Iris neovascularization
• E. Agonist of prostaglandin F receptor increasing aqueous fluid outflow

Explanation: ***Muscarinic antagonist inhibiting pupillary sphincter muscle contraction*** - A muscarinic antagonist, such as **atropine** or **homatropine eye drops**, would cause **mydriasis** (pupil dilation) by inhibiting the **pupillary sphincter muscle**. - In children with narrow angles, this sustained dilation can precipitate **acute angle-closure glaucoma**, leading to symptoms like severe eye pain, headache, nausea, vomiting, and a hard, dilated eye on examination. *M3 agonist causing ciliary muscle contraction* - An **M3 agonist** (e.g., pilocarpine) would cause **miosis** (pupil constriction) and contraction of the ciliary muscle, which generally **opens the anterior chamber angle** and facilitates aqueous outflow. - This effect would typically **decrease intraocular pressure** and would not cause the described symptoms of acute angle-closure glaucoma. *Alpha-adrenergic agonist increasing aqueous fluid production* - While some alpha-adrenergic agonists can increase aqueous production or reduce outflow, they are not typically the primary cause of acute angle-closure glaucoma in this context. - Medications like **phenylephrine** (an alpha-1 agonist) cause mydriasis but usually do not dramatically increase intraocular pressure in healthy eyes without a pre-existing narrow angle. *Iris neovascularization* - **Iris neovascularization** is a pathological condition involving abnormal blood vessel growth on the iris, often due to **ischemia from conditions like diabetes or retinal vein occlusion**. - While it can lead to **neovascular glaucoma**, it's a chronic process and not directly related to an acute presentation caused by eye drops in a healthy 4-year-old. *Agonist of prostaglandin F receptor increasing aqueous fluid outflow* - **Prostaglandin F receptor agonists** (e.g., latanoprost) primarily increase **uveoscleral outflow** of aqueous humor, effectively **lowering intraocular pressure**. - This mechanism would **treat (not cause)** glaucoma and is not associated with acute angle closure or pupillary dilation from eye drops.

Question 711: A 30-year-old man presents with heartburn for the past couple of weeks. He says he feels a burning sensation in his chest, at times reaching his throat, usually worse after eating spicy foods. He is overweight and actively trying to lose weight. He also has tried other lifestyle modifications for the past couple of months, but symptoms have not improved. He denies any history of cough, difficulty swallowing, hematemesis, or melena. The patient says he often drinks a can of beer in the evening after work and does not smoke. His blood pressure is 124/82 mm Hg, pulse is 72/min and regular, and respiratory rate is 14/min. Abdominal tenderness is absent. Which of the following is the next best step in the management of this patient?

• A. Start oral antacids.
• B. H. pylori screening
• C. Start omeprazole. (Correct Answer)
• D. Start sucralfate.
• E. Start famotidine.

Explanation: ***Start omeprazole.*** - This patient presents with classic symptoms of **gastroesophageal reflux disease (GERD)** that have not improved with lifestyle modifications. A **proton pump inhibitor (PPI)** like omeprazole is the most effective initial medical therapy for GERD. - The absence of **alarm symptoms** (e.g., dysphagia, weight loss, hematemesis) in an adult under 60-65 years old allows for empirical PPI therapy without immediate endoscopy. *Start famotidine.* - **H2-receptor blockers** like famotidine are less potent and less effective than PPIs for healing esophagitis and providing complete symptom relief in moderate to severe GERD. - While they can be used for mild, intermittent symptoms, they are not the next best step when lifestyle modifications have failed and a patient presents with persistent GERD symptoms. *Start oral antacids.* - **Antacids** provide only temporary relief of GERD symptoms by neutralizing stomach acid. They do not prevent acid production or heal esophageal inflammation. - Given the patient's persistent symptoms despite lifestyle changes, a more potent and long-acting medication is required. *Start sucralfate.* - **Sucralfate** is a mucosal protective agent that forms a barrier over ulcers and erosions, primarily used in peptic ulcer disease and stress ulcer prophylaxis. - It is not a primary treatment for GERD and does not reduce acid production or address the underlying reflux mechanism. *H. pylori screening* - While **H. pylori infection** can cause dyspepsia, its symptoms often include a gnawing or burning pain in the epigastric region, which can be distinguished from typical GERD symptoms. - There is no indication from the patient's symptoms (predominantly heartburn and regurgitation) to suggest *H. pylori* testing as the immediate next step in managing his GERD.

Question 712: A 65-year-old veteran with a history of hypertension, diabetes, and end-stage renal disease presents with nausea, vomiting, and abdominal pain. The patient was found to have a small bowel obstruction on CT imaging. He is managed conservatively with a nasogastric tube placed for decompression. After several days in the hospital, the patient’s symptoms are gradually improving. Today, he complains of left leg swelling. On physical exam, the patient has a swollen left lower extremity with calf tenderness on forced dorsiflexion of the ankle. An ultrasound confirms a deep vein thrombus. An unfractionated heparin drip is started. What should be monitored to adjust heparin dosing?

• A. Prothrombin time
• B. Activated partial thromboplastin time (Correct Answer)
• C. Internationalized Normal Ratio (INR)
• D. Creatinine level
• E. Liver transaminase levels

Explanation: ***Activated partial thromboplastin time*** - The **aPTT** is regularly monitored to assess the anticoagulant effect of **unfractionated heparin (UFH)**. - UFH primarily exerts its effect by binding to **antithrombin III**, which in turn inactivates clotting factors such as thrombin and factor Xa, thereby prolonging the aPTT. *Prothrombin time* - The **prothrombin time (PT)** is primarily used to monitor the extrinsic pathway of coagulation and the effect of warfarin. - It is not the standard test for adjusting unfractionated heparin dosing. *Internationalized Normal Ratio (INR)* - The **INR** is derived from the PT and is specifically used to standardize the monitoring of **warfarin** therapy, which inhibits vitamin K-dependent clotting factors. - It is not relevant for monitoring unfractionated heparin. *Creatinine level* - **Creatinine** levels are used to assess **kidney function**, which is important for drug excretion in general, but not for directly monitoring the anticoagulant effect of heparin. - While patients with **end-stage renal disease** require careful dosing adjustments for many medications, creatinine itself does not guide heparin titration. *Liver transaminase levels* - **Liver transaminases** (ALT, AST) are indicators of **liver function or injury** and are not used to monitor the anticoagulant effect of heparin. - They might be checked in the context of drug-induced liver injury, but not for routine heparin monitoring.

Question 713: A 28-year-old woman presents to a physician with complaints of fever, cough, and cold for the last 2 days. She does not have any other symptoms and she has no significant medical history. She has recently started using combined oral contraceptive pills (OCPs) for birth control. On physical examination, the temperature is 38.3°C (101.0°F), the pulse is 98/min, the blood pressure is 122/80 mm Hg, and the respiratory rate is 14/min. The nasal mucosa and pharynx are inflamed, but there is no purulent discharge. Auscultation of the chest does not reveal any abnormalities. She mentions that she has been a heavy smoker for the last 5 years, smoking about 15–20 cigarettes per day. The physician suggests she should discontinue using combined OCPs and choose an alternative contraception method. Which of the following best explains the rationale behind the physician's suggestion?

• A. Smoking inhibits CYP1A2, therefore there is an increased risk of estrogen-related side effects of OCPs
• B. Smoking inhibits CYP3A4, therefore there is an increased risk of progestin-related side effects of OCPs
• C. Smoking induces CYP3A4, therefore OCPs would be ineffective
• D. Smoking induces CYP1A2, therefore OCPs would be ineffective
• E. Smoking is likely to increase the risk of developing deep vein thrombosis and pulmonary embolism in women taking OCPs (Correct Answer)

Explanation: ***Smoking is likely to increase the risk of developing deep vein thrombosis and pulmonary embolism in women taking OCPs*** - **Combined OCPs** increase the risk of **venous thromboembolism (VTE)** due to the pro-coagulant effects of estrogen, and this risk is significantly amplified by **smoking**, especially in women over 35 or heavy smokers. - The combination of **smoking** and **combined OCPs** creates a synergistic effect that elevates the risk of serious cardiovascular events such as **deep vein thrombosis (DVT)** and **pulmonary embolism (PE)**, making alternative contraception advisable. *Smoking inhibits CYP1A2, therefore there is an increased risk of estrogen-related side effects of OCPs* - **Smoking** is known to **induce**, not inhibit, hepatic enzymes like CYP1A2, which would typically lead to increased metabolism and potentially lower drug efficacy, rather than increased side effects from elevated levels. - The primary concern with smoking and OCPs is not increased estrogen-related side effects due to enzyme inhibition, but rather the **thrombogenic risk**. *Smoking inhibits CYP3A4, therefore there is an increased risk of progestin-related side effects of OCPs* - **Smoking** generally acts as an **inducer** of CYP enzymes, not an inhibitor, meaning it would likely increase the metabolism of drugs, rather than leading to higher levels and increased side effects. - The clinical significance of smoking concerning OCPs revolves around **cardiovascular risk**, not primarily progestin-related side effects due to enzyme inhibition. *Smoking induces CYP3A4, therefore OCPs would be ineffective* - While smoking can **induce some CYP enzymes**, CYP3A4 induction by smoking is less consistently cited as a major concern for OCP effectiveness compared to its impact on other pathways. - The main reason for discontinuing OCPs in heavy smokers is the **increased risk of thromboembolic events**, not predominantly a concern about contraceptive failure due to enzyme induction. *Smoking induces CYP1A2, therefore OCPs would be ineffective* - Smoking does **induce CYP1A2** which can increase the metabolism of certain drugs, but the primary clinical relevance for OCPs is not reduced efficacy through this mechanism. - The crucial risk associated with smoking and OCP use is the greatly enhanced likelihood of **thrombotic complications**, overshadowing concerns about CYP1A2-mediated ineffectiveness.

Question 714: A 26-year-old man undergoing surgical correction of his deviated septum experiences excessive bleeding on the operating room table. Preoperative prothrombin time and platelet count were normal. The patient’s past medical history is significant for frequent blue blemishes on his skin along with easy bruising since he was a child. He indicated that he has some sort of genetic blood disorder running in his family but could not recall any details. Which of the following is the most appropriate treatment for this patient’s most likely condition?

• A. Cryoprecipitate
• B. Fresh frozen plasma
• C. Red blood cell transfusion
• D. Recombinant factor IX
• E. Desmopressin and tranexamic acid (Correct Answer)

Explanation: **Desmopressin and tranexamic acid** * The patient's clinical presentation, including excessive bleeding during surgery and a history of easy bruising and blue blemishes since childhood, are highly suggestive of **Von Willebrand Disease (VWD)**. * **Desmopressin (DDAVP)** is the primary treatment for type 1 VWD, as it promotes the release of endogenous **von Willebrand factor (VWF)** and **factor VIII** from endothelial cells. **Tranexamic acid** is an antifibrinolytic agent that helps stabilize clots and reduce bleeding. *Cryoprecipitate* * While cryoprecipitate contains vWF, factor VIII, and fibrinogen, it is a **blood product** and carries the risks associated with transfusion. It is typically reserved for **severe types of VWD** or when desmopressin is ineffective or contraindicated. * The initial management of VWD, especially for bleeding episodes or surgical prophylaxis, usually starts with desmopressin, given its efficacy and lower risk profile. *Fresh frozen plasma* * **Fresh frozen plasma (FFP)** contains all clotting factors but at lower concentrations than cryoprecipitate for vWF. It is primarily used for **multiple factor deficiencies** or **warfarin reversal**. * Its primary role in VWD management is limited, as direct vWF replacement or stimulation is preferred for this condition. *Red blood cell transfusion* * **Red blood cell (RBC) transfusion** is indicated for patients with **significant blood loss** leading to anemia, but it does not address the underlying clotting defect in VWD. * While this patient is experiencing excessive bleeding, an RBC transfusion would only treat the symptom of blood loss, not the cause. *Recombinant factor IX* * **Recombinant factor IX** is used to treat **hemophilia B**, which is a deficiency in factor IX. * The patient's symptoms are inconsistent with hemophilia B; his normal platelet count and PTT (implicitly, since PT is normal and PTT is often affected in severe VWD or hemophilia) point away from hemophilia and towards a primary hemostasis defect like VWD.

Question 715: A 75-year-old woman is being treated for atrial fibrillation. She presents to the clinic with complaints of nausea, vomiting, photophobia, and yellow-green vision with yellow halos around the lights. She has a heart rate of 64/min, blood pressure is 118/76 mm Hg, and respiratory rate is 15/min. Physical examination reveals regular heart sounds with clear lung sounds bilaterally. Liver function tests are normal. Toxicity of which of the following anti-arrhythmic drugs would best fit this clinical picture?

• A. Sotalol
• B. Propafenone
• C. Digoxin (Correct Answer)
• D. Atenolol
• E. Amiodarone

Explanation: ***Digoxin*** - **Digoxin toxicity** is classically associated with **pathognomonic visual disturbances** like yellow-green vision (xanthopsia) and halo effects, along with gastrointestinal symptoms such as nausea and vomiting. - The patient's presentation of a **slow heart rate (bradycardia)** and treatment for atrial fibrillation further supports digoxin as the likely cause, given its use in rate control and its known narrow therapeutic index. - The combination of xanthopsia, GI symptoms, and bradycardia makes digoxin toxicity the clear diagnosis. *Sotalol* - This is a **beta-blocker** with potassium channel blocking properties (Class III), commonly used for atrial fibrillation. - Its adverse effects include **bradycardia**, dizziness, fatigue, and potential for **Torsades de Pointes** (QT prolongation), but not the specific visual or gastrointestinal symptoms seen here. *Propafenone* - Propafenone is a **Class IC antiarrhythmic** agent that can cause side effects like dizziness, metallic taste, and gastrointestinal upset. - However, it does not typically cause the specific visual changes (yellow-green vision, halos) associated with the presented case. *Atenolol* - Atenolol is a **beta-1 selective beta-blocker** primarily used for rate control in atrial fibrillation and hypertension. - Common side effects include **bradycardia**, fatigue, and dizziness, but it does not cause yellow-green vision or halos. *Amiodarone* - Amiodarone is a **Class III antiarrhythmic** with a wide range of side effects, including pulmonary fibrosis, thyroid dysfunction, and corneal deposits (which can cause halos around lights). - While it can cause halos, it does not typically lead to the specific yellow-green vision (xanthopsia) described, and corneal deposits develop gradually with chronic use, not acutely as in this case.

Question 716: A 20-year-old woman presents to the emergency department after developing a widespread rash when she was playing in the park. She states she feels somewhat light-headed. She is otherwise healthy and has no significant past medical history. Her temperature is 97.0°F (36.1°C), blood pressure is 84/54 mmHg, pulse is 130/min, respirations are 22/min, and oxygen saturation is 95% on room air. Physical exam is notable for bilateral wheezing and a diffuse urticarial rash. Which of the following is the next best step in management?

• A. Normal saline
• B. Continuous monitoring
• C. Diphenhydramine
• D. Albuterol
• E. Epinephrine (Correct Answer)

Explanation: ***Epinephrine*** - The patient presents with classic signs of **anaphylaxis**, including a widespread urticarial rash, wheezing, hypotension, and lightheadedness. **Epinephrine** is the first-line treatment for anaphylaxis due to its alpha-1 agonist effects (increasing blood pressure and reducing angioedema) and beta-2 agonist effects (bronchodilation). - Delaying administration of **epinephrine** can lead to rapid progression of symptoms and potentially fatal outcomes. *Normal saline* - While **intravenous fluids** like normal saline may be indicated later to help manage hypotension in anaphylaxis, they are not the immediate priority. - **Epinephrine** addresses the underlying pathophysiological processes of anaphylaxis more directly and quickly than fluid resuscitation alone. *Continuous monitoring* - While continuous monitoring is always important in unstable patients, it is not an intervention. - The patient's vital signs and clinical presentation require immediate therapeutic intervention, not just observation. *Diphenhydramine* - **Diphenhydramine**, an H1 antihistamine, can help alleviate cutaneous symptoms like urticaria and pruritus. - However, it does not address the life-threatening aspects of anaphylaxis, such as hypotension, bronchospasm, or upper airway edema, and should only be used as an adjunct to epinephrine. *Albuterol* - **Albuterol** is a beta-2 adrenergic agonist that can help with bronchospasm and wheezing. - While it may be a useful adjunct, it does not address the cardiovascular collapse (hypotension) or the generalized systemic reaction of anaphylaxis, making epinephrine the more comprehensive and life-saving initial treatment.

Question 717: A 47-year-old woman presents to the emergency department in a frantic state and demands immediate treatment for an allergic reaction, which started soon after she had lunch (approximately 1 hour ago). She had her usual meal consisting of homemade salad and lemonade. She was recently started on niacin because she could not tolerate statins. The only other medication she takes is captopril for hypertension. She has no respiratory difficulty and denies rhinorrhea, epiphora, and diarrhea. She is complaining of a stinging sensation on her face. She has no history of allergies and no family history of allergies. The vital signs include: pulse 90/min, respirations 16/min, blood pressure 120/80 mm Hg, and oxygen saturation, 98% on room air. On physical examination, the face and trunk have a flushed appearance. The rest of the physical examination is unremarkable. The attending physician reassures her that she is not in any immediate danger, and in fact, her symptoms subsided over the next hour. She is advised to take aspirin 30 minutes before her other medications and sent home. Which of the following is the etiology of her symptoms?

• A. Drug overdose
• B. A mild allergic reaction
• C. Serotonin
• D. Anxiety
• E. Prostaglandin release (Correct Answer)

Explanation: ***Prostaglandin release*** - The patient's symptoms of **flushing**, **stinging** sensation, and **non-allergic** reaction occurring after starting **niacin** are highly characteristic of a **prostaglandin-mediated response**. Niacin (Vitamin B3) often causes flushing due to its effect on prostaglandin D2 (PGD2) release from mast cells and keratinocytes. - The recommendation to take **aspirin** 30 minutes before niacin specifically targets this mechanism, as aspirin inhibits **cyclooxygenase (COX) enzymes**, thereby reducing prostaglandin synthesis and mitigating the flushing. *Drug overdose* - The patient's vital signs are stable, and the clinical presentation, including isolated flushing and stinging that resolves spontaneously, does not align with typical symptoms of a **drug overdose**. An overdose would likely present with more severe and systemic effects. - The symptoms are directly attributable to the **therapeutic use of niacin**, not an excessive dose, as they are a known side effect at standard dosages. *A mild allergic reaction* - The patient denies typical allergic symptoms like **rhinorrhea**, **epiphora** (watery eyes), **respiratory difficulty**, or **diarrhea**, and there is no history or family history of allergies. Her symptoms are specifically limited to flushing and stinging. - The clinical course, especially the spontaneous resolution and the effectiveness of aspirin in prevention, points away from an **IgE-mediated allergic reaction**. *Serotonin* - While serotonin can cause flushing, it is typically associated with **carcinoid syndrome**, which presents with additional symptoms such as **diarrhea**, **wheezing**, and **tachycardia**, often in the context of neuroendocrine tumors. - The patient's stable vital signs and lack of other systemic symptoms, as well as the clear temporal relationship with niacin, make **serotonin release** an unlikely primary etiology. *Anxiety* - While anxiety can precipitate some physical symptoms, the acute onset of **flushing** and **stinging** in a defined pattern, immediately following a meal and shortly after starting a known flushing-inducing medication (**niacin**), is less consistent with a primary anxiety attack. - Her anxiety appears to be secondary to the physical symptoms she is experiencing, rather than the underlying cause of the **flushing** and **stinging**.

Question 718: A 64-year-old woman presents to the emergency department with a 1-hour history of shortness of breath and chest pain. She said that the symptoms came on suddenly and that the chest pain is worse when she tries to take a deep breath. Her past medical history is significant for a previous deep venous thrombosis for which she was taking a blood thinner. She also has diabetes, hypertension, hyperlipidemia, and partial seizures which are treated with metformin, lisinopril, atorvastatin, and carbamazepine and valproic acid, respectively. Which of these drugs is most likely responsible for causing this patient's blood thinner medications to fail?

• A. Valproic acid
• B. Lisinopril
• C. Carbamazepine (Correct Answer)
• D. Atorvastatin
• E. Metformin

Explanation: ***Carbamazepine*** - **Carbamazepine** is a potent **CYP450 enzyme inducer**, which means it can increase the metabolism of other drugs, including many **warfarin-type anticoagulants**. - By accelerating the breakdown of the blood thinner, carbamazepine can effectively reduce its concentration in the blood, leading to a **subtherapeutic anticoagulant effect** and an increased risk of **thrombosis**. *Valproic acid* - Valproic acid is generally considered a **CYP450 enzyme inhibitor**, meaning it would typically increase the concentration of co-administered drugs rather than decrease them. - While it can have complex drug interactions, its primary effect on anticoagulants would usually be to **potentiate their effects**, increasing bleeding risk, not reducing efficacy. *Lisinopril* - **Lisinopril** is an **ACE inhibitor** and does not significantly interact with the cytochrome P450 enzyme system responsible for metabolizing most anticoagulants. - It is unlikely to cause a failure of blood thinner medications through pharmacokinetic interactions. *Atorvastatin* - **Atorvastatin** is primarily metabolized by CYP3A4, and while it can have some minor drug interactions, it is not a potent inducer of the metabolizing enzymes for common anticoagulants. - It does not significantly alter the efficacy of blood thinners like warfarin to the extent that it would cause treatment failure. *Metformin* - **Metformin** is primarily excreted unchanged by the kidneys and does not undergo significant hepatic metabolism via the CYP450 system. - Therefore, it has minimal drug interactions with anticoagulants and would not be expected to cause their failure.

Question 719: A 72-year-old man with a 4-year history of Parkinson disease comes to the physician for evaluation of his medication. Since his last visit one year ago, he has had increased tremor and bradykinesia up to an hour before his next scheduled dose and sometimes feels like he does not respond to some doses at all. One week ago, he was entirely unable to move for about a minute when he wanted to exit an elevator. The physician prescribes a drug that increases the bioavailability of levodopa by preferentially preventing its peripheral methylation. This patient was most likely prescribed which of the following drugs by the physician?

• A. Carbidopa
• B. Amantadine
• C. Entacapone (Correct Answer)
• D. Rasagiline
• E. Ropinirole

Explanation: ***Entacapone*** - Entacapone is a **catechol-O-methyltransferase (COMT) inhibitor** that acts peripherally, preventing the methylation of levodopa to 3-O-methyldopa. - By reducing peripheral breakdown, entacapone **increases the bioavailability and half-life of levodopa**, which is useful for managing "wearing-off" phenomena and "on-off" fluctuations present in this patient. *Carbidopa* - Carbidopa is a **dopa decarboxylase inhibitor** that prevents the peripheral conversion of levodopa to dopamine, reducing systemic side effects and increasing levodopa's entry into the brain. - While essential for levodopa therapy, it does not act by preventing levodopa's methylation and aims to prevent its decarboxylation, not methylation. *Amantadine* - Amantadine is an **antiviral drug** that also has dopaminergic properties, used primarily to treat **dyskinesias** associated with long-term levodopa therapy in Parkinson disease. - It does not directly affect the metabolism or bioavailability of levodopa through methylation pathways. *Rasagiline* - Rasagiline is a **monoamine oxidase-B (MAO-B) inhibitor** that selectively blocks the breakdown of dopamine in the brain, thereby increasing dopamine levels. - It helps to reduce "off" time but does not primarily work by affecting the peripheral methylation of levodopa. *Ropinirole* - Ropinirole is a **dopamine agonist** that directly stimulates dopamine receptors in the brain, acting as a substitute for dopamine. - It is used to manage Parkinson symptoms but does not modulate levodopa's metabolism or bioavailability.

Question 720: A 77-year-old man with type 2 diabetes mellitus is admitted to the hospital because of chest pain and dyspnea. Serum troponin levels are elevated and an ECG shows ST-segment depressions in the lateral leads. Percutaneous coronary angiography is performed and occlusion of the distal left anterior descending coronary artery is identified. Pharmacotherapy with eptifibatide is initiated and a drug-eluting stent is placed in the left anterior descending coronary artery. The mechanism by which eptifibatide acts is similar to the underlying pathophysiology of which of the following conditions?

• A. Von Willebrand disease
• B. Glanzmann thrombasthenia (Correct Answer)
• C. Vitamin K deficiency
• D. Protein C deficiency
• E. Thrombotic thrombocytopenic purpura

Explanation: ***Glanzmann thrombasthenia*** - Eptifibatide is a **glycoprotein IIb/IIIa receptor inhibitor**, preventing platelet aggregation by blocking the binding of **fibrinogen** to activated platelets. - **Glanzmann thrombasthenia** is an inherited disorder characterized by a quantitative or qualitative defect in the **glycoprotein IIb/IIIa receptor**, leading to impaired platelet aggregation despite normal platelet count. *Von Willebrand disease* - This condition involves a deficiency or defect in **von Willebrand factor**, which is crucial for **platelet adhesion** to the subendothelium and as a carrier protein for factor VIII. - Eptifibatide directly targets **platelet aggregation**, not platelet adhesion or von Willebrand factor function. *Vitamin K deficiency* - Vitamin K is essential for the synthesis of **coagulation factors II, VII, IX, and X**, as well as proteins C and S. - A deficiency in vitamin K primarily affects the **coagulation cascade** and not platelet function directly. *Protein C deficiency* - **Protein C** is a natural anticoagulant that inactivates factors Va and VIIIa, thus regulating coagulation. - A deficiency leads to a **hypercoagulable state** by impairing the anticoagulant pathway, which is distinct from platelet aggregation inhibition. *Thrombotic thrombocytopenic purpura* - This is a microangiopathic hemolytic anemia caused by a deficiency of **ADAMTS13**, an enzyme that cleaves large von Willebrand factor multimers, leading to abnormal platelet aggregation and thrombi formation. - While it involves platelet aggregation, the mechanism is due to a defect in ADAMTS13 and vWF, not a direct issue with the **IIb/IIIa receptor**.

Question 721: An 18-year-old man presents to his primary care provider for a routine checkup. He feels well and has no complaints. He is the captain of his high school football team and will be attending college on a football scholarship the following year. His past medical history is unremarkable. He underwent a laparoscopic appendectomy at age 13. He takes no medications and has no allergies. His temperature is 99.1°F (37.3°C), blood pressure is 155/85 mmHg, pulse is 96/min, and respirations are 16/min. On examination, he has severe nodulocystic acne. He has gained 15 pounds and 1/2 inch in height since his last visit one year ago. Mild gynecomastia and testicular shrinkage are noted. This patient is at the greatest risk of developing which of the following?

• A. Type 1 diabetes mellitus
• B. Renal cyst
• C. Hepatocellular carcinoma
• D. Testicular enlargement
• E. Hepatic adenoma (Correct Answer)

Explanation: ***Hepatic adenoma*** - The patient's presentation with **severe nodulocystic acne**, **mild gynecomastia**, **testicular shrinkage**, and **hypertension** in an athletic young male strongly suggests anabolic steroid abuse. - **Anabolic steroid use** is associated with an increased risk of developing **hepatic adenomas**, which are benign liver tumors that can rupture and cause life-threatening hemorrhage. *Type 1 diabetes mellitus* - This condition is an **autoimmune destruction of pancreatic beta cells**, typically presenting with polyuria, polydipsia, and weight loss. - The patient's symptoms are not consistent with new-onset diabetes, and steroid use is more linked to insulin resistance (Type 2) rather than Type 1 diabetes. *Renal cyst* - **Renal cysts** are typically asymptomatic and discovered incidentally. While some genetic conditions can cause multiple cysts, there's no direct link between anabolic steroid use and the development of isolated renal cysts. - The patient's symptoms do not point towards kidney pathology as the primary concern. *Hepatocellular carcinoma* - While prolonged and high-dose anabolic steroid use can increase the risk of certain liver complications, including a rare association with hepatocellular carcinoma, **hepatic adenoma** is a more common and acute risk in the context of steroid abuse, especially with the potential for rupture. - The immediate and often life-threatening complication associated with anabolic steroid-induced liver changes is typically hepatic adenoma rupture. *Testicular enlargement* - Anabolic steroid use leads to **exogenous testosterone suppression of endogenous testosterone production**, resulting in **testicular atrophy** or shrinkage, not enlargement. - The scenario explicitly mentions testicular shrinkage, which directly contradicts testicular enlargement.

Question 722: A 60-year-old male presents to your office for follow-up after an upper gastrointestinal (GI) endoscopy revealed the presence of esophageal varices. His medical history is significant for cirrhosis caused by heavy alcohol abuse for the past 20 years. He was instructed to follow-up with his primary care physician for management of his condition. Which of the following is the most appropriate next step for prevention of future variceal bleeding?

• A. Octreotide
• B. Nadolol (Correct Answer)
• C. Transjugular intrahepatic portosystemic shunt
• D. Isosorbide mononitrate
• E. Careful observation

Explanation: ***Nadolol*** - **Nadolol** is a non-selective beta-blocker that reduces portal pressure by causing **splanchnic vasoconstriction** and decreasing cardiac output, thereby preventing initial variceal bleeding in patients with cirrhosis. - Beta-blockers like nadolol are considered **first-line therapy** for the primary prevention of variceal bleeding in patients with esophageal varices. *Octreotide* - **Octreotide** is primarily used in the **acute management** of variceal bleeding to reduce splanchnic blood flow and portal pressure, not for long-term primary prevention. - Its mechanism involves inhibiting vasodilator peptides, which differs from the sustained effects needed for prevention. *Transjugular intrahepatic portosystemic shunt* - **TIPS** is typically reserved for patients with **recurrent variceal bleeding** despite medical and endoscopic therapy, or intractable ascites, and is not a first-line primary prevention strategy due to its invasiveness and potential complications. - It involves creating a shunt between the portal and hepatic veins to decompress the portal system, a more aggressive intervention. *Isosorbide mononitrate* - **Isosorbide mononitrate** is a **vasodilator** that can reduce portal pressure but has been shown to increase the risk of adverse events and **does not improve survival** in primary prophylaxis of variceal bleeding. - Its use in this context is generally discouraged due to lack of efficacy and safety concerns compared to beta-blockers. *Careful observation* - Given the patient has known **esophageal varices** and a history of cirrhosis due to alcohol abuse, **careful observation** without intervention is not an appropriate strategy. - There is a high risk of life-threatening variceal bleeding, necessitating active primary prevention.

Question 723: A 36-year-old woman is admitted to the hospital because of irritability, nausea, and diarrhea. She has a history of recreational oxycodone use and last took a dose 48 hours ago. Physical examination shows mydriasis, rhinorrhea, and piloerection. A drug is administered that provides an effect similar to oxycodone but does not cause euphoria. Which of the following best explains the difference in effect?

• A. Lower efficacy (Correct Answer)
• B. Lower bioavailability
• C. Lower potency
• D. Lower affinity
• E. Lower tolerance

Explanation: ***Lower efficacy*** - The administered drug acts as a **partial opioid agonist**, meaning it produces an effect similar to oxycodone (an opioid agonist) but with a **lower maximal effect**, explaining the absence of euphoria. - While it can suppress withdrawal symptoms, its **intrinsic activity** at the opioid receptor is less than that of a full agonist. *Lower bioavailability* - **Bioavailability** refers to the fraction of an administered dose that reaches the systemic circulation; it does not directly explain differences in **maximal effect** or the absence of euphoria. - A drug with lower bioavailability would simply require a higher dose to achieve the desired effect, but its inherent efficacy would remain the same. *Lower potency* - **Potency** refers to the concentration or dose of a drug required to produce 50% of that drug's maximal effect, which is about the affinity of the drug to the receptor. - A drug can be potent but still achieve a high maximal effect, which would cause euphoria. *Lower affinity* - **Affinity** describes how strongly a drug binds to its receptor; a drug with lower affinity would simply require higher concentrations to bind to the receptors, and it does not explain the absence of a maximal effect. - **Affinity** is a determinant of potency but not of the **intrinsic activity** or maximal efficacy of the drug. *Lower tolerance* - **Tolerance** is a phenomenon where the body adapts to a drug, requiring higher doses over time to achieve the same effect; it is a patient-specific response, not a property of the drug itself. - Tolerance develops over time with repeated exposure and does not explain why an initial drug administration lacks euphoria.

Question 724: A 51-year-old Caucasian female presents to her primary care provider complaining of intermittent chest pain. She reports that over the past 6 months, she has developed burning chest pain that occurs whenever she exerts herself. The pain decreases when she rests. Her past medical history is notable for type II diabetes mellitus. Her family history is notable for multiple myocardial infarctions in her father and paternal grandmother. She currently takes aspirin and metformin. Her primary care provider starts her on a medication which is indicated given her medical history and current symptoms. However, 10 days later, she presents to the emergency room complaining of weakness and muscle pain. Her plasma creatine kinase level is 250,000 IU/L. This patient was most likely started on a medication that inhibits an enzyme that produces which of the following?

• A. Farnesyl pyrophosphate
• B. Mevalonic acid (Correct Answer)
• C. HMG-CoA
• D. Lanosterol
• E. Squalene

Explanation: ***Mevalonic acid*** - The patient's symptoms (chest pain with exertion, resolving with rest) suggest **angina**, likely due to **atherosclerosis** in the context of **type II diabetes** and a strong family history of myocardial infarctions. - The medication initiated was likely a **statin**, which inhibits **HMG-CoA reductase**, the enzyme responsible for synthesizing **mevalonic acid** from HMG-CoA, a key step in cholesterol synthesis. The subsequent presentation with **severe myopathy** (weakness, muscle pain, extremely elevated **creatine kinase**) confirms statin-induced rhabdomyolysis. *Farnesyl pyrophosphate* - Farnesyl pyrophosphate is an intermediate in the **cholesterol synthesis pathway**, downstream of mevalonic acid. - While inhibitors could affect cholesterol, the primary target of statins, the most common anti-atherosclerotic drug class in this scenario, is the production of mevalonic acid. *HMG-CoA* - **HMG-CoA** is the substrate for **HMG-CoA reductase**, the enzyme inhibited by statins. - The medication inhibits the *conversion* of HMG-CoA, not HMG-CoA itself. *Lanosterol* - **Lanosterol** is a sterol precursor formed later in the **cholesterol biosynthesis pathway**, after mevalonate and squalene. - Inhibiting the production of lanosterol would occur at a later step than the site of action for statins. *Squalene* - **Squalene** is an intermediate in the **cholesterol synthesis pathway**, formed from farnesyl pyrophosphate, downstream of mevalonic acid. - No commonly used anti-dyslipidemic medications directly inhibit the production of squalene to the same clinical effect seen with statins.

Question 725: A 58-year-old woman presents with frequent headaches for the past few months. She says the pain starts randomly and is unrelated to any stimulus. She also says that she has difficulty falling asleep and has had problems concentrating at work for several months. While she occasionally thinks about committing suicide, she denies any suicidal plans. Her appetite is diminished. No significant past medical history. No current medications. There is no family history of depression or psychiatric illness. The physical exam is unremarkable. The thyroid-stimulating hormone (TSH) level is 3.5 uU/mL. The patient is started on amitriptyline and asked to follow-up in 2 weeks. At her follow-up visit, the patient reports slight improvement in her mood and has no more headaches, but she complains of lightheadedness when she rises out of bed in the morning or stands up from her desk at work. Which of the following pharmacological effects of amitriptyline is most likely responsible for her lightheadedness?

• A. Blockage of muscarinic receptors
• B. Decreased reuptake of serotonin
• C. Blockage of H1 histamine receptors
• D. Decreased reuptake of norepinephrine
• E. Blockage of α1 adrenergic receptors (Correct Answer)

Explanation: ***Blockage of α1 adrenergic receptors*** - **Orthostatic hypotension**, characterized by lightheadedness upon standing, is a common side effect of tricyclic antidepressants (TCAs) like amitriptyline due to their **α1-adrenergic receptor blocking properties**. This blockade prevents adequate vasoconstriction in response to changes in posture. - The patient's symptoms of lightheadedness when rising or standing are classic for orthostatic hypotension. *Blockage of muscarinic receptors* - This effect leads to **anticholinergic side effects** such as dry mouth, constipation, blurred vision, and urinary retention. - While amitriptyline has potent anticholinergic effects, they do not directly cause orthostatic hypotension. *Decreased reuptake of serotonin* - Amitriptyline is a **tricyclic antidepressant (TCA)** that inhibits reuptake of both serotonin and norepinephrine, and increased serotonin levels contribute to its antidepressant effects. - However, the cardiovascular side effect of orthostatic hypotension is not primarily mediated by serotonin reuptake inhibition. *Blockage of H1 histamine receptors* - Blockade of H1 histamine receptors by amitriptyline contributes to its **sedative effects** and can cause weight gain. - This effect is not directly responsible for orthostatic hypotension. *Decreased reuptake of norepinephrine* - Similar to serotonin, this mechanism contributes to amitriptyline's **antidepressant and pain-modulating effects** by increasing norepinephrine levels in the synaptic cleft. - While norepinephrine is involved in blood pressure regulation, the specific problem of orthostatic hypotension with TCAs is more directly linked to α1-adrenergic blockade rather than norepinephrine reuptake inhibition itself.

Question 726: A 61-year-old female is referred to an oncologist for evaluation of a breast lump that she noticed two weeks ago while doing a breast self-examination. Her past medical history is notable for essential hypertension and major depressive disorder for which she takes lisinopril and escitalopram, respectively. Her temperature is 98.6°F (37°C), blood pressure is 120/65 mmHg, pulse is 82/min, and respirations are 18/min. Biopsy of the lesion confirms a diagnosis of invasive ductal carcinoma with metastatic disease in the ipsilateral axillary lymph nodes. The physician starts the patient on a multi-drug chemotherapeutic regimen. The patient successfully undergoes mastectomy and axillary dissection and completes the chemotherapeutic regimen. However, several months after completion of the regimen, the patient presents to the emergency department with dyspnea, chest pain, and palpitations. A chest radiograph demonstrates an enlarged cardiac silhouette. This patient’s current symptoms could have been prevented by administration of which of the following medications?

• A. Rosuvastatin
• B. Cyclophosphamide
• C. Dexrazoxane (Correct Answer)
• D. Aspirin
• E. Vincristine

Explanation: ***Dexrazoxane***: - This patient likely developed **anthracycline-induced cardiotoxicity** (e.g., from doxorubicin, often used in breast cancer chemotherapy), presenting with **dyspnea, chest pain, palpitations**, and an **enlarged cardiac silhouette** due to heart failure. - **Dexrazoxane** is a **cardioprotective agent** that can chelate iron, thereby reducing the formation of **free radicals** that cause myocardial damage from anthracyclines. *Rosuvastatin*: - **Rosuvastatin** is a **statin** used to lower cholesterol levels and prevent cardiovascular events due to atherosclerosis, which is not the primary cause of her acute symptoms. - While general **cardiovascular health** is important, rosuvastatin would not specifically prevent anthracycline-induced cardiotoxicity. *Cyclophosphamide*: - **Cyclophosphamide** is an **alkylating agent** commonly used in breast cancer treatment, but it is known for causing **hemorrhagic cystitis** and **myelosuppression**, not primary cardiotoxicity that presents acutely as heart failure. - It is part of the chemotherapeutic regimen that could contribute to the patient's cancer treatment but not a preventative measure for the cardiac side effects described here. *Aspirin*: - **Aspirin** is an **antiplatelet agent** used to prevent thrombosis and cardiovascular events like myocardial infarction or stroke, particularly in patients at risk for atherosclerosis. - It would not prevent the **acute cardiotoxicity** resulting from chemotherapy. *Vincristine*: - **Vincristine** is a **microtubule inhibitor** known for significant **neurotoxicity** (e.g., peripheral neuropathy, ileus), but it does not typically cause direct acute cardiotoxicity leading to symptoms of heart failure. - Its side effect profile is distinct from the cardiac issues described in the patient.

Question 727: A 60-year-old woman with a history of atrial arrhythmia arrives in the emergency department with complaints of tinnitus, headache, visual disturbances, and severe diarrhea. The patient is given oxygen by nasal cannula. ECG leads, pulse oximeter and an automated blood pressure cuff are applied. The patient suddenly faints. Her ECG indicates the presence of a multifocal ventricular tachycardia with continuous change in the QRS electrical axis. Which of the following drugs is most likely responsible for this patient's symptoms?

• A. Lidocaine
• B. Amiodarone
• C. Verapamil
• D. Digoxin
• E. Quinidine (Correct Answer)

Explanation: ***Quinidine*** - The constellation of **tinnitus**, **headache**, **visual disturbances**, and **diarrhea** along with **multifocal ventricular tachycardia** (specifically **torsades de pointes** due to polymorphic VT with continuous change in QRS electrical axis) is characteristic of **quinidine toxicity** (cinchonism). - Quinidine is a **Class IA antiarrhythmic** drug known to cause QT prolongation, which can lead to torsades de pointes. *Lidocaine* - **Lidocaine** is a **Class IB antiarrhythmic** that primarily affects ventricular arrhythmias and is not typically associated with tinnitus, visual disturbances, or diarrhea at therapeutic doses. - Its toxicity often manifests as CNS effects like **seizures**, **drowsiness**, or **paresthesias**, and it does not prolong the QT interval or cause torsades de pointes. *Amiodarone* - **Amiodarone** is a **Class III antiarrhythmic** drug that can cause a variety of side effects, but **tinnitus** and **severe diarrhea** are not its primary dose-limiting toxicities. - Its toxicity is more commonly associated with **pulmonary fibrosis**, **thyroid dysfunction**, and **corneal deposits**. *Verapamil* - **Verapamil** is a **calcium channel blocker** used for supraventricular arrhythmias and hypertension. - Its side effects include **bradycardia**, **hypotension**, and **constipation**, but not the specific neurological or gastrointestinal symptoms described, nor does it typically cause torsades de pointes. *Digoxin* - **Digoxin toxicity** can cause **arrhythmias** (including ventricular arrhythmias), **visual disturbances** (e.g., yellow-green halos), and **gastrointestinal symptoms** (nausea, vomiting, anorexia). - However, **tinnitus** and **severe diarrhea** are less typical, and while it *can* cause arrhythmias, **torsades de pointes** (multifocal VT with continuous QRS axis change) is not its characteristic arrhythmia.

Question 728: A 54-year-old man with a long-standing history of chronic obstructive pulmonary disease (COPD) presents to the clinic for progressive shortness of breath. The patient reports generalized fatigue, distress, and difficulty breathing that is exacerbated with exertion. Physical examination demonstrates clubbing of the fingers, and an echocardiogram shows right ventricular hypertrophy. The patient is placed on a medication for symptom control. One month later, the patient returns for follow up with some improvement in symptoms. Laboratory tests are drawn and shown below: Serum: Na+: 137 mEq/L Cl-: 101 mEq/L K+: 4.8 mEq/L HCO3-: 25 mEq/L BUN: 8.5 mg/dL Glucose: 117 mg/dL Creatinine: 1.4 mg/dL Thyroid-stimulating hormone: 1.8 µU/mL Ca2+: 9.6 mg/dL AST: 159 U/L ALT: 201 U/L What is the mechanism of action of the likely medication given?

• A. Prostacyclin with direct vasodilatory effects
• B. Beta-2 agonist
• C. Inhibition of phosphodiesterase-5 (Correct Answer)
• D. Competitive inhibition of muscarinic receptors
• E. Competitive inhibition of endothelin-1 receptors

Explanation: ***Inhibition of phosphodiesterase-5*** - The patient's presentation with **COPD**, **progressive shortness of breath**, **clubbing**, and **right ventricular hypertrophy** is highly suggestive of **cor pulmonale**, a type of **pulmonary hypertension** caused by lung disease. - **Phosphodiesterase-5 (PDE5) inhibitors** (e.g., sildenafil) are used to treat pulmonary hypertension by increasing cGMP levels, leading to **pulmonary vasodilation** and improved symptoms. *Prostacyclin with direct vasodilatory effects* - While prostacyclin analogs (e.g., epoprostenol) are potent **pulmonary vasodilators** used in pulmonary hypertension, they are usually reserved for more severe cases or specific etiologies. - The presented lab values, particularly the elevated AST and ALT, could be a side effect of some medications, but it doesn't specifically point to prostacyclin as the most likely initial treatment given the clinical picture. *Beta-2 agonist* - **Beta-2 agonists** (e.g., albuterol) are used to relieve **bronchospasm** in COPD, but they do not directly address the **pulmonary hypertension** component leading to right ventricular hypertrophy and would not be the primary treatment for cor pulmonale. - While they improve airflow, they don't impact the pulmonary vascular remodeling or pressures. *Competitive inhibition of muscarinic receptors* - **Anticholinergic bronchodilators** (e.g., tiotropium) act by blocking muscarinic receptors in the airways, leading to **bronchodilation**. - Like beta-2 agonists, they target airway obstruction in COPD but do not directly treat the **pulmonary hypertension** and its cardiovascular consequences. *Competitive inhibition of endothelin-1 receptors* - **Endothelin receptor antagonists** (e.g., bosentan) are also used in **pulmonary hypertension** to block the vasoconstrictive effects of endothelin-1. - While a plausible treatment for pulmonary hypertension, **PDE5 inhibitors** are often a first-line oral therapy, and the elevated liver enzymes (AST, ALT) could be a concern with some endothelin receptor antagonists, making it less likely as the initial symptomatic treatment.

Question 729: A 19-year-old boy presents to the emergency department with difficulty breathing, which began 1 hour ago. He has had persistent bronchial asthma since 3 years of age and has been prescribed inhaled fluticasone (400 μg/day) by his pediatrician. He has not taken the preventer inhaler for the last 2 weeks and visited an old house today that had a lot of dust accumulated on the floor. On physical examination, his temperature is 36.8°C (98.4°F), the pulse is 110/min, and the respiratory rate is 24/min. There are no signs of respiratory distress, and chest auscultation reveals bilateral wheezing. Which of the following medications is most likely to provide quick relief?

• A. Inhaled cromolyn
• B. Inhaled albuterol (Correct Answer)
• C. Inhaled salmeterol
• D. Oral montelukast
• E. Inhaled fluticasone

Explanation: ***Inhaled albuterol*** - **Albuterol** is a **short-acting beta-agonist (SABA)** that provides rapid bronchodilation by relaxing airway smooth muscles. - Its quick onset of action makes it ideal for immediate relief of **acute asthma symptoms** like wheezing and shortness of breath. *Inhaled cromolyn* - **Cromolyn** is a **mast cell stabilizer** that works by preventing the release of inflammatory mediators. - It is a **preventive medication** for asthma and does not provide quick relief for acute exacerbations. *Inhaled salmeterol* - **Salmeterol** is a **long-acting beta-agonist (LABA)** used for **long-term control** of asthma. - It has a slower onset of action and is not appropriate for **acute symptom relief**. *Oral montelukast* - **Montelukast** is a **leukotriene receptor antagonist** used for **long-term asthma control** and prevention of exercise-induced bronchoconstriction. - It does not provide immediate relief for an **acute asthma attack**. *Inhaled fluticasone* - **Fluticasone** is an **inhaled corticosteroid (ICS)** used as a **preventer medication** to reduce airway inflammation in asthma. - Its therapeutic effects are not immediate, and it is ineffective for **acute symptom management**.

Question 730: A 53-year-old woman presents for a follow-up. She took some blood tests recently for her yearly physical, and her random blood sugar level was found to be 251 mg/dL. She was asked to repeat her blood sugar and come back with the new reports. At that time, her fasting blood sugar level was 130 mg/dL and the postprandial glucose level was 245 mg/dL. Her HbA1c is 8.9%. She has had occasions where she felt light-headed and felt better only after she had something to eat. Her physician starts her on a drug to help her control her sugar levels. He also advised that she should return for routine follow-up labs and repeat HbA1c in 3 months. Which of the following is the mechanism of action of the drug that she was most likely prescribed?

• A. Decreases the secretion of glucagon.
• B. Stimulates the release of insulin from the pancreas.
• C. Inhibit alpha-glucosidase in the intestines.
• D. Acts as an agonist at the peroxisome proliferator-activated receptor-Ƴ.
• E. Increases the uptake of glucose and reduces peripheral insulin resistance. (Correct Answer)

Explanation: ***Increases the uptake of glucose and reduces peripheral insulin resistance.*** - The patient's presentation with **elevated random, fasting, and postprandial blood sugar levels**, along with an **HbA1c of 8.9%**, is highly indicative of **Type 2 Diabetes Mellitus**. **Metformin**, which works by increasing glucose uptake and reducing insulin resistance, is the **first-line treatment** for this condition. - Metformin primarily acts in the **liver** to decrease **hepatic glucose production**, and in **peripheral tissues** (muscle and fat) to improve **insulin sensitivity** and glucose utilization. *Decreases the secretion of glucagon.* - This is the mechanism of action for drugs like **GLP-1 receptor agonists** (e.g., liraglutide) and **DPP-4 inhibitors** (e.g., sitagliptin), which are typically **second-line agents** or used in combination therapy. - While these drugs are effective in diabetes management, they are generally not the initial choice for newly diagnosed Type 2 diabetes due to the established efficacy and safety profile of metformin. *Stimulates the release of insulin from the pancreas.* - This mechanism describes **sulfonylureas** (e.g., glipizide) and **meglitinides** (e.g., repaglinide). - These drugs carry a higher risk of **hypoglycemia** and weight gain compared to metformin, making them less favorable as initial monotherapy in most patients. *Inhibit alpha-glucosidase in the intestines.* - This is the mechanism of **alpha-glucosidase inhibitors** like **acarbose** and **miglitol**. - These drugs delay carbohydrate absorption, primarily targeting **postprandial hyperglycemia**, but are not typically used as first-line monotherapy due to their modest efficacy and common gastrointestinal side effects. *Acts as an agonist at the peroxisome proliferator-activated receptor-Ƴ.* - This describes the mechanism of **thiazolidinediones** (TZDs) like **pioglitazone** and **rosiglitazone**. - While TZDs improve insulin sensitivity, they are associated with side effects such as **fluid retention, heart failure**, and **bone fractures**, making them less preferred as initial therapy compared to metformin.

Question 731: A 58-year-old woman presents to her primary care physician for a wellness checkup. She recently had a DEXA scan that placed her at 2 standard deviations below the mean for bone density. She is following up today to discuss her results. The patient has a past medical history of asthma, breast cancer, COPD, anxiety, irritable bowel syndrome, endometrial cancer, and depression. She is currently taking clonazepam, albuterol, and fluoxetine. Her temperature is 99.5°F (37.5°C), blood pressure is 127/68 mmHg, pulse is 90/min, respirations are 15/min, and oxygen saturation is 95% on room air. The patient is treated appropriately and sent home. She returns 1 month later for a follow up visit. She has been taking her medications as prescribed. She endorses episodes of feeling febrile/warm which resolve shortly thereafter. Otherwise she is doing well. Which of the following is true of the medication she was most likely started on?

• A. Parathyroid hormone analogue
• B. Induces osteoclast apoptosis
• C. Estrogen receptor antagonist in the uterus (Correct Answer)
• D. Mineral replacement
• E. Estrogen receptor agonist in the uterus

Explanation: ***Estrogen receptor antagonist in the uterus*** - Given her history of **breast cancer** and **endometrial cancer**, the patient was likely started on **raloxifene** for osteoporosis. Raloxifene acts as an **estrogen receptor antagonist** in uterine tissue, which is beneficial in preventing endometrial proliferation and cancer recurrence. - The "feeling febrile/warm" episodes she describes are consistent with **hot flashes**, a common side effect of raloxifene due to its **estrogen receptor antagonism** in other tissues. *Parathyroid hormone analogue* - **Teriparatide**, a parathyroid hormone analogue, is an anabolic agent that stimulates bone formation. However, it is typically reserved for **severe osteoporosis** or patients who have failed other therapies. - While effective, teriparatide is administered daily via injection, and its side effects profile does not perfectly align with the patient's symptoms of feeling febrile/warm. *Induces osteoclast apoptosis* - This describes the mechanism of action of **bisphosphonates** (e.g., alendronate, zoledronic acid), which are common first-line treatments for osteoporosis. - However, bisphosphonates do not typically cause symptoms like "feeling febrile/warm" (hot flashes), which points away from this class of medication in this clinical scenario. *Mineral replacement* - This refers to **calcium and vitamin D supplementation**, which are foundational but usually adjunct therapies for osteoporosis, not the primary treatment that would cause hot flashes. - While essential for bone health, calcium and vitamin D alone would not be sufficient treatment for osteoporosis identified by a DEXA scan 2 standard deviations below the mean, nor would they cause febrile sensations. *Estrogen receptor agonist in the uterus* - This describes **estrogen therapy (ERT)** or some forms of **hormone replacement therapy (HRT)**. While effective for osteoporosis, ERT is **contraindicated** in patients with a history of **breast cancer** and **endometrial cancer** due to the increased risk of recurrence. - Additionally, estrogen receptor agonists would typically *alleviate* hot flashes, rather than cause them, which contradicts the patient's reported symptoms.

Question 732: A 10-year-old girl is brought to the neurologist for management of recently diagnosed seizures. Based on her clinical presentation, the neurologist decides to start a medication that works by blocking thalamic T-type calcium channels. Her parents are cautioned that the medication has a number of side effects including itching, headache, and GI distress. Specifically, they are warned to stop the medication immediately and seek medical attention if they notice skin bullae or sloughing. Which of the following conditions is most likely being treated in this patient?

• A. Absence seizures (Correct Answer)
• B. Simple seizures
• C. Complex seizures
• D. Status epilepticus
• E. Tonic-clonic seizures

Explanation: ***Absence seizures*** - The medication described works by blocking **thalamic T-type calcium channels**, which is the specific mechanism of **ethosuximide**, the first-line treatment for absence seizures. - Ethosuximide selectively targets the thalamic circuits involved in the 3-Hz spike-and-wave pattern characteristic of absence seizures. - While the question mentions serious skin reactions (bullae/sloughing suggestive of **Stevens-Johnson syndrome**), this is more commonly associated with other antiepileptics like **lamotrigine** or **carbamazepine** rather than ethosuximide specifically. However, the T-type calcium channel mechanism definitively points to absence seizure treatment. - Common side effects of ethosuximide include **GI distress, headache**, and rarely blood dyscrasias. *Simple seizures* - **Simple partial seizures** involve focal brain activity without loss of consciousness and do not primarily involve thalamic T-type calcium channels. - These are typically treated with drugs like **carbamazepine**, **phenytoin**, or **lamotrigine**, which work through sodium channel blockade or other mechanisms. *Complex seizures* - **Complex partial seizures** originate focally with impaired consciousness, involving limbic or temporal structures rather than thalamic circuits. - Treatment includes **carbamazepine**, **levetiracetam**, or **valproic acid**, which have different mechanisms than T-type calcium channel blockade. *Status epilepticus* - **Status epilepticus** is a life-threatening emergency requiring immediate intervention with **benzodiazepines** (lorazepam, diazepam) followed by other IV antiepileptics. - This condition requires rapid-acting GABAergic agents, not drugs targeting T-type calcium channels. *Tonic-clonic seizures* - **Generalized tonic-clonic seizures** involve widespread cortical discharge and are treated with broad-spectrum agents like **valproic acid**, **levetiracetam**, or **lamotrigine**. - While some antiepileptics may affect calcium channels, selective T-type calcium channel blockade is not the primary mechanism for treating tonic-clonic seizures.

Question 733: A 42-year-old female with a history of systemic lupus erythematosus (SLE) has a 3-year history of daily prednisone (20 mg) use. Due to long-term prednisone use, she is at increased risk for which of the following?

• A. Systolic hypertension
• B. Weight loss
• C. Pathologic fractures (Correct Answer)
• D. Hair loss
• E. Pancreatic insufficiency

Explanation: ***Pathologic fractures*** - Chronic systemic **corticosteroid use**, like prednisone, can lead to **osteoporosis** by increasing bone resorption and decreasing bone formation. - This weakens bones, making them susceptible to **pathologic fractures** even with minimal trauma. *Systolic hypertension* - While corticosteroids can cause **hypertension**, they typically lead to an increase in both **systolic and diastolic pressures**, not isolated systolic hypertension. - The primary mechanism involves increased fluid retention and vasoconstriction. *Weight loss* - Long-term prednisone use is commonly associated with **weight gain** due to increased appetite, fluid retention, and altered fat distribution (e.g., central obesity). - It does not typically cause weight loss. *Hair loss* - **Hair loss** can be a symptom of SLE itself, but it is not a direct or common side effect of prednisone therapy. - Corticosteroids can sometimes cause hair to grow thicker or change texture. *Pancreatic insufficiency* - Although corticosteroids can cause **pancreatitis** in rare cases, they do not typically lead to chronic **pancreatic insufficiency**. - Pancreatic insufficiency is more commonly associated with conditions like cystic fibrosis or chronic alcohol abuse.

Question 734: An 8-year-old female is given omalizumab for the treatment of bronchial asthma. Omalizumab treats asthma through which mechanism?

• A. Inhibition of leukotriene binding to receptor
• B. Binding to nuclear receptors
• C. Inhibition of phosphodiesterase breakdown of cAMP
• D. Inhibition of IgE binding to mast cells (Correct Answer)
• E. Mediating type IV hypersensitivity reaction

Explanation: ***Inhibition of IgE binding to mast cells*** - **Omalizumab** is a **monoclonal antibody** that specifically targets and binds to **free IgE** in the bloodstream. - By binding to IgE, it prevents IgE from attaching to its receptors on **mast cells** and other inflammatory cells, thereby reducing the release of inflammatory mediators that cause asthma symptoms. *Inhibition of leukotriene binding to receptor* - This mechanism describes drugs like **montelukast** and **zafirlukast**, which are **leukotriene receptor antagonists**. - These drugs block the action of leukotrienes, which are potent bronchoconstrictors and inflammatory mediators, but this is not how omalizumab works. *Binding to nuclear receptors* - This mechanism is characteristic of **corticosteroids** (e.g., prednisone, fluticasone), which bind to intracellular nuclear receptors to modulate gene expression and reduce inflammation. - Omalizumab does not act on nuclear receptors; its primary action is extracellular. *Inhibition of phosphodiesterase breakdown of cAMP* - This is the mechanism of action for **methylxanthines** like **theophylline**, which increase intracellular cAMP levels leading to bronchodilation. - Omalizumab does not inhibit phosphodiesterase; it works upstream by targeting IgE. *Mediating type IV hypersensitivity reaction* - Type IV hypersensitivity reactions (delayed-type hypersensitivity) are cell-mediated, involving **T cells** and **macrophages**, not antibodies like IgE or omalizumab directly. - If anything, omalizumab aims to *reduce* the allergic immune response that can contribute to asthma, not mediate a hypersensitivity reaction itself.

Question 735: A 49-year-old man seeks evaluation at an urgent care clinic with a complaint of palpitations for the past few hours. He denies any chest pain, shortness of breath, or sweating. He is anxious and appears worried. His medical history is unremarkable with the exception of mild bronchial asthma. He only uses medications during an asthma attack and has not used medications since last week. He is a former smoker and drinks a couple of beers on weekends. His heart rate is 146/min, respiratory rate is 16/min, temperature is 37.6°C (99.68°F), and blood pressure is 120/80 mm Hg. The physical examination is unremarkable, and an electrocardiogram is ordered. Which of the following groups of drugs should be given to treat his symptoms?

• A. Non-selective β-receptor antagonist
• B. β-receptor agonist
• C. α-receptor agonist
• D. Selective β1-receptor antagonist (Correct Answer)
• E. α1-receptor antagonist

Explanation: ***Selective β1-receptor antagonist*** - The patient presents with **palpitations** and a heart rate of 146/min, indicating a **tachyarrhythmia**. A selective β1-receptor antagonist is ideal as it can slow the heart rate without significantly affecting β2-receptors in the lungs, which is crucial for a patient with a history of **asthma**. - Medications like **metoprolol** or **atenolol** belong to this class and are preferred in patients with pulmonary conditions. *Non-selective β-receptor antagonist* - While effective at reducing heart rate, a **non-selective β-receptor antagonist** (e.g., **propranolol**) would block both β1 and β2 receptors. - Blocking β2-receptors can lead to **bronchoconstriction**, potentially exacerbating the patient's underlying **asthma**. *β-receptor agonist* - A **β-receptor agonist** would **increase heart rate** and cardiac contractility, worsening the patient's existing palpitations and tachycardia. - This class of drugs is primarily used for conditions like asthma (e.g., **albuterol**, a β2-agonist) or heart failure, not for treating tachycardia. *α-receptor agonist* - **α-receptor agonists** primarily cause **vasoconstriction** and can increase blood pressure (e.g., **phenylephrine**). - They are not indicated for treating palpitations or tachycardia and may further elevate heart rate reflexively due to increased peripheral resistance. *α1-receptor antagonist* - **α1-receptor antagonists** (e.g., **prazosin**) are primarily used to treat **hypertension** or **benign prostatic hyperplasia** by causing vasodilation. - They would not directly address the patient's palpitations or tachycardia and could potentially cause **hypotension**.

Question 736: A 62-year-old man is brought to the emergency room because of pain in his right hip. He was found lying on the floor several hours after falling onto his right side. Ten years ago, he received a renal transplant from a living related donor. He has a 4-year history of type 2 diabetes. Current medications include prednisone, cyclosporine, and metformin. Examination shows a shortened and externally rotated right leg. There is extensive bruising over the right buttock and thigh. X-ray of the right hip shows a displaced femoral neck fracture. The patient is resuscitated in the emergency room and taken to surgery for a right total hip replacement. Post-operative laboratory studies show: Hemoglobin 11.2 g/dL Serum Na+ 148 mmol/L K+ 7.1 mmol/L Cl- 119 mmol/L HCO3- 18 mmol/L Urea nitrogen 22 mg/dL Creatinine 1.6 mg/dL Glucose 200 mg/dL Creatine kinase 1,562 U/L His urine appears brown. Urine dipstick is strongly positive for blood. ECG shows peaked T waves. Intravenous calcium gluconate is administered. What is the most appropriate next step in management?

• A. Administer intravenous furosemide and normal saline
• B. Initiate hemodialysis
• C. Administer nebulized albuterol
• D. Administer intravenous sodium bicarbonate
• E. Administer intravenous insulin and glucose (Correct Answer)

Explanation: ***Administer intravenous insulin and glucose*** - The patient has severe **hyperkalemia (K+ 7.1 mmol/L)** with **ECG changes (peaked T waves)**, necessitating urgent treatment to shift potassium into cells. - **Insulin and glucose** drive potassium into cells by stimulating the Na+/K+-ATPase pump, rapidly lowering serum potassium and stabilizing the cardiac membrane. *Administer intravenous furosemide and normal saline* - While furosemide can increase potassium excretion, it is less effective for emergent hyperkalemia with significant ECG changes, and **saline infusion** alone does not address the intracellular shift needed. - The patient also likely has **rhabdomyolysis** (elevated CK, brown urine, positive blood on dipstick without RBCs), which requires aggressive fluid resuscitation, but this specific combination does not directly resolve the immediate threat of hyperkalemia. *Initiate hemodialysis* - Hemodialysis is the most effective way to remove potassium from the body and would be indicated for refractory or severe hyperkalemia, especially in the setting of renal impairment. - However, **insulin and glucose** provide a more rapid initial intervention to stabilize the patient while preparations for hemodialysis are made. *Administer nebulized albuterol* - Nebulized albuterol can transiently lower serum potassium by stimulating the Na+/K+-ATPase pump, similar to insulin, but it is generally less potent and has a variable response. - It could be considered as an adjunct, but is not the primary or most reliable acute treatment for severe hyperkalemia with ECG changes. *Administer intravenous sodium bicarbonate* - Sodium bicarbonate can shift potassium into cells by correcting acidosis, which this patient likely has (bicarbonate 18 mmol/L). - However, its effect is typically slower and less predictable than insulin and glucose, especially in non-acidotic hyperkalemia or when rapid membrane stabilization is critical.

Question 737: A 58-year-old Caucasian male who is being treated for atrial fibrillation and angina complains of dyspnea on exertion. On exam, his heart rate 104-115/min and irregularly irregular at rest. He has no chest pain. You believe his rate control for atrial fibrillation is suboptimal and the likely cause of his dyspnea. You are considering adding verapamil to his current metoprolol for additional rate control of his atrial fibrillation. Which of the following side effects should you be most concerned about with this additional medication?

• A. Hypotension (Correct Answer)
• B. Diarrhea
• C. Torsades de pointes
• D. Tachycardia
• E. Shortening of action potential length at the AV node

Explanation: ***Hypotension*** - **Verapamil** (a non-dihydropyridine calcium channel blocker) and **metoprolol** (a beta-blocker) both have significant **negative inotropic** and **chronotropic** effects, as well as vasodilatory properties. - Their combined use can lead to synergistic **blood pressure lowering**, increasing the risk of symptomatic hypotension, especially in a patient with **angina** where careful blood pressure management is crucial. *Diarrhea* - Diarrhea is not a common or significant side effect of either **verapamil** or **metoprolol** that would cause major concern in this clinical scenario. - While gastrointestinal side effects can occur with many medications, **constipation** is more frequently associated with verapamil. *Torsades de pointes* - **Torsades de pointes** is a form of polymorphic ventricular tachycardia typically caused by drugs that prolong the **QT interval**. - Neither **verapamil** nor **metoprolol** are known to significantly prolong the QT interval or cause Torsades de pointes. *Tachycardia* - Both **verapamil** and **metoprolol** are used to **slow heart rate**, particularly in conditions like **atrial fibrillation** and **angina**. - Combining these medications would be expected to further decrease the heart rate, not cause tachycardia. *Shortening of action potential length at the AV node* - Both **verapamil** and **beta-blockers** like metoprolol primarily act to **slow conduction** through the **AV node** by extending the refractory period and **prolonging the action potential duration** (or decreasing excitability), thereby decreasing ventricular rate in atrial fibrillation. - Shortening the action potential length at the AV node would theoretically lead to faster conduction and an increased heart rate, which is the opposite of the intended effect of these medications.

Question 738: A 67-year-old man presents to his primary care physician for a decline in his hearing that he noticed over the past week. The patient has a past medical history of hypertension and diabetes mellitus and was recently diagnosed with bladder cancer which is currently appropriately being treated. The patient is a hunter and often goes shooting in his spare time. His recent sick contacts include his grandson who is being treated with amoxicillin for ear pain. Physical exam is notable for decreased hearing bilaterally. The Weber test does not localize to either ear, and the Rinne test demonstrates air conduction is louder than bone conduction. Which of the following is the most likely etiology for this patient's hearing loss?

• A. Otitis externa
• B. Presbycusis
• C. Otosclerosis
• D. Medication regimen (Correct Answer)
• E. Otitis media

Explanation: ***Medication regimen*** - The patient's history of bladder cancer treatment suggests recent exposure to **chemotherapeutic agents**, such as **cisplatin**, which are known to be **ototoxic**. - A **sudden decline in hearing** over the past week points to an acute cause, such as drug-induced hearing loss. *Otitis externa* - This condition typically presents with **ear pain**, **pruritus**, and **discharge**, none of which are mentioned in the patient's presentation. - The **Weber and Rinne test results** (normal AC > BC, no lateralization) are inconsistent with a conductive hearing loss typically associated with otitis externa. *Presbycusis* - **Presbycusis** is an age-related **sensorineural hearing loss** that typically develops **gradually over years**, not suddenly over a week. - While the patient's age (67) is a risk factor, the acute onset makes this diagnosis less likely. *Otosclerosis* - **Otosclerosis** usually causes a **progressive conductive hearing loss**, often starting in young adulthood. - The **Weber and Rinne test results** (normal AC > BC, no lateralization) are inconsistent with a conductive hearing loss. *Otitis media* - **Otitis media** typically presents with **ear pain**, **fullness**, and often **fever** or **discharge**, which are absent in this patient. - The **Weber and Rinne test results** (normal AC > BC, no lateralization) are inconsistent with the conductive hearing loss that would be expected with otitis media.

Question 739: Benzodiazepines are clinically useful because of their inhibitory effects on the central nervous system. Which of the following correctly pairs the site of action of benzodiazepines with the molecular mechanism by which they exert their effects?

• A. GABA-A receptors; increasing the frequency of activation of a chloride ion channel (Correct Answer)
• B. GABA-B receptors; activating potassium channels
• C. GABA-A receptors; increasing the duration of activation of a chloride ion channel
• D. GABA-A receptors; blocking action of GABA
• E. GABA-B receptors; activating a G-protein coupled receptor

Explanation: ***GABA-A receptors; increasing the frequency of activation of a chloride ion channel*** - Benzodiazepines bind to a specific site on the **GABA-A receptor**, which is a **ligand-gated chloride ion channel**. - Their binding enhances the effect of GABA by increasing the **frequency of channel opening**, leading to increased chloride influx and neuronal hyperpolarization. *GABA-B receptors; activating potassium channels* - Benzodiazepines **do not act on GABA-B receptors**, which are G-protein coupled receptors. - GABA-B receptor activation typically leads to the activation of **potassium channels** or inhibition of calcium channels, not directly influenced by benzodiazepines. *GABA-A receptors; increasing the duration of activation of a chloride ion channel* - This describes the mechanism of action of **barbiturates**, not benzodiazepines. - Barbiturates increase the **duration of chloride channel opening**, leading to a more pronounced and potentially dangerous central nervous system depression compared to benzodiazepines. *GABA-A receptors; blocking action of GABA* - Benzodiazepines are **agonists** (or positive allosteric modulators) of GABA's action, not blockers. - They enhance, rather than inhibit, the inhibitory effects of GABA. *GABA-B receptors; activating a G-protein coupled receptor* - While GABA-B receptors are indeed **G-protein coupled receptors**, benzodiazepines do not exert their effects by activating these receptors. - Their primary site of action is the **GABA-A receptor**.

Question 740: A 45-year-old man with type 2 diabetes mellitus presents to his family physician for a follow-up appointment. He is currently using a 3-drug regimen consisting of metformin, sitagliptin, and glipizide. Despite this therapeutic regimen, his most recent hemoglobin A1c level is 8.1%. Which of the following is the next best step for this patient?

• A. Discontinue metformin; initiate basal-bolus insulin
• B. Discontinue sitagliptin; initiate basal-bolus insulin
• C. Discontinue metformin; initiate insulin aspart at mealtimes
• D. Discontinue metformin; initiate insulin glargine 10 units at bedtime
• E. Discontinue glipizide; initiate insulin glargine 10 units at bedtime (Correct Answer)

Explanation: ***Discontinue glipizide; initiate insulin glargine 10 units at bedtime*** - The patient's **hemoglobin A1c of 8.1%** indicates that his current triple oral therapy is inadequate, requiring further intensification of treatment. - **Glipizide**, a sulfonylurea, carries a significant risk of **hypoglycemia** and should be discontinued before initiating basal insulin to avoid cumulative effects and reduce this risk. - **Metformin** and **sitagliptin** can be safely continued with basal insulin therapy. *Discontinue metformin; initiate basal-bolus insulin* - **Metformin** is typically the **first-line agent** for type 2 diabetes due to its efficacy, low risk of hypoglycemia, and potential cardiovascular benefits, and should generally be continued unless contraindicated. - Initiating a full **basal-bolus insulin** regimen is often too aggressive as a next step, especially when the patient is already on triple oral therapy; a **basal insulin** addition is usually preferred initially. *Discontinue sitagliptin; initiate basal-bolus insulin* - **Sitagliptin**, a DPP-4 inhibitor, has a **low risk of hypoglycemia** and generally contributes to A1c reduction without significant side effects, so there is no compelling reason to discontinue it in favor of basal-bolus insulin. - As mentioned, a **basal-bolus insulin** regimen is often not the initial step for intensification when basal insulin monotherapy can be tried first. *Discontinue metformin; initiate insulin aspart at mealtimes* - Again, **metformin** should generally be continued due to its benefits and safety profile, unless contraindicated. - Adding **mealtime insulin (insulin aspart)** without a basal insulin component is usually not effective for overall glycemic control in patients with an A1c of 8.1% who are already on triple oral therapy. *Discontinue metformin; initiate insulin glargine 10 units at bedtime* - **Metformin** should not be discontinued as it is a foundational drug in type 2 diabetes management due to its efficacy and safety profile. - While **basal insulin (insulin glargine)** is an appropriate next step, discontinuing metformin unnecessarily removes a beneficial agent.

Question 741: A 37-year-old woman presents to the emergency department with a chief complaint of severe pain in her face. She states that over the past week she has experienced episodic and intense pain in her face that comes on suddenly and resolves on its own. She states she feels the pain over her cheek and near her eye. The pain is so severe it causes her eyes to tear up, and she is very self conscious about the episodes. She fears going out in public as a result and sometimes feels her symptoms come on when she thinks about an episode occurring while in public. While she is waiting in the emergency room her symptoms resolve. The patient has a past medical history of diabetes, constipation, irritable bowel syndrome, and anxiety. She is well known to the emergency department for coming in with chief complaints that often do not have an organic etiology. Her temperature is 99.5°F (37.5°C), blood pressure is 177/108 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. Cardiopulmonary and abdominal exams are within normal limits. Neurological exam reveals cranial nerves II-XII are grossly intact. The patient's pupils are equal and reactive to light. Pain is not elicited with palpation of the patient's face. Which of the following is the best initial step in management?

• A. Regular outpatient follow up
• B. Ibuprofen
• C. High flow oxygen
• D. Alprazolam
• E. Carbamazepine (Correct Answer)

Explanation: ***Carbamazepine*** - The patient's presentation of **sudden, episodic, severe facial pain** in the V2 (maxillary) and V1 (ophthalmic) distributions, associated with **lacrimation** and triggering anxiety, is highly characteristic of **trigeminal neuralgia**. - **Carbamazepine** is the **first-line treatment** for trigeminal neuralgia due to its efficacy in managing neuropathic pain, especially reducing the frequency and severity of paroxysms. *Regular outpatient follow up* - While follow-up is important, this patient is in severe pain right now, and her symptoms resolved while in the ED. Her **acute pain** requires immediate management to prevent recurrence and improve her quality of life. - Delaying treatment with only outpatient follow-up would prolong her suffering and potentially lead to further emergency department visits for symptom exacerbations. *Ibuprofen* - **Ibuprofen**, a non-steroidal anti-inflammatory drug (NSAID), is effective for **nociceptive pain** (e.g., musculoskeletal pain, inflammatory pain) but is generally **ineffective for neuropathic pain** conditions like trigeminal neuralgia. - The pain in trigeminal neuralgia arises from nerve dysfunction, for which NSAIDs do not target the underlying mechanism. *High flow oxygen* - **High-flow oxygen** is a specific treatment for **cluster headaches**, which present with severe, unilateral head pain, autonomic symptoms, and occur in clusters. - The patient's symptoms are localized to the trigeminal distribution, are episodic and lightning-like, and lack the typical temporal pattern and location of cluster headaches. *Alprazolam* - **Alprazolam** is a benzodiazepine used to treat **anxiety** and panic disorders, which may be a co-morbidity or consequence of the patient's pain. - It does not directly address the **neuropathic pain** of trigeminal neuralgia, and while it might reduce anxiety, it will not resolve the underlying pain episodes.

Question 742: A 14-year-old boy presents to an urgent care clinic complaining of a runny nose that has lasted for a few weeks. He also reports sneezing attacks that last up to an hour, nasal obstruction, and generalized itching. He has similar episodes each year during the springtime that prevent him from going out with his friends or trying out for sports. His younger brother has a history of asthma. Which of the following diseases has a similar pathophysiology?

• A. Irritant contact dermatitis
• B. Dermatitis herpetiformis
• C. Allergic contact dermatitis
• D. Atopic dermatitis (Correct Answer)
• E. Systemic lupus erythematosus

Explanation: ***Atopic dermatitis*** - This patient's symptoms are highly suggestive of **allergic rhinitis**, a **type I hypersensitivity reaction** mediated by IgE antibodies, which also underlies atopic dermatitis. - The family history of asthma (part of the **atopic triad** – allergic rhinitis, asthma, atopic dermatitis) further supports a common underlying allergic predisposition. *Irritant contact dermatitis* - This is a **non-allergic inflammatory reaction** caused by direct skin irritation from chemical or physical agents, not an immunological hypersensitivity. - It does not involve IgE-mediated mechanisms or a systemic allergic predisposition like the patient's condition. *Dermatitis herpetiformis* - This is a **chronic blistering skin condition** strongly associated with **celiac disease** and characterized by IgA deposition in the skin. - It involves an autoimmune response to gluten and is not related to the IgE-mediated allergic response seen in allergic rhinitis. *Allergic contact dermatitis* - This is a **type IV delayed-type hypersensitivity reaction** mediated by T cells, often occurring days after exposure to an allergen (e.g., poison ivy, nickel). - It is distinct from the immediate IgE-mediated (type I) hypersensitivity responsible for allergic rhinitis. *Systemic lupus erythematosus* - This is a **chronic autoimmune disease** characterized by systemic inflammation and autoantibody production against various self-antigens, leading to diverse organ involvement. - It is a complex autoimmune disorder with different immunological mechanisms (e.g., type III hypersensitivity) rather than the IgE-mediated allergy seen in this case.

Question 743: A 60-year-old woman presents to the emergency department with progressive nausea and vomiting. She reports that approximately one day prior to presentation she experienced abdominal discomfort that subsequently worsened to severe nausea, vomiting, and two episodes of watery diarrhea. She recently noticed that her vision has become blurry along with mild alterations in color perception. Medical history is significant for congestive heart failure with a low ejection fraction. She cannot recall which medications she is currently taking but believes she is taking them as prescribed. Which of the following is a characteristic of the likely offending drug that led to this patient’s clinical presentation?

• A. Ratio of toxic dose to effective dose close to 1 (Correct Answer)
• B. High potency
• C. Ratio of toxic dose to effective dose much greater than 1
• D. Low bioavailability
• E. Low potency

Explanation: ***Ratio of toxic dose to effective dose close to 1*** - The patient's symptoms (nausea, vomiting, diarrhea, blurry vision, color perception changes) are classic for **digoxin toxicity**, which commonly occurs due to its **narrow therapeutic index**. - A **narrow therapeutic index** means that the difference between the therapeutically effective dose and the toxic dose is small, making the ratio of toxic dose to effective dose close to 1. *High potency* - While digoxin is a potent drug, **potency** refers to the amount of drug needed to produce a clinical effect, not its safety margin. - A drug can be potent but still have a wide therapeutic window if its toxic dose is much higher than its effective dose. *Ratio of toxic dose to effective dose much greater than 1* - This characteristic describes drugs with a **wide therapeutic index**, meaning there is a large safety margin between effective and toxic doses. - This is the opposite of the situation with digoxin, which has a narrow therapeutic index and is prone to toxicity. *Low bioavailability* - **Bioavailability** is the proportion of a drug that enters the circulation unchanged, which does not directly characterize its safety margin. - Digoxin generally has good oral bioavailability (around 70-80% for tablet preparations). *Low potency* - Digoxin is known for its **high potency**, meaning small doses achieve significant therapeutic effects. - Low potency would imply that large doses are needed to achieve a therapeutic effect, which is not the case for digoxin.

Question 744: A 24-year-old obese woman presents with a severe right-sided frontotemporal headache that started 2 days ago. There is no improvement with over-the-counter pain medications. Yesterday, the pain was so intense that she stayed in bed all day in a dark, quiet room instead of going to work. This morning she decided to come in after an episode of vomiting. She says she has experienced 5–6 similar types of headaches each lasting 12–24 hours over the last 6 months but never this severe. She denies any seizures, visual disturbances, meningismus, sick contacts or focal neurologic deficits. Her past medical history is significant for moderate persistent asthma, which is managed with ipratropium bromide and an albuterol inhaler. She is currently sexually active with 2 men, uses condoms consistently, and regularly takes estrogen-containing oral contraceptive pills (OCPs). Her vital signs include: blood pressure 122/84 mm Hg, pulse 86/min, respiratory rate 19/min, and blood oxygen saturation (SpO2) 98% on room air. Physical examination, including a complete neurologic exam, is unremarkable. A magnetic resonance image (MRI) of the brain appears normal. Which of the following is the best prophylactic treatment for this patient’s most likely condition?

• A. Ibuprofen
• B. Amitriptyline
• C. Sumatriptan
• D. Methysergide
• E. Gabapentin (Correct Answer)

Explanation: ***Gabapentin*** - This patient presents with **migraine without aura** (recurrent unilateral headaches lasting 12-24 hours with photophobia, phonophobia, and nausea/vomiting). - With **5-6 episodes over 6 months**, she meets criteria for **migraine prophylaxis** (≥4 attacks per month or debilitating attacks). - **Key clinical consideration**: She has **moderate persistent asthma**, which significantly limits prophylaxis options. - **Gabapentin** is an excellent choice for migraine prophylaxis in this patient because: - It is **safe in asthma** (no bronchospasm risk) - Effective for migraine prevention - Well-tolerated with minimal drug interactions - No cardiovascular contraindications - While typically considered second-line, gabapentin becomes a preferred option when first-line agents (beta-blockers, amitriptyline) are contraindicated by asthma. *Amitriptyline* - While **amitriptyline** (tricyclic antidepressant) is a **first-line agent for migraine prophylaxis** in general populations, it has **antimuscarinic (anticholinergic) properties**. - In patients with **asthma**, anticholinergic effects can cause **bronchial smooth muscle effects** and potentially worsen respiratory symptoms. - Should be used with **caution or avoided** in asthma patients. *Ibuprofen* - **Ibuprofen** is an NSAID used for **acute migraine treatment**, not prophylaxis. - While effective for symptomatic relief, it does not prevent future migraine attacks. - Not appropriate for a patient requiring prophylactic therapy due to frequent attacks. *Sumatriptan* - **Sumatriptan** is a **5-HT1B/1D agonist (triptan)** used as an **abortive medication** for acute migraine attacks. - It is **not indicated for migraine prophylaxis**. - Used to treat attacks once they have started, not to prevent them. *Methysergide* - **Methysergide** is an **ergot alkaloid** historically used for migraine prophylaxis but has **fallen out of favor** due to serious side effects. - Risk of **retroperitoneal fibrosis**, **pleuropulmonary fibrosis**, and **cardiac valvular fibrosis** with chronic use. - Rarely used in modern practice due to safer alternatives available.

Question 745: A 55-year-old man comes to the physician for a follow-up examination. He feels well. He has hyperlipidemia and type 2 diabetes mellitus. He takes medium-dose simvastatin and metformin. Four months ago, fasting serum studies showed a LDL-cholesterol of 136 mg/dL and his medications were adjusted. Vital signs are within normal limits. On physical examination, there is generalized weakness of the proximal muscles. Deep tendon reflexes are 2+ bilaterally. Fasting serum studies show: Total cholesterol 154 mg/dL HDL-cholesterol 35 mg/dL LDL-cholesterol 63 mg/dL Triglycerides 138 mg/dL Glucose 98 mg/dL Creatinine 1.1 mg/dL Creatine kinase 260 mg/dL Which of the following is the most appropriate next step in management of this patient's hyperlipidemia?

• A. Increase the dose of simvastatin
• B. Discontinue simvastatin, start niacin in 3 weeks
• C. Continue simvastatin, add niacin
• D. Discontinue simvastatin, start fenofibrate now
• E. Discontinue simvastatin, start pravastatin in 3 weeks (Correct Answer)

Explanation: ***Discontinue simvastatin, start pravastatin in 3 weeks*** - The patient presents with **proximal muscle weakness** and an elevated **creatine kinase (CK)** level (260 U/L), which are clinical signs consistent with **statin-induced myopathy**. - Discontinuing the current statin and switching to a more hydrophilic statin like **pravastatin** (after a washout period) is appropriate to mitigate muscle side effects while continuing lipid-lowering therapy. *Increase the dose of simvastatin* - Increasing the dose of simvastatin would exacerbate the existing **myopathy**, as higher doses of lipophilic statins are more prone to causing muscle-related side effects. - The patient's **LDL-C is already well-controlled** at 63 mg/dL, so a dose increase is not necessary from a lipid-lowering perspective. *Discontinue simvastatin, start niacin in 3 weeks* - While niacin can address lipid goals, it is **not a primary treatment for hyperlipidemia** when a statin is indicated, especially given the patient's history of type 2 diabetes and high cardiovascular risk. - Niacin has its own side effects, such as **flushing** and potential worsening of insulin resistance, and an alternative statin is preferable to manage both lipids and myopathy. *Continue simvastatin, add niacin* - Continuing simvastatin would ignore the clear signs of **statin-induced myopathy** (proximal muscle weakness and elevated CK). - Adding niacin would not resolve the myopathy and introduces additional medication with potential side effects, which is not the priority when **statin intolerance** is suspected. *Discontinue simvastatin, start fenofibrate now* - Fenofibrate is primarily used to lower **triglycerides** and can raise HDL, but it is less effective than statins at lowering LDL-C, which is the primary goal in patients with hyperlipidemia and diabetes. - While statin-fibrate combinations can increase the risk of myopathy, fenofibrate alone is not the most appropriate first-line replacement for a statin in this context, especially with a well-controlled triglyceride level.

Question 746: A 35-year-old woman comes to the physician because of headaches, irregular menses, and nipple discharge for the past 4 months. Breast examination shows milky white discharge from both nipples. Her thyroid function tests and morning cortisol concentrations are within the reference ranges. A urine pregnancy test is negative. An MRI of the brain is shown. Which of the following sets of changes is most likely in this patient? $$$ Serum estrogen %%% Serum progesterone %%% Dopamine synthesis $$$

• A. ↑ ↑ ↔
• B. ↓ ↓ ↑ (Correct Answer)
• C. ↔ ↔ ↔
• D. ↑ ↔ ↔
• E. ↓ ↓ ↓

Explanation: **↓ ↓ ↑** - This patient's symptoms of irregular menses, galactorrhea, and headaches, along with the MRI finding of a pituitary mass (suggesting a **prolactinoma**), indicate **hyperprolactinemia**. High prolactin levels **inhibit GnRH** release, leading to decreased **LH and FSH**, which in turn causes **decreased estrogen and progesterone synthesis** by the ovaries. - The compensatory mechanism for the reduced dopamine inhibition on prolactin (due to the mass effect or damage to the stalk) would be an **increase in dopamine synthesis** in an attempt to re-establish control. *↑ ↑ ↔* - Elevated estrogen and progesterone levels are typically seen in conditions like **pregnancy** or **ovarian cysts**, neither of which fits the clinical picture or MRI findings here. - Normal dopamine synthesis would not account for the **hyperprolactinemia** and its effects on gonadal hormones. *↔ ↔ ↔* - Normal levels of hormones would not explain the patient's symptoms of galactorrhea, irregular menses, and headaches. - A functional pituitary adenoma (like a prolactinoma) would significantly alter endocrine function, not leave it at baseline. *↑ ↔ ↔* - Elevated estrogen without changes in progesterone and dopamine synthesis would not cause **galactorrhea** or **amenorrhea** in the context of a pituitary mass. - Unchanged progesterone and dopamine also don't fit the pathophysiology of a prolactinoma. *↓ ↓ ↓* - While estrogen and progesterone would be decreased, **decreased dopamine synthesis** would only exacerbate the hyperprolactinemia, making it less likely as a compensatory response. - The body would typically attempt to increase dopamine to counteract the high prolactin.

Question 747: A 54-year-old man with a history of hyperlipidemia presents to the emergency department complaining of left sided chest pain. He says the pain began 3 hours ago while he was cooking dinner in his kitchen. The pain radiates to his left arm and stomach. He also complains of feeling anxious and heart palpitations. Temperature is 98.7°F (37.1°C), blood pressure is 130/80 mmHg, pulse is 101/min, and respirations are 22/min. Inspection demonstrates a diffuse diaphoresis, and cardiac auscultation reveals an S4 gallop. Cardiac catheterization reveals occlusion of the left anterior descending artery, and a vascular stent is placed. The patient is discharged on aspirin, atorvastatin, and an antiplatelet medication. Which of the following is the mechanism of action of the most likely prescribed antiplatelet medication?

• A. Reversible ADP receptor antagonism (Correct Answer)
• B. Irreversible ADP receptor antagonism
• C. Direct factor Xa inhibition
• D. GPIIb/IIIa inhibition
• E. Antithrombin III activation

Explanation: ***Reversible ADP receptor antagonism*** - Following percutaneous coronary intervention (PCI) with stent placement, **P2Y12 inhibitors** are a cornerstone of dual antiplatelet therapy. These include **ticagrelor** and **prasugrel** (often preferred over clopidogrel in acute coronary syndromes), which are **reversible ADP receptor antagonists**. - This mechanism prevents **ADP-mediated platelet activation and aggregation**, reducing the risk of stent thrombosis and recurrent ischemic events. *Irreversible ADP receptor antagonism* - **Clopidogrel** acts via **irreversible ADP receptor antagonism**, providing a sustained antiplatelet effect, but it has a slower onset and variable metabolism. - Newer agents like ticagrelor and prasugrel are generally favored in acute coronary syndrome due to their more potent, faster, and more consistent antiplatelet effect. *Direct factor Xa inhibition* - **Direct factor Xa inhibitors** (e.g., rivaroxaban, apixaban) are primarily used for **anticoagulation** in conditions like atrial fibrillation or venous thromboembolism, not as primary antiplatelet therapy after PCI. - These agents target the coagulation cascade rather than direct platelet aggregation. *GPIIb/IIIa inhibition* - **Glycoprotein IIb/IIIa inhibitors** (e.g., abciximab, eptifibatide, tirofiban) directly block the final common pathway of platelet aggregation, the **binding of fibrinogen to GPIIb/IIIa receptors**. - They are potent antiplatelet agents used **intravenously during PCI** for very high-risk patients but are not typically prescribed for long-term antiplatelet therapy post-discharge. *Antithrombin III activation* - **Heparin** (unfractionated and low molecular weight) exerts its anticoagulant effect by **activating antithrombin III**, which then inactivates thrombin and Factor Xa. - These are used for acute anticoagulation but are not considered antiplatelet medications for long-term dual antiplatelet therapy after stent placement.

Question 748: A 43-year-old Caucasian female with a long history of uncontrolled migraines presents to general medical clinic with painless hematuria. She is quite concerned because she has never had symptoms like this before. Vital signs are stable, and her physical examination is benign. She denies any groin pain, flank pain, or costovertebral angle tenderness. She denies any recent urinary tract infections or dysuria. Urinary analysis confirms hematuria and a serum creatinine returns at 3.0. A renal biopsy reveals papillary necrosis and a tubulointerstitial infiltrate. What is the most likely diagnosis?

• A. Analgesic nephropathy (Correct Answer)
• B. Kidney cancer
• C. Sickle cell disease
• D. Bladder cancer
• E. Kidney stone

Explanation: ***Analgesic nephropathy*** - The patient's history of **uncontrolled migraines** suggests chronic use of analgesic medications, which can lead to **papillary necrosis** and chronic **tubulointerstitial nephritis**. - **Painless hematuria** and elevated creatinine with biopsy-confirmed papillary necrosis and tubulointerstitial infiltrate are classic manifestations of analgesic nephropathy. *Kidney cancer* - While kidney cancer can cause **painless hematuria**, it typically presents with a **mass on imaging** and often results in symptoms like flank pain or palpable mass with progression. - The specific renal biopsy findings of **papillary necrosis** and **tubulointerstitial infiltrate** are not characteristic of kidney cancer. *Sickle cell disease* - **Sickle cell nephropathy** can cause papillary necrosis and hematuria, but this patient is a **Caucasian female** and has no history or symptoms indicative of sickle cell disease. - The disease is primarily seen in individuals of African, Mediterranean, or South Asian descent. *Bladder cancer* - **Bladder cancer** can cause painless hematuria, but it typically presents with **bladder lesions** on cystoscopy and biopsies show malignancy, not papillary necrosis or tubulointerstitial infiltrate. - The renal pathology here points to a problem originating in the kidneys, not the bladder. *Kidney stone* - **Kidney stones** usually present with **severe flank pain** (renal colic), and often hematuria, but the pain would be a prominent symptom. - A biopsy would show evidence of stone formation or obstruction, not tubulointerstitial infiltrate or papillary necrosis unless complicated by infection or obstruction.

Question 749: A 73-year-old female presents to you for an office visit with complaints of getting lost. The patient states that over the last several years, the patient has started getting lost in places that she is familiar with, like in her neighborhood while driving to her church. She also has difficulty remembering to pay her bills. She denies any other complaints. Her vitals are normal, and her physical exam does not reveal any focal neurological deficits. Her mini-mental status exam is scored 19/30. Work up for secondary causes of cognitive decline is negative. Which of the following should be included in the patient's medication regimen to slow the progression of disease?

• A. Pramipexole
• B. Pergolide
• C. Ropinirole
• D. Bromocriptine
• E. Memantine (Correct Answer)

Explanation: ***Memantine*** - Memantine is an **NMDA receptor antagonist** used to treat **moderate to severe Alzheimer's disease**, which aligns with the patient's symptoms of memory loss, disorientation, and cognitive decline (MMSE 19/30). - It works by **blocking the effects of excessive glutamate**, a neurotransmitter that, in high concentrations, can contribute to neuronal damage in Alzheimer's. *Pramipexole* - **Pramipexole** is a **dopamine agonist** primarily used to treat **Parkinson's disease** and restless legs syndrome. - It does not have an established role in treating the cognitive symptoms of Alzheimer's disease. *Pergolide* - **Pergolide** is a **dopamine agonist** that was previously used for Parkinson's disease but has been **withdrawn from the market** in many countries due to an increased risk of valvular heart disease. - It does not treat the cognitive decline associated with Alzheimer's disease. *Ropinirole* - **Ropinirole** is a **dopamine agonist** used in the treatment of **Parkinson's disease** and restless legs syndrome. - It is not indicated for the management of cognitive symptoms in Alzheimer's disease. *Bromocriptine* - **Bromocriptine** is a **dopamine agonist** used to treat Parkinson's disease and **hyperprolactinemia**. - It does not address the underlying pathology or symptoms of Alzheimer's disease.

Question 750: A 56-year-old woman comes to the emergency department because of a 3-day history of malaise, dysuria, blurred vision, and a painful, itchy rash. The rash began on her chest and face and spread to her limbs, palms, and soles. One week ago, she was diagnosed with trigeminal neuralgia and started on a new medicine. She appears ill. Her temperature is 38°C (100.4°F) and pulse is 110/min. Physical examination shows conjunctival injection and ulceration on the tongue and palate. There is no lymphadenopathy. Examination of the skin shows confluent annular, erythematous macules, bullae, and desquamation of the palms and soles. The epidermis separates when the skin is lightly stroked. Which of the following is the most likely diagnosis?

• A. Drug-induced lupus erythematosus
• B. DRESS syndrome
• C. Pemphigus vulgaris
• D. Stevens-Johnson syndrome (Correct Answer)
• E. Bullous pemphigoid

Explanation: ***Stevens-Johnson syndrome*** - The patient's symptoms, including **malaise**, **dysuria**, **blurred vision**, and a **painful, itchy rash** that began on the chest and face and spread to the limbs, palms, and soles, are highly suggestive of **Stevens-Johnson Syndrome (SJS)**. - The presence of **conjunctival injection**, **ulceration on the tongue and palate**, **confluent annular, erythematous macules, bullae, and desquamation of the palms and soles**, along with a **positive Nikolsky sign** (epidermis separates when skin is lightly stroked), and a recent history of starting a **new medication** for trigeminal neuralgia (likely an anticonvulsant, a common trigger for SJS), all strongly point to this diagnosis. *Drug-induced lupus erythematosus* - This condition typically presents with **arthralgias, myalgias, serositis, and malar rash**, often without the severe blistering, mucosal ulceration, and epidermal detachment seen here. - While drug-induced lupus can be triggered by medications, the **acute severe mucocutaneous and systemic manifestations** in this patient are not characteristic of lupus. *DRESS syndrome* - **DRESS (Drug Rash with Eosinophilia and Systemic Symptoms)** syndrome involves a rash, fever, **lymphadenopathy**, and **organ involvement** (e.g., hepatitis, nephritis). - The patient exhibits fever and rash, but the prominent **bullae, desquamation, severe mucosal involvement, and absence of lymphadenopathy** make SJS a more fitting diagnosis. *Pemphigus vulgaris* - This is an **autoimmune blistering disease** characterized by flaccid bullae and erosions on the skin and mucous membranes, with a positive Nikolsky sign. - However, pemphigus vulgaris is not typically associated with the acute onset, systemic symptoms (fever, malaise), and rapid progression seen after a new medication, which are hallmarks of **drug-induced SJS**. *Bullous pemphigoid* - Bullous pemphigoid presents with **tense bullae** in older individuals, often with **pruritus**, but usually **spares mucous membranes**. - The patient's widespread **mucosal involvement** (tongue, palate, conjunctiva) and **flaccid bullae with desquamation** are inconsistent with bullous pemphigoid.

Question 751: A 27-year-old woman presents for a checkup. She is 20 weeks pregnant and has been admitted to the hospital multiple times during her pregnancy for seizures. She has a known seizure disorder but discontinued her valproic acid when she became pregnant. The patient's past medical history is otherwise unremarkable. She does not smoke, drink alcohol, or use any drugs. She generally prefers not to take medications and sees a shaman for her care typically. Given her recent hospitalization, the patient agrees to start carbamazepine. Which of the following is the most appropriate treatment for this patient at this time?

• A. Vitamin B12
• B. Folate (Correct Answer)
• C. Iron
• D. Magnesium
• E. Vitamin D

Explanation: ***Folate*** - **Carbamazepine**, a common anti-epileptic drug (AED), is known to interfere with **folate metabolism**, making supplementation crucial during pregnancy. - Adequate **folate** intake is vital to prevent **neural tube defects** (NTDs) in the developing fetus, a risk exacerbated by AEDs like carbamazepine. *Vitamin B12* - While important for neurological health and red blood cell formation, **vitamin B12** deficiency is not directly caused or worsened by carbamazepine in a way that necessitates immediate supplementation more than folate in this context. - Routine B12 supplementation is not a primary recommendation for pregnant women on carbamazepine when compared to folate. *Iron* - **Iron** supplementation is commonly recommended during pregnancy to prevent **anemia**, but it is not specifically indicated for women on carbamazepine, nor does carbamazepine interfere with iron absorption significantly. - Although important, iron deficiency is a general obstetric concern rather than a specific interaction with carbamazepine. *Magnesium* - **Magnesium** is important for various bodily functions, including muscle and nerve function, but there is no direct interaction with **carbamazepine** that would necessitate its supplementation over other nutrients. - Magnesium is not primarily used to mitigate the adverse effects of carbamazepine or prevent congenital malformations. *Vitamin D* - There is some evidence that certain AEDs can affect **vitamin D metabolism** and bone health, but this is less critical than folate in preventing immediate, severe birth defects like NTDs. - While vitamin D supplementation may be beneficial in pregnancy, it does not address the most urgent risk associated with carbamazepine exposure during fetal development.

Question 752: A 34-year-old woman comes to the emergency department complaining of severe headache and anxiety, diaphoresis, and palpitations for the last 30 minutes. She has had several similar episodes over the past few weeks. She has no significant past medical history and has a 10 pack-year smoking history. She takes no illicit drugs. Her blood pressure on arrival is 181/80 mmHg and her pulse is 134/min. If this patient was given metoprolol, how would her blood pressure respond?

• A. Hypotension due to alpha-1-adrenergic receptor blockade
• B. Hypertension due to alpha-1-adrenergic receptor blockade
• C. Hypertension due to alpha- and beta-adrenergic receptor blockade
• D. Hypotension due to beta-adrenergic receptor blockade (Correct Answer)
• E. Hypertension due to alpha-1-adrenergic receptor stimulation

Explanation: ***Hypotension due to beta-adrenergic receptor blockade*** - The patient's symptoms (severe headache, anxiety, diaphoresis, palpitations, hypertension, and tachycardia) are highly suggestive of a **pheochromocytoma**, which releases excessive amounts of **norepinephrine** and **epinephrine**. - Metoprolol is a **selective beta-1 adrenergic receptor antagonist**. Blocking beta-1 receptors would counteract the effects of excess catecholamines on the heart (e.g., reducing heart rate and contractility), leading to a decrease in **cardiac output** and subsequently **blood pressure** (hypotension). *Hypotension due to alpha-1-adrenergic receptor blockade* - While alpha-1 antagonists can cause hypotension, metoprolol primarily blocks **beta-1 receptors**, not alpha-1 receptors. - Using an alpha-1 blocker alone in a pheochromocytoma crisis can lead to a reflex **tachycardia** due to unopposed beta stimulation, but the primary mechanism of hypotension from metoprolol is beta-blockade. *Hypertension due to alpha-1-adrenergic receptor blockade* - **Alpha-1 blockade** typically leads to **vasodilation** and **hypotension**, not hypertension. This option misaligns the effect of alpha-1 blockade with the outcome. - Metoprolol does not block alpha-1 receptors, so this mechanism is not relevant to metoprolol's action. *Hypertension due to alpha- and beta-adrenergic receptor blockade* - This statement is incorrect because simultaneous blockade of both alpha and beta receptors (e.g., with labetalol) would primarily lead to a **reduction in blood pressure**, although the immediate effect of *unselective* beta blockade in a pheochromocytoma (due to unopposed alpha-1 vasoconstriction) can initially worsen hypertension if not preceded by alpha blockade. - Metoprolol does not block alpha receptors, making this explanation inaccurate for the drug in question. *Hypertension due to alpha-1-adrenergic receptor stimulation* - Metoprolol is a **beta-adrenergic receptor blocker**, not an alpha-1 adrenergic receptor stimulator. Stimulation of alpha-1 receptors would indeed cause **vasoconstriction** and hypertension, but this is the opposite of metoprolol's action. - In an unblocked pheochromocytoma crisis, there is already significant alpha-1 stimulation from excess catecholamines. Metoprolol's action would be to block beta-receptors, which could indirectly lead to *unopposed alpha-1 stimulation* if used alone without alpha blockade, but the drug itself does not stimulate alpha-1 receptors.

Question 753: A 43-year-old woman comes to the physician with a 2-week history of new pruritic plaques on the scalp and extensor surfaces of the elbows and knees. Ten years ago, she was diagnosed with psoriasis. Her only medication is topical calcipotriene. Physical examination shows well-demarcated, symmetrical, erythematous plaques with silvery scale. There is pitting of the nails on all fingers. Therapy with a high-potency topical medication that inhibits NF-κB and phospholipase A2 is begun. Long-term use of this agent is most likely to result in which of the following?

• A. Hair growth on upper lip
• B. Dermal collagen loss (Correct Answer)
• C. Nonblanchable pinpoint macules
• D. Dysplastic nevi
• E. Decreased sebum production

Explanation: ***Dermal collagen loss*** - This patient is being treated with a **high-potency topical corticosteroid**. Long-term use of such medications can lead to **atrophy of the skin**, characterized by thinning due to loss of collagen and elastic fibers. - Clinical manifestations of dermal collagen loss include **skin thinning, striae, telangiectasias, and easy bruising**. *Hair growth on upper lip* - **Hirsutism**, or excessive hair growth, is typically associated with systemic corticosteroid use or conditions causing androgen excess, not commonly with topical corticosteroids applied to the scalp and extensor surfaces. - While systemic absorption can occur, it's less likely to cause localized hirsutism on the upper lip compared to other systemic side effects. *Nonblanchable pinpoint macules* - **Petechiae**, which are nonblanchable pinpoint macules, are usually indicative of capillary bleeding and can be a side effect of prolonged corticosteroid use due to skin thinning and fragility. - However, **dermal collagen loss** is a more direct and fundamental structural change leading to the overall skin atrophy and fragility seen with long-term topical steroid use. *Dysplastic nevi* - **Dysplastic nevi** are atypical moles that can be precursors to melanoma and are primarily linked to genetic factors and sun exposure, not a direct side effect of topical corticosteroid use. - Topical corticosteroids do not have a known association with the development of dysplastic nevi or increased risk of melanoma. *Decreased sebum production* - Topical corticosteroids do not significantly alter **sebum production**. In fact, they can sometimes promote **steroid acne**, which involves follicular changes rather than a decrease in sebum. - **Sebum production** is primarily regulated by hormonal factors, particularly androgens.

Question 754: A 52-year-old woman status-post liver transplant presents to her transplant surgeon because she has noticed increased urination over the last 3 weeks. Six months ago she received a liver transplant because of fulminant liver failure after viral hepatitis. Since then, she has noticed that she has been drinking more water and urinating more. Her husband has also noticed that she has been eating a lot more. She says that she never had these symptoms prior to her transplant and has been taking her medications on time. After confirmatory tests, she is started on a medication that binds to an ATP-gated potassium channel. The drug that increases the risk of the complication experienced by this patient most likely has which of the following mechanisms of action?

• A. Targeting the a-chain of the IL-2 receptor
• B. Conversion into 6-mercaptopurine
• C. Inosine monophosphate dehydrogenase inhibitor
• D. Binding to FKBP-12 to inhibit calcineurin (Correct Answer)
• E. Binding to cyclophilin A to inhibit calcineurin

Explanation: ***Binding to FKBP-12 to inhibit calcineurin*** - The patient's symptoms of **increased urination, thirst (polydipsia), and appetite (polyphagia)**, especially after an organ transplant, are highly suggestive of **new-onset diabetes mellitus (NODM)**, a known complication of immunosuppressive therapy. - **Tacrolimus**, a calcineurin inhibitor given post-transplant, binds to **FKBP-12** and is known to cause **NODM** by impairing insulin secretion and increasing insulin resistance. *Binding to cyclophilin A to inhibit calcineurin* - This describes the mechanism of **cyclosporine**, another calcineurin inhibitor, which also causes NODM. However, given the context of a drug binding to an **ATP-gated potassium channel** to treat the complication, the question is asking about the mechanism of the *original* drug that caused the diabetes, not the treatment. - While cyclosporine does inhibit calcineurin, the specific binding protein mentioned (FKBP-12) points more directly to tacrolimus, which is a stronger contributor to NODM. *Targeting the a-chain of the IL-2 receptor* - This mechanism describes **basiliximab** and **daclizumab**, which are anti-CD25 antibodies used for **induction therapy** in transplant patients. - These drugs are generally associated with a lower risk of diabetes compared to calcineurin inhibitors and are not typically the sole maintenance immunosuppressants causing such a prominent side effect. *Inosine monophosphate dehydrogenase inhibitor* - This mechanism belongs to **mycophenolate mofetil (MMF)**, an immunosuppressant commonly used in transplant patients. - While MMF has various side effects, **new-onset diabetes** is less commonly associated with it compared to calcineurin inhibitors. *Conversion into 6-mercaptopurine* - This describes the mechanism of **azathioprine**, another immunosuppressant widely used in transplantation. - Azathioprine is primarily associated with **bone marrow suppression** and **gastrointestinal side effects**, with **new-onset diabetes** being a rare complication compared to calcineurin inhibitors.

Question 755: A 33-year-old woman presents with weight gain and marks on her abdomen (as seen in the image below). She does not have any significant past medical history. She is a nonsmoker and denies any alcohol use. Her blood pressure is 160/110 mm Hg and pulse is 77/min. A T1/T2 MRI of the head shows evidence of a pituitary adenoma, and she undergoes surgical resection of the tumor. Which of the following therapies is indicated in this patient to ensure normal functioning of her hypothalamic-pituitary-adrenal (HPA) axis?

• A. Hydrocortisone (Correct Answer)
• B. Fludrocortisone
• C. Methotrexate
• D. Bilateral adrenalectomy
• E. Mometasone

Explanation: ***Hydrocortisone*** - This patient presents with signs and symptoms consistent with **Cushing's syndrome** (weight gain, hypertension, striae), likely caused by a **pituitary adenoma** (Cushing's disease). - Following surgical resection of a pituitary adenoma causing Cushing's disease, the chronically suppressed adrenal glands may not immediately resume normal **cortisol production**. Therefore, **glucocorticoid replacement therapy** (e.g., hydrocortisone) is crucial to prevent acute adrenal insufficiency, gradually tapered as the HPA axis recovers. *Fludrocortisone* - **Fludrocortisone** is a potent synthetic **mineralocorticoid** primarily used to treat conditions associated with mineralocorticoid deficiency, such as Addison's disease or congenital adrenal hyperplasia. - While it can be used for adrenal insufficiency, this patient's primary need after pituitary surgery for Cushing's disease is **glucocorticoid replacement** for suppressed cortisol production, not mineralocorticoid effects unless specifically determined to be deficient. *Methotrexate* - **Methotrexate** is an **immunosuppressant** and **chemotherapeutic agent** used in conditions like cancer, rheumatoid arthritis, and psoriasis. - It has no role in the management of pituitary adenomas or the restoration of HPA axis function post-surgical resection. *Bilateral adrenalectomy* - **Bilateral adrenalectomy** is a surgical procedure to remove both adrenal glands, used in cases of intractable Cushing's syndrome where other treatments have failed. - While it effectively reduces cortisol, it induces permanent **adrenal insufficiency**, requiring lifelong glucocorticoid and mineralocorticoid replacement, and is typically a last resort, not the initial post-surgical therapy for a resected pituitary adenoma. *Mometasone* - **Mometasone** is a **synthetic corticosteroid** primarily used topically (e.g., for skin conditions or asthma) for its anti-inflammatory effects. - It is not an appropriate systemic therapy for replacing cortisol and supporting HPA axis recovery after pituitary surgery due to its different potency and formulation.

Question 756: A 4-year-old boy presents to the Emergency Department with wheezing and shortness of breath after playing with the new family pet. Which of the following immunological factors is most involved in generating the antibodies necessary for mast cell Fc-receptor cross-linking and degranulation?

• A. IL-5
• B. IL-13
• C. IL-2
• D. IL-4 (Correct Answer)
• E. IL-10

Explanation: **IL-4** - **IL-4** is a primary cytokine responsible for promoting **Th2 differentiation** and inducing **B cell class switching to IgE**, which is critical for allergic reactions. - The IgE antibodies then bind to **Fc receptors on mast cells**, leading to cross-linking and degranulation upon re-exposure to the allergen. *IL-5* - **IL-5** is primarily involved in the growth, differentiation, and activation of **eosinophils**, which are important in late-phase allergic reactions and parasitic infections. - While it plays a role in allergic inflammation, it does not directly drive the production of IgE antibodies crucial for initial mast cell sensitization. *IL-13* - **IL-13** shares many functions with IL-4, including promoting **IgE production** and contributing to airway hyperresponsiveness and mucus secretion in asthma. - However, **IL-4** is considered the foundational cytokine for initial IgE class switching, even though IL-13 can synergize or contribute later. *IL-2* - **IL-2** is primarily known for its role in the **proliferation and differentiation of T cells**, including regulatory T cells, and general immune activation. - It does not directly promote B cell class switching to IgE or directly induce allergic antibody production. *IL-10* - **IL-10** is an **immunosuppressive cytokine** that *inhibits* the production of pro-inflammatory cytokines and can downregulate immune responses. - Its role is generally to *suppress* allergic responses rather than generate the antibodies (IgE) necessary for mast cell degranulation.

Question 757: A 62-year-old woman is brought to the emergency room at a nearby hospital after being involved in a roadside accident in which she sustained severe chest trauma. Enroute to the hospital, morphine is administered for pain control. Upon arrival, the patient rapidly develops respiratory failure and requires intubation and mechanical ventilation. She is administered pancuronium in preparation for intubation but suddenly develops severe bronchospasm and wheezing. Her blood pressure also quickly falls from 120/80 mm Hg to 100/60 mm Hg. Which of the following best explains the most likely etiology of this complication?

• A. Autonomic stimulation
• B. Histamine release (Correct Answer)
• C. Underlying neuromuscular disease
• D. Drug interaction
• E. Skeletal muscle paralysis

Explanation: ***Histamine release*** - In this clinical scenario, the **bronchospasm, wheezing, and hypotension** occurring after drug administration suggest **histamine release**. - **Morphine** (administered enroute) is well-known to cause **direct histamine release** from mast cells, which can lead to bronchospasm, hypotension, and urticaria. - While **pancuronium** itself has **minimal histamine-releasing properties** (unlike atracurium, mivacurium, or tubocurarine), the combination of morphine-induced histamine release followed by the stress of intubation preparation may have precipitated this **anaphylactoid reaction**. - The temporal relationship and clinical presentation are most consistent with a **histamine-mediated adverse effect**. *Autonomic stimulation* - Pancuronium has **vagolytic (antimuscarinic) effects** that typically cause **tachycardia and increased blood pressure**, not hypotension and bronchospasm. - While autonomic responses can influence respiratory and cardiovascular function, they do not explain the acute bronchospasm and hypotension seen here. *Underlying neuromuscular disease* - Neuromuscular diseases affect the response to neuromuscular blockers by altering receptor numbers or function (e.g., prolonged paralysis in myasthenia gravis, resistance in denervation injuries). - They do not cause acute bronchospasm and hypotension with drug administration. *Drug interaction* - While morphine and pancuronium can both be used together safely in anesthesia, there is no specific pharmacokinetic or pharmacodynamic interaction between them that would precipitate this severe reaction. - The clinical presentation is more consistent with a direct pharmacological effect (histamine release) rather than a drug interaction. *Skeletal muscle paralysis* - Pancuronium's primary effect is **skeletal muscle paralysis** by blocking nicotinic acetylcholine receptors at the neuromuscular junction. - Muscle paralysis itself does not cause bronchospasm, wheezing, or hypotension; these are adverse effects related to histamine release or other pharmacological mechanisms.

Question 758: A 45-year-old man is brought into the emergency department after he was hit by a car. The patient was intoxicated and walked into oncoming traffic. He is currently unconscious and has a Glasgow coma scale score of 3. The patient has been admitted multiple times for alcohol intoxication and pancreatitis. The patient is resuscitated with fluid and blood products. An initial trauma survey reveals minor scrapes and abrasions and pelvic instability. The patient’s pelvis is placed in a binder. After further resuscitation the patient becomes responsive and states he is in pain. He is given medications and further resuscitation ensues. One hour later, the patient complains of numbness surrounding his mouth and in his extremities. Which of the following is the most likely explanation of this patient’s current symptoms?

• A. Transfusion complication (Correct Answer)
• B. Trauma to the spinal cord
• C. Hypokalemia
• D. Medication complication
• E. Late-onset edema surrounding the spinal cord

Explanation: ***Transfusion complication*** - The patient's symptoms of **perioral numbness** and **extremity paresthesias** after massive transfusion are highly suggestive of **citrate toxicity**. Citrate, used as an anticoagulant in blood products, can chelate calcium and magnesium, leading to **hypocalcemia** and **hypomagnesemia**. - This is exacerbated by **hypothermia**, **liver dysfunction** (common in chronic alcoholics), and **rapid transfusion rates**, all of which can impair citrate metabolism. *Trauma to the spinal cord* - While spinal cord injury can cause numbness and paresthesias, it typically presents with a **dermatomal distribution** or clear sensory level, and often motor deficits. - The described numbness around the mouth and general extremity involvement is less typical for a focal spinal cord injury. *Hypokalemia* - **Hypokalemia** can cause muscle weakness, cramps, and cardiac arrhythmias, but **paresthesias** and **perioral numbness** are not classic symptoms. - The presenting symptoms are more consistent with electrolyte disturbances involving calcium or magnesium. *Medication complication* - While medications can cause side effects, the specific constellation of **perioral paresthesia** and **extremity numbness** following massive transfusion points strongly to **citrate toxicity** rather than a generic medication reaction. - The context of **massive transfusion** makes a direct link to transfusion-related electrolyte shifts far more probable. *Late-onset edema surrounding the spinal cord* - Acute spinal cord edema causing neurological symptoms would typically manifest with more localized, dermatomal deficits and potentially motor weakness. - The rapid onset of widespread paresthesias and perioral numbness is not a typical presentation of delayed spinal cord edema.

Question 759: A 37-year-old woman is brought to the emergency department by police after being found naked outside a government building. She is accompanied by her husband who reports that she has been having "crazy" ideas. The patient's speech is pressured and she switches topics quickly from how she is going to be president one day to how she is going to learn 20 languages fluently by the end of the year. Upon further questioning, it is revealed that she has struggled with at least 2 depressive episodes in the past year. Her medical history is significant for hypertension, hyperlipidemia, gout, and chronic migraines. She was recently diagnosed with a urinary tract infection and given nitrofurantoin. She has also been taking indomethacin for an acute gout flare. Her other medications include atorvastatin, allopurinol, metoprolol, and acetazolamide. She is prescribed lithium and instructed to follow-up with a primary care physician. At a follow-up appointment, she complains of nausea, vomiting, and increased urinary frequency. On examination, she has a coarse tremor and diffuse hyperreflexia. Which of the following medications is most likely responsible for the patient's current presentation?

• A. Nitrofurantoin
• B. Indomethacin (Correct Answer)
• C. Acetazolamide
• D. Metoprolol
• E. Atorvastatin

Explanation: ***Indomethacin*** - This patient is likely experiencing **lithium toxicity**, characterized by nausea, vomiting, increased urinary frequency, coarse tremor, and hyperreflexia. **NSAIDs** like indomethacin can decrease renal lithium clearance, leading to elevated lithium levels and toxicity. - **Lithium** is primarily cleared by the kidneys, and NSAIDs inhibit prostaglandin-mediated renal vasodilation, thus reducing **glomerular filtration rate** and increasing lithium reabsorption in the renal tubules. *Nitrofurantoin* - This antibiotic is used for **urinary tract infections** and is generally well-tolerated. - It is not known to significantly interact with lithium to cause toxicity or the presented symptoms. *Acetazolamide* - This **carbonic anhydrase inhibitor** actually increases lithium excretion. - It would typically cause a *decrease* in lithium levels, making lithium toxicity less likely. *Metoprolol* - This **beta-blocker** primarily affects the cardiovascular system. - It does not have a significant interaction with lithium that would lead to increased lithium levels or toxicity. *Atorvastatin* - This **statin** is used to lower cholesterol. - It is not known to interact with lithium or cause the symptoms of lithium toxicity described.

Question 760: A 9-year-old boy is brought to the emergency department by his mother because of painful swelling in his right knee that started after he collided with another player during a soccer game. He has no history of serious illness except for an episode of prolonged bleeding following a tooth extraction a few months ago. Physical examination shows marked tenderness and swelling of the right knee joint. There are multiple bruises on the lower extremities in various stages of healing. Laboratory studies show a platelet count of 235,000/mm3, partial thromboplastin time of 78 seconds, prothrombin time of 14 seconds, and bleeding time of 4 minutes. The plasma concentration of which of the following is most likely to be decreased in this patient?

• A. Plasmin
• B. Factor VII
• C. Protein C
• D. Thrombin
• E. Von Willebrand factor (Correct Answer)

Explanation: ***Von Willebrand factor*** - The patient's history of **prolonged bleeding** after a tooth extraction, **joint hemorrhage** (hemarthrosis) after minor trauma, and **multiple bruises** are classic signs of a **coagulation disorder**. - The laboratory results showing a **normal platelet count**, **normal prothrombin time (PT)**, **normal bleeding time**, and **prolonged partial thromboplastin time (PTT)** are highly suggestive of **hemophilia A or B**, or **severe von Willebrand disease (VWD)**. However, considering the typical presentation (hemarthrosis) of hemophilia and knowing that vWF is a carrier of factor VIII, severe vWD is the most common hereditary bleeding disorder. - Severe VWD can cause sufficiently low Factor VIII levels to result in a prolonged PTT. *Plasmin* - **Plasmin** is involved in fibrinolysis (breaking down clots) and is not directly related to the **prolonged PTT** seen in this patient. - A decrease in plasmin would typically lead to a **pro-thrombotic state**, not a bleeding disorder. *Factor VII* - **Factor VII** is part of the **extrinsic coagulation pathway**. A deficiency in Factor VII would primarily prolong the **prothrombin time (PT)**, not the PTT. - This patient has a normal PT, making Factor VII deficiency unlikely. *Protein C* - **Protein C** is a natural anticoagulant that inactivates coagulation factors Va and VIIIa. - A deficiency in Protein C would lead to a **hypercoagulable state** (increased risk of clotting), which contradicts the patient's bleeding symptoms. *Thrombin* - **Thrombin** is a key enzyme in the coagulation cascade that converts fibrinogen to fibrin. - While overall coagulation is impaired in this patient, the individual measurement of thrombin concentration is not directly indicated by the prolonged PTT. A low factor VIII (which can be caused by low vWF) is primarily responsible for the prolonged PTT.

Question 761: A 5-year-old boy is brought to the physician by his parents for the evaluation of an episode of loss of consciousness while he was playing soccer earlier that morning. He was unconscious for about 15 seconds and did not shake, bite his tongue, or lose bowel or bladder control. He has been healthy except for 1 episode of simple febrile seizure. His father died suddenly at the age of 34 of an unknown heart condition. The patient does not take any medications. He is alert and oriented. His temperature is 37°C (98.6°F), pulse is 95/min and regular, and blood pressure is 90/60 mm Hg. Physical examination shows no abnormalities. Laboratory studies are within normal limits. An ECG shows sinus rhythm and a QT interval corrected for heart rate (QTc) of 470 milliseconds. Which of the following is the most appropriate next step in treatment?

• A. Propranolol (Correct Answer)
• B. Implantable cardioverter defibrillator
• C. Amiodarone
• D. Procainamide
• E. Magnesium sulfate

Explanation: ***Propranolol*** - This patient presents with **syncope during exertion** and a **prolonged QTc (470 ms)**, coupled with a **family history of sudden cardiac death**. These signs are highly suggestive of **Long QT Syndrome (LQTS)**. - **Beta-blockers**, such as propranolol, are the **first-line treatment** for LQTS to prevent life-threatening arrhythmias by attenuating adrenergic stimulation. *Implantable cardioverter defibrillator* - An **ICD** is typically reserved for LQTS patients who have experienced **cardiac arrest**, have recurrent syncope despite beta-blocker therapy, or are at very high risk for sudden cardiac death. - While it may be considered in severe cases, it is **not the initial management step** for a newly diagnosed, stable patient. *Amiodarone* - **Amiodarone** is an antiarrhythmic drug known to **prolong the QT interval**, making it **contraindicated in LQTS** as it could worsen the condition and increase the risk of Torsades de Pointes. - Its use is generally reserved for other types of refractory arrhythmias. *Procainamide* - **Procainamide** is a Class IA antiarrhythmic agent that also **prolongs the QT interval** and is associated with a risk of Torsades de Pointes. - It would be **inappropriate and potentially harmful** in a patient with LQTS. *Magnesium sulfate* - **Magnesium sulfate** is the treatment of choice for **Torsades de Pointes**, especially when associated with hypomagnesemia or drug-induced QT prolongation. - While LQTS can lead to Torsades, magnesium sulfate is not indicated as a primary prophylactic treatment for stable LQTS.

Question 762: A 61-year-old woman presents to her physician with foot tingling, numbness, and pain. She describes her pain as constant and burning and gives it 5 out of 10 on the visual analog pain scale. She also recalls several falls due to the numbness in her feet. She was diagnosed with diabetes mellitus and diabetic retinopathy 5 years ago. Since then, she takes metformin 1000 mg twice daily and had no follow-up visits to adjust her therapy. Her weight is 110 kg (242.5 lb), and her height is 176 cm (5 ft. 7 in). The vital signs are as follows: blood pressure is 150/90 mm Hg, heart rate is 72/min, respiratory rate is 12/min, and the temperature is 36.6°C (97.9°F). The patient has increased adiposity in the abdominal region with stretch marks. The respiratory examination is within normal limits. The cardiovascular exam is significant for a bilateral carotid bruit. The neurological examination shows bilateral decreased ankle reflex, symmetrically decreased touch sensation and absent vibration sensation in both feet up to the ankle. The gait is mildly ataxic. The Romberg test is positive with a tendency to fall to both sides, and significant worsening on eye closure. Which of the following medications should be used to manage the patient’s pain?

• A. Topiramate
• B. Nortriptyline (Correct Answer)
• C. Morphine
• D. Tramadol
• E. Diclofenac

Explanation: ***Nortriptyline*** - **Diabetic peripheral neuropathy (DPN)** is characterized by **neuropathic pain**, for which tricyclic antidepressants (TCAs) like nortriptyline are considered **first-line agents** due to their efficacy in modulating chronic pain pathways. - The patient's symptoms of **burning pain**, numbness, tingling, and sensory deficits in a "stocking-glove" distribution are characteristic of DPN, making TCAs an appropriate choice for symptom management. *Topiramate* - Primarily used for **epilepsy** and **migraine prophylaxis**, topiramate is not a first-line treatment for diabetic peripheral neuropathy pain. - It carries a risk of significant side effects like **cognitive impairment** and **renal calculi**, which may not be well-tolerated in this patient with multiple comorbidities. *Morphine* - While effective for severe pain, **long-term opioid use** like morphine for chronic neuropathic pain is generally discouraged due to risks of **dependence**, addiction, and side effects like constipation and respiratory depression. - Opioids are usually reserved for cases refractory to other treatments or for acute severe pain. *Tramadol* - Tramadol is an **opioid analgesic** with additional serotonin and norepinephrine reuptake inhibition properties, offering some benefit in neuropathic pain. - However, similar to other opioids, it carries risks of **dependence** and **serotonin syndrome** when combined with other serotonergic agents (though none are specified here), and it is generally not a first-line agent for chronic DPN. *Diclofenac* - Diclofenac is a **non-steroidal anti-inflammatory drug (NSAID)** primarily used for inflammatory and nociceptive pain, not neuropathic pain. - It is ineffective for the **burning, tingling, and numbness** associated with nerve damage and poses risks of **gastrointestinal bleeding** and **cardiovascular events**, especially in an older patient with hypertension.

Question 763: A 59-year-old female presents to the emergency department after a fall. She reports severe pain in her right hip and an inability to move her right leg. Her past medical history is notable for osteoporosis, rheumatoid arthritis, and has never undergone surgery before. The patient was adopted, and her family history is unknown. She has never smoked and drinks alcohol socially. Her temperature is 98.8°F (37.1°C), blood pressure is 150/90 mmHg, pulse is 110/min, and respirations are 22/min. Her right leg is shortened, abducted, and externally rotated. A radiograph demonstrates a displaced femoral neck fracture. She is admitted and eventually brought to the operating room to undergo right hip arthroplasty. While undergoing induction anesthesia with inhaled sevoflurane, she develops severe muscle contractions. Her temperature is 103.4°F (39.7°C). A medication with which of the following mechanisms of action is indicated in the acute management of this patient’s condition?

• A. Ryanodine receptor antagonist (Correct Answer)
• B. Acetylcholine receptor agonist
• C. Serotonin 1B/1D agonist
• D. NMDA receptor antagonist
• E. GABA agonist

Explanation: ***Ryanodine receptor antagonist*** - The patient's presentation with **high fever**, **muscle rigidity**, and **tachycardia** shortly after induction with **sevoflurane** is highly suggestive of **malignant hyperthermia (MH)**. - **Dantrolene**, a **ryanodine receptor antagonist**, is the specific treatment for MH, as it blocks the excessive release of **calcium** from the sarcoplasmic reticulum in muscle cells. *Acetylcholine receptor agonist* - **Acetylcholine receptor agonists** (e.g., succinylcholine) stimulate muscle contraction and would worsen the muscle rigidity seen in malignant hyperthermia. - These agents are often triggers for malignant hyperthermia when combined with volatile anesthetics. *Serotonin 1B/1D agonist* - **Serotonin 1B/1D agonists** (e.g., triptans) are primarily used in the acute treatment of migraines. - They have no role in the management of malignant hyperthermia and would not address the underlying pathophysiology. *NMDA receptor antagonist* - **NMDA receptor antagonists** (e.g., ketamine) are dissociative anesthetics and analgesics. - They do not directly affect the calcium release channels in skeletal muscle responsible for malignant hyperthermia. *GABA agonist* - **GABA agonists** (e.g., benzodiazepines, propofol) are central nervous system depressants used for sedation and anesthesia. - While they can have muscle relaxant properties, they do not specifically target the **ryanodine receptor** pathway involved in malignant hyperthermia.

Question 764: A previously healthy 52-year-old woman comes to the physician because of a 3-month history of chest pain on exertion. She takes no medications. Cardiopulmonary examination shows no abnormalities. Cardiac stress ECG shows inducible ST-segment depressions in the precordial leads that coincide with the patient's report of chest pain and resolve upon cessation of exercise. Pharmacotherapy with verapamil is initiated. This drug is most likely to have which of the following sets of effects? $$$ End-diastolic volume (EDV) %%% Blood pressure (BP) %%% Contractility %%% Heart rate (HR) $$$

• A. No change no change no change no change
• B. ↓ ↓ no change ↑
• C. ↓ ↓ ↓ ↑
• D. ↓ ↓ ↓ no change
• E. ↑ ↓ ↓ ↓ (Correct Answer)

Explanation: ***↑ ↓ ↓ ↓*** - **Verapamil**, a **non-dihydropyridine calcium channel blocker**, reduces **cardiac contractility**, leading to decreased **heart rate** and **blood pressure**, while increasing **end-diastolic volume**. - Its therapeutic effect in **exertional angina** is primarily due to reduced myocardial oxygen demand, achieved by decreasing **heart rate**, **contractility** (both leading to reduced work of heart), and **afterload** (due to vasodilation which decreases blood pressure). *No change no change no change no change* - This option is incorrect because verapamil has significant **pharmacological effects** on the cardiovascular system. - Verapamil is prescribed to treat the patient's symptoms, implying a need for **hemodynamic changes**, not stasis. *↓ ↓ no change ↑* - Verapamil typically **decreases heart rate** due to its action on the sinoatrial (SA) node, making an increase unlikely. - While it decreases **blood pressure** and **contractility**, the absence of an effect on heart rate and an increase in heart rate are inconsistent with verapamil's known pharmacology. *↓ ↓ ↓ ↑* - This option incorrectly suggests an **increase in heart rate**, whereas verapamil is known to cause a dose-dependent **decrease in heart rate**. - The other parameters (decreased EDV, BP, contractility) are also not fully aligned with verapamil's effects; EDV tends to increase due to better filling time and reduced contractility. *↓ ↓ ↓ no change* - This option suggests a **decrease in EDV**, which is generally incorrect; verapamil tends to allow for **increased ventricular filling** due to a reduced heart rate and prolonged diastole. - The absence of a change in heart rate is also incorrect, as verapamil is a known **negative chronotropic agent**.

Question 765: A 35-year-old woman is brought to the emergency department 30 minutes after the onset of severe dyspnea. On arrival, she is unresponsive. Her pulse is 160/min, respirations are 32/min, and blood pressure is 60/30 mm Hg. CT angiography of the chest shows extensive pulmonary embolism in both lungs. She is given a drug that inhibits both thrombin and factor Xa. Which of the following medications was most likely administered?

• A. Fondaparinux
• B. Ticagrelor
• C. Unfractionated heparin (Correct Answer)
• D. Apixaban
• E. Tenecteplase

Explanation: ***Unfractionated heparin*** - **Unfractionated heparin** inhibits both **thrombin (factor IIa)** and **factor Xa** by binding to **antithrombin III**, which then inactivates these coagulation factors. - Given the patient's severe, life-threatening **pulmonary embolism** with **hemodynamic instability** (shock, unresponsive, severe hypotension), rapid-acting intravenous unfractionated heparin is the anticoagulant of choice for immediate effect. *Fondaparinux* - **Fondaparinux** is a synthetic **pentasaccharide** that selectively inhibits **factor Xa** but does not directly inhibit thrombin. - It is typically administered subcutaneously and has a slower onset of action compared to intravenous unfractionated heparin, making it less suitable for emergent, life-threatening situations where immediate full anticoagulation is critical. *Ticagrelor* - **Ticagrelor** is an **oral antiplatelet agent** that works by inhibiting the P2Y12 receptor on platelets, preventing platelet aggregation. - It does not inhibit thrombin or factor Xa and is primarily used in acute coronary syndromes to prevent arterial thrombosis, not for acute treatment of venous thromboembolism like pulmonary embolism. *Apixaban* - **Apixaban** is an **oral direct factor Xa inhibitor** that does not inhibit thrombin. - While effective for venous thromboembolism, its oral administration means a slower onset of action and it is generally not used as the initial anticoagulant for hemodynamically unstable pulmonary embolism where immediate, titratable intravenous anticoagulation is required. *Tenecteplase* - **Tenecteplase** is a **fibrinolytic (thrombolytic) agent** that works by converting plasminogen to plasmin, leading to the breakdown of fibrin clots. - While it is a treatment option for massive pulmonary embolism with hemodynamic instability, it is not an anticoagulant and does not inhibit thrombin or factor Xa; its mechanism of action is clot lysis, not preventing new clot formation via coagulation factor inhibition.

Question 766: A drug discovery team is conducting research to observe the characteristics of a novel drug under different experimental conditions. The drug is converted into the inactive metabolites by an action of an enzyme E. After multiple experiments, the team concludes that as compared to physiologic pH, the affinity of the enzyme E for the drug decreases markedly in acidic pH. Co-administration of an antioxidant A increases the value of Michaelis-Menten constant (Km) for the enzyme reaction, while co-administration of a drug B decreases the value of Km. Assume the metabolism of the novel drug follows Michaelis-Menten kinetics at the therapeutic dose, and that the effects of different factors on the metabolism of the drug are first-order linear. For which of the following conditions will the metabolism of the drug be the slowest?

• A. Acidic pH, co-administration of antioxidant A and of drug B
• B. Acidic pH, co-administration of antioxidant A, no administration of drug B (Correct Answer)
• C. Physiologic pH, co-administration of antioxidant A, no administration of drug B
• D. Acidic pH, co-administration of drug B, no administration of antioxidant A
• E. Acidic pH, without administration of antioxidant A or drug B

Explanation: ***Acidic pH, co-administration of antioxidant A, no administration of drug B*** - **Decreased affinity** at acidic pH reduces the enzyme's ability to bind the drug, slowing metabolism. - Co-administration of **antioxidant A increases Km**, indicating a further reduction in enzyme affinity and thus slower metabolism. *Acidic pH, co-administration of antioxidant A and of drug B* - While acidic pH and antioxidant A slow metabolism, co-administration of **drug B decreases Km**, which would increase enzyme affinity and counteract the slowing effect to some extent. - The combination would result in a slower metabolism than baseline, but likely not the slowest possible due to the partially opposing effects of A and B. *Physiologic pH, co-administration of antioxidant A, no administration of drug B* - At **physiologic pH**, the enzyme's affinity for the drug is higher than at acidic pH, promoting faster metabolism. - Although antioxidant A increases Km, the favorable pH for enzyme activity means metabolism will not be as slow as under acidic conditions. *Acidic pH, co-administration of drug B, no administration of antioxidant A* - **Acidic pH** reduces enzyme affinity, slowing metabolism. - However, the co-administration of **drug B decreases Km**, which increases enzyme affinity and would partially offset the reduced affinity caused by the acidic pH, leading to a faster metabolism compared to when antioxidant A is present. *Acidic pH, without administration of antioxidant A or drug B* - At **acidic pH**, the enzyme's affinity for the drug decreases, which slows metabolism. - However, in this condition, there are no additional factors (like antioxidant A) further increasing Km, nor factors (like drug B) decreasing Km, so the metabolic rate would be slower than physiologic pH but not as slow as when antioxidant A is also present.

Question 767: A 75-year-old man with a 35-pack-year history of smoking is found to be lethargic three days after being admitted with a femur fracture following a motor vehicle accident. His recovery has been progressing well thus far, though pain continued to be present. On exam, the patient is minimally responsive with pinpoint pupils. Vital signs are blood pressure of 115/65 mmHg, HR 80/min, respiratory rate 6/min, and oxygen saturation of 87% on room air. Arterial blood gas (ABG) shows a pH of 7.24 (Normal: 7.35-7.45), PaCO2 of 60mm Hg (normal 35-45mm Hg), a HCO3 of 23 mEq/L (normal 21-28 mEq/L) and a Pa02 of 60 mmHg (normal 80-100 mmHg). Which of the following is the most appropriate therapy at this time?

• A. Naloxone (Correct Answer)
• B. Heparin
• C. Glucocorticoids
• D. Repeat catheterization
• E. Emergent cardiac surgery

Explanation: ***Naloxone*** - The patient's presentation with **lethargy**, pinpoint pupils, **respiratory depression** (RR 6/min, low PaO2, high PaCO2), and recent use of pain medication for a fracture strongly suggests **opioid overdose**. - **Naloxone** is a **mu-opioid receptor antagonist** that rapidly reverses the effects of opioid overdose, including respiratory depression and CNS depression. *Heparin* - This patient does not exhibit classic signs or symptoms of a **thromboembolic event** such as deep vein thrombosis (DVT) or pulmonary embolism (PE), which would warrant heparin administration. - While a femur fracture increases DVT risk, the primary and acute issue is severe **respiratory depression** and altered mental status. *Glucocorticoids* - **Glucocorticoids** are used for inflammatory conditions, allergic reactions, or adrenal insufficiency, none of which are indicated by the patient's acute presentation. - They would not address the immediate life-threatening respiratory depression and altered mental status. *Repeat catheterization* - There is no clinical information suggesting a primary **cardiac event** that would necessitate a repeat cardiac catheterization. - The patient's symptoms are neurological and respiratory, not cardiac in origin. *Emergent cardiac surgery* - The patient's presentation does not point to an acute cardiac emergency requiring **surgery**, such as aortic dissection or massive myocardial infarction with mechanical complications. - The primary problem is an acute drug toxicity causing respiratory and CNS depression.

Question 768: A 64-year-old man is brought to the emergency department because of dull lower abdominal pain for 3 hours. He has not urinated for 24 hours and has not passed stool for over 3 days. He was diagnosed with herpes zoster 4 weeks ago and continues to have pain even after his rash resolved. He has hypertension, benign prostatic hyperplasia, and coronary artery disease. Physical examination shows a tender, palpable suprapubic mass. Bowel sounds are hypoactive. Abdominal ultrasound shows a large anechoic mass in the pelvis. Which of the following drugs most likely accounts for this patient's current symptoms?

• A. Valproate
• B. Desipramine (Correct Answer)
• C. Amlodipine
• D. Pregabalin
• E. Simvastatin

Explanation: ***Desipramine*** - Desipramine is a **tricyclic antidepressant** with significant **anticholinergic side effects**. These effects, such as **urinary retention** and **constipation**, are highly consistent with the patient's symptoms (not urinated for 24 hours, not passed stool for 3 days), especially in a patient with pre-existing **benign prostatic hyperplasia**. - The patient's ongoing pain after herpes zoster suggests **postherpetic neuralgia**, which is a common indication for TCAs because of their **neuromodulating properties**. This drug, therefore, explains both his presenting symptoms and the reason for its prescription. *Valproate* - Valproate is an **anticonvulsant** and mood stabilizer, but it is **not typically used for postherpetic neuralgia**. - Its side effects include gastrointestinal upset, but it does **not commonly cause severe constipation or urinary retention** to the degree described. *Amlodipine* - Amlodipine is a **calcium channel blocker** used for hypertension and coronary artery disease, which the patient has. However, it does **not cause significant constipation or urinary retention**. - Constipation can be a minor side effect, but **severe bowel and bladder dysfunction** as described is not characteristic of amlodipine. *Pregabalin* - Pregabalin is an **anticonvulsant** and gabapentinoid commonly used to manage **neuropathic pain**, including postherpetic neuralgia. - While it can cause some dizziness or somnolence, it is **not associated with severe anticholinergic effects** like acute urinary retention or profound constipation. *Simvastatin* - Simvastatin is a **statin** used to manage hyperlipidemia and coronary artery disease, which the patient has. - Its primary side effects include **muscle pain (myalgia)** and liver enzyme elevation; it does not cause bladder or bowel obstruction.

Question 769: A 16-year-old girl who recently immigrated to the United States from Bolivia presents to her primary care physician with a chief complaint of inattentiveness in school. The patient's teacher describes her as occasionally "day-dreaming" for periods of time during which the patient does not respond or participate in school activities. Nothing has helped the patient change her behavior, including parent-teacher conferences or punishment. The patient has no other complaints herself. The only other concern that the patient's mother has is that upon awakening she notices that sometimes the patient's arm will jerk back and forth. The patient states she is not doing this intentionally. The patient has an unknown past medical history and is currently not on any medications. On physical exam you note a young, healthy girl whose neurological exam is within normal limits. Which of the following is the best initial treatment?

• A. Ethosuximide
• B. Valproic acid (Correct Answer)
• C. Carbamazepine
• D. Cognitive behavioral therapy
• E. Lamotrigine

Explanation: ***Valproic acid*** - This patient presents with symptoms highly suggestive of **juvenile myoclonic epilepsy (JME)**, characterized by **absence seizures** ("day-dreaming") and **myoclonic jerks**, particularly upon awakening. Valproic acid is considered a first-line agent for JME due to its broad spectrum of action against various seizure types. - While ethosuximide is effective for absence seizures, valproic acid is preferred in JME because it also effectively controls the associated myoclonic jerks, addressing both seizure types seen in this patient. *Ethosuximide* - Ethosuximide is the drug of choice for **absence seizures** only, effectively preventing the "day-dreaming" spells. - However, it is not effective against the **myoclonic jerks** described by the patient's mother, which are a characteristic feature of juvenile myoclonic epilepsy. *Carbamazepine* - Carbamazepine is primarily used for **focal (partial) seizures** and **tonic-clonic seizures**. - It can actually **exacerbate absence and myoclonic seizures**, making it an inappropriate choice for this patient's presentation. *Cognitive behavioral therapy* - Cognitive behavioral therapy (CBT) is a **psychological intervention** primarily used for mental health conditions like anxiety, depression, or behavioral disorders. - While helpful for addressing emotional or behavioral responses to a chronic illness, it does not treat the underlying **electrical abnormalities in the brain** that cause seizures. *Lamotrigine* - Lamotrigine is a broad-spectrum antiepileptic drug that can be effective for various seizure types, including **absence and myoclonic seizures**. - However, it can sometimes **exacerbate myoclonic seizures** in some individuals with JME, and while sometimes used as an alternative, valproic acid is generally the first-line choice for its established efficacy in controlling all seizure types in JME.

Question 770: An experimental new drug (SD27C) is being studied. This novel drug delivers insulin via the intranasal route. Consent is obtained from participants who are diabetic and are taking insulin as their current treatment regimen to participate in a clinical trial. 500 patients consent and are divided into 2 groups, and a double-blind clinical trial was conducted. One group received the new formulation (SD27C), while the second group received regular insulin via subcutaneous injection. The results showed that the treatment outcomes in both groups are the same. SD27C is currently under investigation in which phase of the clinical trial?

• A. Phase II
• B. Phase III (Correct Answer)
• C. Post-market surveillance
• D. Phase I
• E. Phase IV

Explanation: ***Phase III*** - **Phase III trials** involve a large number of participants (hundreds to thousands) and compare the new drug to standard treatment or placebo to assess its **efficacy** and monitor for adverse effects. - The description of a **double-blind clinical trial** with 500 patients divided into two groups, comparing the new drug (SD27C) to regular insulin with similar treatment outcomes, is characteristic of a Phase III study. *Phase II* - **Phase II trials** typically involve a smaller group of patients (tens to a few hundred) to evaluate the drug's **effectiveness**, further assess safety, and determine the optimal dosage. - The sample size of 500 patients in this scenario is too large for a typical Phase II trial. *Post-market surveillance* - This term is synonymous with **Phase IV trials**, which occur after the drug has been approved and marketed, focusing on long-term safety and effectiveness in a broader population. - The drug is still "under investigation" and being compared to existing treatment, indicating it has not yet been approved. *Phase I* - **Phase I trials** are the initial human trials, usually involving a small number of **healthy volunteers**, to evaluate the drug's safety, dosage range, and pharmacokinetics. - The study involves diabetic patients, not healthy volunteers, and the focus is on efficacy comparison, not just basic safety. *Phase IV* - **Phase IV trials** (or post-market surveillance) take place **after a drug has been approved** and marketed, monitoring its long-term effects, optimal use, and safety in a real-world setting. - The drug is still in a comparative efficacy trial and has not yet received approval for general use.

Question 771: A 52-year-old woman presents to her primary care provider with shortness of breath. She reports a 3-month history of difficulty breathing with exertion that has progressed to affect her at rest. She swims 45 minutes every day but has had trouble swimming recently due to her breathing difficulties. Her past medical history is notable for well-controlled mild intermittent asthma and generalized anxiety disorder. She has a 15 pack-year smoking history but quit 15 years ago. She does not drink alcohol. Her mother died at the age of 60 from heart failure and was a lifetime non-smoker. Her temperature is 99°F (37.2°C), blood pressure is 135/85 mmHg, pulse is 85/min, and respirations are 22/min. Her BMI is 23 kg/m^2. On exam, she has slightly increased work of breathing. Cardiac auscultation reveals a normal S1 and loud P2. An echocardiogram is performed demonstrating right ventricular hypertrophy. Her pulmonary artery pressure is 24 mmHg at rest and 40 mmHg with exercise. This patient’s condition is associated with a mutation in a gene that does which of the following?

• A. Internalizes low-density lipoprotein
• B. Inhibits smooth muscle proliferation (Correct Answer)
• C. Inhibits free radical formation
• D. Degrades proteases
• E. Promotes intracellular chloride transport

Explanation: **Inhibits smooth muscle proliferation** - The patient's presentation with progressive dyspnea, normal BMI, well-controlled asthma, family history of early heart failure, loud P2, right ventricular hypertrophy, and elevated pulmonary artery pressures (both at rest and with exercise) is highly suggestive of **hereditary pulmonary arterial hypertension (PAH)**. - Hereditary PAH is most commonly associated with mutations in the **BMPR2 gene**, which encodes a receptor for bone morphogenetic proteins. This receptor normally functions to **inhibit vascular smooth muscle cell proliferation**; thus, a loss-of-function mutation leads to unchecked proliferation and remodeling of pulmonary arteries. *Internalizes low-density lipoprotein* - This function is primarily associated with the **LDL receptor gene**, mutations in which cause **familial hypercholesterolemia**. - Familial hypercholesterolemia is characterized by elevated LDL cholesterol and increased risk of early **atherosclerotic cardiovascular disease**, which does not align with this patient's presentation of isolated pulmonary hypertension. *Inhibits free radical formation* - This is the role of various **antioxidant enzymes** (e.g., superoxide dismutase, catalase). - While oxidative stress plays a role in many diseases, a specific inherited disorder causing isolated PAH due to a defect in inhibiting free radical formation is not the most common genetic cause. *Degrades proteases* - This function is characteristic of **alpha-1 antitrypsin**, a deficiency of which leads to **emphysema and liver disease** due to unopposed proteolytic activity. - The patient's symptoms are not consistent with alpha-1 antitrypsin deficiency, as she has no signs of emphysema or chronic liver disease, and her smoking history is remote. *Promotes intracellular chloride transport* - This is the primary function of the **cystic fibrosis transmembrane conductance regulator (CFTR) protein**. - Mutations in the CFTR gene cause **cystic fibrosis**, a multi-systemic disorder characterized by chronic lung disease with thick mucus, pancreatic insufficiency, and elevated sweat chloride, none of which are described in this patient.

Question 772: A 58-year-old woman presents to the physician for a routine health maintenance examination. She has a history of dyslipidemia and chronic hypertension. Her medications include atorvastatin, hydrochlorothiazide, and lisinopril. She exercises every day and follows a healthy diet. She does not smoke. There is no family history of chronic disease. Her blood pressure is 130/80 mm Hg, which is confirmed on repeat measurement. Her BMI is 22 kg/m2. The physical examination shows no abnormal findings. The laboratory test results show: Serum Total cholesterol 193 mg/dL Low-density lipoprotein (LDL-C) 124 mg/dL High-density lipoprotein (HDL-C) 40 mg/dL Triglycerides 148 mg/dL The patient's 10-year risk of cardiovascular disease (CVD) is 4.6%. Which of the following is the most appropriate next step in pharmacotherapy?

• A. Fish oils
• B. No additional pharmacotherapy at this time
• C. Niacin
• D. Fenofibrate
• E. Ezetimibe (Correct Answer)

Explanation: ***Ezetimibe*** - The patient has an **LDL-C of 124 mg/dL** despite being on atorvastatin. According to the 2018 AHA/ACC guidelines, adding **ezetimibe** to a statin is recommended when LDL-C remains elevated (>70 mg/dL secondary prevention, >100 mg/dL primary prevention with high ASCVD risk) after maximally tolerated statin therapy to further reduce cardiovascular risk. - Adding **ezetimibe** to atorvastatin would help further lower her LDL-C levels, which is crucial given her dyslipidemia and hypertension, despite her overall healthy lifestyle. *Fish oils* - **Fish oils**, specifically high-dose omega-3 fatty acids, are primarily considered for patients with **severe hypertriglyceridemia** (>500 mg/dL) or those with elevated triglycerides (135-499 mg/dL) despite statin therapy and elevated cardiovascular risk, particularly if their HDL-C is low and they have established CVD. - While this patient has mild hypertriglyceridemia (148 mg/dL) and low HDL-C, her primary concern for further intervention is her elevated LDL-C, making ezetimibe a more appropriate first-line additive. *No additional pharmacotherapy at this time* - While the patient has a relatively low 10-year CVD risk (4.6%) and healthy lifestyle, her **LDL-C of 124 mg/dL** remains elevated despite atorvastatin. This level, in conjunction with her history of dyslipidemia and hypertension, warrants further intervention to reduce her lifetime ASCVD risk. - Given her established risk factors, maintaining an elevated LDL-C when further reduction is achievable through safe and effective pharmacotherapy is not ideal for long-term cardiovascular health. *Niacin* - **Niacin** can lower LDL-C and triglycerides while increasing HDL-C, but multiple clinical trials have failed to show a consistent benefit in reducing cardiovascular events when added to statin therapy, often due to significant side effects (e.g., flushing, insulin resistance, hepatotoxicity). - Its use has largely declined in favor of other agents due to unfavorable risk-benefit profiles in combination with statins. *Fenofibrate* - **Fenofibrate** is primarily used to treat **hypertriglyceridemia** and can also raise HDL-C, but it has not consistently shown benefit in reducing cardiovascular outcomes when added to statins in patients with mild-to-moderate hypertriglyceridemia. - While her triglycerides are slightly elevated, her primary lipid target for further management remains LDL-C reduction.

Question 773: A 58-year-old man comes to the physician because of severe muscle aches and fatigue for 3 days. Last week he was diagnosed with atypical pneumonia and treated with clarithromycin. He has hyperlipidemia for which he takes lovastatin. Physical examination shows generalized tenderness of the proximal muscles in the upper and lower extremities. Serum studies show an elevated creatine kinase concentration. This patient's current symptoms are most likely caused by inhibition of which of the following hepatic enzymes?

• A. CYP2E1
• B. CYP3A4 (Correct Answer)
• C. CYP2C9
• D. CYP1A2
• E. CYP2C19

Explanation: ***CYP3A4*** - The patient is taking **lovastatin**, which is metabolized by **CYP3A4**. **Clarithromycin** is a potent **CYP3A4 inhibitor**. - Inhibition of **CYP3A4** by clarithromycin leads to increased lovastatin levels, causing statin-induced **myopathy** (muscle aches, fatigue, and elevated creatine kinase). *CYP2E1* - This enzyme is primarily involved in the metabolism of compounds like **ethanol** and **acetaminophen**, not lovastatin. - Its inhibition would not explain the interaction between clarithromycin and lovastatin. *CYP2C9* - This enzyme metabolizes drugs such as **warfarin** and **NSAIDs**, but it is not the primary enzyme responsible for lovastatin metabolism or its interaction with clarithromycin. - Inhibition of **CYP2C9** would not lead to the described myopathy in this context. *CYP1A2* - **CYP1A2** is involved in the metabolism of drugs like **caffeine** and **theophylline**. - It does not play a significant role in the metabolism of lovastatin, and its inhibition would not cause the observed symptoms. *CYP2C19* - **CYP2C19** metabolizes drugs such as **clopidogrel** and **omeprazole**. - It is not the target enzyme for the interaction between lovastatin and clarithromycin.

Question 774: A 66-year-old male with a history of deep venous thrombosis is admitted to the hospital with shortness of breath and pleuritic chest pain. He is treated with an anticoagulant, but he develops significant hematochezia. His BP is now 105/60 and HR is 117; both were within normal limits on admission. The effects of the anticoagulant are virtually completely reversed with the administration of protamine. Which of the following was the anticoagulant most likely administered to this patient?

• A. Enoxaparin
• B. Dabigatran
• C. Bivalirudin
• D. Warfarin
• E. Heparin (Correct Answer)

Explanation: ***Heparin*** - **Protamine sulfate** is the specific and virtually complete antidote for **unfractionated heparin (UFH)** and, to a lesser extent, low molecular weight heparins (LMWH). - The patient's presentation with **shortness of breath** and **pleuritic chest pain** suggests a **pulmonary embolism (PE)**, a common indication for heparin. *Enoxaparin* - Enoxaparin is a **low molecular weight heparin (LMWH)**. While protamine can partially reverse LMWH effects, it is **not complete** (only 60-75% reversal) compared to UFH. - LMWHs have a **longer half-life** and less predictable reversal with protamine than UFH. *Dabigatran* - Dabigatran is a **direct thrombin inhibitor** and its antidote is **idarucizumab**, not protamine. - This drug is not reversible by protamine. *Bivalirudin* - Bivalirudin is a **direct thrombin inhibitor** used mainly during percutaneous coronary intervention and its effects are **not reversible with protamine**. - Its short half-life often makes reversal agents unnecessary, but there is no specific antidote listed. *Warfarin* - Warfarin is a **vitamin K antagonist** and its effects are reversed by **vitamin K**, fresh frozen plasma (FFP), or prothrombin complex concentrates (PCCs), not protamine. - Warfarin also has a **delayed onset of action**, making it less suitable for acute treatment of a suspected PE.

Question 775: A 21-year-old man with a recent history of traumatic right femur fracture status post open reduction and internal fixation presents for follow-up. The patient says his pain is controlled with the oxycodone but he says he has been severely constipated the past 4 days. No other past medical history. Current medications are oxycodone and ibuprofen. The patient is afebrile and vital signs are within normal limits. On physical examination, surgical incision is healing well. Which of the following is correct regarding the likely role of opiates in this patient’s constipation?

• A. Opiates decrease the sympathetic activity of the gut wall
• B. Opiates increase the production and secretion of pancreatic digestive enzymes
• C. Opiates increase fluid absorption from the lumen leading to hard stools (Correct Answer)
• D. Opiates cause rapid gastrointestinal transit
• E. Opiates activate the excitatory neural pathways in the gut

Explanation: ***Opiates increase fluid absorption from the lumen leading to hard stools*** - Opiates act on **opioid receptors** in the GI tract, increasing **fluid absorption** and decreasing secretion, which makes stools drier and harder. - This effect contributes significantly to **opioid-induced constipation** (OIC) by slowing stool transit and making defecation difficult. *Opiates decrease the sympathetic activity of the gut wall* - Opiates primarily affect the **parasympathetic nervous system** and enteric nervous system, rather than directly decreasing sympathetic activity. - Their main impact on motility is to **decrease acetylcholine release**, which reduces gut contractions. *Opiates increase the production and secretion of pancreatic digestive enzymes* - Opiates are known to **decrease pancreatic enzyme secretion**, not increase it. - This effect is not a primary mechanism for opioid-induced constipation. *Opiates cause rapid gastrointestinal transit* - Opiates actually **slow down gastrointestinal transit** by disrupting propulsive contractions and increasing non-propulsive segmental contractions. - This delayed transit time is a major contributor to constipation. *Opiates activate the excitatory neural pathways in the gut* - Opiates typically **inhibit excitatory neural pathways** in the gut, particularly those mediated by acetylcholine, which reduces smooth muscle contractions. - Their action leads to reduced peristalsis and overall decreased gut motility.

Question 776: A 58-year-old male presents to his primary care doctor with the complaint of vision changes over the last several months. The patient's past medical history is notable for schizophrenia which has been well-controlled for the last 25 years on chlorpromazine. Which of the following is likely to be seen on ophthalmoscopy?

• A. Optic disc cupping
• B. Drusen deposits
• C. Retinal hemorrhage
• D. Retinal pigmentary changes (Correct Answer)
• E. Bone spicule pigmentation

Explanation: ***Retinal pigmentary changes*** - **Chlorpromazine**, a first-generation antipsychotic, is known to cause **pigmentary retinopathy** in high doses or with long-term use. - This side effect can lead to **vision changes** due to deposition of pigment in the retina, affecting photoreceptor function. *Optic disc cupping* - This finding is characteristic of **glaucoma**, a condition generally associated with elevated intraocular pressure and optic nerve damage. - There is no information in the patient's presentation that suggests glaucoma. *Drusen deposits* - **Drusen** are yellow deposits under the retina associated with **age-related macular degeneration (ARMD)**. - While the patient's age makes ARMD plausible, chlorpromazine's known ocular side effects are a more directed answer given the patient's history. *Retinal hemorrhage* - **Retinal hemorrhages** are often associated with conditions like **hypertension**, **diabetes**, or **retinal vein occlusions**. - There is no mention of these underlying systemic diseases or acute vascular events in the patient's history. *Bone spicule pigmentation* - This is a hallmark finding of **retinitis pigmentosa**, a group of inherited retinal degenerative diseases. - The patient's history of vision changes over months in the context of chronic chlorpromazine use points away from a genetic, progressive condition like retinitis pigmentosa.

Question 777: A 60-year-old Hispanic man presents to the office for a regular health checkup. He has been waiting for his hip replacement surgery for osteoarthritis, which he was diagnosed with for the past 5 years. He admits to having taken high doses of painkillers for hip pain management, but now they don't provide any pain relief. His vital signs include: blood pressure 110/70 mm Hg, pulse 78/min, temperature 36.7°C (98.1°F), and respiratory rate 10/min. On physical examination, there is a limited range of motion of his right hip. The laboratory results are as follows: Hemoglobin 12 g/dL Red blood cell 5.1 million cells/µL Hematocrit 45% Total leukocyte count 6,500 cells/µL Neutrophils 71% Lymphocytes 14% Monocytes 4% Eosinophils 11% Basophils 0% Platelets 240,000 cells/µL Urinalysis shows: pH 6.2 Color light yellow RBC 7–8/HPF WBC 10-12/HPF Protein 1+ Cast none Glucose absent Crystal none Ketone absent Nitrite negative 24-hr urine protein excretion 0.9 g Urine for culture: No growth noted after 48 hours of inoculation at 37.0°C (98.6°F) What is the most likely diagnosis?

• A. Chronic pyelonephritis
• B. Membranous nephropathy
• C. Acute tubular necrosis
• D. Analgesic nephropathy (Correct Answer)
• E. Diffuse cortical necrosis

Explanation: ***Analgesic nephropathy*** - Chronic use of **high doses of painkillers** for osteoarthritis and the presence of **sterile pyuria (WBCs in urine with no bacterial growth)**, mild hematuria, and proteinuria strongly suggest analgesic nephropathy. - This condition is characterized by **papillary necrosis** and chronic interstitial nephritis due to cumulative exposure to NSAIDs or combinations of analgesics. *Chronic pyelonephritis* - While chronic pyelonephritis can present with sterile pyuria and chronic kidney disease, it typically involves a history of recurrent **urinary tract infections** and imaging findings of renal scarring, which are not mentioned. - The patient's history of extensive analgesic use makes analgesic nephropathy a more direct and probable cause of the observed renal findings. *Membranous nephropathy* - Membranous nephropathy usually presents with **nephrotic syndrome** (heavy proteinuria >3.5 g/24hr, hypoalbuminemia, edema, hyperlipidemia), which is not evident here given the 0.9 g/24hr protein excretion. - It is also typically an immune-mediated glomerular disease, without direct links to analgesic use or significant sterile pyuria. *Acute tubular necrosis* - Acute tubular necrosis (ATN) is often associated with **acute kidney injury** caused by ischemia or nephrotoxic agents, presenting with a rapid decline in renal function. - While drugs can cause ATN, the patient's long-standing use of painkillers and the chronic nature of the findings (mild proteinuria, hematuria, sterile pyuria) point away from an acute process. *Diffuse cortical necrosis* - Diffuse cortical necrosis is a severe and **rare cause of acute kidney injury**, often associated with obstetric catastrophes, sepsis, or snake bites, leading to widespread necrosis of the renal cortex. - It is typically a **fulminant condition** with severe oliguria or anuria and marked azotemia, which does not align with the patient's presentation of chronic symptoms and relatively stable vital signs.

Question 778: A 48-year-old woman presents to her primary care physician for a wellness visit. She states she is generally healthy and currently has no complaints. She drinks 1 alcoholic beverage daily and is currently sexually active. Her last menstrual period was 1 week ago and it is regular. She smokes 1 pack of cigarettes per day and would like to quit. She describes her mood as being a bit down in the winter months but otherwise feels well. Her family history is notable for diabetes in all of her uncles and colon cancer in her mother and father at age 72 and 81, respectively. She has been trying to lose weight and requests help with this as well. Her diet consists of mostly packaged foods. Her temperature is 98.0°F (36.7°C), blood pressure is 122/82 mmHg, pulse is 80/min, respirations are 12/min, and oxygen saturation is 98% on room air. Her BMI is 23 kg/m^2. Physical exam reveals a healthy woman with no abnormal findings. Which of the following is the most appropriate initial intervention for this patient?

• A. Bupropion
• B. Colonoscopy
• C. Alcohol cessation
• D. Varenicline and nicotine gum (Correct Answer)
• E. Weight loss, exercise, and nutrition consultation

Explanation: **Varenicline and nicotine gum** - **Smoking cessation** is the most critical and impactful intervention for this patient's long-term health, as it significantly reduces risks for numerous chronic diseases. - Combining **varenicline** (a partial nicotinic acetylcholine receptor agonist) with **nicotine gum** (a nicotine replacement therapy) is a highly effective **combination therapy** for smoking cessation. *Bupropion* - While bupropion is an effective aid for smoking cessation, it is a **monotherapy** and typically less effective than combination therapy, especially for patients with significant smoking history. - Bupropion also has benefits for **seasonal affective disorder**, which the patient hints at, but addressing the imminently dangerous behavior of smoking takes precedence. *Colonoscopy* - Given her family history of colon cancer, a **screening colonoscopy** is appropriate, but the **optimal age for initiation** is 40 or 10 years younger than the youngest affected relative (whichever comes first), or 40-45 in the general population. Her parents were affected at 72 and 81, so her risk is not immediate. - Despite being an important screening measure, it does not address an immediate lifestyle modification that has a broader impact on health like smoking cessation. *Alcohol cessation* - While **alcohol consumption** should be discussed in the context of general health, her current intake of one drink daily is within **recommended low-risk limits** for women. - Her stated goal is to quit smoking, and while alcohol reduction is beneficial, it is not the most urgent or patient-identified priority requiring intervention here. *Weight loss, exercise, and nutrition consultation* - The patient's **BMI of 23 kg/m²** is within the normal range, indicating that her weight is not an immediate health concern, though dietary advice can always be beneficial. - While her desire for weight loss and a healthier diet should be addressed, the **immediate and most significant risk factor** for her health that needs intervention is smoking.

Question 779: A 33-year-old woman with Crohn’s disease colitis presents to her physician after 2 days of photophobia and blurred vision. She has had no similar episodes in the past. She has no abdominal pain or diarrhea and takes mesalazine, azathioprine, and prednisone as maintenance therapy. Her vital signs are within normal range. Examination of the eyes shows conjunctival injection. The physical examination is otherwise normal. Slit-lamp examination by an ophthalmologist shows evidence of inflammation in the anterior chamber. Which of the following is the most appropriate modification to this patient’s medication at this time?

• A. Adding infliximab
• B. Increasing dose of prednisone (Correct Answer)
• C. No modification of therapy at this time
• D. Discontinuing mesalazine
• E. Decreasing dose of azathioprine

Explanation: ***Increasing dose of prednisone*** - This patient is presenting with **anterior uveitis**, a common **extraintestinal manifestation of Crohn’s disease**, characterized by photophobia, blurred vision, and inflammation of the anterior chamber. - **Corticosteroids** (like prednisone) are the **first-line treatment for acute uveitis**, and increasing the dose will help control the inflammation effectively. *Adding infliximab* - While **biologics like infliximab** can be effective for refractory uveitis or systemic disease control, they are **not the immediate first-line treatment for an acute uveitis flare**, especially when corticosteroids are already part of the regimen. - Adding a new biologic would also involve a longer onset of action and additional risks, making it less suitable for urgent symptom control compared to adjusting prednisone. *No modification of therapy at this time* - The patient clearly has **acute anterior uveitis**, which is a potentially serious ocular condition requiring prompt treatment to prevent complications such as synechiae, glaucoma, and vision loss. - Doing nothing would lead to worsening inflammation and potential irreversible damage. *Discontinuing mesalazine* - **Mesalazine** (an aminosalicylate) is primarily used for maintaining remission in inflammatory bowel disease and is **not implicated in causing uveitis**, nor is discontinuing it a treatment for uveitis. - It would also risk a flare of her Crohn's disease. *Decreasing dose of azathioprine* - **Azathioprine** is an **immunosuppressant** used to maintain remission in Crohn’s disease and is not a direct treatment for acute uveitis. - Decreasing the dose would weaken her overall immunosuppression, potentially leading to a flare of her Crohn's disease or making her more susceptible to other issues, without directly addressing the acute ocular inflammation.

Question 780: A 45-year-old man presents to the emergency department with complaint of dizziness and nausea for the past hour. He says that he can feel his heartbeat racing. He also reports of generalized weakness that began in the morning. He was diagnosed with end-stage renal disease 2 years ago and currently on dialysis, but he missed his last dialysis session. He has also been diabetic for the past 15 years and managed with insulin, and was also diagnosed with celiac disease 8 years ago. He does not smoke or drink alcohol. The family history is insignificant. The temperature is 36.7°C (98.0°F), blood pressure is 145/90 mm Hg, pulse is 87/min, and respiratory rate is 14/min. On physical examination, the patient looks fatigued and exhausted. The muscle strength in the lower limbs is 4/5 bilaterally. An ECG is ordered which shows peaked and narrow T waves and prolongation of PR interval. The lab test results are as follows: Serum Sodium 132 mEq/L Serum Potassium 8 mEq/L Serum Creatinine 5 mg/dL Blood urea nitrogen (BUN) 25 mg/dL What is the mechanism of action of the most likely initial treatment for the patient's condition?

• A. Prevents platelet aggregation
• B. Blocks beta adrenergic receptors
• C. Antagonizes the membrane action of hyperkalemia (Correct Answer)
• D. Increase potassium loss from the gastrointestinal tract
• E. Blocks Na+/K+ ATPase

Explanation: ***Antagonizes the membrane action of hyperkalemia*** - The patient's presentation with **dizziness**, **nausea**, **racing heartbeat**, **generalized weakness**, **missed dialysis**, and ECG findings of **peaked T waves** and **prolonged PR interval** are classic for **severe hyperkalemia** (potassium 8 mEq/L). - The most immediate and life-saving initial treatment for hyperkalemia with ECG changes is **intravenous calcium (e.g., calcium gluconate or calcium chloride)**, which **stabilizes the cardiac myocyte membrane** by antagonizing the direct membrane effects of elevated potassium, without lowering serum potassium levels. *Prevents platelet aggregation* - This is the mechanism of action for **antiplatelet drugs** like aspirin or clopidogrel, which are used to prevent thrombus formation in conditions like myocardial infarction or stroke. - Platelet aggregation is not the primary issue in acute hyperkalemia. *Blocks beta adrenergic receptors* - This is the mechanism of action of **beta-blockers**, used to treat conditions like hypertension, angina, and certain arrhythmias. - Beta-blockers are not indicated for the immediate treatment of hyperkalemia. *Increase potassium loss from the gastrointestinal tract* - This is the mechanism of action of **potassium binders** such as sodium polystyrene sulfonate (Kayexalate) or patiromer. - While these can lower potassium, their action is much slower and not the initial life-saving intervention needed in severe hyperkalemia with ECG changes. *Blocks Na+/K+ ATPase* - This is the mechanism of action of **cardiac glycosides** like **digoxin**, which increase intracellular calcium and myocardial contractility. - Blocking the Na+/K+ ATPase can worsen hyperkalemia (as Na+/K+ ATPase normally pumps K+ into cells) and is not a treatment for hyperkalemia.

Question 781: A 4-day-old boy is monitored in the well baby nursery. He was born to a G1P1 mother at 36 weeks gestation. The child is doing well, and the mother is recovering from vaginal delivery. On physical exam, there is an arousable infant who is crying vigorously and is mildly cyanotic. A red reflex is noted bilaterally on ophthalmologic exam. The infant's fontanelle is soft, and his sucking reflex is present. A positive Babinski sign is noted on physical exam bilaterally. A continuous murmur is auscultated on cardiac exam. Which of the following would most likely have prevented the abnormal finding in this infant?

• A. Prostaglandins
• B. Indomethacin (Correct Answer)
• C. Folic acid
• D. Betamethasone
• E. Oxygen therapy

Explanation: ***Indomethacin*** - The continuous murmur and mild cyanosis in a premature infant (36 weeks gestation) suggest a **patent ductus arteriosus (PDA)**. - **Prophylactic indomethacin** given to premature infants shortly after birth can prevent the development of a symptomatic PDA by inhibiting prostaglandin synthesis, which promotes ductal closure. - Indomethacin, a **prostaglandin inhibitor**, prevents prostaglandin-mediated vasodilation and facilitates closure of the ductus arteriosus in the early postnatal period. - This is particularly important in premature infants who are at higher risk for persistent PDA due to immature ductal responsiveness. *Prostaglandins* - **Prostaglandins** (specifically PGE1) are used to *keep* the ductus arteriosus open, which is desirable in certain cyanotic congenital heart defects that require ductal patency for systemic or pulmonary blood flow (e.g., transposition of great arteries, pulmonary atresia). - Administering prostaglandins in this case would worsen the **patent ductus arteriosus** by preventing its closure. *Folic acid* - **Folic acid** supplementation during pregnancy is crucial for preventing neural tube defects such as spina bifida and anencephaly. - It has no role in preventing or treating a **patent ductus arteriosus** or other cardiovascular abnormalities in newborns. *Betamethasone* - **Betamethasone** is a corticosteroid given to pregnant mothers at risk of preterm delivery (between 24-34 weeks) to accelerate fetal lung maturity and reduce respiratory distress syndrome. - While it improves neonatal outcomes in premature infants, it does not directly prevent the development of **patent ductus arteriosus**. *Oxygen therapy* - **Oxygen therapy** is used to treat hypoxemia and improve tissue oxygenation in cyanotic infants. - While increased oxygen tension can contribute to ductal constriction, oxygen therapy alone is not a primary or reliable preventative measure for PDA in premature infants. - Indomethacin remains the definitive pharmacologic intervention for prevention of symptomatic PDA.

Question 782: A 52-year-old woman presents to the emergency room complaining of chest pain. She reports a 4-hour history of dull substernal pain radiating to her jaw. Her history is notable for hypertension, diabetes mellitus, and alcohol abuse. She has a 30 pack-year smoking history and takes lisinopril and metformin but has an allergy to aspirin. Her temperature is 99.1°F (37.3°C), blood pressure is 150/90 mmHg, pulse is 120/min, and respirations are 22/min. Physical examination reveals a diaphoretic and distressed woman. An electrocardiogram reveals ST elevations in leads I, aVL, and V5-6. She is admitted with plans for immediate transport to the catheterization lab for stent placement. What is the mechanism of the next medication that should be given to this patient?

• A. Cyclooxygenase activator
• B. ADP receptor inhibitor (Correct Answer)
• C. Phosphodiesterase activator
• D. Thrombin inhibitor
• E. Vitamin K epoxide reductase inhibitor

Explanation: ***ADP receptor inhibitor*** - This patient is experiencing an **ST-elevation myocardial infarction (STEMI)** as evidenced by ST elevations in leads I, aVL, and V5-6 (lateral wall infarction) - **Dual antiplatelet therapy** is the standard of care for STEMI, typically consisting of aspirin plus a P2Y12 inhibitor (ADP receptor inhibitor) - Since this patient has an **aspirin allergy**, an ADP receptor inhibitor such as **clopidogrel, ticagrelor, or prasugrel** becomes the critical next antiplatelet medication - These agents **irreversibly or reversibly block the P2Y12 receptor** on platelets, preventing ADP-mediated platelet activation and aggregation - This is essential for preventing further thrombotic complications during and after percutaneous coronary intervention (PCI) *Cyclooxygenase activator* - No cyclooxygenase activator exists in clinical practice for cardiovascular disease - Aspirin works as a **cyclooxygenase inhibitor**, blocking COX-1 to prevent thromboxane A2 synthesis, but the patient is allergic to aspirin - "Activating" cyclooxygenase would promote platelet aggregation, which is counterproductive in acute MI *Phosphodiesterase activator* - Phosphodiesterase activation would decrease cAMP/cGMP levels, which is not therapeutically beneficial - **Phosphodiesterase inhibitors** (such as cilostazol or dipyridamole) can have antiplatelet effects by increasing cAMP, but they are not first-line agents for acute STEMI - An activator would have the opposite and undesirable effect *Thrombin inhibitor* - Thrombin inhibitors (e.g., **bivalirudin, heparin**) are anticoagulants that prevent conversion of fibrinogen to fibrin - While **anticoagulation is important in STEMI management**, it is used as adjunctive therapy alongside antiplatelet agents - Given the aspirin allergy, the immediate priority is **antiplatelet therapy with an ADP receptor inhibitor** - Anticoagulation would typically be given concurrently but is not "the next" critical medication in this specific context *Vitamin K epoxide reductase inhibitor* - Warfarin is a vitamin K epoxide reductase inhibitor used for chronic anticoagulation - It has a **slow onset of action** (days) and is inappropriate for acute STEMI management - It is used for long-term anticoagulation in conditions like atrial fibrillation or mechanical heart valves, not for acute coronary syndromes requiring rapid platelet inhibition

Question 783: A 55-year-old man comes to the physician because of difficulties achieving an erection for the past year. A medication is prescribed that inhibits cyclic GMP phosphodiesterase type 5. Which of the following is the most likely site of action of the prescribed drug?

• A. Corpus spongiosum
• B. Pelvic splanchnic nerves
• C. Pudendal nerve
• D. Prostate smooth muscle
• E. Corpus cavernosum (Correct Answer)

Explanation: ***Corpus cavernosum*** - **Erectile dysfunction** is primarily due to insufficient blood flow into the **corpus cavernosum**, which are the main erectile tissues of the penis. - **cGMP phosphodiesterase type 5 (PDE5) inhibitors** like sildenafil work by increasing cGMP levels in the smooth muscle cells of the corpus cavernosum, leading to vessel relaxation and improved blood inflow. *Corpus spongiosum* - The **corpus spongiosum** primarily surrounds the urethra and prevents its compression during erection; it plays a secondary role in penile rigidity. - While it does contain smooth muscle, it is not the primary target for medications aimed at enhancing penile rigidity. *Pelvic splanchnic nerves* - The **pelvic splanchnic nerves** are involved in the neural initiation of erection by releasing **nitric oxide (NO)**, which triggers cGMP production. - However, the prescribed medication acts on the cGMP breakdown *within* the erectile tissue, not on the nerves that initiate the process. *Pudendal nerve* - The **pudendal nerve** is mainly responsible for carrying sensory information from the penis and innervating the external urethral sphincter and perineal muscles. - It does not directly control the vascular smooth muscle relaxation necessary for erection, so it is not the site of action for PDE5 inhibitors. *Prostate smooth muscle* - While the **prostate** contains smooth muscle, it is not directly involved in the erectile process itself. - Some PDE5 inhibitors are used for **benign prostatic hyperplasia (BPH)** symptoms by relaxing smooth muscle in the prostate and bladder neck, but this is a secondary effect distinct from their primary erectile function.

Question 784: A 30-year-old man presents to his psychiatrist for a follow-up visit. He was diagnosed with schizophrenia 6 months ago and has been taking fluphenazine. He says that his symptoms are well controlled by the medication, and he no longer has auditory hallucinations. The psychiatrist also notes that his delusions and other psychotic symptoms have improved significantly. However, the psychiatrist notices something while talking to the patient that prompts him to say, “I know the drug has effectively controlled your symptoms but I think you should discontinue it now otherwise this side effect is likely to be irreversible.” Which of the following did the psychiatrist most likely notice in this patient?

• A. Choreoathetoid movements of face (Correct Answer)
• B. Crossing and uncrossing legs constantly
• C. Involuntary sustained twisting of neck
• D. Resting tremors
• E. Reduced spontaneous movements while walking

Explanation: ***Choreoathetoid movements of face*** - The psychiatrist is concerned about **tardive dyskinesia (TD)**, a late-onset side effect of dopamine receptor blocking agents like fluphenazine. Its hallmark symptoms include **choreoathetoid (involuntary, jerky, writhing) movements**, often affecting the face (e.g., lip smacking, grimacing, tongue protrusion). - TD can become **irreversible** if the offending medication is continued, necessitating drug discontinuation to prevent permanent motor dysfunction. *Reduced spontaneous movements while walking* - This symptom, along with a "shuffling gait" and **bradykinesia**, is characteristic of drug-induced **Parkinsonism**. - While concerning, Parkinsonism is generally **reversible** upon dose reduction or discontinuation of the antipsychotic, or with the addition of anticholinergic agents, making the psychiatrist's urgent warning about irreversibility less likely for this specific side effect. *Crossing and uncrossing legs constantly* - This behavior is indicative of **akathisia**, an inner sense of restlessness that manifests as an inability to sit still. - Akathisia is a common extrapyramidal side effect that is typically **reversible** with dose reduction, medication change, or treatment with beta-blockers, and is not usually considered irreversible like tardive dyskinesia. *Involuntary sustained twisting of neck* - This describes **dystonia**, an extrapyramidal side effect characterized by sustained or repetitive muscle contractions leading to abnormal postures, such as **torticollis** (twisting of the neck). - Dystonia, while distressing, is usually **reversible** with acute treatment (e.g., anticholinergics like benztropine) and medication adjustment, rarely becoming irreversible. *Resting tremors* - **Resting tremors** are a feature of drug-induced **Parkinsonism**, often accompanied by rigidity and bradykinesia. - Similar to other Parkinsonian symptoms, these tremors are generally **reversible** with appropriate medication management and are not typically considered an irreversible side effect if the offending drug is discontinued promptly.

Question 785: A 72-year-old woman is brought to the emergency department by her son after he noticed that she was slurring her speech. He also noticed that she appeared to have difficulty using her fork about halfway through dinner when the speech problems started. He brought her to the emergency department immediately and he estimates that only 1 hour has passed since the beginning of the symptoms. An immediate exam is conducted. A medication is administered to ameliorate the effects of this patient's condition that would not be available for use if the patient had presented significantly later. An hour later the patient's condition becomes significantly worse and new deficits are found. Which of the following agents should be used at this point?

• A. Protamine sulfate
• B. Antivenin
• C. Aminocaproic acid
• D. Plasma transfusion (Correct Answer)
• E. Vitamin K

Explanation: ***Plasma transfusion*** - The patient's clinical presentation (acute focal neurological deficits within 1 hour) indicates **ischemic stroke**, and the "medication administered to ameliorate effects...not available if presented significantly later" is **tissue plasminogen activator (tPA/alteplase)**, which must be given within 3-4.5 hours of symptom onset. - The subsequent **worsening with new deficits** after initial tPA administration strongly suggests **hemorrhagic transformation** of the ischemic stroke, a known complication of thrombolytic therapy. - **Fresh frozen plasma (FFP)** is the appropriate treatment because tPA depletes **fibrinogen and clotting factors** through systemic fibrinolysis, and FFP directly replaces these consumed clotting factors to help control bleeding. - Management of tPA-related hemorrhage includes: stopping tPA, emergent neuroimaging, and administration of **cryoprecipitate** (to replace fibrinogen) and/or **FFP** (to replace clotting factors). *Aminocaproic acid* - **Aminocaproic acid** is an antifibrinolytic agent that inhibits plasminogen activation. - While it can theoretically help in fibrinolytic-related bleeding, it is **NOT first-line therapy** for tPA-associated hemorrhagic transformation. - **Cryoprecipitate and FFP** are preferred because they directly replace the fibrinogen and clotting factors depleted by tPA, addressing the underlying coagulopathy. *Protamine sulfate* - **Protamine sulfate** reverses **heparin** anticoagulation by binding to and inactivating heparin. - This patient received tPA (a thrombolytic), not heparin, so protamine would not be effective. *Antivenin* - **Antivenin** is used to neutralize venom from snake or spider bites. - This patient's presentation is consistent with stroke and tPA complication, not envenomation. *Vitamin K* - **Vitamin K** reverses **warfarin** by promoting hepatic synthesis of vitamin K-dependent clotting factors (II, VII, IX, X). - Warfarin reversal takes hours to days; in acute bleeding, **FFP or prothrombin complex concentrate (PCC)** provides immediate factor replacement. - This patient's complication is related to tPA (thrombolytic), not warfarin.

Question 786: A 35-year-old woman is started on a new experimental intravenous drug X. In order to make sure that she is able to take this drug safely, the physician in charge of her care calculates the appropriate doses to give to this patient. Data on the properties of drug X from a subject with a similar body composition to the patient is provided below: Weight: 100 kg Dose provided: 1500 mg Serum concentration 15 mg/dL Bioavailability: 1 If the patient has a weight of 60 kg and the target serum concentration is 10 mg/dL, which of the following best represents the loading dose of drug X that should be given to this patient?

• A. 300 mg
• B. 450 mg
• C. 150 mg
• D. 1000 mg
• E. 600 mg (Correct Answer)

Explanation: ***600 mg*** - First, calculate the **volume of distribution (Vd)** using the provided data: **Vd = Total Dose / Serum Concentration**. Converting units: 15 mg/dL = 150 mg/L. Therefore, Vd = 1500 mg / 150 mg/L = **10 L** (for the 100 kg subject). - Since the Vd value is for a 100 kg person, Vd per kg = 10 L / 100 kg = **0.1 L/kg**. For the 60 kg patient, the Vd = 0.1 L/kg × 60 kg = **6 L**. - The **loading dose = Target Serum Concentration × Vd / Bioavailability**. Converting target concentration: 10 mg/dL = 100 mg/L. Therefore: (100 mg/L × 6 L) / 1 = **600 mg**. *300 mg* - This value is obtained if an incorrect **Vd** or target concentration was used, potentially through miscalculation or incorrect unit conversion. - For instance, if the **Vd** was inaccurately calculated at 3 L (instead of 6 L), this could lead to the incorrect answer. *450 mg* - This result might occur if the **Vd calculation** was flawed or if the target concentration was incorrectly interpreted. - A potential error could involve using a Vd of 4.5 L which would result in 450 mg, or if the drug amount was simply prorated by weight without properly considering the Vd per kg. *150 mg* - This value suggests a significant error in the calculation of the **volume of distribution** or the target concentration. - It might be obtained if the **Vd** was mistakenly taken as 1.5 L or if the dose was divided by the original serum concentration without accounting for the new patient's weight and desired concentration. *1000 mg* - This value is significantly higher than the correct answer, indicating an overestimation of the **Vd** or target concentration. - It could result from using the original dose (1500 mg) and attempting to scale it incorrectly by weight alone (1500 mg × 60/100 = 900 mg, close to 1000), or if unit conversions were mishandled during the Vd determination.

Question 787: A 36-year-old man is brought to the emergency department by his girlfriend because of increasing confusion for the past 6 hours. He drinks large amounts of alcohol daily and occasionally uses illicit drugs. He is lethargic and oriented only to person. Physical examination shows jaundice, hepatomegaly, and scattered petechiae over the trunk and back. Neurologic examination shows normal, reactive pupils and a flapping tremor when the wrists are extended. A drug with which of the following mechanism of action would be most appropriate for this patient's condition?

• A. Production of NH3
• B. Activation of GABA receptors
• C. Excretion of free iron
• D. Inhibition of D2 receptors
• E. Excretion of NH4 (Correct Answer)

Explanation: ***Excretion of NH4*** - The patient presents with **hepatic encephalopathy**, characterized by **confusion**, **jaundice**, **hepatomegaly**, **petechiae**, and a **flapping tremor (asterixis)**, stemming from chronic alcohol abuse and liver damage. The main pathophysiology in hepatic encephalopathy is the accumulation of **ammonia (NH3)**, which is neurotoxic. - Excretion of **NH4** (ammonium) through drug mechanisms such as **lactulose** (which acidifies the colon, trapping ammonia as ammonium for excretion) is the primary therapeutic target to reduce ammonia levels and improve neurological symptoms. *Production of NH3* - This mechanism would exacerbate the patient's condition by increasing the toxic load of **ammonia (NH3)**, which is already elevated in hepatic encephalopathy. - Therapeutic interventions aim to decrease, not increase, ammonia production or absorption. *Activation of GABA receptors* - While **GABA receptor activation** is involved in the neurological effects of some substances that contribute to confusion, it is not the primary target for treating the underlying pathophysiology of **hepatic encephalopathy**. - Medications that activate GABA receptors (e.g., benzodiazepines) can worsen encephalopathy by further depressing CNS function. *Excretion of free iron* - **Iron overload** can cause liver damage, but the acute confusion and flapping tremor are more indicative of **hepatic encephalopathy** due to ammonia toxicity, not primarily iron accumulation. - Excreting free iron (e.g., with chelation therapy) is for conditions like hemochromatosis and would not address the immediate, life-threatening neurological symptoms in this patient. *Inhibition of D2 receptors* - This mechanism is characteristic of some **antipsychotic medications**. While dopamine imbalances can play a role in some neurological disorders, inhibiting D2 receptors is not a primary therapeutic target for **hepatic encephalopathy**. - Such medications could have side effects that might complicate the clinical picture in a patient with acute liver failure.

Question 788: A 25-year-old G1P0 woman at an estimated gestational age of 9 weeks presents for her first prenatal visit following a positive home pregnancy test. She says she missed 2 periods but assumed it was due to stress at work. She has decided to continue with the pregnancy. Her past medical history is significant for migraine headaches, seizures, and asthma. She takes multiple medications for her condition. Physical examination is unremarkable. An ultrasound confirms a 9-week-old intrauterine pregnancy. Which of the following medications poses the greatest risk to the fetus?

• A. Valproic acid (Correct Answer)
• B. Budesonide
• C. Acetaminophen
• D. Sumatriptan
• E. Albuterol

Explanation: ***Valproic acid*** - **Valproic acid** is a known **teratogen** strongly associated with a high incidence of **neural tube defects** (e.g., spina bifida, anencephaly) when used during the first trimester of pregnancy. - It can also lead to other malformations, including cardiac defects and facial dysmorphism, as part of **fetal valproate syndrome**. *Budesonide* - **Budesonide** is an inhaled corticosteroid commonly used for asthma, considered a relatively **safe medication** during pregnancy (FDA pregnancy category B). - Studies have shown no increased risk of major congenital malformations with its use. *Acetaminophen* - **Acetaminophen** is a widely used analgesic and antipyretic considered **safe** for use throughout pregnancy at recommended doses. - There is no strong evidence linking acetaminophen to an increased risk of birth defects. *Sumatriptan* - **Sumatriptan** is a serotonin receptor agonist used for migraine headaches. It is generally considered to be of **low risk** during pregnancy (FDA pregnancy category C). - While some studies have suggested a minimal risk of certain birth defects, overall data supports its use when necessary. *Albuterol* - **Albuterol** is a short-acting beta-agonist used to treat asthma symptoms and is considered **safe** for use during pregnancy (FDA pregnancy category C). - There is no evidence of teratogenicity, and the benefits of controlling asthma outweigh the potential risks.

Question 789: A 62-year-old woman with a history of subarachnoid hemorrhage is brought to the emergency department because of shortness of breath and sharp chest pain that worsens on inspiration. She underwent surgery for a hip fracture 3 weeks ago. Her pulse is 110/min, respirations are 20/min, and blood pressure is 112/74 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 92%. The lungs are clear to auscultation and there is no jugular venous distention. A ventilation and perfusion scan shows a small perfusion defect in the left lower lung. A drug with which of the following mechanisms of action is most appropriate for this patient?

• A. Inhibition of adenosine diphosphate receptors
• B. Activation of plasminogen
• C. Inhibition of cyclooxygenase
• D. Inhibition of vitamin K epoxide reductase
• E. Activation of antithrombin III (Correct Answer)

Explanation: ***Activation of antithrombin III*** - The patient's symptoms (shortness of breath, sharp chest pain worsening on inspiration, tachycardia, tachypnea, hypoxia) and history (hip fracture surgery 3 weeks ago, subarachnoid hemorrhage) are highly suggestive of a **pulmonary embolism (PE)**, further supported by the perfusion defect on V/Q scan. - **Heparin**, which activates antithrombin III, is the most appropriate initial therapy for PE because of its rapid onset of action and ability to prevent further clot formation, especially given the patient's history of subarachnoid hemorrhage, which contraindicates thrombolytics unless absolutely necessary for hemodynamic instability. *Inhibition of adenosine diphosphate receptors* - Drugs that inhibit ADP receptors, such as **clopidogrel**, are **antiplatelet agents** used to prevent arterial clots (e.g., in myocardial infarction or stroke). - They are not the primary treatment for an acute venous thromboembolism like a pulmonary embolism, which requires anticoagulation to prevent further fibrin formation. *Activation of plasminogen* - **Thrombolytic agents** (e.g., tissue plasminogen activator) activate plasminogen to dissolve existing clots. - While effective in severe PE, their use is associated with a high risk of bleeding, especially in a patient with a recent history of **subarachnoid hemorrhage**, making them contraindicated in this scenario unless the patient is hemodynamically unstable. *Inhibition of cyclooxygenase* - **Aspirin** inhibits cyclooxygenase (COX), reducing prostaglandin and thromboxane A2 synthesis, thereby inhibiting platelet aggregation. - It is an **antiplatelet agent** primarily used for arterial thrombosis prophylaxis and is not the first-line treatment for acute pulmonary embolism. *Inhibition of vitamin K epoxide reductase* - Drugs like **warfarin** inhibit vitamin K epoxide reductase, which interferes with the synthesis of vitamin K-dependent clotting factors. - Warfarin is used for long-term anticoagulation, but its **slow onset of action** makes it unsuitable for acute management of pulmonary embolism; heparin is typically initiated first.

Question 790: A 17-year-old girl is brought to the emergency department by her friends who were at a party with her and found her unconscious in the bathroom. They admit that alcohol was present at the party. The patient's blood pressure is 118/78 mm Hg, pulse is 40/min, respiratory rate is 16/min, and temperature is 36.7°C (98.1°F). On physical examination, she is unresponsive to verbal commands but does respond to noxious stimuli. Her pupils are pinpoint and her mucous membranes are moist. Her heart is bradycardic without murmurs, and her respiratory rate is slowed but clear to auscultation. What is the most likely cause of her symptoms?

• A. Overdose of cocaine
• B. Ethylene glycol ingestion
• C. Overdose of heroin (Correct Answer)
• D. 3,4-methylenedioxy-methamphetamine (MDMA) ingestion
• E. Alcohol poisoning

Explanation: ***Overdose of heroin*** - The patient's presentation with **unresponsiveness**, **pinpoint pupils**, **bradycardia**, and **respiratory depression** is highly characteristic of opioid overdose. - While alcohol was present, the specific constellation of symptoms points more strongly to an opioid, such as heroin, which is a potent **CNS depressant**. *Overdose of cocaine* - Cocaine overdose typically causes **sympathomimetic effects** such as **tachycardia**, **hypertension**, **mydriasis (dilated pupils)**, and agitation, which are absent here. - The patient's bradycardia, pinpoint pupils, and respiratory depression contradict cocaine intoxication. *Ethylene glycol ingestion* - Ethylene glycol poisoning can cause CNS depression but is more commonly associated with **renal failure**, **metabolic acidosis** (with an anion gap), and **calcium oxalate crystalluria**, none of which are suggested by the provided data. - The immediate clinical picture often includes initial euphoria followed by lethargy, but the combination of pinpoint pupils and severe bradycardia is less specific for ethylene glycol than for opioids. *3,4-methylenedioxy-methamphetamine (MDMA) ingestion* - MDMA primarily causes **sympathomimetic effects** including increased heart rate, blood pressure, body temperature, and dilated pupils, along with altered perception and euphoria. - The patient's **bradycardia** and **pinpoint pupils** are directly opposite to the expected effects of MDMA. *Alcohol poisoning* - While alcohol was present and can cause CNS depression, **profound bradycardia** and **pinpoint pupils** are more classic signs of opioid overdose than typical alcohol intoxication. - Severe alcohol poisoning usually presents with **hypotension**, **hypothermia**, and respiratory depression, but the specific combination of bradycardia and pinpoint pupils strongly points away from alcohol as the sole or primary cause.

Question 791: A 32-year-old woman presents to her primary care physician for recent onset headaches, weight loss, and restlessness. Her symptoms started yesterday, and since then she has felt sweaty and generally uncomfortable. The patient's past medical history is unremarkable except for a recent viral respiratory infection which resolved on its own. The patient is not currently on any medications. Her temperature is 99.5°F (37.5°C), blood pressure is 127/68 mmHg, pulse is 110/min, respirations are 14/min, and oxygen saturation is 98% on room air. On physical exam, you see a sweaty and uncomfortable woman who has a rapid pulse. The patient demonstrates no abnormalities on HEENT exam. The patient's laboratory values are ordered as seen below. Hemoglobin: 12 g/dL Hematocrit: 36% Leukocyte count: 8,500/mm^3 with normal differential Platelet count: 195,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 102 mEq/L K+: 4.4 mEq/L HCO3-: 24 mEq/L BUN: 20 mg/dL Glucose: 99 mg/dL Creatinine: 1.0 mg/dL Ca2+: 10.2 mg/dL TSH: .03 mIU/L AST: 12 U/L ALT: 10 U/L The patient is prescribed propranolol and propylthiouracil. She returns 1 week later complaining of severe fatigue. Laboratory values are ordered as seen below. Hemoglobin: 12 g/dL Hematocrit: 36% Leukocyte count: 8,500/mm^3 with normal differential Platelet count: 195,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 102 mEq/L K+: 4.4 mEq/L HCO3-: 24 mEq/L BUN: 20 mg/dL Glucose: 99 mg/dL Creatinine: 1.0 mg/dL Ca2+: 10.2 mg/dL TSH: 6.0 mIU/L AST: 12 U/L ALT: 10 U/L Which of the following is the best next step in management?

• A. Decrease dose of current medications
• B. Discontinue current medications (Correct Answer)
• C. Discontinue current medications and add ibuprofen
• D. Discontinue medications and add T3
• E. Discontinue current medications and add T4

Explanation: ***Discontinue current medications*** - The initial presentation with **low TSH (0.03 mIU/L)** and symptoms of **hyperthyroidism** (headaches, weight loss, restlessness, sweating, rapid pulse) suggests conditions like **thyroiditis** or **Graves' disease**. Given the history of a recent viral respiratory infection, **subacute thyroiditis** is a strong possibility, which is often self-limiting. - After one week of treatment with **propylthiouracil** (an antithyroid drug) and **propranolol**, the patient's **TSH has risen significantly to 6.0 mIU/L**, indicating a shift from hyperthyroidism towards **hypothyroidism**. This, coupled with severe fatigue, suggests that the initial hyperthyroid phase has resolved (possibly due to thyroiditis resolving or overtreatment) and continued antithyroid medication is now causing hypothyroidism. Therefore, discontinuing the antithyroid medication (propylthiouracil) is the appropriate next step. *Decrease dose of current medications* - While a decrease in dose might be considered in some cases of continued hyperthyroidism with mild overtreatment, the **TSH level of 6.0 mIU/L** clearly indicates that the patient is now **hypothyroid**. Simply decreasing the dose of antithyroid medication would likely not fully reverse the hypothyroidism. - The severe fatigue further points to significant hypothyroidism, meaning the patient needs complete cessation of the suppressive therapy, not just a reduction. *Discontinue current medications and add ibuprofen* - Discontinuing the current medications is appropriate given the iatrogenic hypothyroidism. However, adding **ibuprofen** is not indicated solely for fatigue. - Ibuprofen is an NSAID and would primarily be used for pain or inflammation, neither of which is the primary complaint or underlying issue after the shift to hypothyroidism. *Discontinue medications and add T3* - While the patient is now hypothyroid and might eventually need thyroid hormone replacement, adding **T3 (liothyronine)** immediately is not the best first step. **T4 (levothyroxine)** is generally preferred for thyroid replacement due to its longer half-life and more stable blood levels. - The initial hyperthyroidism was likely transient (e.g., due to subacute thyroiditis), meaning the thyroid gland could recover its function. Discontinuing antithyroid medication and reassessing thyroid function is necessary before initiating replacement therapy. *Discontinue current medications and add T4* - Discontinuing the current medications is correct, but immediately adding **T4 (levothyroxine)** may be premature. The rise in TSH suggests the patient is indeed hypothyroid, but it's important to allow the thyroid gland time to recover function after stopping the antithyroid drug, especially if the initial hyperthyroidism was transient (e.g., subacute thyroiditis). - If symptoms persist and TSH remains elevated after observational period off the medication, then T4 replacement would be considered.

Question 792: A 53-year-old man with a history of hypertension, hyperlipidemia, and obesity presents to you in clinic for a yearly physical. His current medication regimen includes a beta blocker, angiotensin converting enzyme inhibitor, and a statin. You review his recent lab work and note that despite being on a maximum statin dose, his LDL cholesterol remains elevated. You decide to prescribe another medication to improve his lipid profile. The additional medication prescribed was niacin (nicotinic acid). One month later, you receive a telephone call from your patient; he complains of turning bright red and feeling "scorching hot" every time he takes his medications. You decide to prescribe which of the following medications to alleviate his symptoms:

• A. Acetaminophen
• B. Diphenhydramine
• C. Coenzyme Q10
• D. Aspirin (Correct Answer)
• E. Hydroxyzine

Explanation: Aspirin - **Aspirin** can reduce the **prostaglandin-mediated flushing** associated with niacin by inhibiting prostaglandin synthesis. - This symptom is often transient and can be mitigated by taking aspirin 30 minutes before niacin or by gradually increasing the niacin dose. *Acetaminophen* - **Acetaminophen** is an analgesic and antipyretic but does not effectively block the **prostaglandin-mediated vasodilation** responsible for niacin flush. - It would not alleviate the "bright red" and "scorching hot" sensation caused by niacin. *Diphenhydramine* - **Diphenhydramine** is an antihistamine primarily used to block histamine receptors, which are not the primary mediators of niacin-induced flushing. - While it may provide some sedation, it would not directly address the **vasodilatory effects** of niacin. *Coenzyme Q10* - **Coenzyme Q10** is sometimes supplemented for **statin-induced myopathy**, but it has no role in preventing or treating niacin-induced flushing [1]. - Its primary function is in cellular energy production, not in modulating prostaglandin pathways [1]. *Hydroxyzine* - **Hydroxyzine** is an antihistamine with sedative properties, sometimes used for anxiety or pruritus. - Similar to diphenhydramine, it does not target the **prostaglandin pathway** responsible for niacin flushing and would not be an effective intervention.

Question 793: A 67-year-old man comes to the physician because of progressive burning pain and intermittent "electrical shocks" in his right chest for 3 months. Over the last 2 weeks, the pain has increased to an extent that he can no longer tolerate clothing on the affected area. Three months ago, he had a rash around his right nipple and axilla that resolved a week later. The patient had a myocardial infarction 2 years ago. He has smoked one pack of cigarettes daily for 47 years. Current medications include aspirin, simvastatin, metoprolol, and ramipril. His temperature is 36.9°C (97.9°F), pulse is 92/min, and blood pressure is 150/95 mm Hg. Examination shows increased sensation to light touch over the right chest. The remainder of the physical examination shows no abnormalities. Which of the following is the most appropriate next step in management?

• A. Sublingual nitrates
• B. Oral famciclovir
• C. Intrathecal glucocorticoids
• D. Oral tricyclic antidepressants
• E. Oral gabapentin (Correct Answer)

Explanation: ***Oral gabapentin*** - The patient's presentation with a history of a unilateral vesicular rash followed by persistent, burning pain, "electrical shocks," and **allodynia** (increased sensation to light touch) in the same dermatomal distribution is highly characteristic of **postherpetic neuralgia (PHN)**. - **Gabapentin** (and pregabalin) are first-line medications for neuropathic pain conditions like PHN as they modulate calcium channels in the central nervous system, reducing neurotransmitter release. *Sublingual nitrates* - Sublingual nitrates are used for immediate relief of **anginal chest pain**, which is typically described as pressure or heaviness, often radiating to the arm or jaw, and relieved by rest or nitrates. - The described pain is neuropathic (burning, electrical shocks, allodynia) and does not fit the pattern of angina, despite the patient's history of MI. *Oral famciclovir* - **Famciclovir** (and acyclovir, valacyclovir) are antiviral medications used to treat acute **herpes zoster (shingles)** to shorten the duration of the rash and reduce the risk of PHN if given within 72 hours of rash onset. - The patient's rash resolved 3 months ago, meaning the acute viral phase is over, and antiviral therapy at this stage would not be effective for PHN. *Intrathecal glucocorticoids* - **Intrathecal glucocorticoids** are rarely used for PHN and are generally reserved for severe, refractory cases as a last resort due to potential side effects and invasiveness. - They are not a first-line treatment for PHN, especially before trying oral neuropathic pain medications. *Oral tricyclic antidepressants* - **Tricyclic antidepressants (TCAs)** like amitriptyline are effective for neuropathic pain, including PHN, and are considered first-line agents alongside gabapentinoids. - However, in elderly patients with a history of cardiac disease (MI, hypertension, on metoprolol and ramipril), TCAs carry a higher risk of **cardiac side effects** (e.g., arrhythmias, orthostatic hypotension) and anticholinergic side effects compared to gabapentin.

Question 794: A 13-year-old girl is brought to the physician by her father because of a worsening pruritic rash for 2 days. Five weeks ago, she was diagnosed with juvenile myoclonic epilepsy and treatment with lamotrigine was begun. Her immunizations are up-to-date. Her temperature is 38.8°C (101.8°F). Physical examination shows facial edema and a partially confluent morbilliform rash over the face, trunk, and extremities. There is swelling of the cervical and inguinal lymph nodes and hepatomegaly. Further evaluation is most likely to show which of the following?

• A. Anti-measles IgM antibodies
• B. Elevated antistreptolysin-O titer
• C. Positive heterophile antibody test
• D. Increased absolute eosinophil count (Correct Answer)
• E. Fragmented red blood cells

Explanation: ***Increased absolute eosinophil count*** - The patient's symptoms (fever, rash, facial edema, lymphadenopathy, hepatomegaly) developing 5 weeks after starting **lamotrigine** are highly suggestive of **Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome**. - **Eosinophilia** is a hallmark laboratory finding in DRESS syndrome, often accompanied by atypical lymphocytosis and elevated liver enzymes. *Anti-measles IgM antibodies* - Measles (rubeola) typically presents with a maculopapular rash developing after a prodrome of cough, coryza, conjunctivitis, and **Koplik spots**, which are not described here. - While measles can cause rash and fever, the onset following medication initiation and the systemic involvement point away from a viral exanthem in an immunized child. *Elevated antistreptolysin-O titer* - An elevated **antistreptolysin-O (ASO) titer** is indicative of a recent **Streptococcus pyogenes** infection, often associated with acute rheumatic fever or post-streptococcal glomerulonephritis. - The clinical picture of a drug-induced hypersensitivity reaction with systemic symptoms does not align with a streptococcal infection. *Positive heterophile antibody test* - A positive **heterophile antibody test** (Monospot test) is characteristic of **infectious mononucleosis**, caused by the Epstein-Barr virus. - While mononucleosis can present with fever, lymphadenopathy, and hepatomegaly, the timing linked to new medication and the specific rash pattern are not typical of mononucleosis. *Fragmented red blood cells* - **Fragmented red blood cells (schistocytes)** are a sign of **microangiopathic hemolytic anemia (MAHA)**, seen in conditions such as thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS). - These conditions involve severe thrombocytopenia and renal involvement, which are not mentioned in the patient's presentation, and do not fit the DRESS syndrome.

Question 795: A 65-year-old man with a history of diabetes, hypertension, hyperlipidemia, and obesity is transferred from the cardiac catheterization lab to the cardiac critical care unit after sustaining a massive myocardial infarction. He received a bare metal stent and has now stabilized. However, shortly after being transferred, he reports palpitations. EKG reveals ventricular tachycardia. Your attending wishes to start an anti-arrhythmic drug with a high selectivity for ischemic cardiac myocytes. You call the nurse and ask her to begin intravenous:

• A. Dofetilide
• B. Procainamide
• C. Lidocaine (Correct Answer)
• D. Flecainide
• E. Quinidine

Explanation: ***Lidocaine*** - **Lidocaine** is a Class IB antiarrhythmic that preferentially binds to **ischemic or depolarized cardiac myocytes**, making it highly effective for ventricular arrhythmias post-MI. - It selectively blocks **sodium channels** in depolarized tissue, stabilizing the membrane and terminating re-entrant pathways. *Dofetilide* - **Dofetilide** is a Class III antiarrhythmic that blocks **potassium channels**, prolonging the action potential duration and effective refractory period. - While effective for atrial fibrillation and flutter, it does not have specific selectivity for ischemic myocytes in the way lidocaine does for ventricular arrhythmias. *Procainamide* - **Procainamide** is a Class IA antiarrhythmic that blocks **sodium channels** and also has some potassium channel blocking effects. - It is effective for both atrial and ventricular arrhythmias but lacks the specific selectivity for ischemic tissue that makes lidocaine preferred in the post-MI setting. *Flecainide* - **Flecainide** is a Class IC antiarrhythmic that strongly blocks **sodium channels**, causing a significant reduction in conduction velocity. - It is **contraindicated in patients with structural heart disease**, including post-MI, due to an increased risk of proarrhythmia. *Quinidine* - **Quinidine** is a Class IA antiarrhythmic that blocks both **sodium channels** and **potassium channels**, prolonging action potential duration. - While used for various arrhythmias, it is generally less preferred for acute ventricular tachycardia post-MI compared to lidocaine due to its broader effects and potential for adverse effects such as **QT prolongation** which increase the risk of **Torsades de Pointes**.

Question 796: A 38-year-old woman with a history of Crohn’s disease presents with a 3-week history of weight gain. The patient also presents with a 1-month history of abdominal pain, cramping, and bloody diarrhea consistent with worsening of her inflammatory bowel disease. Past medical history is significant for Crohn’s disease diagnosed 2 years ago for which she currently takes an oral medication daily and intermittently receives intravenous medication she cannot recall the name of. Her temperature is 37.0°C (98.6°F), blood pressure is 120/90 mm Hg, pulse is 68/min, respiratory rate is 14/min, and oxygen saturation is 99% on room air. Physical examination reveals significant truncal weight gain. The patient has excessive facial hair in addition to purplish striae on her abdomen. Which of the following laboratory findings would most likely be found in this patient?

• A. Hyperglycemia (Correct Answer)
• B. Hypoglycemia
• C. Metabolic acidosis
• D. Hyperkalemia
• E. Hypokalemia

Explanation: ***Hyperglycemia*** - The patient exhibits **Cushing's syndrome** due to chronic corticosteroid use for Crohn's disease, with classic features including truncal obesity, hirsutism, and purplish striae. - **Hyperglycemia is the most common and expected metabolic abnormality** with chronic glucocorticoid therapy, occurring in 30-40% of patients. - Glucocorticoids cause hyperglycemia by **increasing gluconeogenesis**, **promoting glycogenolysis**, and **inducing insulin resistance** in peripheral tissues. - This is a direct and prominent effect of glucocorticoid excess, making it the most likely laboratory finding in this clinical scenario. *Hypokalemia* - While possible with high-dose corticosteroids, hypokalemia is **less common** with modern synthetic glucocorticoids (prednisone, methylprednisolone) which have minimal mineralocorticoid activity. - Hypokalemia primarily occurs with corticosteroids having significant mineralocorticoid effects (hydrocortisone, cortisone) or at very high doses. - Compared to hyperglycemia, this is not the "most likely" finding in typical glucocorticoid therapy. *Hypoglycemia* - Glucocorticoids cause **hyperglycemia**, not hypoglycemia, due to their counter-regulatory effects on glucose metabolism. - This is the opposite of what occurs with steroid excess. *Metabolic acidosis* - **Metabolic alkalosis**, not acidosis, can occur with Cushing's syndrome due to mineralocorticoid effects promoting hydrogen ion excretion. - The hypokalemia that may develop is typically accompanied by alkalosis, not acidosis. *Hyperkalemia* - Glucocorticoids promote **potassium excretion** through mineralocorticoid receptor activation, making hyperkalemia unlikely. - This would contradict the known effects of corticosteroid excess.

Question 797: A 34-year-old business executive presents to her primary care provider because of difficulty falling asleep on her trips. She makes 4–5 business trips from California to China every month. Her typical direct Los Angeles to Hong Kong flight leaves Los Angeles at 12:30 a.m. and reaches Hong Kong at 7:00 p.m. (local time) the next day. She complains of difficulty falling asleep at night and feeling sleepy the next morning. On arriving back in Los Angeles 2–3 days later, she feels extremely weak, has muscle soreness, and abdominal distension, all of which self-resolve in a few days. She is otherwise healthy and does not take any medications. Physical examination is unremarkable. After discussing general sleep hygiene recommendations, which of the following is the best next step for this patient’s condition?

• A. Escitalopram
• B. Polysomnography
• C. Temazepam
• D. Zolpidem
• E. Melatonin (Correct Answer)

Explanation: ***Melatonin*** - The patient is suffering from **jet lag** due to frequent transcontinental travel across multiple time zones, characterized by **insomnia**, fatigue, and gastrointestinal symptoms. **Melatonin** is effective for jet lag, especially for eastward travel, as it helps to **resynchronize the body's circadian rhythm**. - The flight pattern (Los Angeles to Hong Kong) involves traveling **eastward across multiple time zones**, which is known to cause more significant jet lag, and melatonin helps to shift sleep patterns earlier to match the destination time. *Escitalopram* - **Escitalopram** is a selective serotonin reuptake inhibitor (SSRI) used to treat **depression and anxiety disorders**, which are not the primary issues described. - While sleep disturbances can be part of depression, the patient's symptoms are clearly linked to **time zone changes and resolve upon return**, indicating jet lag. *Polysomnography* - **Polysomnography** is a sleep study used to diagnose sleep disorders like **sleep apnea** or **narcolepsy**. - The patient's symptoms are directly related to **time zone changes** and **not indicative of a primary sleep disorder** requiring a sleep study. *Temazepam* - **Temazepam** is a **benzodiazepine hypnotic** used for short-term treatment of insomnia and can be used for jet lag, but it has potential side effects like **sedation, dependence, and rebound insomnia**. - Given it is a controlled substance and that there are other safer options, it is not the best first-line choice for this executive, who needs to travel often. *Zolpidem* - **Zolpidem** is a non-benzodiazepine hypnotic (**Z-drug**) for short-term insomnia, with a risk of side effects like **daytime sleepiness, dependency, and unusual sleep behaviors**. - Like temazepam, it's generally **not preferred for chronic or recurrent situational sleep disturbances** like jet lag when other options like melatonin are available.

Question 798: A 72-year-old man presents to the outpatient clinic today. He has New York Heart Association class III heart failure. His current medications include captopril 20 mg, furosemide 40 mg, potassium chloride 10 mg twice daily, rosuvastatin 20 mg, and aspirin 81 mg. He reports that he generally feels well and has not had any recent worsening of his symptoms. His blood pressure is 132/85 mm Hg and heart rate is 84/min. Physical examination is unremarkable except for trace pitting edema of the bilateral lower extremities. What other medication should be added to his heart failure regimen?

• A. Losartan
• B. Metoprolol tartrate
• C. Isosorbide dinitrate/hydralazine
• D. Metoprolol succinate (Correct Answer)
• E. Digoxin

Explanation: ***Metoprolol succinate*** - Current guidelines recommend adding a **beta-blocker** (specifically metoprolol succinate, carvedilol, or bisoprolol) as part of guideline-directed medical therapy (GDMT) for **NYHA class II-IV heart failure with reduced ejection fraction (HFrEF)**. - This patient is already on an **ACE inhibitor and diuretic** but is missing a **beta-blocker**, which is a cornerstone of HFrEF therapy. - Beta-blockers **reduce mortality and morbidity** in HFrEF by counteracting chronic sympathetic activation, improving cardiac remodeling, and reducing heart rate. - Metoprolol succinate is the **long-acting formulation** preferred for chronic heart failure management. ***Incorrect Option: Losartan*** - The patient is already on an **ACE inhibitor (captopril)**, which acts on the renin-angiotensin-aldosterone system. - Adding an **ARB (angiotensin receptor blocker)** like losartan to an ACE inhibitor is generally not recommended due to increased risk of hyperkalemia, hypotension, and renal dysfunction without significant additional benefit. - ARBs are typically used as an alternative when patients cannot tolerate ACE inhibitors (e.g., due to cough or angioedema). ***Incorrect Option: Metoprolol tartrate*** - While metoprolol tartrate is a beta-blocker, it is a **short-acting formulation** typically used for acute conditions like hypertension or angina. - For **chronic heart failure management**, **long-acting beta-blockers** such as metoprolol succinate are preferred due to sustained therapeutic levels, better adherence, and proven mortality benefit in clinical trials. ***Incorrect Option: Isosorbide dinitrate/hydralazine*** - This combination is primarily indicated for **African American patients with NYHA class III-IV HFrEF** who remain symptomatic despite optimal therapy, or as an alternative in patients who cannot tolerate ACE inhibitors/ARBs. - While the patient has class III heart failure, he is **not yet on a beta-blocker**, which is a more fundamental component of GDMT and should be added first. - This combination is typically added as a fourth-line agent. ***Incorrect Option: Digoxin*** - Digoxin is considered for patients with **HFrEF who remain symptomatic** despite optimized therapy with ACE inhibitors/ARBs, beta-blockers, and mineralocorticoid receptor antagonists (MRAs). - It primarily helps **improve symptoms and reduce hospitalizations** but does not reduce mortality. - Since this patient is not yet on a beta-blocker, adding the beta-blocker takes priority.

Question 799: A 17-year-old man presents to his primary care physician concerned about excessive sleepiness that has persisted his entire life. He notes that he has been having difficulty with his job as a waiter because he often falls asleep suddenly during the day. He also experiences a sensation of dreaming as he goes to sleep even though he still feels awake. He sleeps about 10 hours per day and still feels tired throughout the day. The patient has even reported driving into a tree once as he fell asleep while driving. The patient often stays up late at night working on the computer. Physical exam demonstrates an obese young man who appears tired. His oropharynx demonstrates high palatal ridges and good dental hygiene. Which of the following is the best next step in management?

• A. Recommend scheduling regular naps and more time for sleep at night
• B. Start a selective serotonin reuptake inhibitor
• C. Begin inhibitor of dopamine reuptake
• D. Order sleep study with Multiple Sleep Latency Test (Correct Answer)
• E. Continuous positive airway pressure at night

Explanation: ***Order sleep study with Multiple Sleep Latency Test*** - This patient presents with classic symptoms of **narcolepsy**: **excessive daytime sleepiness**, **sudden sleep attacks**, and **hypnagogic hallucinations** (sensation of dreaming while still feeling awake). - The **Multiple Sleep Latency Test (MSLT)** following overnight **polysomnography** is the **gold standard for diagnosing narcolepsy**. The MSLT measures how quickly the patient falls asleep during daytime nap opportunities and detects **sleep-onset REM periods (SOREMPs)**, which are characteristic of narcolepsy. - **Diagnosis must precede treatment**: Before initiating pharmacotherapy with controlled substances like modafinil, **definitive diagnosis is required** for both medical/legal standards and insurance approval. - While the patient has safety concerns (fell asleep driving), the immediate management includes **counseling about driving restrictions** and **ordering diagnostic testing** as the next step. *Begin inhibitor of dopamine reuptake* - **Modafinil** or **armodafinil** (dopamine reuptake inhibitors) are first-line treatments for **confirmed narcolepsy** to promote wakefulness and reduce excessive daytime sleepiness. - However, these medications are **controlled substances** that require a confirmed diagnosis before initiation. Starting treatment without diagnostic confirmation violates standard medical practice and would not be covered by insurance without proper diagnosis codes. - This would be the appropriate step **after** confirming narcolepsy with sleep study and MSLT. *Recommend scheduling regular naps and more time for sleep at night* - While **sleep hygiene** and **scheduled naps** can be adjunctive measures in narcolepsy management, they do not address the underlying pathophysiology and are insufficient as primary management. - The patient already sleeps 10 hours per day, suggesting that simply increasing sleep time will not resolve the pathological sleepiness. - This does not provide diagnostic confirmation, which is essential before any treatment plan. *Start a selective serotonin reuptake inhibitor* - **SSRIs** or **SNRIs** (like venlafaxine) can be used to treat **cataplexy** (sudden loss of muscle tone triggered by emotions) in narcolepsy patients. - This patient does not describe clear cataplexy symptoms, and the primary complaint is excessive daytime sleepiness and sleep attacks. - Like dopamine reuptake inhibitors, SSRIs should only be started **after diagnostic confirmation** of narcolepsy. *Continuous positive airway pressure at night* - **CPAP** is the primary treatment for **obstructive sleep apnea (OSA)**, which can cause daytime sleepiness due to fragmented sleep from apneic episodes. - While this patient is **obese** (a risk factor for OSA) and has **high palatal ridges**, his symptoms of **hypnagogic hallucinations** and **sudden irresistible sleep attacks** are characteristic of **narcolepsy, not OSA**. - The polysomnography portion of the sleep study will also rule out OSA as a contributing factor, but the primary diagnosis here is narcolepsy.

Question 800: A 43-year-old woman walks into the clinic for an annual check-up appointment with her family physician. When asked about any changes in her life, she states that she lost her job about 6 months ago. Since then, she has lived with her boyfriend who is also unemployed. She frequently uses laxatives and takes some over the counter medications to help her sleep. Her blood pressure is 129/87 mm Hg, respirations are 12/min, pulse is 58/min, and temperature is 36.7°C (98.1°F). Her physical exam is mostly benign. Her pupils appear mildly constricted and she appears drowsy and subdued. The physician suspects that the physical findings in this patient are caused by a substance she is likely abusing. Which of the following is the substance?

• A. Cocaine
• B. Alprazolam
• C. Codeine (Correct Answer)
• D. Clonazepam
• E. Ketamine

Explanation: ***Codeine*** - **Miosis** (constricted pupils), **drowsiness**, **bradycardia** (pulse 58/min), and **reduced respiratory rate** (12/min) represent the classic **opioid toxidrome**. - The patient's use of **laxatives** suggests chronic opioid use to manage opioid-induced constipation, a common side effect. - Codeine is available in many over-the-counter preparations and is commonly abused. *Cocaine* - Cocaine is a **sympathomimetic stimulant** that causes **mydriasis** (pupil dilation), tachycardia, hypertension, and increased alertness or agitation. - The patient's presentation of miosis, bradycardia, and sedation is completely opposite to cocaine intoxication. *Alprazolam* - While alprazolam (a benzodiazepine) can cause drowsiness and sedation, it does **not typically cause miosis**. - Benzodiazepines may cause respiratory depression at high doses but are not associated with the pronounced **miosis** and **bradycardia** seen in this patient. - The opioid toxidrome is more specific to this clinical presentation. *Clonazepam* - Clonazepam, another benzodiazepine, shares similar effects with alprazolam, causing **sedation** and potential respiratory depression at high doses. - However, like other benzodiazepines, it does **not cause miosis** or bradycardia, which are hallmark features of opioid intoxication. *Ketamine* - Ketamine causes a **dissociative state** with **nystagmus**, and typically produces **hypertension and tachycardia** (not bradycardia). - It does not cause the **miosis**, bradycardia, or classic sedated presentation characteristic of opioid intoxication.

Question 801: A 55-year-old woman comes to the physician because of involuntary rhythmic shaking of both hands for several months. More recently, she also noticed involuntary head nodding movements. The shaking seems to improve after having one or two glasses of wine. Her father had similar symptoms starting at the age of 60. Neurologic examination shows a symmetric hand tremor that worsens with voluntary movement of the respective extremity. The most appropriate pharmacotherapy for this patient's symptoms is also recommended for the treatment of which of the following conditions?

• A. Malignant hyperthermia
• B. Restless legs syndrome
• C. Hyperthyroidism (Correct Answer)
• D. Sleepwalking
• E. Motion sickness

Explanation: ***Hyperthyroidism*** - The patient presents with **essential tremor**, characterized by **bilateral symmetric hand tremor** that worsens with action, head nodding, and improvement with alcohol. The first-line treatment for essential tremor is **propranolol**, a non-selective beta-blocker. - Propranolol is also the primary symptomatic treatment for the adrenergic symptoms of **hyperthyroidism**, such as **tachycardia**, tremor, and anxiety, by blocking beta-adrenergic receptors. *Malignant hyperthermia* - This is a life-threatening, rare pharmacogenetic disorder triggered by certain anesthetic agents, leading to **skeletal muscle rigidity**, hyperthermia, and metabolic acidosis. - The primary treatment is **dantrolene**, a muscle relaxant, not propranolol. *Restless legs syndrome* - Characterized by an irresistible urge to move the legs, often accompanied by unpleasant sensations, typically worse at rest and in the evening. - First-line treatments include **dopamine agonists** (e.g., pramipexole, ropinirole) or gabapentin, not propranolol. *Sleepwalking* - A type of parasomnia characterized by complex behaviors while partially aroused from NREM sleep, with no memory of the event upon awakening. - While sometimes managed with low-dose benzodiazepines or antidepressants, propranolol is not a standard treatment. *Motion sickness* - Caused by a mismatch between visual and vestibular sensory input, leading to nausea, vomiting, and dizziness. - Treated with anticholinergic agents like **scopolamine**, or antihistamines such as dimenhydrinate, primarily targeting the vestibular system and central nervous system.

Question 802: The drug cilostazol is known for its ability to relax vascular smooth muscle and therefore cause vasodilation through its inhibition of phosphodiesterase 3. Given this mechanism of action, what other effect would be expected?

• A. Antiarrhythmic action
• B. Negative chronotropy
• C. Angioedema
• D. Increased left ventricular end-diastolic volume
• E. Positive inotropy (Correct Answer)

Explanation: ***Positive inotropy*** - **Cilostazol** inhibits **phosphodiesterase 3 (PDE3)**, leading to an increase in **cAMP** levels within cardiac myocytes. - Increased **cAMP** in the heart results in enhanced calcium influx and release, which strengthens myocardial contraction, leading to **positive inotropy**. *Antiarrhythmic action* - While some drugs affecting **cAMP** can have antiarrhythmic effects, **PDE3 inhibitors** like cilostazol can sometimes **increase heart rate** and potentially cause or worsen arrhythmias due to increased conduction and excitability. - Their primary mechanism of action for cardiac effects is **inotropy**, not rhythm stabilization. *Negative chronotropy* - **Negative chronotropy** refers to a decrease in heart rate, which is typically seen with drugs that reduce **cAMP** or directly inhibit the **sinoatrial node**. - As a **PDE3 inhibitor**, cilostazol leads to increased **cAMP**, which usually causes a modest increase in heart rate (**positive chronotropy**), not a decrease. *Angioedema* - **Angioedema** is a side effect often associated with **ACE inhibitors** or certain allergic reactions, mediated by bradykinin or histamine release. - It is not a known or expected effect of **cilostazol** based on its mechanism of **PDE3 inhibition** and cAMP modulation. *Increased left ventricular end-diastolic volume* - **Cilostazol** causes **vasodilation**, which **reduces peripheral vascular resistance** and thus **afterload**. - This reduction in afterload, combined with its **positive inotropic** effects, tends to improve cardiac output and can actually lead to a **decrease** in **left ventricular end-diastolic volume** due to more efficient ejection, rather than an increase.

Question 803: A 68-year-old man presents to his primary care physician with a 4-week history of back pain. He says that the pain does not appear to be associated with activity and is somewhat relieved by taking an NSAID. Furthermore, he says that he has had increasing difficulty trying to urinate. His past medical history is significant for kidney stones and a 30-pack-year smoking history. Radiographs reveal osteoblastic lesions in the spine. Which of the following drugs would most likely be effective in treating this patient's disease?

• A. Imatinib
• B. Tamsulosin
• C. Pulsatile leuprolide
• D. Rituximab
• E. Continuous leuprolide (Correct Answer)

Explanation: ***Continuous leuprolide*** - The patient's presentation with **back pain**, urinary difficulties (**dysuria**), and **osteoblastic lesions** in an elderly male with a history of smoking is highly suggestive of **metastatic prostate cancer**. - **Continuous leuprolide** (a GnRH agonist) causes an initial surge in testosterone followed by downregulation of GnRH receptors leading to chemical castration, which is an effective treatment for hormone-sensitive prostate cancer. *Imatinib* - **Imatinib** is a **tyrosine kinase inhibitor** primarily used to treat **chronic myeloid leukemia (CML)** and gastrointestinal stromal tumors (GIST). - It works by inhibiting the BCR-ABL tyrosine kinase in CML and KIT/PDGFRA in GIST, neither of which is relevant to prostate cancer. *Tamsulosin* - **Tamsulosin** is an **alpha-1 adrenergic antagonist** used to improve urinary flow in patients with **benign prostatic hyperplasia (BPH)**. - While the patient has urinary difficulties, the presence of bone metastases (osteoblastic lesions) and back pain points towards malignancy, making BPH treatment alone insufficient. *Pulsatile leuprolide* - **Pulsatile leuprolide** administration (a GnRH agonist) mimics the natural pulsatile release of GnRH and is used to **stimulate gonadotropin release** for treating infertility. - This would increase testosterone levels, which would be detrimental in the treatment of androgen-sensitive prostate cancer. *Rituximab* - **Rituximab** is a **monoclonal antibody** targeting the **CD20 antigen** found on B-lymphocytes. - It is primarily used in the treatment of **non-Hodgkin lymphoma**, chronic lymphocytic leukemia, and certain autoimmune diseases, not prostate cancer.

Question 804: A 63-year-old man comes to the physician because of generalized fatigue and malaise for 2 months. He has been unable to engage in his daily activities. Three months ago, he was treated for a urinary tract infection with trimethoprim-sulfamethoxazole. He has hypertension, asthma, and chronic lower back pain. Current medications include hydrochlorothiazide, an albuterol inhaler, naproxen, and an aspirin-caffeine combination. Vital signs are within normal limits. Examination shows conjunctival pallor. The remainder of the examination shows no abnormalities. Laboratory studies show: Hemoglobin 9.1 g/dL Leukocyte count 8,900/mm3 Erythrocyte sedimentation rate 13 mm/h Serum Na+ 136 mEq/L K+ 4.8 mEq/L Cl- 102 mEq/L Urea nitrogen 41 mg/dL Glucose 70 mg/dL Creatinine 2.4 mg/dL Calcium 9.8 mg/dL Urine Protein 1+ Blood 1+ RBCs none WBCs 8–9/hpf Bacteria none Urine cultures are negative. Ultrasound shows shrunken kidneys with irregular contours and papillary calcifications. Which of the following is the most likely underlying mechanism of this patient's renal failure?

• A. Inhibition of prostaglandin synthesis (Correct Answer)
• B. Precipitation of drugs within the renal tubules
• C. Hypersensitivity reaction
• D. MUC1 gene mutation
• E. Excess amount of light chain production

Explanation: ***Inhibition of prostaglandin synthesis*** - This patient's chronic use of **naproxen** (an NSAID) and **aspirin-caffeine combination** is the most probable cause of his **chronic kidney disease** (analgesic nephropathy). NSAIDs inhibit **cyclooxygenase (COX) enzymes**, blocking **prostaglandin synthesis** (including PGE2 and PGI2), which are crucial for maintaining **afferent arteriolar dilation** and renal blood flow, especially in patients with comorbidities like hypertension. - The imaging findings of **shrunken kidneys with irregular contours and papillary calcifications** are classic for **analgesic nephropathy** from prolonged NSAID use. The elevated **creatinine** (2.4 mg/dL) and **urea nitrogen** (41 mg/dL), along with fatigue and malaise, indicate significant chronic renal impairment. *Precipitation of drugs within the renal tubules* - While drug precipitation can cause acute kidney injury (e.g., from certain antibiotics, acyclovir, or methotrexate), it typically leads to **acute tubular necrosis** or **obstructive nephropathy** with crystalluria. - The presentation here suggests **chronic, insidious kidney damage** over months to years. The specific drugs used by this patient are not primary causes of tubular precipitation leading to this chronic presentation with papillary calcifications. *Hypersensitivity reaction* - A **hypersensitivity reaction** (acute interstitial nephritis) typically presents as **acute kidney injury** with features like fever, rash, eosinophilia, and eosinophiluria. - While trimethoprim-sulfamethoxazole can cause acute interstitial nephritis, the patient was treated **3 months ago** and the symptoms are chronic (2 months duration). The urinalysis does not show characteristic findings like **eosinophiluria** or WBC casts, and the chronic imaging findings point to a different etiology. *MUC1 gene mutation* - A **MUC1 gene mutation** is associated with **autosomal dominant tubulointerstitial kidney disease (ADTKD)**, formerly called medullary cystic kidney disease type 1, an inherited disorder leading to progressive chronic kidney disease. - While this can present with shrunken kidneys, the **papillary calcifications** are characteristic of **analgesic nephropathy**, not ADTKD. Additionally, there is no family history or age of onset typical for a genetic disorder (usually presents earlier in life). *Excess amount of light chain production* - **Excess light chain production** is seen in **multiple myeloma**, which can lead to **cast nephropathy** (myeloma kidney), causing renal failure. - While myeloma can cause fatigue and anemia, other classic features are absent: **normal calcium** (9.8 mg/dL, not hypercalcemic), **normal ESR** (13 mm/h, typically markedly elevated in myeloma), and no evidence of monoclonal protein. The **papillary calcifications** are not typical for myeloma kidney.

Question 805: A 54-year-old male presents to clinic complaining that he is not sleeping well because he has to get up from bed to urinate multiple times throughout the night. He says that he strains to void, has terminal dribbling, and has urinary urgency. Past medical history is significant for orthostatic hypotension. On digital rectal exam, you note symmetric firm enlargement of the prostate. Free Prostate-Specific-Antigen (PSA) level is 4.6 ng/mL. Before you finish your physical exam, the patient asks if there is anything you can do for his male-pattern baldness. What is the mechanism of action of the drug that would pharmacologically treat this patient’s urinary issues and his male-pattern baldness?

• A. Squalene epoxidase inhibition
• B. 5-alpha reductase inhibition (Correct Answer)
• C. 17,20-desmolase inhibition
• D. Phosphodiesterase-5 inhibition
• E. Alpha-1 blockade

Explanation: ***5-alpha reductase inhibition*** - The patient's symptoms (nocturia, straining, terminal dribbling, urgency, and prostatic enlargement) are consistent with **benign prostatic hyperplasia (BPH)**. - **5-alpha reductase inhibitors** (e.g., finasteride, dutasteride) block the conversion of **testosterone to dihydrotestosterone (DHT)**, which is responsible for both prostatic growth and male-pattern baldness. - These drugs are **FDA-approved for both BPH and androgenic alopecia (male-pattern baldness)**, making them ideal for this patient. - Importantly, they do not worsen orthostatic hypotension, unlike alpha-1 blockers, making them especially suitable given this patient's history. *Squalene epoxidase inhibition* - This mechanism of action is associated with **terbinafine**, an antifungal drug used to treat conditions like onychomycosis. - It has no role in treating BPH or male-pattern baldness. *17,20-desmolase inhibition* - **Abiraterone**, a drug used in metastatic prostate cancer, inhibits **17,20-desmolase (CYP17)**, thereby preventing the synthesis of androgens. - While it affects androgen-dependent prostate conditions, it is reserved for advanced prostate cancer, not BPH, and is not used for male-pattern baldness. *Phosphodiesterase-5 inhibition* - **PDE5 inhibitors** (e.g., tadalafil) are FDA-approved for **erectile dysfunction and BPH** by increasing cGMP, which relaxes smooth muscle. - While effective for BPH urinary symptoms, they do not address male-pattern baldness. *Alpha-1 blockade* - **Alpha-1 blockers** (e.g., tamsulosin, terazosin) relax the smooth muscle in the prostate and bladder neck, improving urinary flow in BPH. - While effective for urinary symptoms of BPH, they have no impact on male-pattern baldness. - Additionally, they can **worsen orthostatic hypotension**, which is a concern in this patient with a history of orthostatic hypotension.

Question 806: An otherwise healthy 23-year-old man comes to the physician because of a 3-day history of mild persistent bleeding from the site of a tooth extraction. He has no prior history of medical procedures or surgeries and no history of easy bruising. He appears well. Vital signs are within normal limits. Laboratory studies show: Hemoglobin 12.4 g/dL Platelets 200,000/mm3 Serum Prothrombin time 25 seconds Partial thromboplastin time (activated) 35 seconds Deficiency of which of the following coagulation factors is the most likely cause of this patient’s condition?

• A. Factor II
• B. Factor XIII
• C. Factor X
• D. Factor VII (Correct Answer)
• E. Factor V

Explanation: ***Factor VII*** - An **isolated prolonged PT** with a normal aPTT, platelets, and hemoglobin points to a defect in the **extrinsic pathway** of coagulation. - **Factor VII** is the sole coagulation factor exclusively in the extrinsic pathway, making its deficiency the most likely cause. *Factor II* - **Factor II (prothrombin)** is a common pathway factor, so its deficiency would prolong both PT and aPTT. - The patient's aPTT is normal, ruling out a significant deficiency of Factor II. *Factor XIII* - **Factor XIII** is responsible for stabilizing the fibrin clot but does not affect PT or aPTT. - A deficiency would present with delayed bleeding or poor wound healing, not a prolonged PT. *Factor X* - **Factor X** is a common pathway factor, and its deficiency would prolong both PT and aPTT. - The normal aPTT in this patient makes Factor X deficiency unlikely. *Factor V* - **Factor V** is a common pathway factor, and its deficiency would result in prolongation of both PT and aPTT. - The normal aPTT makes a Factor V deficiency improbable.

Question 807: You are currently employed as a clinical researcher working on clinical trials of a new drug to be used for the treatment of Parkinson's disease. Currently, you have already determined the safe clinical dose of the drug in a healthy patient. You are in the phase of drug development where the drug is studied in patients with the target disease to determine its efficacy. Which of the following phases is this new drug currently in?

• A. Phase 4
• B. Phase 1
• C. Phase 2 (Correct Answer)
• D. Phase 0
• E. Phase 3

Explanation: ***Phase 2*** - **Phase 2 trials** involve studying the drug in patients with the target disease to assess its **efficacy** and further evaluate safety, typically involving a few hundred patients. - The question describes a stage after safe dosing in healthy patients (Phase 1) and before large-scale efficacy confirmation (Phase 3), focusing on efficacy in the target population. *Phase 4* - **Phase 4 trials** occur **after a drug has been approved** and marketed, monitoring long-term effects, optimal use, and rare side effects in a diverse patient population. - This phase is conducted post-market approval, whereas the question describes a drug still in development prior to approval. *Phase 1* - **Phase 1 trials** primarily focus on determining the **safety and dosage** of a new drug in a **small group of healthy volunteers** (or sometimes patients with advanced disease if the drug is highly toxic). - The question states that the safe clinical dose in a healthy patient has already been determined, indicating that Phase 1 has been completed. *Phase 0* - **Phase 0 trials** are exploratory, very early-stage studies designed to confirm that the drug reaches the target and acts as intended, typically involving a very small number of doses and participants. - These trials are conducted much earlier in the development process, preceding the determination of safe clinical doses and large-scale efficacy studies. *Phase 3* - **Phase 3 trials** are large-scale studies involving hundreds to thousands of patients to confirm **efficacy**, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug to be used safely. - While Phase 3 does assess efficacy, it follows Phase 2 and is typically conducted on a much larger scale before submitting for regulatory approval.

Question 808: A 70 year-old man comes to the emergency department for sudden loss of vision in the right eye over the last 24 hours. He has noticed progressive bilateral loss of central vision over the last year. He has had difficulty reading his newspaper and watching his television. He has smoked 1 pack daily for 50 years. Ophthalmologic examination shows visual acuity of 20/60 in the left eye and 20/200 in the right eye. The pupils are equal and reactive to light. Tonometry reveals an intraocular pressure of 18 mm Hg in the right eye and 20 mm Hg in the left eye. Anterior segment exam is unremarkable. Slit-lamp examination shows subretinal fluid and small hemorrhage with grayish-green discoloration in the macular area in the right eye, and multiple drusen in the left eye with retinal pigment epithelial changes. Which of the following is the most appropriate initial treatment for the patient's illness?

• A. Macular translocation surgery
• B. Etanercept
• C. Ranibizumab (Correct Answer)
• D. Thermal laser photocoagulation
• E. Photodynamic therapy

Explanation: ***Ranibizumab*** - The presence of **subretinal fluid**, hemorrhage, and grayish-green discoloration in the macula of the right eye, along with sudden vision loss, is highly suggestive of **wet age-related macular degeneration (AMD)**. - **Ranibizumab**, an anti-VEGF agent, is the **first-line treatment** for wet AMD, as it inhibits abnormal blood vessel growth and leakage. *Macular translocation surgery* - This is an **invasive surgical procedure** considered for select cases of wet AMD, but it is not the initial or preferred treatment due to its complexity and potential complications. - It involves repositioning the macula to a healthier RPE, typically reserved for cases unresponsive to less invasive therapies. *Etanercept* - **Etanercept** is a TNF-alpha inhibitor used primarily for inflammatory conditions like **rheumatoid arthritis** and **psoriasis**. - It has no role in the treatment of wet AMD, which is a degenerative condition involving angiogenesis. *Thermal laser photocoagulation* - While historically used for some types of macular disease, **thermal laser photocoagulation** destroys retinal tissue and can cause **scotomas**. - It is generally **contraindicated for subfoveal lesions** and has largely been replaced by anti-VEGF therapy for wet AMD due to poorer visual outcomes. *Photodynamic therapy* - **Photodynamic therapy (PDT)** with verteporfin was previously used for some forms of wet AMD, particularly those with **predominantly classic choroidal neovascularization**. - However, **anti-VEGF injections** like ranibizumab are now considered superior with better visual outcomes and are the preferred initial treatment.

Question 809: A 45-year-old man is brought into the clinic by his wife. She reports that her husband has been feeling down since he lost a big project at work 2 months ago. The patient says he feels unmotivated to work or do things around the house. He also says he is not eating or sleeping as usual and spends most of his day pacing about his room. He feels guilty for losing such a project this late in his career and feels overwhelming fear about the future of his company and his family’s well-being. During the interview, he appears to be in mild distress and is wringing his hands. The patient is prescribed citalopram and buspirone. Which of the following side effects is most commonly seen with buspirone?

• A. Lightheadedness (Correct Answer)
• B. Sleepwalking
• C. Respiratory depression
• D. Dry mouth
• E. Anterograde amnesia

Explanation: ***Lightheadedness*** - **Lightheadedness** and dizziness are among the most frequently reported side effects of **buspirone**, particularly at the initiation of treatment or with dose adjustments. - This is thought to be related to its modulation of **serotonin receptors** and its impact on the central nervous system. *Sleepwalking* - **Sleepwalking** is not a common side effect associated with buspirone; it is more frequently linked with sedatives like **zolpidem**. - Buspirone is generally considered to have a different mechanism of action and side effect profile than drugs that induce sleepwalking. *Respiratory depression* - **Respiratory depression** is a serious side effect most commonly associated with **benzodiazepines** or **opioids**, especially when taken in overdose or combined with other central nervous system depressants. - Buspirone is known for its **lack of sedative and respiratory depressant effects**, which is a key advantage over benzodiazepines. *Dry mouth* - While **dry mouth** can occur with various medications, it is not a primary or most common side effect specifically associated with **buspirone**. - It's more often seen with drugs that have **anticholinergic properties**, such as tricyclic antidepressants. *Anterograde amnesia* - **Anterograde amnesia** is a well-known side effect of **benzodiazepines**, where a person cannot form new memories after taking the drug. - Buspirone does not typically cause this type of memory impairment, which contributes to its safer profile compared to benzodiazepines.

Question 810: A 19-year-old woman comes to the physician because of a delayed menstrual period. She has had regular menses since menarche at age 11. Her last menstrual period was 7 weeks ago. She is sexually active with two male partners. A urine pregnancy test is positive. An ultrasound of the pelvis shows a viable intrauterine pregnancy with an estimated gestational age of 6 weeks and 5 days. She does not wish to continue with the pregnancy. After carefully weighing the options with her physician, she is prescribed two medications, one of which is mifepristone. Which of the following is this drug's primary mechanism of action?

• A. Activation of prostaglandin E1 receptors
• B. Inhibition of dihydrofolate reductase
• C. Blockage of progesterone receptor (Correct Answer)
• D. Agonist at oxytocin receptors
• E. Antagonist at gonadotropin-releasing hormone receptors

Explanation: ***Blockage of progesterone receptor*** - **Mifepristone** is a **progesterone receptor antagonist**, meaning it blocks the action of progesterone. - Progesterone is essential for maintaining early pregnancy by supporting the **endometrium** and preventing uterine contractions. *Activation of prostaglandin E1 receptors* - This is the primary mechanism of action for **misoprostol**, the second medication often used in medical abortion protocols. - **Misoprostol** causes **uterine contractions** and cervical ripening, which expels the uterine contents after mifepristone has prepared the uterus. *Inhibition of dihydrofolate reductase* - This is the mechanism of action for **methotrexate**, an antifolate drug that can also be used for medical abortion. - **Methotrexate** inhibits DNA synthesis in rapidly dividing cells, leading to the termination of the pregnancy. *Agonist at oxytocin receptors* - **Oxytocin agonists** (like oxytocin itself) are typically used for labor induction or to control postpartum hemorrhage, not for early medical abortion. - They cause strong uterine contractions but are usually administered later in pregnancy or postpartum. *Antagonist at gonadotropin-releasing hormone receptors* - **GnRH antagonists** (e.g., cetrorelix, ganirelix) are used in assisted reproductive technologies to prevent premature ovulation. - They do not directly cause medical abortion by blocking progesterone's action or directly inducing uterine contractions.

Question 811: A 28-year-old woman visits the clinic expressing a desire to become pregnant. She was seen for depressed mood and disinterest in her usual leisure activities a few months ago. She also had decreased sleep and appetite and was not able to concentrate at work. She was started on fluoxetine and has been compliant for the last 6 months despite experiencing some of the side effects. She now feels significantly better and would like to stop the medication because she plans to become pregnant and thinks it is unnecessary now. Which of the following is the most appropriate counseling regarding her antidepressant therapy?

• A. It requires careful risk-benefit analysis during pregnancy. (Correct Answer)
• B. Most side effects persist throughout therapy.
• C. It has the longest half-life of any drugs in the same class.
• D. It can cause anorgasmia.
• E. It can increase levels of concurrent medications metabolized by CYP2D6.

Explanation: ***It requires careful risk-benefit analysis during pregnancy.*** - This is the **most appropriate counseling** for this patient who wants to discontinue fluoxetine due to pregnancy planning. - The decision to continue or discontinue **fluoxetine** during pregnancy involves weighing the risks of medication exposure to the fetus against the risks of **untreated maternal depression**, such as preterm birth, low birth weight, poor prenatal care, and postpartum depression. - **Abrupt discontinuation** in a patient who has responded well increases the risk of depression relapse, which can be harmful during pregnancy. - While fluoxetine is **FDA Pregnancy Category C**, it is generally considered one of the safer SSRIs for use in pregnancy when clinically indicated, with an individualized **risk-benefit discussion** being crucial. *Most side effects persist throughout therapy.* - Many common **side effects** of fluoxetine, such as nausea, insomnia, and anxiety, are often **transient** and tend to diminish within the first few weeks of therapy as the body adjusts. - While some side effects, such as sexual dysfunction, may persist, most side effects do not endure throughout the entire course of treatment. - This statement is **not the most relevant** counseling for a patient planning pregnancy. *It has the longest half-life of any drugs in the same class.* - **Fluoxetine** does have the longest half-life among SSRIs: approximately **2-4 days** for the parent compound and **7-15 days** for its active metabolite, **norfluoxetine**. - While this is a **true statement** and has clinical implications (reduced withdrawal symptoms, less need for tapering), it is **not the most appropriate counseling** for this patient's specific concern about pregnancy planning. *It can cause anorgasmia.* - **Sexual dysfunction**, including **decreased libido**, **delayed orgasm**, and **anorgasmia**, is a common side effect of SSRIs like fluoxetine, occurring in 30-60% of patients. - While this is a **true statement** about fluoxetine, it does not address the patient's primary concern about pregnancy planning and is therefore **not the most appropriate counseling** in this context. *It can increase levels of concurrent medications metabolized by CYP2D6.* - **Fluoxetine** is a **potent inhibitor** of the **CYP2D6 enzyme**, which can increase plasma levels of other drugs metabolized by this pathway (e.g., tricyclic antidepressants, beta-blockers, antiarrhythmics, antipsychotics). - While this is a **true and clinically important statement**, it is **not the most relevant counseling** for this patient who is planning pregnancy and considering discontinuation.

Question 812: A 52-year-old woman makes a follow-up appointment with her primary care physician for evaluation of her diabetes medications. Specifically, she complains that she has been experiencing flushing, nausea, and palpitations after drinking a glass of wine with dinner after she started the latest regimen for her diabetes. She was warned that this was a side-effect of one of her medications but she did not understand the severity of the reaction. Given this experience, she asks to be placed on an alternative regimen that does not involve the medication that caused this reaction. Her physician therefore replaces the medication with another one that interacts with the same target though at a different binding site. Which of the following is a side-effect of the new medication?

• A. Hepatotoxicity
• B. Pancreatitis
• C. Weight gain (Correct Answer)
• D. Lactic acidosis
• E. Urinary tract infection

Explanation: ***Weight gain*** - The patient experienced a **disulfiram-like reaction** with alcohol, indicative of a **sulfonylurea** medication like glipizide or glyburide. The physician replaces it with another medication that interacts with the same target (sulfonylurea receptor on pancreatic beta cells) but at a different binding site, which describes a **meglitinide (e.g., repaglinide)**. - **Weight gain** is a common side effect of meglitinides, similar to sulfonylureas, due to increased insulin secretion. *Hepatotoxicity* - While some diabetes medications can affect the liver, **hepatotoxicity** is not a primary or common side effect associated with meglitinides. - Pioglitazone, for instance, has a black box warning for liver failure, but is not the drug class described. *Pancreatitis* - **Pancreatitis** is not a characteristic side effect of meglitinides. - This adverse effect is more commonly associated with GLP-1 receptor agonists (e.g., exenatide, liraglutide) and DPP-4 inhibitors (e.g., sitagliptin). *Lactic acidosis* - **Lactic acidosis** is a rare but serious side effect specifically associated with **metformin**, especially in patients with renal impairment or conditions causing tissue hypoxia. - This side effect is not seen with meglitinides. *Urinary tract infection* - **Urinary tract infections (UTIs)** are a common side effect of **SGLT2 inhibitors** (e.g., canagliflozin, empagliflozin) due to increased glucose excretion in the urine which promotes bacterial growth. - This is not a typical side effect of meglitinides.

Question 813: Eight days after sigmoid resection for acute diverticulitis, a 61-year-old man has left-sided flank pain. He has been on bowel rest since admission. Other than multiple admissions for alcohol withdrawal, he has no history of serious illness. Current medications include intravenous cefepime and morphine. His temperature is 36.9°C (98.4°F), pulse is 89/min, and blood pressure is 118/75 mm Hg. Abdominal exam shows a well-healing incision with minimal serous drainage. Examination of the skin shows scattered spider angiomas, a large hematoma on the left flank, and numerous bruises over the abdomen and extremities. He complains of pain when his left hip is extended. Laboratory studies show: Hemoglobin 8.4 g/dL Mean corpuscular volume 102 μm3 Leukocyte count 8,200/mm3 Platelet count 170,000/mm3 Serum Bleeding time 4 minutes Prothrombin time 26 seconds Partial thromboplastin time (activated) 39 seconds Which of the following is the most likely underlying cause of this patient's current symptoms?

• A. Deficiency of folic acid
• B. Decreased synthesis of thrombopoietin
• C. Resistance of Factor V inactivation
• D. Vitamin K deficiency (Correct Answer)
• E. Administration of heparin

Explanation: ***Vitamin K deficiency*** - The patient's several signs of **coagulopathy** (large hematoma, numerous bruises, prolonged PT, slightly prolonged aPTT) following a surgery and bowel rest, coupled with a history of **alcohol abuse** and current antibiotic use (cefepime), strongly suggest vitamin K deficiency. Alcoholism causes **malnutrition** and impaired hepatic storage of vitamin K, while antibiotics like cefepime can reduce gut flora responsible for vitamin K synthesis. - **Vitamin K** is essential for the synthesis of coagulation factors II, VII, IX, and X, as well as proteins C and S. Deficiency leads to impaired clotting and an increased **PT** (due to factor VII's short half-life and dependence on extrinsic pathway), and later a prolonged **aPTT**. The left-sided flank pain exacerbated by hip extension suggests a **retroperitoneal hematoma**, possibly involving the psoas muscle, a common complication of bleeding disorders. *Deficiency of folic acid* - **Folic acid deficiency** primarily causes **macrocytic anemia** (elevated MCV), which is present here. However, it does not directly explain the coagulation abnormalities such as prolonged PT and easy bruising. - While folic acid deficiency can coexist with vitamin K deficiency in malnutrition, it is not the direct cause of the **bleeding diathesis**. *Decreased synthesis of thrombopoietin* - **Thrombopoietin** regulates platelet production. Decreased synthesis would lead to **thrombocytopenia** (low platelet count). - This patient's platelet count of 170,000/mm³ is within the normal range, indicating that thrombopoietin synthesis is likely adequate and not the cause of his symptoms. *Resistance of Factor V inactivation* - **Resistance to activated protein C (Factor V Leiden mutation)** is a common cause of **thrombophilia** (increased clotting risk), not a bleeding disorder. - This condition would lead to a tendency for **thrombosis**, rather than the hematoma and bruising seen in this patient. *Administration of heparin* - **Heparin** prolongs the **aPTT** significantly more than the PT, which is inconsistent with the patient's lab values where PT is markedly prolonged. - While heparin can cause bleeding complications, the pattern of **coagulation derangement** and the strong predisposing factors for vitamin K deficiency make it a less likely primary diagnosis.

Question 814: A 72-year-old patient is referred to an ophthalmologist because he has noticed some mild discomfort in his eyes though his vision remains unchanged. He cannot recall when this feeling started. His past medical history is significant for diabetes mellitus and two myocardial infarctions that have led to significant cardiac dysfunction. Specifically, he has dyspnea and peripheral edema and occasionally decompensates into more severe pulmonary edema requiring hospitalization. Testing reveals increased intra-ocular pressure so the ophthalmologist prescribes several medications. The medication for this disorder that is most likely to be contraindicated in this patient has which of the following characteristics?

• A. It increases adenylyl cyclase activity
• B. It alters bicarbonate metabolism
• C. It decreases intracellular cyclic AMP levels (Correct Answer)
• D. It increases intracellular calcium levels
• E. It is produced by cyclooxygenase

Explanation: ***It decreases intracellular cyclic AMP levels*** - This describes **beta-blockers** (e.g., timolol, betaxolol), which decrease intraocular pressure by reducing aqueous humor production through beta-adrenergic receptor blockade. - Beta-blockers are **contraindicated in patients with cardiac dysfunction** and heart failure due to their negative inotropic and chronotropic effects, which can exacerbate the patient's existing heart condition and precipitate acute decompensation. *It increases adenylyl cyclase activity* - This mechanism does not accurately describe any major class of glaucoma medications. - **Alpha-2 adrenergic agonists** (e.g., brimonidine) actually *decrease* adenylyl cyclase activity (Gi-coupled) and reduce aqueous humor production. - **Prostaglandin analogs** (e.g., latanoprost) work through FP receptors to increase uveoscleral outflow, not through adenylyl cyclase. - Both drug classes are generally safe in patients with cardiac dysfunction. *It alters bicarbonate metabolism* - This describes **carbonic anhydrase inhibitors** (e.g., acetazolamide, dorzolamide), which reduce aqueous humor production by inhibiting bicarbonate formation in the ciliary body. - While they can cause systemic electrolyte imbalances and are contraindicated in patients with sulfa allergy or severe renal dysfunction, they are generally not contraindicated in cardiac dysfunction. *It increases intracellular calcium levels* - This mechanism is not associated with any class of glaucoma medications. - Medications that increase intracellular calcium would theoretically worsen cardiac contractility issues, but such agents are not used for glaucoma treatment. *It is produced by cyclooxygenase* - **Prostaglandin analogs** (e.g., latanoprost, bimatoprost) are used for glaucoma, but the therapeutic agents are *synthetic analogs*, not naturally produced by cyclooxygenase. - These medications increase uveoscleral outflow and are first-line treatments for glaucoma with minimal systemic cardiovascular effects, making them safe in cardiac patients.

Question 815: A 25-year-old Caucasian female presents with symptoms of Graves' disease. Her doctor prescribes medications and sends the patient home. After two months of therapy, the patient returns upset that her exophthalmos has not gone away. Which of the following drugs should the physician have prescribed to treat the exophthalmos?

• A. Corticosteroids (Correct Answer)
• B. PTU
• C. No treatment as this will resolve naturally
• D. Propranolol
• E. Metoprolol

Explanation: ***Corticosteroids*** - **Corticosteroids** are the first-line medical treatment for **Graves' ophthalmopathy** (exophthalmos), as they reduce the inflammation and swelling behind the eyes. - They work by suppressing the immune response that targets the **orbital fibroblasts and muscles**, leading to orbital tissue expansion. *PTU* - **Propylthiouracil (PTU)** is an **antithyroid drug** used to treat hyperthyroidism by inhibiting thyroid hormone synthesis. - While it addresses the systemic symptoms of Graves' disease, it does **not directly treat the exophthalmos**, which is an immune-mediated orbital disease. *No treatment as this will resolve naturally* - **Graves' ophthalmopathy** can progress and cause significant vision impairment if left untreated, and it often does not resolve naturally. - Early intervention, especially with inflammation-reducing agents, is crucial to prevent irreversible changes and protect ocular health. *Propranolol* - **Propranolol** is a **beta-blocker** used to manage the adrenergic symptoms of hyperthyroidism, such as palpitations, tremor, and anxiety. - It does not address the underlying autoimmune inflammation responsible for exophthalmos. *Metoprolol* - **Metoprolol** is another **beta-blocker** primarily used for cardiovascular conditions and to control hyperthyroid symptoms like **tachycardia**. - Similar to other beta-blockers, it has no therapeutic effect on the inflammation or progression of Graves' ophthalmopathy.

Question 816: A 23-year-old college student presents with his parents for a follow-up appointment. He was recently diagnosed with schizophrenia and was started on risperidone approx. 2 months ago. He reports a significant improvement since the start of treatment. His parents report that their son’s symptoms of delusions, hallucinations, and paranoid behavior have been ameliorated. On physical examination, the patient seems uncomfortable. He frequently fidgets and repeatedly crosses and uncrosses his legs. When asked if something is troubling him, he gets up and starts pacing. He says, “It’s always like this. I cannot sit still. It is frustrating.” What is the most likely diagnosis?

• A. Generalized anxiety disorder
• B. Tardive dyskinesia
• C. Ataxia
• D. Akathisia (Correct Answer)
• E. Restless legs syndrome

Explanation: ***Akathisia*** - This patient presents with **motor restlessness** (fidgeting, pacing, inability to sit still) that emerged after starting an antipsychotic medication, risperidone. These are classic symptoms of **akathisia**, a medication side effect. - The patient's verbalization, "I cannot sit still. It is frustrating," further supports the internal experience of restlessness characteristic of akathisia. *Generalized anxiety disorder* - While anxiety can cause restlessness, the specific description of physical agitation and the strong temporal relationship with starting a new antipsychotic make **akathisia** a more likely diagnosis. - Generalized anxiety disorder typically involves chronic, excessive worry and is not primarily characterized by an irresistible urge to move. *Tardive dyskinesia* - Tardive dyskinesia involves **involuntary, repetitive body movements**, often in the face (e.g., grimacing, tongue protrusion) or limbs. - It usually develops after **long-term use** of antipsychotics (months to years), whereas akathisia can occur shortly after initiation or dose changes. *Ataxia* - Ataxia refers to a lack of **voluntary coordination** of muscle movements, leading to an unsteady gait or impaired balance. - The patient's symptoms are of restlessness and an uncontrollable urge to move, not a lack of coordination. *Restless legs syndrome* - Restless legs syndrome is characterized by an **uncomfortable sensation in the legs** with an urge to move them, typically worse at rest and relieved by movement. - This patient's restlessness is more pervasive, involving whole-body agitation and an inability to simply sit still, not just an uncomfortable sensation primarily in the legs.

Question 817: A 5-year-old boy is brought to the emergency department by his parents with complaints of severe muscle cramping and abdominal pain. They live in Virginia. The parents state that about 2 hours before, the child was playing in their outdoor shed when he suddenly ran inside crying, saying he was bitten by a bug. One hour following the bite, the child developed the symptoms of cramping and pain. He has no known medical history and takes no medications. His blood pressure is 132/86 mm Hg, the heart rate is 116/min, and the respiratory rate is 20/min. Vital signs reveal tachycardia and hypertension. On exam, there is a 1 cm area of erythema to the dorsum of his right hand without any further dermatologic findings. Palpation of his abdomen reveals firm rigidity but no discernable rebound tenderness. What arthropod is most likely responsible for his symptoms?

• A. Cryptopid centipede
• B. Bark scorpion
• C. Black widow (Correct Answer)
• D. Brown recluse
• E. Tick

Explanation: ***Black widow*** - The patient's symptoms, including **severe muscle cramping**, **abdominal pain**, **hypertension**, and **tachycardia**, are classic signs of **latrodectism** caused by a black widow spider bite. - The location (shed in Virginia), rapid onset of symptoms (within 1-2 hours), and general systemic effects are highly consistent with this diagnosis. *Cryptopid centipede* - Bites from cryptopid centipedes typically cause **localized pain**, swelling, and erythema, but generally do not lead to the severe systemic symptoms of muscle cramping, abdominal rigidity, and autonomic instability described. - While generally painful, their venom is not known to produce the neurotoxic effects seen with black widow spider envenomation. *Bark scorpion* - Bark scorpion stings (**Centruroides sculpturatus**) are primarily found in the **southwestern United States** (e.g., Arizona, New Mexico), making them unlikely in Virginia. - While scorpions can cause severe pain and neurological symptoms, the geographical location and specific constellation of symptoms (especially significant muscle cramping and rigidity) point away from a bark scorpion sting. *Brown recluse* - Bites from a brown recluse spider (**Loxosceles reclusa**) are characterized by a **necrotic lesion** that develops over several days or weeks, often an **"_eschar_,"** which is not observed in this patient. - Systemic symptoms are rare with brown recluse bites and typically only include fever, chills, and malaise, not the acute neurotoxic symptoms seen here. *Tick* - Tick bites are typically **painless** and can transmit various diseases, but they do not cause acute, severe muscle cramping and abdominal pain within hours of the bite. - Some ticks can cause **tick paralysis**, which involves progressive *flaccid paralysis* rather than muscle rigidity and cramping, and usually takes days to develop after prolonged tick attachment.

Question 818: A 35-year-old male is picked up by paramedics presenting with respiratory depression, pupillary constriction, and seizures. Within a few minutes, the male dies. On autopsy, fresh tracks marks are seen on both arms. Administration of which of the following medications would have been appropriate for this patient?

• A. Methadone
• B. Flumazenil
• C. Bupropion
• D. Naloxone (Correct Answer)
• E. Diazepam

Explanation: ***Naloxone*** - The patient's presentation with **respiratory depression**, **pupillary constriction**, and **fresh track marks** is highly indicative of an **opioid overdose**. - **Naloxone** is a potent **opioid receptor antagonist** that rapidly reverses the effects of opioid overdose, including respiratory depression. *Methadone* - **Methadone** is a **long-acting opioid agonist** used for pain management and **opioid dependence treatment**. - Administering methadone would worsen an opioid overdose by increasing the opioid effect, potentially deepening respiratory depression. *Flumazenil* - **Flumazenil** is an **antidote for benzodiazepine overdose**, acting as a competitive antagonist at the GABA-A receptor. - It would not be effective in reversing an opioid overdose, as the patient's symptoms are not consistent with benzodiazepine intoxication. *Bupropion* - **Bupropion** is an **antidepressant** and **smoking cessation aid** that works by inhibiting the reuptake of norepinephrine and dopamine. - It has no role in the acute management of opioid overdose and would not address the life-threatening respiratory depression. *Diazepam* - **Diazepam** is a **benzodiazepine** that has sedative, anxiolytic, anticonvulsant, and muscle relaxant properties. - While it could address seizures, it would exacerbate the underlying respiratory depression in an opioid overdose.

Question 819: An otherwise healthy 49-year-old man presents to his primary care physician for follow-up for a high HbA1C. 3 months ago, his HbA1c was 8.9% on routine screening. Today, after lifestyle modifications, it is 8.1% and his serum glucose is 270 mg/dL. Which of the following is the best initial therapy for this patient's condition?

• A. Metformin added to a glucagon-like peptide 1 (GLP-1) agonist
• B. Metformin added to basal insulin
• C. Metformin added to an insulin secretagogue
• D. Metformin (Correct Answer)
• E. Metformin added to a dipeptidyl peptidase-4 (DPP-4) inhibitor

Explanation: ***Metformin*** - **Metformin** is the recommended **first-line pharmacological therapy** for most patients with **Type 2 Diabetes Mellitus**, especially those who are overweight or obese. - It primarily works by **decreasing hepatic glucose production** and increasing insulin sensitivity. *Metformin added to a glucagon-like peptide 1 (GLP-1) agonist* - While **GLP-1 agonists** are effective, they are typically considered **second-line agents** or added therapy, especially for patients with established **cardiovascular disease** or **chronic kidney disease**, or for more aggressive glycemic control not achieved with metformin alone. - The patient's current HbA1c, while high, does not immediately warrant dual therapy without an initial trial of metformin monotherapy. *Metformin added to basal insulin* - **Basal insulin** is usually reserved for patients with very high HbA1c levels (typically >10%), significant symptoms of hyperglycemia, or failure to achieve glycemic targets with multiple oral agents. - Starting with **insulin** as initial therapy alongside metformin is generally too aggressive given the patient's current HbA1c of 8.1% after some improvement with lifestyle modifications. *Metformin added to an insulin secretagogue* - **Insulin secretagogues** (e.g., sulfonylureas) are usually **second-line agents** and stimulate insulin release from pancreatic beta cells. - While effective, they carry a **higher risk of hypoglycemia** and weight gain compared to metformin, making them less ideal for initial therapy. *Metformin added to a dipeptidyl peptidase-4 (DPP-4) inhibitor* - **DPP-4 inhibitors** are also considered **second-line agents** when metformin alone is insufficient or not tolerated. - They improve glycemic control with a low risk of hypoglycemia and are weight-neutral, but **metformin monotherapy** remains the preferred initial step.

Question 820: A 43-year-old woman was admitted to the hospital for anticoagulation following a pulmonary embolism. She was found to have a deep venous thrombosis on further workup after a long plane ride coming back from visiting China. She denies any personal history of blood clots in her past, but she says that her mother has also had to be treated for pulmonary embolism in the recent past. Her past medical history is significant for preeclampsia, hypertension, polycystic ovarian syndrome, and hypercholesterolemia. She currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and she currently denies any illicit drug use. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 111/min, and respiratory rate 23/min. On physical examination, her pulses are bounding and complexion is pale, but breath sounds remain clear. Oxygen saturation was initially 81% on room air, with a new oxygen requirement of 8 L by face mask. On day 6 of combined heparin and warfarin anticoagulation, her platelet count decreases from 182,000/mcL to 63,000/mcL. Her international normalized ratio (INR) is not yet therapeutic. What is the next best step in therapy?

• A. Continue heparin and warfarin until INR is therapeutic for 24 hours
• B. Discontinue heparin and warfarin (Correct Answer)
• C. Continue heparin and warfarin, and administer vitamin K
• D. Discontinue heparin; continue warfarin
• E. Continue heparin; discontinue warfarin

Explanation: ***Discontinue heparin and warfarin*** - The significant drop in platelet count (from 182,000 to 63,000/mcL) on day 6 of heparin therapy strongly suggests **heparin-induced thrombocytopenia (HIT)**, an immune-mediated adverse drug reaction. - **Immediate management requires:** (1) discontinuation of ALL heparin products, and (2) initiation of an alternative non-heparin anticoagulant such as a direct thrombin inhibitor (argatroban, bivalirudin) or fondaparinux. - Warfarin must NOT be continued as monotherapy in HIT because it causes transient **hypercoagulability** due to depletion of protein C and S before depleting clotting factors, which can worsen thrombotic complications. - **Among the options provided**, discontinuing both heparin and warfarin is the correct first step, with the understanding that alternative anticoagulation would be initiated immediately in practice. *Continue heparin and warfarin until INR is therapeutic for 24 hours* - Continuing heparin would be dangerous given the suspected **HIT**, as it could lead to further platelet activation, worsening thrombocytopenia, and an increased risk of **paradoxical thrombosis**. - While achieving therapeutic anticoagulation is important for PE/DVT, the priority is managing the acute, life-threatening complication of HIT. *Continue heparin and warfarin, and administer vitamin K* - Administering vitamin K would reverse warfarin effects, which is contraindicated in a patient requiring anticoagulation for PE and DVT unless there is active bleeding or supratherapeutic INR. - Continuing heparin in the setting of suspected **HIT** is contraindicated and would exacerbate the prothrombotic state. *Discontinue heparin; continue warfarin* - While discontinuing heparin is correct in suspected **HIT**, continuing warfarin alone is **dangerous** and contraindicated. - Warfarin monotherapy in acute HIT causes transient **hypercoagulability** due to rapid depletion of protein C and S (shorter half-lives) before depletion of clotting factors II, IX, and X, leading to increased thrombotic risk including **warfarin-induced venous limb gangrene**. - An **alternative non-heparin anticoagulant** (direct thrombin inhibitor or fondaparinux) must be initiated before warfarin can be safely restarted. *Continue heparin; discontinue warfarin* - Continuing heparin in the presence of a rapid and significant drop in platelet count is **contraindicated** due to the high suspicion of **HIT**. - Discontinuing warfarin alone would leave the patient exposed to continued HIT complications while still receiving the offending agent (heparin).

Question 821: A 55-year-old man comes to the physician because of intermittent palpitations that occur when he is stressed, exercising, or when he drinks alcohol. Physical examination shows an irregularly irregular pulse. An ECG shows irregular QRS complexes without any discrete P waves. Pharmacotherapy with carvedilol is initiated for his condition. Compared to treatment with propranolol, which of the following adverse effects is most likely?

• A. Bradycardia
• B. Bronchospasm
• C. Hyperkalemia
• D. Hypotension (Correct Answer)
• E. Hyperglycemia

Explanation: ***Hypotension*** - **Carvedilol** is a non-selective beta-blocker with additional **alpha-1 adrenergic receptor blocking activity**, which leads to peripheral vasodilation and a greater potential for **hypotension** compared to propranolol (a pure beta-blocker). - The **alpha-1 blockade** causes a reduction in peripheral vascular resistance, leading to a more pronounced decrease in blood pressure. *Bradycardia* - Both carvedilol and propranolol are beta-blockers and can cause **bradycardia** by reducing heart rate. - However, the question asks for an adverse effect **more likely** with carvedilol compared to propranolol, and while both can cause bradycardia, carvedilol's additional alpha-blocking activity makes hypotension more distinguishing. *Bronchospasm* - Both carvedilol and propranolol are **non-selective beta-blockers** (blocking both beta-1 and beta-2 receptors) and can cause **bronchospasm** by blocking beta-2 receptors in the bronchi. - Therefore, this adverse effect is common to both and not more likely with carvedilol specifically in comparison to propranolol. *Hyperkalemia* - Neither carvedilol nor propranolol is directly associated with causing **hyperkalemia** as a primary adverse effect. - Beta-blockers can sometimes lead to minor shifts in potassium, but it's not a common or more significant side effect compared to others listed. *Hyperglycemia* - **Non-selective beta-blockers** like propranolol can impair the recovery from **hypoglycemia** and mask its symptoms. - While beta-blockers can have some metabolic effects, **hyperglycemia** is not a generally recognized or more prominent adverse effect of carvedilol compared to propranolol.

Question 822: A 50-year-old woman is brought to the emergency department following a motor vehicle accident. She is awake but slow to respond. Her breath smells of alcohol. The emergency medical technician reports that her blood pressure has been dropping despite intravenous fluids. Ultrasound reveals a hypoechoic rim around the spleen, suspicious for a splenic laceration. The patient is brought into the operating room for abdominal exploration and a splenic embolization is performed. Since arriving to the hospital, the patient has received 8 units of packed red blood cells and 2 units of fresh frozen plasma. She is stabilized and admitted for observation. The next morning on rounds, the patient complains of numbness and tingling of her mouth and cramping of her hands. Her temperature is 99°F (37.2°C), blood pressure is 110/69 mmHg, and pulse is 93/min. On physical examination, her abdomen is mildly tender without distention. The surgical wound is clean, dry, and intact. Jugular venous pressure is normal. Periodic spasms of the muscles of her bilateral upper and lower extremities can be seen and tapping of the facial nerve elicits twitching of he facial muscles. Which of the following is most likely to improve the patient’s symptoms?

• A. Sodium bicarbonate
• B. Lorazepam
• C. Calcium gluconate (Correct Answer)
• D. Dextrose
• E. Thiamine

Explanation: ***Calcium gluconate*** - The patient's symptoms of perioral numbness, tingling, hand cramping, muscle spasms, and a positive **Chvostek's sign** (tapping of the facial nerve eliciting twitching) are classic signs of **hypocalcemia**. - Her extensive transfusion history (8 units PRBCs, 2 units FFP) likely led to **citrate toxicity**, as citrate in transfused blood products chelates calcium, causing a transient decrease in **ionized calcium** levels. *Sodium bicarbonate* - While a massive transfusion can sometimes lead to transient acidosis, **sodium bicarbonate** would not address the underlying **hypocalcemia** causing the current symptoms. - Furthermore, **alkalosis** can worsen **hypocalcemia** by increasing protein binding of calcium. *Lorazepam* - **Lorazepam** is a benzodiazepine used to treat seizures or severe muscle spasms, but it would only mask the symptoms without addressing the underlying cause of **hypocalcemia**. - The muscle spasms are a direct result of **neuromuscular excitability** due to low calcium. *Dextrose* - **Dextrose** is used to treat hypoglycemia, which is not indicated by the patient's symptoms or clinical context. - There is no information suggesting the patient has low blood sugar. *Thiamine* - **Thiamine** is crucial for preventing Wernicke-Korsakoff syndrome, especially in patients with chronic alcohol use, but it does not treat **hypocalcemia** or its associated symptoms. - While the patient's breath smelled of alcohol, her acute symptoms are directly related to electrolyte imbalance.

Question 823: A 32-year-old man comes to the emergency department because of abdominal pain, a runny nose, and chills for 6 hours. He has also had diarrhea and difficulty sleeping. He appears irritable. His temperature is 37.1°C (98.8°F), pulse is 110/min, and blood pressure is 140/90 mm Hg. Examination shows cool, damp skin with piloerection. The pupils are 7 mm in diameter and equal in size. Cardiopulmonary examination shows no abnormalities. The abdomen is tender to palpation. Bowel sounds are hyperactive. Deep tendon reflexes are 3+ bilaterally. Withdrawal from which of the following substances is the most likely cause of this patient's symptoms?

• A. Barbiturates
• B. Phencyclidine
• C. Cannabis
• D. Heroin (Correct Answer)
• E. Gamma-hydroxybutyric acid

Explanation: ***Heroin*** - The patient's symptoms, including **piloerection** (goosebumps), **rhinorrhea** (runny nose), diaphoresis (cool, damp skin), diarrhea, dilated pupils, and hyperactive reflexes, are classic signs of **opioid withdrawal**. - **Opioid withdrawal** is characterized by an overactivity of the autonomic nervous system and presents with symptoms often described as a severe flu-like illness, along with intense drug cravings. *Barbiturates* - **Barbiturate withdrawal** can cause anxiety, tremors, insomnia, and sometimes seizures or delirium, but it typically does not present with the specific features of piloerection or hyperactive bowel sounds seen here. - The pupils are often constricted or normal, and gastrointestinal symptoms are less prominent compared to opioid withdrawal. *Phencyclidine* - **Phencyclidine (PCP) withdrawal** is not a clearly defined or severe syndrome; chronic users typically experience cravings, depression, and memory problems. - Acute PCP intoxication is characterized by nystagmus, hypertension, tachycardia, and often violent behavior, which are not present in this patient's withdrawal picture. *Cannabis* - **Cannabis withdrawal** symptoms are generally mild and include irritability, anxiety, sleep disturbances, decreased appetite, and some physical discomfort, but do not involve the pronounced autonomic hyperactivity, piloerection, or severe gastrointestinal symptoms seen in this patient. - Unlike opioid withdrawal, it does not typically cause significantly dilated pupils or hyperactive bowel sounds. *Gamma-hydroxybutyric acid* - **GHB withdrawal** can manifest as anxiety, insomnia, tremors, and severe cases can involve delirium and seizures, similar to alcohol or benzodiazepine withdrawal. - It does not typically present with the specific constellation of symptoms like piloerection, rhinorrhea, and severe gastrointestinal distress that are characteristic of opioid withdrawal.

Question 824: A 30-year-old woman, gravida 2, para 1, at 40 weeks' gestation is admitted to the hospital in active labor. Her first pregnancy and delivery were complicated by iron deficiency anemia and pregnancy-induced hypertension. She has had no routine prenatal care during this pregnancy but was diagnosed with oligohydramnios 4 weeks ago. The remainder of her medical history is not immediately available. A 2400-g (5.4-lb) female newborn is delivered vaginally. Examination of the newborn shows a short, mildly webbed neck and low-set ears. Ocular hypertelorism along with slanted palpebral fissures are noted. A cleft palate and hypoplasia of the nails and distal phalanges are present. There is increased coarse hair on the body and face. Which of the following best explains the clinical findings found in this newborn?

• A. Maternal phenytoin therapy (Correct Answer)
• B. Fetal X chromosome monosomy
• C. Fetal posterior urethral valves
• D. Maternal diabetes mellitus
• E. Maternal alcohol intake

Explanation: ***Maternal phenytoin therapy*** - The constellation of **craniofacial anomalies** (short, webbed neck, low-set ears, ocular hypertelorism, slanted palpebral fissures, cleft palate), **nail hypoplasia**, and **hirsutism** are characteristic features of **fetal hydantoin syndrome**, caused by **phenytoin exposure** in utero. - Oligohydramnios can be associated with complications of antiepileptic drug use, such as **renal dysfunction**, further supporting this diagnosis. *Fetal X chromosome monosomy* - This condition, also known as **Turner syndrome**, is characterized by a **short webbed neck** and **low-set ears**, but typically presents with **gonadal dysgenesis**, **coarctation of the aorta**, and **lymphedema**, which are not mentioned. - **Nail hypoplasia** and **hirsutism** are not typical features of Turner syndrome. *Fetal posterior urethral valves* - **Posterior urethral valves** cause **urinary tract obstruction** in male fetuses, leading to **oligohydramnios**, **pulmonary hypoplasia**, and characteristic facial features (Potter facies) due to decreased amniotic fluid pressure. - The patient is female, and the specific facial anomalies and nail/hair findings are not consistent with **Potter sequence** but rather with a teratogenic exposure syndrome. *Maternal diabetes mellitus* - **Maternal diabetes** can cause a range of fetal complications, including **macrosomia**, **cardiac defects**, and **caudal regression syndrome**. - While it can be associated with increased risk of certain birth defects and occasionally oligohydramnios, the specific combination of **craniofacial features**, **nail hypoplasia**, and **hirsutism** seen here is not characteristic of diabetic embryopathy. *Maternal alcohol intake* - **Maternal alcohol intake** leads to **fetal alcohol syndrome (FAS)**, characterized by **growth restriction**, **facial anomalies** (smooth philtrum, thin upper lip, short palpebral fissures), and **CNS dysfunction**. - While some facial features might overlap, **nail hypoplasia** and **hirsutism** as described are not typical of FAS.

Question 825: A 17-year-old female is brought to the emergency room by her parents shortly after a suicide attempt by aspirin overdose. Which of the following acid/base changes will occur FIRST in this patient?

• A. Metabolic alkalosis
• B. Respiratory acidosis
• C. Anion gap metabolic acidosis
• D. Respiratory alkalosis (Correct Answer)
• E. Non-anion gap metabolic acidosis

Explanation: ***Respiratory alkalosis*** - **Aspirin overdose** initially causes direct stimulation of the **respiratory center in the medulla**, leading to **hyperventilation**. - This increased rate and depth of breathing blows off CO2, resulting in a primary **respiratory alkalosis**. *Metabolic alkalosis* - This is an unlikely primary event in aspirin overdose, which typically causes acidosis. - While aspirin can cause electrolyte disturbances, a direct metabolic alkalosis as the *first* change is not characteristic. *Respiratory acidosis* - Respiratory depression, leading to respiratory acidosis, can occur in *severe* and *late-stage* aspirin overdose due to central nervous system depression. - However, the initial effect is stimulation of respiration, causing alkalosis. *Anion gap metabolic acidosis* - This is a significant acid-base disturbance that *does* occur in aspirin overdose, but it develops *later*. - Salicylates uncouple oxidative phosphorylation and impair cellular metabolism, leading to the accumulation of organic acids (e.g., lactic acid), causing a high anion gap metabolic acidosis. *Non-anion gap metabolic acidosis* - This type of acidosis is characterized by a preservation of the anion gap and is often associated with conditions like diarrhea or renal tubular acidosis. - It is not the expected initial or primary acid-base disturbance in aspirin overdose.

Question 826: A 35-year-old woman presents to her physician with a complaint of pain and stiffness in her hands. She says that the pain began 6 weeks ago a few days after she had gotten over a minor upper respiratory infection. She admits that the pain is worse in the morning, and she occasionally notes subjective fever but has not taken her temperature. She also admits that her appetite has mildly decreased, but she denies any change in weight. The pain is partially alleviated by ibuprofen, but she has been unsatisfied with the results. She is concerned about her condition as it makes caring for her two young children very difficult. Temperature is 99.4°F (37.4°C), blood pressure is 119/73 mmHg, pulse is 75/min, and respirations are 18/min. Physical examination demonstrates swelling and tenderness over the wrists and metacarpophalangeal joints bilaterally. Bilateral radiographs of the hands demonstrate mild periarticular osteopenia around the left fifth metacarpophalangeal joint. Which of the following is the next best step in management of this patient's acute symptoms?

• A. Etanercept
• B. Prednisone (Correct Answer)
• C. Reassurance
• D. Anakinra
• E. Methotrexate

Explanation: **Prednisone** - Given her **acute, debilitating symptoms** impacting daily life (caring for children), **oral glucocorticoids** like prednisone are appropriate for rapid symptom control while awaiting the effects of disease-modifying antirheumatic drugs (DMARDs). - She presents with symptoms highly suggestive of **rheumatoid arthritis**, including bilateral symmetrical polyarthritis, morning stiffness, and constitutional symptoms, making rapid inflammation control crucial. *Etanercept* - **Etanercept** is a biologic DMARD, typically reserved for patients who have not adequately responded to conventional DMARDs like methotrexate. - It is a **TNF-alpha inhibitor** and takes several weeks to exert its full therapeutic effect, making it unsuitable for acute symptom management alone. *Reassurance* - Her symptoms are significantly impacting her quality of life and are likely indicative of an **inflammatory arthropathy**, not something that can be resolved with simple reassurance. - The physical exam and radiographic findings (periarticular osteopenia) further support a **pathological process** requiring intervention. *Anakinra* - **Anakinra** is an IL-1 receptor antagonist, primarily used for conditions like still's disease and cryopyrin-associated periodic syndromes, not typically as a first-line agent for acute symptom control in suspected rheumatoid arthritis. - While it can act relatively quickly, **glucocorticoids are more commonly used** for rapid bridging therapy in this context. *Methotrexate* - **Methotrexate** is a cornerstone DMARD for rheumatoid arthritis, but its **onset of action is slow** (weeks to months), making it ineffective for immediate relief of acute, severe symptoms. - It would likely be initiated concurrently, but it is not the best step for managing her acute pain and stiffness.

Question 827: A 19-year-old man with a history of generalized tonic-clonic seizures comes to the physician for a routine health maintenance examination. He is a known user of intravenous cocaine. His vital signs are within normal limits. Physical examination shows multiple hyperpigmented lines along the forearms. Oral examination shows marked overgrowth of friable, ulcerated gingival mucosa. Which of the following is the most likely cause of this patient's oral examination findings?

• A. Cyclosporine
• B. Lacosamide
• C. Carbamazepine
• D. Phenytoin (Correct Answer)
• E. Lamotrigine

Explanation: ***Phenytoin*** - **Phenytoin** is a common cause of **gingival hyperplasia**, presenting with marked overgrowth of friable, ulcerated gingival mucosa due to its effect on fibroblast proliferation and collagen production. - This medication is frequently used to manage **tonic-clonic seizures**, consistent with the patient's history. *Cyclosporine* - While **cyclosporine** can cause **gingival hyperplasia**, it is an **immunosuppressant** primarily used in organ transplantation or autoimmune conditions, which is not indicated in the patient's seizure history. - The patient's presentation does not suggest any condition for which cyclosporine would be prescribed. *Lacosamide* - **Lacosamide** is an anticonvulsant that stabilizes hyperexcitable neuronal membranes, but it is **not typically associated with gingival hyperplasia**. - Its known side effects are primarily neurological, such as dizziness, headache, and nausea. *Carbamazepine* - **Carbamazepine** is an anticonvulsant effective for focal and tonic-clonic seizures, but **gingival hyperplasia is a rare side effect** with this medication. - More common side effects include dizziness, drowsiness, and bone marrow suppression. *Lamotrigine* - **Lamotrigine** is an anticonvulsant used for various seizure types, but **gingival hyperplasia is not a recognized side effect**. - It is more commonly associated with skin rashes, including severe reactions like **Stevens-Johnson syndrome**.

Question 828: A 59-year-old man with a history of major depressive disorder, asthma, and erectile dysfunction presents to his family physician complaining of depressed mood, amotivation, overeating, and anhedonia. He currently takes no medications. The patient has a 3 pack-year smoking history and would like to quit but has been unsuccessful in the past. His BMI is 29 kg/m^2. The physician suggests starting an antidepressant for the patient's mood symptoms. The patient is reluctant, as he used to take sertraline, but stopped it after his erectile dysfunction worsened. Which of the following antidepressants would be most appropriate for this patient?

• A. Citalopram
• B. Bupropion (Correct Answer)
• C. Sertraline
• D. Mirtazapine
• E. Amitriptyline

Explanation: **Bupropion** - **Bupropion** is an antidepressant that does not typically cause **sexual dysfunction** and can aid in **smoking cessation**, addressing two key concerns for this patient. - It acts by inhibiting the reuptake of **norepinephrine** and **dopamine**, which can also help with **amotivation** and **anhedonia**. *Citalopram* - **Citalopram** is an **SSRI** (selective serotonin reuptake inhibitor), a class of drugs commonly associated with causing or worsening **sexual dysfunction**, which is a significant concern for this patient. - While effective for depression, it does not offer the additional benefit of aiding in **smoking cessation**. *Sertraline* - The patient previously stopped **sertraline** due to worsening **erectile dysfunction**, indicating that this **SSRI** is not a suitable option for him. - Reintroducing **sertraline** would likely lead to similar adverse effects and patient non-adherence. *Mirtazapine* - **Mirtazapine** is an antidepressant that can cause **weight gain** and **sedation**, which would be undesirable for a patient with a BMI of 29 kg/m^2 who also needs to quit smoking. - Although it has a lower incidence of sexual dysfunction compared to SSRIs, it does not offer benefits for **smoking cessation**. *Amitriptyline* - **Amitriptyline** is a **tricyclic antidepressant (TCA)** known for significant side effects such as **anticholinergic effects** (e.g., dry mouth, constipation, urinary retention), **sedation**, and **cardiac toxicity** in overdose. - Given the patient's age and history, a TCA would likely be poorly tolerated and poses higher risks compared to other options.

Question 829: A 32-year-old woman presents for a follow-up visit. She was diagnosed with type 2 diabetes mellitus a month ago but refused to start medications despite counseling due to her fear of gaining weight. She tried exercising and eating healthy in an attempt to ''cure'' her diabetes. She managed to lose 1.8 kg (4 lb) in a month. Today she still complains of increased urinary frequency, the same symptom that leads to her initial suspicion of diabetes. No other significant past medical history. She is happily married and plans on having kids in the next few years. The patient is a non-smoker, denies illicit drug use, and drinks socially. Her vital signs show a pulse of 80/min, a respiratory rate of 16/min, a blood pressure of 120/80 mm Hg, and a temperature of 36.9°C (98.4°F). Her BMI is 33.0 kg/m2. Physical exam findings are unremarkable. Her fingerstick glucose today is 214 mg/dL. Laboratory findings reveal the following: Glycated Hemoglobin (HbA1c) 7.1% Blood glucose (fasting) 130 mg/dL Serum: Sodium 142 mEq/L Potassium 3.9 mEq/L Chloride 101 mEq/L Serum creatinine 0.8 mg/dL Blood urea nitrogen 9 mg/dL Urinalysis shows: Glucose Positive Ketones Negative Leukocytes Negative Nitrites Negative RBCs Negative Casts Negative Which of the following is the best treatment option for this patient?

• A. Start empagliflozin.
• B. Start glipizide.
• C. Start metformin. (Correct Answer)
• D. Start exenatide.
• E. Start insulin.

Explanation: ***Start metformin*** is the correct answer. - **Metformin is the first-line pharmacological treatment** for type 2 diabetes mellitus according to ADA and AACE guidelines due to its proven efficacy, safety profile, and multiple benefits. - It has a **weight-neutral to modest weight loss effect** (~2-3 kg), directly addressing this patient's primary concern about weight gain from medications. - **Low risk of hypoglycemia** when used as monotherapy, making it safe for this active patient. - **Cardiovascular benefits** and potential reduction in microvascular complications with long-term use. - **Cost-effective** and well-tolerated, with GI side effects that typically diminish over time. - The patient has **normal renal function** (Cr 0.8 mg/dL), so metformin is safe to use (contraindicated only when eGFR <30 mL/min/1.73m²). *Start empagliflozin* is incorrect. - Empagliflozin is an **SGLT2 inhibitor** that promotes glycosuria, leading to weight loss (~2-4 kg) and provides cardiovascular and renal protective benefits. - While increasingly popular and beneficial for weight management, it is typically used as **second-line therapy** or added to metformin, or used first-line specifically in patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. - Not the standard initial monotherapy choice in this uncomplicated T2DM patient. *Start glipizide* is incorrect. - Glipizide is a **sulfonylurea** that stimulates pancreatic beta cells to release insulin, effectively lowering blood glucose. - However, it is **strongly associated with weight gain** (2-5 kg), which directly contradicts the patient's primary concern and motivation. - **Significant risk of hypoglycemia**, particularly with missed meals or increased activity. - Now considered a later-line option due to these adverse effects. *Start exenatide* is incorrect. - Exenatide is a **GLP-1 receptor agonist** that enhances glucose-dependent insulin secretion, suppresses glucagon, and delays gastric emptying. - **Promotes significant weight loss** (3-5 kg) and has cardiovascular benefits, making it attractive for this patient's profile. - However, it is **injectable** (requires patient training), more expensive than metformin, and commonly causes GI side effects (nausea, vomiting). - Typically used as **second-line therapy** after metformin or as first-line in specific cases with compelling cardiovascular indications. - Not the standard initial choice for uncomplicated T2DM. *Start insulin* is incorrect. - Insulin therapy is the most potent glucose-lowering agent and is essential for type 1 diabetes and advanced type 2 diabetes with beta-cell failure. - However, it is **strongly associated with weight gain** (2-4 kg) and carries a **high risk of hypoglycemia**, both of which are undesirable for this patient. - Reserved for patients who have failed multiple oral agents or have severe hyperglycemia (e.g., HbA1c >10%, symptomatic hyperglycemia). - This patient's HbA1c of 7.1% does not warrant insulin as initial therapy.

Question 830: A 48-year-old woman presents to the emergency room because of severe back pain after a fall. She says that she was walking home from work when she slipped on a patch of ice on the sidewalk. Since she did not have anything to hold onto, she fell backwards and landed on her posterior iliac crests bilaterally. Immediately after the fall, she started experiencing back pain and tenderness that concerned her enough to call for an ambulance. Her past medical history is significant for arthritis, diabetes, and hypertension. On arrival, her temperature is 99°F (37.2°C), blood pressure is 129/86 mmHg, pulse is 112/min, respirations are 19/min. Physical exam reveals tenderness to palpation over the middle of her lower back. A drug that may have predisposed this patient to this outcome most likely has which of the following mechanisms?

• A. Inhibition of leukotriene and prostaglandin production
• B. Inhibition of circulating cytokine
• C. Inhibition of folate processing
• D. Stimulation of adipocyte transcription factor (Correct Answer)
• E. Inhibition of prostaglandin production alone

Explanation: ***Stimulation of adipocyte transcription factor*** - The patient's presentation with a **vertebral fracture** after a minor fall, combined with a history of **arthritis**, strongly suggests **osteoporosis** as a predisposing factor. - **Glucocorticoids** are commonly used to treat arthritis and stimulate **adipocyte transcription factors** (like PPAR-γ), leading to **reduced bone formation** and increased bone resorption, causing osteoporosis. *Inhibition of leukotriene and prostaglandin production* - This mechanism describes **NSAIDs**, which are used for pain and inflammation but do not typically cause osteoporosis or increase fracture risk through this specific mechanism. - While NSAIDs can have gastrointestinal side effects, they are not directly linked to the bone fragility seen in this case. *Inhibition of circulating cytokine* - This mechanism is characteristic of **biologic agents** used in immunosuppression, such as TNF-α inhibitors. - These drugs are not typically associated with increased fracture risk or osteoporosis in the same way glucocorticoids are. *Inhibition of folate processing* - This mechanism is characteristic of **methotrexate**, a disease-modifying antirheumatic drug (DMARD) used in arthritis. - While methotrexate has side effects, it is not primarily known to induce osteoporosis or increase fracture risk as seen with glucocorticoids. *Inhibition of prostaglandin production alone* - This mechanism broadly refers to drugs like **NSAIDs** (non-selective COX inhibitors) or selective COX-2 inhibitors. - As mentioned, these drugs do not typically cause the bone fragility leading to spontaneous fractures seen with long-term glucocorticoid use.

Question 831: A 71-year-old woman presents to the clinic after an X-ray that revealed compression fractures of her L1 and L2 vertebral bodies due to osteoporotic changes. The patient has a history of hypertension for which she takes hydrochlorothiazide, and rheumatoid arthritis, for which she has been taking prednisone for the last 2 years. The patient states that she had a dual-energy X-ray absorptiometry (DEXA) scan 3 years ago that was normal and attributes that finding to regularly taking calcium and vitamin D supplements since then. The patient states that her pain from the fractures is stopping her from participating in her regular activities, such as exercising and gardening. Which of the following is the main cause of her osteoporosis?

• A. Hydrochlorothiazide (HCTZ) therapy
• B. Calcium malabsorption
• C. Decreased estrogen levels
• D. Undiagnosed hyperparathyroidism
• E. Bone depletion due to chronic corticosteroid use (Correct Answer)

Explanation: ***Bone depletion due to chronic corticosteroid use*** - The patient's long-term **prednisone** use for rheumatoid arthritis for **2 years** is a significant risk factor for **secondary osteoporosis**. - **Glucocorticoids** directly inhibit osteoblast activity, increase osteoclast activity, and impair calcium absorption, leading to accelerated bone loss. *Hydrochlorothiazide (HCTZ) therapy* - **Thiazide diuretics** like HCTZ are often associated with a **reduced risk of osteoporosis** because they decrease urinary calcium excretion, potentially leading to increased bone mineral density. - Therefore, HCTZ is unlikely to be the cause of her current osteoporosis. *Calcium malabsorption* - While **calcium malabsorption** can contribute to osteoporosis, the patient's history of taking **calcium and vitamin D supplements** suggests she is actively trying to mitigate this risk. - Furthermore, chronic **corticosteroid use** is a more direct and potent cause of bone loss than general calcium malabsorption in this clinical context. *Decreased estrogen levels* - Decreased estrogen levels are a primary cause of **postmenopausal osteoporosis** in women. While this patient is 71 and postmenopausal, her **corticosteroid use** is a more dominant and specific cause of bone loss in this case. - Her normal DEXA 3 years ago implies that postmenopausal bone loss alone might not fully explain the rapid development of severe osteoporosis leading to vertebral fractures. *Undiagnosed hyperparathyroidism* - **Hyperparathyroidism** causes increased bone resorption due to elevated **parathyroid hormone (PTH)**, leading to osteoporosis. - However, there is no information in the vignette to suggest hyperparathyroidism, such as elevated calcium levels or specific symptoms like kidney stones. **Chronic corticosteroid use** is a much more direct and established cause in this patient's history.

Question 832: You are working in the emergency room of a children's hospital when a 4-year-old girl is brought in by ambulance due to "difficulty breathing." The patient had been eating lunch on a school field trip when she suddenly complained of abdominal pain. Shortly thereafter, she was noted to have swelling of the lips, a rapidly developing red rash and difficulty breathing. In the ambulance her blood pressure was persistently 80/50 mmHg despite intramuscular epinephrine. In the course of stabilization and work up of the patient, you note an elevated tryptase level. What is the mechanism behind this elevated tryptase level?

• A. IgM mediated complement activation
• B. Cross-linking of IgE on mast cells (Correct Answer)
• C. IgG production by plasma cells
• D. Antibody-antigen immune complexes
• E. Cross-linking of IgG on mast cells

Explanation: **Cross-linking of IgE on mast cells** - The rapid onset of symptoms like **lip swelling**, **rash**, and **difficulty breathing** after eating, along with **hypotension** despite epinephrine, points to **anaphylaxis**, which is primarily mediated by **IgE**. - **Tryptase** is a serine protease selectively stored in the secretory granules of **mast cells** and is released upon mast cell activation, making it a reliable marker for **anaphylaxis**. *IgM mediated complement activation* - **IgM-mediated complement activation** is primarily involved in host defense against infections and in autoimmune conditions, but not typically in acute allergic reactions like anaphylaxis. - While complement activation can occur in severe allergic reactions, the direct trigger and primary mechanism for tryptase release in anaphylaxis is **IgE cross-linking**. *IgG production by plasma cells* - **IgG production by plasma cells** is part of the adaptive immune response, responsible for long-term immunity and neutralizing toxins and pathogens. - It is not the immediate mechanism for **mast cell degranulation** and **tryptase release** in an acute allergic reaction such as anaphylaxis. *Antibody-antigen immune complexes* - **Antibody-antigen immune complexes** are typically associated with Type III hypersensitivity reactions, which involve deposition of complexes in tissues, leading to inflammation (e.g., lupus, serum sickness). - These reactions generally have a delayed onset and a different clinical presentation, not the acute, systemic symptoms of **anaphylaxis** seen here. *Cross-linking of IgG on mast cells* - While **IgG** can play a role in some immune responses, the primary immunoglobulin involved in immediate hypersensitivity reactions like anaphylaxis, leading to mast cell degranulation, is **IgE**, not IgG. - Mast cells have **Fc receptors** for IgE, not IgG, that, when cross-linked by allergen, trigger the release of mediators including **tryptase**.

Question 833: A research team is studying the effects of a novel drug that was discovered to treat type 2 diabetes. In order to learn more about its effects, they follow patients who are currently taking the drug and determine whether there are adverse effects that exceed anticipated levels and may therefore be drug-related. They discover that the drug causes an excess of sudden cardiac death in 19 patients with renal failure out of 2 million total patients that are followed. Based on these results, an additional warning about this serious adverse effect is added to the investigator brochure for the drug. Which of the following clinical phase studies does this study most likely describe?

• A. Phase IV (Correct Answer)
• B. Phase II
• C. Phase V
• D. Phase III
• E. Phase I

Explanation: ***Phase IV*** - This study occurs **after a drug has been approved and marketed**, focusing on post-marketing surveillance for long-term safety, effectiveness, and real-world side effects in a large and diverse patient population. - The discovery of a rare but serious adverse effect (sudden cardiac death) in a large patient population (2 million) after the drug is already in use is characteristic of a **Phase IV clinical trial**. *Phase II* - Phase II trials involve a **larger group of patients (hundreds)** and focus on evaluating the drug's effectiveness and further assessing safety in patients with the target condition. - This phase is typically conducted **before widespread marketing** and would not involve 2 million patients. *Phase V* - There is **no widely recognized "Phase V"** in standard clinical trial terminology (Phases I-IV focus on drug development and post-marketing surveillance). - This term is sometimes used informally to refer to **health economics and outcomes research** or implementation studies, which are not described in the scenario. *Phase III* - Phase III trials are large-scale studies involving **thousands of patients** to confirm effectiveness, monitor side effects, compare the drug to standard treatments, and collect information for safe use. - While large, these trials are conducted **before regulatory approval** and marketing, and would not typically follow 2 million patients already taking the drug in the real world. *Phase I* - Phase I trials are the **first stage of human testing**, involving a small group of healthy volunteers (20-100) to assess safety, dosage, and pharmacokinetics. - The primary goal is to determine if the drug is safe enough for further testing, not to identify rare adverse events in a large patient population.

Question 834: A 55-year-old woman comes to the physician because of involuntary hand movements that improve with alcohol consumption. Physical examination shows bilateral hand tremors that worsen when the patient is asked to extend her arms out in front of her. The physician prescribes a medication that is associated with an increased risk of bronchospasms. This drug has which of the following immediate effects on the cardiovascular system? Stroke volume | Heart rate | Peripheral vascular resistance

• A. ↓ ↓ ↓
• B. ↓ ↓ ↑ (Correct Answer)
• C. ↓ ↑ ↑
• D. ↑ ↑ ↑
• E. ↑ ↑ ↓

Explanation: ***↓ ↓ ↑*** - This patient likely has **essential tremor**, which is characterized by **bilateral hand tremors** that improve with alcohol and worsen with intention (postural tremor). The prescribed medication is a **beta-blocker** (e.g., propranolol), which is associated with an increased risk of bronchospasms due to blocking **beta-2 receptors** in the airways. - Beta-blockers **decrease heart rate** (negative chronotropic effect) and **stroke volume** (negative inotropic effect) by blocking beta-1 receptors in the heart, reducing cardiac output. - **Peripheral vascular resistance increases** acutely due to: (1) **unopposed alpha-1 adrenergic tone** in blood vessels (loss of beta-2 mediated vasodilation), and (2) baroreceptor-mediated reflex vasoconstriction in response to decreased cardiac output. This helps maintain blood pressure despite reduced cardiac output. *↓ ↓ ↓* - While beta-blockers decrease **heart rate** and **stroke volume**, peripheral vascular resistance does not decrease acutely. A decrease in all three parameters would cause severe hypotension. - The loss of beta-2 receptor-mediated vasodilation and baroreceptor reflexes lead to increased, not decreased, peripheral vascular resistance. *↓ ↑ ↑* - Beta-blockers **decrease heart rate** through beta-1 blockade, not increase it. This is their primary cardiac mechanism of action. - An increase in heart rate would be expected with sympathomimetic drugs or anticholinergics, not beta-blockers. *↑ ↑ ↑* - This combination indicates increased cardiovascular activity, which is the opposite effect of **beta-blockers**. - Beta-blockers reduce heart rate and stroke volume by blocking beta-1 receptors; they do not increase these parameters. - This pattern would suggest sympathetic activation or administration of an adrenergic agonist. *↑ ↑ ↓* - Beta-blockers **decrease** (not increase) both heart rate and stroke volume through beta-1 receptor blockade. - While decreased peripheral vascular resistance occurs with vasodilators, beta-blockers acutely **increase** PVR due to unopposed alpha-adrenergic tone.

Question 835: A 66-year-old man with congestive heart failure presents to the emergency department complaining of worsening shortness of breath. These symptoms have worsened over the last 3 days. He has a blood pressure of 126/85 mm Hg and heart rate of 82/min. Physical examination is notable for bibasilar crackles. A chest X-ray reveals bilateral pulmonary edema. His current medications include metoprolol succinate and captopril. You wish to add an additional medication targeted towards his symptoms. Of the following, which statement is correct regarding loop diuretics?

• A. Loop diuretics can cause metabolic acidosis
• B. Loop diuretics can cause ammonia toxicity
• C. Loop diuretics can cause hyperlipidemia
• D. Loop diuretics decrease sodium, magnesium, and chloride but increase calcium
• E. Loop diuretics inhibit the action of the Na+/K+/Cl- cotransporter (Correct Answer)

Explanation: ***Loop diuretics inhibit the action of the Na+/K+/Cl- cotransporter*** - Loop diuretics, like furosemide, directly block the **Na+/K+/2Cl- cotransporter** in the **thick ascending limb of the loop of Henle**, preventing the reabsorption of these ions. - This inhibition leads to increased excretion of water, sodium, potassium, and chloride, which is beneficial in conditions like **pulmonary edema** due to **congestive heart failure**. *Loop diuretics can cause metabolic acidosis* - Loop diuretics typically cause **metabolic alkalosis**, not acidosis, because they increase the excretion of hydrogen ions and potassium, leading to a compensatory increase in bicarbonate. - The increased delivery of sodium to the collecting duct can also stimulate potassium and hydrogen secretion, contributing to alkalosis. *Loop diuretics can cause ammonia toxicity* - Loop diuretics do not directly cause **ammonia toxicity**; this is more commonly associated with conditions like **hepatic encephalopathy** or certain other medications. - Their primary mechanism of action is on renal ion transport, not ammonia metabolism. *Loop diuretics can cause hyperlipidemia* - While some diuretics like **thiazide diuretics** can cause mild increases in **lipid levels**, loop diuretics are not typically associated with significant **hyperlipidemia**. - The most common metabolic side effects of loop diuretics include electrolyte imbalances. *Loop diuretics decrease sodium, magnesium, and chloride but increase calcium* - Loop diuretics decrease the reabsorption of **sodium**, **magnesium**, and **chloride**, leading to their increased excretion. - They also increase **calcium excretion** (cause hypocalcemia), rather than increasing serum calcium levels, by inhibiting its reabsorption in the thick ascending limb of the loop of Henle.

Question 836: A 26-year-old woman (gravida 3 para 1) with no prenatal care delivers a boy at 37 weeks gestation. His Apgar score is 5 at 1 minute and 8 at 5 minutes. His weight is 2.1 kg (4.2 lb) and length is 47 cm (1 ft 7 in). The mother’s history is significant for chronic pyelonephritis, atrial fibrillation, and gastroesophageal reflux disease. She has a 5-pack-year smoking history and also reports alcohol consumption during pregnancy. Examination of the infant shows a short depressed nasal bridge, wide nose, brachydactyly, and a short neck. Ophthalmoscopy reveals bilateral cataracts. What is the most likely cause of the newborn’s symptoms?

• A. Omeprazole
• B. Warfarin (Correct Answer)
• C. Atenolol
• D. Alcohol
• E. Gentamicin

Explanation: **Warfarin** - The constellation of **nasal hypoplasia (short depressed nasal bridge, wide nose)**, **stippled epiphyses (brachydactyly)**, and **ophthalmologic abnormalities (bilateral cataracts)** are classic features of **warfarin embryopathy (fetal warfarin syndrome)**. - Warfarin crosses the placenta and inhibits **vitamin K-dependent carboxylation**, affecting bone and cartilage development and leading to these characteristic fetal anomalies. *Omeprazole* - **Omeprazole** is a proton pump inhibitor generally considered **safe in pregnancy** and is not associated with teratogenic effects like those described. - It is commonly used to treat **gastroesophageal reflux disease** during pregnancy. *Atenolol* - **Atenolol** is a beta-blocker that can cause **fetal growth restriction** and **neonatal bradycardia** or **hypoglycemia** if used in late pregnancy. - However, it does not typically cause the specific craniofacial or skeletal malformations seen in this infant. *Alcohol* - **Fetal alcohol syndrome** is characterized by **growth restriction**, **facial dysmorphology (e.g., short palpebral fissures, smooth philtrum, thin upper lip)**, and **CNS abnormalities**. - While the infant has growth restriction, the specific facial and skeletal features do not align with fetal alcohol syndrome. *Gentamicin* - **Gentamicin** is an aminoglycoside antibiotic that can cause **ototoxicity** (hearing loss) and **nephrotoxicity** in both the mother and fetus. - It is not associated with the **craniofacial, skeletal, or ocular anomalies** described in this case.

Question 837: An 8-year-old girl is brought to the physician because of repetitive involuntary movements, including neck twisting, grimacing, grunting, and blinking, for the past 18 months. Her symptoms seem to improve with concentration and worsen with fatigue. During the past 3 months, they have become so severe that she has missed many school days. Her mother says she also has too much anxiety about her involuntary movements to see her friends and prefers staying home in her room. Her birth and development until 18 months ago were normal. Her father suffers from bipolar disorder. Vital signs are within normal limits. Mental status examination shows intact higher mental function and thought processes. Neurological examination shows multiple motor and vocal tics. Physical examination is otherwise within normal limits. Which of the following is the most appropriate initial pharmacotherapy for this condition?

• A. Fluoxetine
• B. Alprazolam
• C. Chlorpromazine
• D. Risperidone (Correct Answer)
• E. Buspirone

Explanation: ***Risperidone*** - This patient's symptoms are highly suggestive of **Tourette syndrome**, characterized by multiple motor and vocal tics persisting for over a year, and *risperidone*, an **atypical antipsychotic**, is a first-line treatment for severe tics. - Risperidone works by blocking **D2 dopamine receptors**, which helps reduce the frequency and severity of tics, especially when symptoms cause functional impairment. *Fluoxetine* - *Fluoxetine* is a **selective serotonin reuptake inhibitor (SSRI)** primarily used to treat depression, anxiety, and obsessive-compulsive disorder. - While comorbidities like anxiety or OCD are common in Tourette patients, *fluoxetine* would not directly address the **tics** themselves as a first-line agent. *Alprazolam* - *Alprazolam* is a **benzodiazepine** used for short-term relief of anxiety or panic disorders, working by enhancing *GABA*ergic activity. - It does not effectively treat tics associated with Tourette syndrome and carries risks of **tolerance and dependence**. *Chlorpromazine* - *Chlorpromazine* is a **typical antipsychotic** that could reduce tics, but it has a higher risk of **extrapyramidal symptoms** and other side effects compared to atypical antipsychotics like *risperidone*. - It is generally reserved for cases unresponsive to newer, better-tolerated agents. *Buspirone* - *Buspirone* is an **anxiolytic** that primarily affects serotonin receptors, used for generalized anxiety disorder. - It does not have significant efficacy in treating the motor and vocal tics of **Tourette syndrome**.

Question 838: While playing in the woods with friends, a 14-year-old African-American male is bitten by an insect. Minutes later he notices swelling and redness at the site of the insect bite. Which substance has directly led to the wheal formation?

• A. IFN-gamma
• B. IL-4
• C. IL-22
• D. Histamine (Correct Answer)
• E. Arachidonic acid

Explanation: ***Histamine*** - **Histamine** is a key mediator released by **mast cells** and basophils during immediate hypersensitivity reactions, such as an insect bite. - It causes vasodilation, increased vascular permeability, and itching, leading to the characteristic **wheal and flare** response. *IFN-gamma* - **IFN-gamma** is primarily involved in **Type IV hypersensitivity** (delayed-type) reactions and viral/intracellular bacterial defense. - It would not directly cause immediate wheal formation from an insect bite. *IL-4* - **IL-4** is crucial for **Th2 differentiation** and IgE production, which is involved in allergic reactions. - While essential for the underlying allergic response, it does not directly cause the acute wheal formation. *IL-22* - **IL-22** is involved in host defense, particularly against extracellular bacteria, and plays a role in tissue repair and inflammation, especially in epithelial tissues. - It is not a primary mediator of immediate hypersensitivity reactions or wheal formation. *Arachidonic acid* - **Arachidonic acid** is a precursor to eicosanoids (prostaglandins, leukotrienes), which mediate later phases of inflammation and pain. - While contributing to the overall inflammatory response, it does not directly cause the initial, rapid wheal formation.

Question 839: A 34-year-old woman with a history of depression is brought to the emergency department by her husband 45 minutes after ingesting an unknown amount of a termite poison in a suicide attempt. She has abdominal pain, nausea, and vomiting. Her husband reports that she has had two episodes of watery diarrhea on the way to the emergency department. A distinct, garlic-like odor on the breath is noted on examination. An ECG shows sinus tachycardia and QTc prolongation. Administration of which of the following is most appropriate?

• A. Deferoxamine
• B. Dimercaprol (Correct Answer)
• C. Fomepizole
• D. N-acetylcysteine
• E. Physostigmine

Explanation: ***Dimercaprol*** - The patient's symptoms (abdominal pain, nausea, vomiting, watery diarrhea, garlic-like odor on breath, QTc prolongation, and ingestion of termite poison) are highly suggestive of **acute arsenic poisoning**. - **Dimercaprol** (BAL) is a chelating agent indicated for severe arsenic poisoning by forming stable renally excreted complexes with arsenic. *Deferoxamine* - Is a chelating agent primarily used for **iron overdose** by binding to free iron in the bloodstream. - It is not effective for arsenic poisoning and would not address the patient's specific symptoms. *Fomepizole* - Is an **alcohol dehydrogenase inhibitor** used in cases of **methanol** or **ethylene glycol poisoning** to prevent the formation of toxic metabolites. - It has no role in the management of arsenic poisoning due to a different mechanism of toxicity. *N-acetylcysteine* - Is an antidote primarily used for **acetaminophen overdose** by replenishing glutathione stores, and as a mucolytic. - It is not indicated for arsenic poisoning and would not mitigate the toxic effects of arsenic. *Physostigmine* - Is an **acetylcholinesterase inhibitor** used to reverse anticholinergic toxicity. - The patient's symptoms are not consistent with anticholinergic poisoning, and physostigmine would be inappropriate and potentially harmful.

Question 840: A 44-year-old man presents to his primary care physician due to a tremor. His tremor has been progressively worsening over the course of several weeks and he feels embarrassed and anxious about going to social events. He says these movements are involuntary and denies having an urge to have these movements. Medical history is significant for depression which is being treated with escitalopram. His mother is currently alive and healthy but his father committed suicide and had a history of depression. Physical examination is remarkable for impaired saccade initiation and brief, abrupt, and non-stereotyped movements involved the right arm. He also has irregular finger tapping. Which of the following is the best treatment for this patient's symptoms?

• A. Cognitive behavioral therapy
• B. Switch to sertraline
• C. Valproic acid
• D. Deutetrabenazine (Correct Answer)
• E. Carbidopa-levodopa

Explanation: ***Deutetrabenazine*** - This patient's symptoms of **abrupt, non-stereotyped movements**, **impaired saccade initiation**, irregular finger tapping, and a **family history of psychiatric illness** are highly suggestive of **Huntington's disease**. Deutetrabenazine is a **vesicular monoamine transporter 2 (VMAT2) inhibitor** approved for the treatment of **chorea** associated with Huntington's disease. - VMAT2 inhibitors reduce the amount of dopamine released into the synapse, which helps alleviate the **hyperkinetic movements (chorea)** characteristic of Huntington's disease. *Cognitive behavioral therapy* - While **cognitive behavioral therapy (CBT)** can be beneficial for managing **anxiety** and **depression** often associated with chronic neurological conditions, it does not directly address the **neurological signs** and movement disorders themselves. - CBT is a psychotherapy approach, not a pharmacological treatment for **chorea**. *Switch to sertraline* - Switching antidepressants from **escitalopram to sertraline** would primarily target the patient's **depressive symptoms**, but would not directly treat the **involuntary movements**. - While some antidepressants can have mild effects on movement, they are not indicated as a primary treatment for **chorea** in Huntington's disease. *Valproic acid* - **Valproic acid** is an **anticonvulsant** and mood stabilizer primarily used for epilepsy, bipolar disorder, and migraine prevention. - It does not have a primary role in the treatment of **chorea** associated with Huntington's disease. *Carbidopa-levodopa* - **Carbidopa-levodopa** is the cornerstone treatment for **Parkinson's disease**, aiming to increase dopamine levels in the brain to alleviate **bradykinesia** and rigidity. - In Huntington's disease, the primary issue is **dopamine overactivity**, so increasing dopamine with carbidopa-levodopa would worsen, rather than improve, the **chorea**.

Question 841: A 65-year-old man presents to the emergency department by ambulance following a motor vehicle accident. He was a restrained passenger. At the hospital, he is bleeding heavily from a large wound in his left leg. A review of medical records reveals a history of atrial fibrillation for which he takes warfarin. His international normalized ratio (INR) 2 days ago was 2.6. On physical exam he is cool and clammy. The vital signs include: heart rate 130/min and blood pressure 96/54 mm Hg. Aggressive resuscitation with intravenous normal saline is begun. Which of the following is the next best step to correct this patient's underlying coagulopathy?

• A. Give platelets
• B. Give intravenous vitamin K
• C. Give fresh frozen plasma (FFP) (Correct Answer)
• D. Give cryoprecipitate
• E. Give packed red blood cells

Explanation: ***Give fresh frozen plasma (FFP)*** - This patient is in **hemorrhagic shock** due to severe bleeding while on **warfarin**, evidenced by tachycardia (HR 130), hypotension (BP 96/54), and cool/clammy skin with an INR of 2.6. - **Fresh frozen plasma (FFP)** contains all vitamin K-dependent clotting factors (II, VII, IX, X) and is the best option **among those listed** to immediately reverse warfarin's effects in this life-threatening hemorrhage. - FFP provides rapid reversal within minutes to hours, though it requires large volumes (10-15 mL/kg) and carries risk of transfusion-associated circulatory overload (TACO). - **Note:** In modern practice, **4-factor prothrombin complex concentrate (PCC)** is preferred over FFP for warfarin reversal (faster, smaller volume, fewer complications), but it is not listed among the options here. *Give intravenous vitamin K* - **Vitamin K** reverses warfarin by enabling synthesis of vitamin K-dependent clotting factors (II, VII, IX, X). - However, it takes **6-24 hours** to produce clinical effect, making it unsuitable as monotherapy for **life-threatening acute bleeding**. - Vitamin K should be given as **adjunct therapy** alongside FFP, but cannot be the sole intervention in hemorrhagic shock. *Give platelets* - **Platelets** are indicated for **thrombocytopenia** (typically <50,000 in active bleeding) or **platelet dysfunction**. - Warfarin affects **clotting factors**, not platelet count or function, so platelets will not reverse the coagulopathy. - No indication of thrombocytopenia is mentioned in this case. *Give cryoprecipitate* - **Cryoprecipitate** contains **fibrinogen, Factor VIII, Factor XIII, von Willebrand factor, and fibronectin**. - It does **not contain** the vitamin K-dependent factors (II, VII, IX, X) depleted by warfarin. - Cryoprecipitate is used for **hypofibrinogenemia** (fibrinogen <100 mg/dL) in massive transfusion or DIC, not for warfarin reversal. *Give packed red blood cells* - **Packed red blood cells (PRBCs)** replace blood volume and improve oxygen-carrying capacity in hemorrhagic shock. - While PRBCs are critical for managing hypovolemia, they **do not contain clotting factors** and will not correct the **warfarin-induced coagulopathy**. - PRBCs should be transfused in this patient, but they must be combined with FFP to address the underlying bleeding disorder.

Question 842: A 3-year-old male is evaluated for frequent nose bleeds. Physical examination shows diffuse petechiae on the patient's distal extremities. Peripheral blood smear shows an absence of platelet clumping. An ELISA binding assay reveals that platelet surfaces are deficient in GpIIb/IIIa receptors. Which of the following drugs pharmacologically mimics this condition?

• A. Clopidogrel
• B. Cilostazol
• C. Aspirin
• D. Abciximab (Correct Answer)
• E. Warfarin

Explanation: ***Abciximab*** - The patient exhibits symptoms of **Glanzmann thrombasthenia**, a genetic disorder characterized by a deficiency or qualitative defect of **glycoprotein IIb/IIIa (GpIIb/IIIa) receptors** on platelet surfaces, leading to impaired platelet aggregation. Abciximab is a **monoclonal antibody** that directly targets and inhibits the **GpIIb/IIIa receptor**, thus pharmacologically mimicking this condition. - Abciximab binds to the **GpIIb/IIIa receptor** on activated platelets, preventing the binding of **fibrinogen** and **von Willebrand factor**, which are essential for platelet aggregation and thrombus formation. *Clopidogrel* - Clopidogrel is an **antiplatelet agent** that works by irreversibly blocking the **P2Y12 ADP receptor** on platelets, preventing **ADP-induced platelet activation** and aggregation. - This mechanism is distinct from inhibiting the GpIIb/IIIa receptor directly and does not mimic Glanzmann thrombasthenia. *Cilostazol* - Cilostazol is a **phosphodiesterase-3 (PDE3) inhibitor** that increases **cyclic AMP (cAMP)** levels in platelets, leading to **reduced platelet aggregation** and **vasodilation**. - Its mechanism of action is primarily related to inhibiting cAMP breakdown, which is different from GpIIb/IIIa receptor dysfunction. *Aspirin* - Aspirin is a **nonsteroidal anti-inflammatory drug (NSAID)** that irreversibly inhibits **cyclooxygenase-1 (COX-1)** in platelets, thereby reducing the production of **thromboxane A2 (TXA2)**. - TXA2 is a potent platelet aggregator and vasoconstrictor. While aspirin is an antiplatelet agent, its mechanism does not involve the GpIIb/IIIa receptor. *Warfarin* - Warfarin is an **oral anticoagulant** that acts as a **vitamin K antagonist**, thereby inhibiting the synthesis of **vitamin K-dependent clotting factors** (II, VII, IX, X, and proteins C and S) in the liver. - This drug affects the coagulation cascade rather than platelet function directly, and therefore does not mimic Glanzmann thrombasthenia.

Question 843: A 72-year-old man presents to his primary care physician with a 1 week history of persistent dry cough and worsening shortness of breath. He says that he has also been experiencing some abdominal pain and weakness. He has never experienced these symptoms before. His past medical history is significant for persistent ventricular tachycardia, and he started a new medication to control this arrhythmia about 1 month prior to presentation. Chest radiograph reveals patchy opacification bilaterally, and computed tomography (CT) scan shows diffuse ground glass changes. The drug that is most likely responsible for this patient's symptoms has which of the following mechanisms of action?

• A. Sodium channel blocker with shortened refractory period
• B. Beta-adrenergic blocker
• C. Potassium channel blocker (Correct Answer)
• D. Sodium channel blocker with prolonged refractory period
• E. Calcium channel blocker

Explanation: ***Potassium channel blocker*** - The patient's symptoms (dry cough, shortness of breath, bilateral patchy opacification, diffuse ground glass changes) developing one month after starting a new antiarrhythmic for **persistent ventricular tachycardia** strongly suggest **amiodarone-induced pulmonary toxicity**. - **Amiodarone** is a **Class III antiarrhythmic** that primarily works by **blocking potassium channels**, which prolongs the action potential duration and refractory period in cardiac tissue. - Amiodarone is highly effective for both ventricular and supraventricular arrhythmias but has numerous serious side effects including **pulmonary fibrosis/pneumonitis** (most serious), thyroid dysfunction (hypo- or hyperthyroidism), hepatotoxicity, corneal deposits, and skin discoloration. - The classic presentation of amiodarone pulmonary toxicity includes dyspnea, dry cough, and ground glass opacities on CT scan, typically occurring weeks to months after initiation. *Sodium channel blocker with prolonged refractory period* - This describes **Class IC antiarrhythmics** (e.g., flecainide, propafenone) which block sodium channels and prolong the action potential. - While these can be used for ventricular arrhythmias, they are not associated with the severe pulmonary toxicity seen in this patient. - These agents carry a risk of proarrhythmic effects, especially in patients with structural heart disease. *Sodium channel blocker with shortened refractory period* - This mechanism is characteristic of **Class IB antiarrhythmics** (e.g., lidocaine, mexiletine), which block sodium channels but shorten the action potential duration. - These agents are used primarily for ventricular arrhythmias but do not cause the diffuse pulmonary toxicity described. - Common side effects are primarily neurological (dizziness, tremor, seizures at high doses). *Beta-adrenergic blocker* - Beta-blockers (e.g., metoprolol, propranolol) primarily slow heart rate and reduce myocardial contractility. - While they can cause bronchospasm in susceptible individuals (especially non-selective beta-blockers), they do not typically cause **pulmonary fibrosis** with ground glass changes as seen in this patient. - Beta-blockers may be used for arrhythmias but are not first-line for persistent ventricular tachycardia. *Calcium channel blocker* - Non-dihydropyridine calcium channel blockers (e.g., verapamil, diltiazem) are used primarily for **supraventricular arrhythmias** and rate control, not persistent ventricular tachycardia. - Their primary side effects include **bradycardia**, **hypotension**, **constipation**, and **peripheral edema**, but they are not associated with pulmonary toxicity.

Question 844: A 72-year-old man with coronary artery disease comes to the physician because of intermittent episodes of substernal chest pain and shortness of breath. The episodes occur only when walking up stairs and resolves after resting for a few minutes. He is a delivery man and is concerned because the chest pain has impacted his ability to work. His pulse is 98/min and blood pressure is 132/77 mm Hg. Physical examination is unremarkable. An ECG shows no abnormalities. A drug that blocks which of the following receptors is most likely to prevent future episodes of chest pain from occurring?

• A. Angiotensin II receptors
• B. M2 muscarinic receptors
• C. Aldosterone receptors
• D. Beta-1 adrenergic receptors (Correct Answer)
• E. Alpha-2 adrenergic receptors

Explanation: ***Beta-1 adrenergic receptors*** - The patient's symptoms are classic for **stable angina**, triggered by exertion and relieved by rest, which indicates myocardial oxygen demand exceeding supply. Blocking **beta-1 adrenergic receptors** with a beta-blocker **reduces heart rate** and **contractility**, thereby decreasing myocardial oxygen consumption. - Beta-blockers are a cornerstone in the treatment of stable angina to prevent future episodes of chest pain by **reducing cardiac workload**. *Angiotensin II receptors* - Blocking **Angiotensin II receptors** (e.g., with ARBs) is primarily used for **hypertension**, **heart failure**, and **renal protection**, not as a first-line treatment for acute angina prevention by reducing myocardial oxygen demand. - While beneficial for overall cardiovascular risk reduction, ARBs do not directly lower heart rate or contractility to the same extent as beta-blockers for immediate angina symptom control. *M2 muscarinic receptors* - Blocking **M2 muscarinic receptors** would primarily **increase heart rate** and contractility by inhibiting parasympathetic tone, which would worsen, not prevent, angina by increasing myocardial oxygen demand. - This is the opposite effect desired for angina management. *Aldosterone receptors* - Aldosterone receptor blockade (e.g., with spironolactone) is mainly used in **heart failure** and **hypertension** to reduce fluid retention and remodeling, but it does not directly impact myocardial oxygen demand or supply to prevent exertional angina. - It does not have a direct anti-anginal effect on heart rate or contractility. *Alpha-2 adrenergic receptors* - Alpha-2 adrenergic receptor agonists (e.g., clonidine) are centrally acting sympatholytics that **decrease sympathetic outflow**, leading to vasodilation and reduced heart rate and blood pressure. However, they are not first-line agents for stable angina due to potential side effects and less direct impact on myocardial oxygen demand compared to beta-blockers. - Their primary role is in **hypertension management**, and sudden discontinuation can lead to **rebound hypertension**.

Question 845: A 62-year-old woman is brought to the emergency department after briefly losing consciousness while walking her dog. She spontaneously regained consciousness 20 seconds later. She has a history of atrial fibrillation. Current medications include metoprolol. She reports that she forgot to take her medication the day before and took double the dose this morning instead. A decrease in which of the following most likely contributed to this patient's episode?

• A. Diastolic efflux of calcium in cardiomyocytes
• B. Activity of protein kinase C in cardiomyocytes
• C. Phosphorylation of myosin light chains in vascular smooth muscle cells
• D. Activity of protein kinase A in vascular smooth muscle cells
• E. Activity of adenylyl cyclase in cardiomyocytes (Correct Answer)

Explanation: ***Activity of adenylyl cyclase in cardiomyocytes*** - A double dose of **metoprolol**, a beta-blocker, would significantly decrease the activity of **adenylyl cyclase** by blocking beta-adrenergic receptors in cardiomyocytes. - Reduced adenylyl cyclase activity leads to decreased cyclic AMP (cAMP) and protein kinase A (PKA) activity, ultimately lowering heart rate and contractility, which could cause a syncopal episode. *Diastolic efflux of calcium in cardiomyocytes* - This process is primarily mediated by the **sodium-calcium exchanger** and sarco/endoplasmic reticulum calcium ATPase (SERCA), and is not directly inhibited by beta-blockers. - While beta-blockers reduce intracellular calcium **influx** during systole, they do not directly decrease diastolic efflux processes. *Activity of protein kinase C in cardiomyocytes* - **Protein kinase C** is primarily involved in pathways activated by phospholipase C and diacylglycerol, which are separate from the beta-adrenergic signaling pathway. - Metoprolol's action as a beta-blocker does not directly inhibit the activity of protein kinase C. *Phosphorylation of myosin light chains in vascular smooth muscle cells* - **Myosin light chain phosphorylation** in vascular smooth muscle primarily mediates **vasoconstriction** and is regulated by calcium-calmodulin-myosin light chain kinase. - Beta-blockers like metoprolol do not directly inhibit this process, although they can indirectly affect vascular tone. *Activity of protein kinase A in vascular smooth muscle cells* - While **PKA** in vascular smooth muscle can cause vasodilation, metoprolol's primary effect is on beta-1 receptors in the heart, not directly lowering PKA activity in vascular smooth muscle. - However, the patient's symptoms are more consistent with a **cardiac origin** due to the acute change in heart function.

Question 846: A 26-year-old woman comes to the physician for evaluation of nausea and fatigue. Her last menstrual period was 8 weeks ago. She has a history of bipolar disorder controlled by a drug known to sometimes cause hypothyroidism and nephrogenic diabetes insipidus. She does not smoke cigarettes or drink alcohol. A urine pregnancy test is positive. An ultrasound of the pelvis shows a viable intrauterine pregnancy. The fetus is most likely at increased risk for which of the following anomalies?

• A. Neural tube defects
• B. Aplasia cutis
• C. Hypoplastic or absent limbs
• D. Abnormal placentation
• E. Atrialization of the right ventricle (Correct Answer)

Explanation: ***Atrialization of the right ventricle*** - The patient's history of **bipolar disorder** controlled by a drug causing **hypothyroidism** and **nephrogenic diabetes insipidus** strongly points to **lithium**. - **Lithium** exposure during the first trimester of pregnancy is associated with an increased risk of **Ebstein's anomaly**, which involves the **apical displacement of the tricuspid valve** leaflets leading to **atrialization of the right ventricle**. *Neural tube defects* - These anomalies are often associated with deficiencies in **folic acid** or exposure to certain **antiepileptic drugs** like valproate, not lithium. - While concerning, there is no information in the vignette to suggest these specific risk factors exist for this patient besides lithium use. *Aplasia cutis* - This is a localized absence of skin at birth, most commonly on the scalp. It is associated with gestational exposure to **methimazole** or **carbimazole**, used to treat hyperthyroidism, which is not indicated here. - There is no direct link between lithium exposure and aplasia cutis. *Hypoplastic or absent limbs* - This type of anomaly is historically associated with exposure to **thalidomide** during early pregnancy. - Lithium is not known to cause limb reduction defects. *Abnormal placentation* - Conditions like **placenta previa** or **placenta accreta** can result from previous uterine surgery (e.g., C-section) or advanced maternal age. - Lithium use is not a recognized risk factor for abnormal placentation.

Question 847: A 60-year-old African-American female presents to your office complaining of dysuria, paresthesias, and blurry vision. Her body mass index is 37.2 kg/m2. Which of the following drugs would most significantly increase the levels of C-peptide in the blood when administered to this patient?

• A. Acarbose
• B. Glipizide (Correct Answer)
• C. Insulin
• D. Metformin
• E. NPH

Explanation: ***Glipizide*** - **Glipizide** is a **sulfonylurea** that stimulates insulin secretion from pancreatic beta cells, leading to increased C-peptide levels. - Increased insulin secretion by glipizide is independent of meals and can cause **hypoglycemia**. *Acarbose* - **Acarbose** is an **alpha-glucosidase inhibitor** that delays glucose absorption from the gut, reducing post-prandial glucose spikes. - It does not directly affect insulin secretion or C-peptide levels. *Insulin* - Administering exogenous **insulin** directly lowers blood glucose but does not stimulate endogenous insulin production, and therefore does not increase C-peptide. - C-peptide is a marker of endogenous insulin secretion; an increase would only be seen if the body produced more insulin. *Metformin* - **Metformin** primarily reduces **hepatic glucose production** and improves insulin sensitivity in peripheral tissues. - It does not directly stimulate insulin secretion from the pancreas and therefore does not increase C-peptide levels. *NPH* - **NPH (Neutral Protamine Hagedorn)** is an intermediate-acting exogenous insulin formulation. - As an exogenous insulin, it does not stimulate the pancreas to produce more insulin or C-peptide.

Question 848: A 54-year-old man comes to the physician for a health maintenance examination. He feels well. He is 173 cm (5 ft 8 in) tall and weighs 84 kg (185 lb); BMI is 28 kg/m2. His vital signs are within normal limits. Physical examination shows no abnormalities. Serum lipid studies show: Total cholesterol 280 mg/dL HDL-cholesterol 30 mg/dL LDL-cholesterol 195 mg/dL Triglycerides 275 mg/dL Treatment with atorvastatin and cholestyramine is initiated. Which of the following changes is most likely induced by both agents?

• A. Increased hepatic bile salt synthesis
• B. Increased LDL receptor expression (Correct Answer)
• C. Increased lipoprotein lipase activity
• D. Decreased hepatic de novo cholesterol synthesis
• E. Increased cholesterol levels in hepatocytes