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?
Q292
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?
Q293
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?
Q294
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?
Q295
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?
Q296
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?
Q297
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?
Q298
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?
Q299
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?
Q300
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?
Autonomic/CV Drugs US Medical PG Practice Questions and MCQs
Question 291: 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 292: 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 293: 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 294: 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 295: 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 296: 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 297: 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 298: 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 299: 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 300: 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.