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?
Q542
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?
Q543
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?
Q544
A medical student is reviewing dose-response curves of various experimental drugs. She is specifically interested in the different factors that cause the curve to shift in different directions. From her study, she plots the following graph (see image). She marks the blue curve for drug A, which acts optimally on a receptor. After drawing the second (green) curve for drug B, she discovers that more of drug B is required to produce the same response as drug A, although drug B can still achieve the same maximum effect. Which of the following terms best describes the activity of drug B in comparison to drug A?
Q545
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?
Q546
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?
Q547
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?
Q548
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?
Q549
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?
Q550
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?
Autonomic/CV Drugs US Medical PG Practice Questions and MCQs
Question 541: 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 542: 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 543: 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 544: A medical student is reviewing dose-response curves of various experimental drugs. She is specifically interested in the different factors that cause the curve to shift in different directions. From her study, she plots the following graph (see image). She marks the blue curve for drug A, which acts optimally on a receptor. After drawing the second (green) curve for drug B, she discovers that more of drug B is required to produce the same response as drug A, although drug B can still achieve the same maximum effect. Which of the following terms best describes the activity of drug B in comparison to drug A?
A. Decreased efficacy
B. Increased affinity
C. Higher potency
D. Higher efficacy
E. Lower potency (Correct Answer)
Explanation: ***Lower potency***
- **Potency** refers to the amount of drug required to produce a given effect; if more of drug B is needed for the same response as drug A, it has lower potency.
- On a dose-response curve, **lower potency** is indicated by a rightward shift of the curve, meaning a higher dose is required to achieve any given effect.
*Decreased efficacy*
- **Efficacy** is the maximum effect a drug can produce, regardless of the dose.
- While drug B has a lower ability to produce a reaction (implying lower efficacy), the statement "more of the second drug B is required to produce the same response as the first one" specifically points to potency, not just the maximal effect.
*Increased affinity*
- **Affinity** describes how strongly a drug binds to its receptor.
- Increased affinity would generally lead to greater potency (less drug needed for an effect), which contradicts the scenario where more drug B is required.
*Higher potency*
- **Higher potency** would mean that less of drug B is required to produce the same effect as drug A, which is the opposite of what is described in the question.
- A drug with higher potency would cause the dose-response curve to shift to the left.
*Higher efficacy*
- **Higher efficacy** would mean drug B could produce a greater maximal effect than drug A, but the question states drug B has a "lower ability to produce a reaction" compared to drug A.
- The peak of the dose-response curve for drug B would be higher than drug A, which is not suggested by the description.
Question 545: 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 546: 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 547: 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 548: 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 549: 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 550: 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].
