A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
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?
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A
Competitive inhibition of endothelin-1 receptorsCorrect. endothelin receptor antagonists (bosentan) competitively inhibit ET-1 at vascular smooth muscle ETA/B receptors; bosentan is well known to cause dose-dependent transaminitis, matching the AST/ALT elevation here.
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B
Competitive inhibition of muscarinic receptorsIncorrect. Muscarinic antagonists like tiotropium are bronchodilators used for COPD, not pulmonary hypertension; they don't typically cause hepatotoxicity.
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C
Inhibition of phosphodiesterase-5Incorrect. PDE5 inhibitors (sildenafil, tadalafil) treat pulmonary hypertension but are not associated with transaminitis — their side effects are headache, flushing, and visual changes.
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D
Prostacylin with direct vasodilatory effectsIncorrect. Prostacyclin analogs cause flushing, jaw pain, and diarrhea, are usually given by infusion or inhalation, and are not associated with hepatotoxicity.
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E
Stimulation of soluble guanylate cyclaseIncorrect. sGC stimulators (riociguat) treat pulmonary hypertension by increasing cGMP independent of nitric oxide; they primarily cause hypotension and syncope, not the transaminitis seen in this patient.
↑ Tap an answer to reveal the reasoning
Answer: A. This COPD patient with progressive dyspnea, clubbing, and right ventricular hypertrophy has developed pulmonary hypertension (Group 3, due to lung disease). The classes of pulmonary vasodilators include endothelin receptor antagonists (bosentan, ambrisentan), phosphodiesterase-5 inhibitors (sildenafil, tadalafil), and prostacyclin analogs (epoprostenol, treprostinil), plus soluble guanylate cyclase stimulators (riociguat).
The key clue is the elevated transaminases (AST 159, ALT 201) after one month of therapy. Bosentan and other endothelin receptor antagonists are notorious for dose-dependent hepatotoxicity — the FDA requires monthly LFT monitoring, and elevated transaminases are seen in roughly 10% of patients on bosentan. The drug competitively blocks endothelin-1 binding to ETA (and ETB for bosentan) receptors on vascular smooth muscle, producing pulmonary vasodilation.
PDE5 inhibitors don't cause hepatotoxicity (sildenafil's side effects are headache, flushing, visual disturbance). Prostacyclins are delivered IV/inhaled and cause flushing, jaw pain, diarrhea — not transaminitis. Muscarinic antagonists (tiotropium, ipratropium) are bronchodilators for COPD itself, not pulmonary hypertension, and wouldn't cause hepatotoxicity.
**Why each option:**
**A.** Correct — endothelin receptor antagonists (bosentan) competitively inhibit ET-1 at vascular smooth muscle ETA/B receptors; bosentan is well known to cause dose-dependent transaminitis, matching the AST/ALT elevation here.
**B.** Muscarinic antagonists like tiotropium are bronchodilators used for COPD, not pulmonary hypertension; they don't typically cause hepatotoxicity.
**C.** PDE5 inhibitors (sildenafil, tadalafil) treat pulmonary hypertension but are not associated with transaminitis — their side effects are headache, flushing, and visual changes.
**D.** Prostacyclin analogs cause flushing, jaw pain, and diarrhea, are usually given by infusion or inhalation, and are not associated with hepatotoxicity.