A 36-year-old woman comes to the office due to dyspnea and weakness that are brought on while doing ordinary chores around the house. The patient has no other medical conditions and takes no medications. She does not use tobacco, alcohol, or illicit drugs. Her mother had similar symptoms and died at age 42. After an extensive workup, a lung biopsy is performed. Light microscopy of the tissue sample shows medial hypertrophy, intimal fibrosis, and decreased intraluminal diameter of the small branches of the pulmonary artery. Which of the following is the most appropriate pharmacotherapy for this patient's current condition?

Question

A 36-year-old woman comes to the office due to dyspnea and weakness that are brought on while doing ordinary chores around the house.  The patient has no other medical conditions and takes no medications.  She does not use tobacco, alcohol, or illicit drugs.  Her mother had similar symptoms and died at age 42.  After an extensive workup, a lung biopsy is performed.  Light microscopy of the tissue sample shows medial hypertrophy, intimal fibrosis, and decreased intraluminal diameter of the small branches of the pulmonary artery.  Which of the following is the most appropriate pharmacotherapy for this patient's current condition?

Quizplus · Accepted Answer

11ec160b_3c63_fe76_9249_f3051670c381_MD0001_00 Pulmonary hypertension causes specific morphologic findings in the branches of the pulmonary arteries, including increased arteriolar smooth muscle thickness (medial hypertrophy), intimal fibrosis, and significant luminal narrowing. In the setting of severe hypertension, lesions can progress to form interlacing tufts of small vascular channels called plexiform lesions. These changes can occur in both pulmonary hypertension due to underlying cardiac, lung, or thrombotic disease and in pulmonary arterial hypertension (PAH). PAH most commonly presents as dyspnea and exercise intolerance in women age 20-40. This patient's family history is suggestive of the familial form of PAH, which is most often caused by inactivating mutations involving the proapoptotic BMPR2 gene. The resulting increase in endothelial and smooth muscle cell proliferation leads to vascular remodeling, elevated pulmonary vascular resistance, and progressively elevated pulmonary arterial pressure. Although lung transplantation is the definitive treatment for PAH, medical therapy targeting the effects of endothelial dysfunction can help improve symptoms. Bosentan is an endothelin-receptor antagonist that blocks the effects of endothelin (a potent vasoconstrictor that also stimulates endothelial proliferation). Bosentan therapy decreases pulmonary arterial pressure and lessens the progression of vascular remodeling and right ventricular hypertrophy. (Choice B) Clopidogrel inhibits ADP-induced platelet aggregation. It is used in atherosclerotic cardiovascular disease and to prevent acute stent thrombosis following percutaneous coronary intervention. (Choice C) Enalapril is an angiotensin-converting enzyme inhibitor. It is used for the treatment of congestive heart failure, hypertension, and diabetic nephropathy. (Choice D) Etanercept inhibits tumor-necrosis factor (TNF) activity by competitively binding to TNF and preventing it from interacting with cell surface receptors. It is an anti-inflammatory agent used for the treatment of rheumatoid arthritis, psoriasis, and psoriatic arthritis. (Choice E) Indomethacin is a nonselective cyclooxygenase inhibitor that suppresses prostaglandin synthesis. It is used as an anti-inflammatory agent and pain reliever. Educational objective: Pulmonary arterial hypertension (PAH) typically affects young women and can be familial. It is characterized by luminal narrowing of the pulmonary arteries and arterioles, with medial hypertrophy, intimal fibrosis, and the eventual development of plexiform lesions. Bosentan is a competitive antagonist of endothelin receptors used for the treatment of PAH.

A 36-Year-Old Woman Comes to the Office Due to Dyspnea