Review Question - QID 109335

The patient presents with dyspnea, a BMPR2 gene mutation, and an increased P2 suggestive of idiopathic pulmonary hypertension. Bosentan is an endothelin-1 receptor antagonist that is used to slow disease progression in patients with idiopathic pulmonary hypertension and is known to be hepatotoxic.

Idiopathic pulmonary hypertension is treated with calcium channel blockers, endothelin-1 receptor antagonists, or phosphodiesterase type 5 inhibitors. Calcium channel blockers are considered the first-line agent in the absence of contraindications; however, this patient failed calcium channel blockers due to drug toxicity (severe edema). Therefore, bosentan, an endothelin-1 receptor antagonist, is indicated to slow disease progression. Endothelins are vasoconstrictive peptides and thus their inhibition at the endothelin-1 receptor leads to decreased vasoconstriction.

Incorrect Answers:
Answer 2: Beta-2 adrenergic receptor agonists such as albuterol are used in the treatment of asthma and chronic obstructive pulmonary disorder. They are not used in the treatment of pulmonary hypertension which represents a primary vascular disorder.

Answer 3: Corticosteroids such as dexamethasone inhibit the activity of phospholipase A2, thereby decreasing levels of arachidonic acid and subsequent production of prostaglandins and leukotrienes. They are used to treat inflammatory and autoimmune conditions but are not considered first-line agents in the treatment of pulmonary hypertension.

Answer 4: Phosphodiesterase type 5 antagonists such as sildenafil block the degradation of cyclic GMP in smooth muscle, thereby promoting vasodilation. They are used in erectile dysfunction and pulmonary hypertension but are not hepatotoxic.

Answer 5: Prostacyclin (PGI2) is a naturally occurring substance produced by healthy endothelial cells with vasodilatory, antithrombotic, and antiproliferative effects. Synthetic prostacyclin (epoprostenol) is sometimes used to treat idiopathic pulmonary hypertension, but it is not hepatotoxic.

Bullet Summary:
Bosentan is an endothelin-1 receptor antagonist with known hepatotoxicity that is used to slow disease progression in patients with idiopathic pulmonary hypertension.