Snapshot A 67-year-old man presents to the clinic with complaints of dyspnea and fatigue for 1 month. He reports that it is difficult to breathe when he walks for 5 minutes (compared to 30 minutes 2 months ago). His past medical history is significant for mitral stenosis secondary to rheumatic fever. A physical examination shows a loud P2 heart sound on auscultation. Overview Treatment of pulmonary hypertension (PH) usually begins with primary therapy that is directed at the underlying cause of PH Treatment/medications directed at PH itself are detailed below Endothelin Receptor Antagonists Mechanism of action competitively antagonizes endothelin-1 receptors, which are potent vasoconstrictors and smooth muscle mitogens decreases pulmonary vascular resistance examples bosentan and macitentan Clinical use pulmonary hypertension Adverse effects hepatic toxicity monitor LFTs while on medication peripheral edema teratogenic Phosphodiesterase Type 5 (PDE5) Inhibitors Mechanism of action inhibits PDE5 which increases cyclic GMP, prolonging the vasodilatory effect of nitric oxide examples sildenafil and tadalafil Clinical use pulmonary hypertension erectile dysfunction Adverse effects severe hypotension headache Prostacyclin Pathway Agonists Mechanism of action PGI2 (prostacyclin) agonist with direct vasodilatory effects on the pulmonary and systemic arterial vascular beds inhibition of platelet aggregation examples epoprostenol, iloprost, treprostinil, and selexipag Clinical use pulmonary hypertension Adverse effects flushing jaw pain hypotension pulmonary edema