Learning Objective:

Understand the pharmacologic strategies used in the management of primary pulmonary hypertension, including mechanisms, administration routes, and key side effects of endothelin receptor antagonists, prostacyclin analogs, and phosphodiesterase-5 inhibitors.

Treatment of Primary Pulmonary Hypertension

Endothelin Receptor Antagonists (ERAs): Bosentan and other “-entans”
Endothelin-1 (ET-1) is a potent vasoconstrictor that acts via ET-A and ET-B receptors. Selective blockade of ET-A receptors leads to pulmonary vasodilation and is effective in reducing pulmonary arterial pressure.

• Administration: Oral
• Side effects: Headache, flushing, hypotension (related to vasodilation)
• Contraindications: Pregnancy

Prostacyclin Analog: Epoprostenol (PGI2)

• Mimics endogenous prostacyclin, causing potent vasodilation of pulmonary arteries and inhibition of platelet aggregation.
• Administration: Continuous intravenous infusion via pump due to short half-life.

Phosphodiesterase-5 Inhibitors: Sildenafil

• Inhibits PDE-5 → increases cGMP levels in pulmonary vascular smooth muscle
• Leads to pulmonary artery relaxation and reduction in pulmonary hypertension
• Administration: Oral

Activity