Pulmonary arterial hypertension drugs (endothelin receptor antagonists and prostacyclins)
Medicines that relax and remodel the narrowed lung arteries of pulmonary arterial hypertension, easing the load on the right heart.
What they are
Specific treatments for pulmonary arterial hypertension (PAH, WHO group 1) that act on its three main pathways. Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) block endothelin-1, a vasoconstrictor and growth signal. Prostacyclin and its analogues (epoprostenol, treprostinil, iloprost) and the receptor agonist selexipag replace the missing prostacyclin signal. The nitric oxide pathway is treated with PDE5 inhibitors (sildenafil, tadalafil) or riociguat. These drugs are often combined.
Mechanism of action
In PAH the endothelium makes too much endothelin-1 and too little prostacyclin and nitric oxide. Endothelin-1 acting on ETA receptors constricts the pulmonary arteries and makes their smooth muscle grow; ETB receptors mainly mediate vasodilation and endothelin clearance. Bosentan blocks both receptors and ambrisentan mainly ETA. Prostacyclin acts on the IP receptor, a Gs-coupled receptor that raises cyclic AMP, relaxes the vessels, slows smooth-muscle growth and inhibits platelets.
Target: Endothelin receptors ETA and ETB (antagonists); prostacyclin IP receptor (prostacyclin and its analogues)
Drugs in this class
- BosentanAn oral endothelin receptor blocker for pulmonary arterial hypertension; it can harm the liver and the fetus, so it…Endothelin receptors type A and type B
- EpoprostenolSynthetic prostacyclin given as a continuous intravenous infusion for severe pulmonary arterial hypertension; it acts…Prostacyclin receptor (IP receptor)
- AmbrisentanAn oral endothelin receptor blocker selective for ETA, used in pulmonary arterial hypertension; it must never be used…Endothelin receptor type A
- TreprostinilA longer-acting prostacyclin analogue for pulmonary arterial hypertension, given by subcutaneous or intravenous…Prostacyclin receptor (IP receptor)
- SotaterceptAn injected activin-signalling inhibitor for pulmonary arterial hypertension. It traps growth factors that drive…Activin A and related ligands (GDF8, GDF11), trapped by an ActRIIA–Fc fusion protein
- IloprostA prostacyclin analogue: inhaled for pulmonary arterial hypertension, and given intravenously for severe frostbite.Prostacyclin receptor (IP receptor)
- MacitentanAn oral dual endothelin receptor blocker for pulmonary arterial hypertension; it can harm the fetus, so pregnancy is…Endothelin receptors type A and type B
- SelexipagAn oral prostacyclin (IP) receptor agonist, not a prostanoid, that delays progression of pulmonary arterial…Prostacyclin receptor (IP receptor)
Others in the class
- Macitentan
- Iloprost
- Selexipag
- Riociguat
Test yourself
Think of the answer, then tap the question to see it.
Which two endothelin receptors exist and which one does ambrisentan mainly block?
ETA (vasoconstriction and smooth-muscle growth) and ETB (vasodilation and endothelin clearance); ambrisentan is selective for ETA.
What is the main pregnancy rule for endothelin receptor antagonists?
They can cause birth defects: pregnancy is excluded before starting, reliable contraception is used during treatment and for a month after.
Why is a sudden stop of an epoprostenol infusion dangerous?
Its effect lasts only minutes, so an interruption can cause rebound pulmonary hypertension with breathlessness and collapse.
Through which second messenger does prostacyclin relax pulmonary arteries?
Cyclic AMP: the IP receptor is coupled to Gs and adenylyl cyclase.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - BOSENTAN tablet, film coated (DailyMed (U.S. National Library of Medicine), 2025); DailyMed - AMBRISENTAN tablet, film coated (DailyMed (U.S. National Library of Medicine), 2025); DailyMed - EPOPROSTENOL injection, powder, lyophilized, for solution (DailyMed (U.S. National Library of Medicine), 2026).
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Representative model, for educational purposes only.