[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Pulmonary arterial hypertension drugs (endothelin receptor antagonists and prostacyclins) # 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. Updated Nov 1, 2026 ## 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) ## Key points - Endothelin receptor antagonists cause birth defects: pregnancy is excluded before treatment and effective contraception is used during it and for a month after. - Bosentan is hepatotoxic (monthly liver tests) and induces CYP3A and CYP2C9, so it lowers hormonal contraceptive and sildenafil levels. - Common to the antagonists: fluid retention and oedema, nasal congestion, falling haemoglobin and lower sperm counts. - Epoprostenol lasts only minutes: it runs as a continuous central intravenous infusion, and any interruption can cause dangerous rebound pulmonary hypertension. - Prostacyclin side effects: flushing, headache, jaw pain, diarrhoea, hypotension and bleeding risk (they inhibit platelets). ## Drugs in this class - [**Bosentan** An 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](https://durgical.com/en/pharmacology/bosentan/) - [**Epoprostenol** Synthetic prostacyclin given as a continuous intravenous infusion for severe pulmonary arterial hypertension; it acts… Prostacyclin receptor (IP receptor)](https://durgical.com/en/pharmacology/epoprostenol/) - [**Ambrisentan** An oral endothelin receptor blocker selective for ETA, used in pulmonary arterial hypertension; it must never be used… Endothelin receptor type A](https://durgical.com/en/pharmacology/ambrisentan/) - [**Treprostinil** A longer-acting prostacyclin analogue for pulmonary arterial hypertension, given by subcutaneous or intravenous… Prostacyclin receptor (IP receptor)](https://durgical.com/en/pharmacology/treprostinil/) - [**Sotatercept** An 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](https://durgical.com/en/pharmacology/sotatercept/) - [**Iloprost** A prostacyclin analogue: inhaled for pulmonary arterial hypertension, and given intravenously for severe frostbite. Prostacyclin receptor (IP receptor)](https://durgical.com/en/pharmacology/iloprost/) - [**Macitentan** An oral dual endothelin receptor blocker for pulmonary arterial hypertension; it can harm the fetus, so pregnancy is… Endothelin receptors type A and type B](https://durgical.com/en/pharmacology/macitentan/) - [**Selexipag** An oral prostacyclin (IP) receptor agonist, not a prostanoid, that delays progression of pulmonary arterial… Prostacyclin receptor (IP receptor)](https://durgical.com/en/pharmacology/selexipag/) ## 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. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/classes/pulmonary-arterial-hypertension-drugs/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) [← All of pharmacology](https://durgical.com/en/pharmacology/) 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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=39b2a85f-4322-42d4-b420-1b1d52569143) (DailyMed (U.S. National Library of Medicine), 2025); [DailyMed - AMBRISENTAN tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291a782a-77e1-8a8e-e1c8-2626f305c2b7) (DailyMed (U.S. National Library of Medicine), 2025); [DailyMed - EPOPROSTENOL injection, powder, lyophilized, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=47f64fcd-cbf7-457a-9548-661fb10ff7e0) (DailyMed (U.S. National Library of Medicine), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/classes/pulmonary-arterial-hypertension-drugs/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). 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