# Pulmonary Hypertension Targeted Therapies > Targeted drugs for pulmonary arterial hypertension in NEET-PG Medicine, covering endothelin antagonists, PDE5 inhibitors, prostacyclins and riociguat by group. - Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/pulmonary-hypertension-targeted-therapies - Exam / course: NEET-PG · Subject: Medicine - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-14 - Last updated: 2026-10-14 - Reference basis: Harrison's Principles of Internal Medicine; Katzung's Basic and Clinical Pharmacology - How to cite: "Pulmonary Hypertension Targeted Therapies", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/pulmonary-hypertension-targeted-therapies ## Direct answer Pulmonary arterial hypertension is treated with drugs that target the endothelin, nitric oxide and prostacyclin pathways, which together control vascular tone in the pulmonary circulation. The main classes are endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, prostacyclin analogues and the soluble guanylate cyclase stimulator riociguat. Targeted drugs treat WHO Group 1 disease, whereas Group 2 pulmonary hypertension from left heart disease is managed by treating the left heart. ## What you must remember - **Endothelin receptor antagonists:** bosentan, ambrisentan and macitentan block endothelin-1 signalling; all are teratogenic, and bosentan needs regular liver function monitoring. - **PDE5 inhibitors:** sildenafil and tadalafil raise cGMP in the pulmonary vessels; they are contraindicated with nitrates because the combination causes severe hypotension. - **Riociguat:** a soluble guanylate cyclase stimulator that acts on the nitric oxide pathway without needing nitric oxide; it is also the main medical drug for chronic thromboembolic pulmonary hypertension. - **Prostacyclin analogues:** epoprostenol, treprostinil and iloprost raise cAMP and dilate pulmonary arterioles; epoprostenol is infused continuously through a central line. - **Selexipag:** an oral prostacyclin receptor agonist, useful when parenteral therapy is not practical. - **Calcium channel blockers:** reserved for the small group of patients who show a positive acute vasoreactivity test at right heart catheterisation. - **Sotatercept:** an activin signalling inhibitor, a newer agent added to established therapy in selected patients. ## A stepwise approach from diagnosis to combination therapy A 34-year-old woman with exertional breathlessness and raised pulmonary pressure on echocardiography needs right heart catheterisation before any drug is chosen. The steps below move from confirming the diagnosis to escalating treatment. 1. **Confirm the diagnosis:** right heart catheterisation shows a mean pulmonary arterial pressure above 20 mmHg, a pulmonary capillary wedge pressure of 15 mmHg or less, and raised pulmonary vascular resistance. 2. **Classify the group:** identify the WHO group first, because targeted drugs apply mainly to Group 1 (and riociguat to Group 4), while Groups 2 and 3 mainly need the underlying cause treated. 3. **Test vasoreactivity:** an acute vasodilator test picks out the rare responders who may benefit from high-dose calcium channel blockers. 4. **Start targeted therapy:** most patients receive an endothelin receptor antagonist, a PDE5 inhibitor or a prostacyclin agent, and current guidance favours early combination for many patients. 5. **Assess risk at follow-up:** patients who are not at low risk are escalated to triple therapy or parenteral prostacyclin, as current guidance advises. 6. **Consider referral for refractory disease:** lung transplantation or atrial septostomy is considered in selected patients who do not respond to escalation. ## Where the exam tries to catch you Most questions on this topic test a contraindication or the WHO group a drug belongs to. - **Trap:** combining sildenafil with glyceryl trinitrate for chest pain — **Correct:** PDE5 inhibitors are contraindicated with nitrates because the combination causes profound hypotension. - **Trap:** starting bosentan without any monitoring — **Correct:** liver enzymes need regular checks and pregnancy must be excluded, because the drug is teratogenic. - **Trap:** giving pulmonary arterial hypertension drugs for left heart failure — **Correct:** Group 2 disease is treated by managing the left heart, and these drugs can be harmful when the left atrial pressure is high. - **Trap:** pairing riociguat with a PDE5 inhibitor — **Correct:** both act on the cGMP pathway, so the combination is contraindicated. ## Frequently asked questions ### Why is riociguat contraindicated with PDE5 inhibitors? Riociguat stimulates soluble guanylate cyclase to raise cGMP, and PDE5 inhibitors slow the breakdown of cGMP. Combining the two produces excessive cGMP effects and a risk of severe hypotension. Riociguat is therefore never prescribed with sildenafil or tadalafil. ### Which pulmonary arterial hypertension drug needs a central line for infusion? Epoprostenol is given as a continuous intravenous infusion through a central venous catheter because of its very short half-life. Interruption of the infusion is dangerous, so a reliable supply and a backup pump are essential. Treprostinil, by contrast, can also be given subcutaneously. ### How is chronic thromboembolic pulmonary hypertension treated medically? Riociguat is the main medical drug for chronic thromboembolic pulmonary hypertension, a Group 4 condition, and it is used when surgery is not possible or the disease persists. Pulmonary endarterectomy is the definitive treatment when clots are accessible surgically. Lifelong anticoagulation forms part of standard care. ### Why are calcium channel blockers used in only a few patients with pulmonary arterial hypertension? Only patients with a positive acute vasoreactivity test at right heart catheterisation respond sustainably to high-dose calcium channel blockers. Most patients do not respond, so the test is essential before these drugs are chosen. Testing identifies the small minority who benefit.