How Do PAH Prostacyclin Agonists Work?

PAH prostacyclin agonists are medications used to treat pulmonary arterial hypertension (PAH), a condition of high blood pressure in the arteries that carry deoxygenated blood from the heart to the lungs. PAH prostacyclin agonists reduce pulmonary hypertension by dilating the pulmonary blood vessels.

Prostacyclin, also known as prostaglandin I2 (PGI2), is a natural substance produced by the endothelial cells which form the inner lining of blood vessels. Prostacyclin dilates blood vessels by preventing the proliferation of vascular smooth muscle cells and prevents blood clotting by inhibiting platelet aggregation.

Prostacyclin works by binding to IP receptors, protein molecules on the surface of vascular smooth muscle cells, and platelets. PAH prostacyclin agonists selectively activate IP receptors and enhance prostacyclin’s vasodilatory and anticoagulant effects.

PAH prostacyclin agonists are administered as oral tablets or intravenous injections to delay disease progression and reduce the risk of hospitalization in patients with the following conditions:

FDA-approved:

• Pulmonary arterial hypertension: A group of chronic diseases that thicken and narrow the pulmonary arteries leading to high blood pressure in the pulmonary arteries, including:
  • Idiopathic PAH
  • Inherited PAH
  • PAH associated with connective tissue disease
  • PAH associated with congenital heart disease with repaired shunts

Orphan designation:

• Chronic thromboembolic pulmonary hypertension (CTEPH): A form of pulmonary hypertension caused by blood clots (embolism) in the lungs

Side effects of PAH prostacyclin agonists may include the following:

• Headache
• Diarrhea
• Jaw pain
• Nausea
• Vomiting
• Pain in extremity
• Myalgia (muscle pain)
• Flushing
• Arthralgia (joint pain)
• Rash
• Decrease in hemoglobin
• Anemia
• Decreased appetite
• Decrease in TSH (thyroid-stimulating hormone)
• Symptomatic hypotension (low blood pressure)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of PAH prostacyclin agonist drugs include:

• selexipag
• Uptravi