Pulmonary arterial hypertension (PAH), a subtype of pulmonary hypertension, is characterized by high blood pressure in the lungs caused by narrowed blood vessels. When the heart tries to pump blood through the blocked vessels, blood pressure in the pulmonary arteries increases, and the heart must work harder.

Medications commonly used in the treatment of PAH include a group of drugs called prostanoids. These agents open the blood vessels between the heart and lungs, lowering blood pressure.

What Are Prostanoids?

Prostanoids are a class of drugs known as vasodilators, which work by relaxing and opening the blood vessels to allow more blood to flow through. This helps relieve high blood pressure.

Prostanoids are helpful drugs for treating different types of PAH, including:

• Idiopathic — Of unknown cause
• Associated — A complication of connective tissue disease or congenital heart disease
• Familial (heritable) — Inherited through genes from a parent

How Do Prostanoids Work?

Prostanoids may be referred to as either prostacyclins or prostaglandins. Prostacyclins, a type of prostaglandin that occurs naturally in the body, are made by the cells that line the arteries in the lungs.

When released by cells into the bloodstream, prostacyclins act as vasodilators and increase blood flow. They can also stop platelets in the blood from forming clots. However, there is a risk of side effects, such as low blood pressure (hypotension), if the blood vessels open too much.

When prostanoids are given to people with PAH, doctors monitor several measures of blood pressure and heart and lung function to determine if the treatment is working. Known as hemodynamics, these measurements include:

• Pulmonary vascular resistance — Resistance of blood flow from the pulmonary artery in the lungs to the left side of the heart
• Cardiac output — Amount of blood the heart pumps in one minute
• Mean pulmonary artery pressure (mPAP) — Average blood pressure in the pulmonary artery. PAH is diagnosed at an mPAP greater than 20 mm Hg.
• Exercise capacity — The greatest amount of exercise a person can tolerate, typically measured using a six-minute walk test

Prostanoids for Treating Pulmonary Hypertension

The three main prostanoids used to treat PAH are epoprostenol (sold as Veletri and Flolan), treprostinil (sold as Remodulin and Tyvaso), and iloprost (Ventavis). These medications are all prostacyclin analogs, which means they are shaped and function similarly to the prostacyclin made by the body.

Another medication used to treat PAH is selexipag (Uptravi). Unlike the prostacyclin analogs, selexipag is a selective nonprostanoid prostacyclin receptor agonist. This medication works by relaxing muscle cells in the same way that prostacyclin analogs do, but it is shaped differently.

Epoprostenol

Epoprostenol, a synthetic prostacyclin used to treat PAH, was approved by the U.S. Food and Drug Administration (FDA) in 1995 and is given as an IV infusion. Many people who use epoprostenol have an infusion pump or a catheter that continuously delivers doses of the drug.

Treprostinil

Treprostinil is a synthetic prostacyclin analog also used to treat PAH. The brand Remodulin was approved by the FDA in 2002. In April 2021, United Therapeutics received approval for another version of the drug, Tyvaso, for the treatment of pulmonary hypertension associated with interstitial lung disease.

Remodulin can be administered continuously through a catheter inserted into a vein or via a tiny tube placed just below the skin. Tyvaso is inhaled through a special device given with the medication.

Iloprost

Iloprost, an inhaled prostacyclin analog, received FDA approval in 2004 for PAH.

Selexipag

Selexipag differs from other PAH treatments. This synthesized medication is not an analog of prostacyclin — it is a nonprostanoid drug that interacts with the same receptor on muscle cells that prostacyclin does, causing blood vessels to relax and open up.

Prostacyclin analogs break down quickly, so they need to be given continuously as infusions. Selexipag, on the other hand, is a more stable drug that is taken as a pill twice a day. For most people, this oral route is much easier than one that requires needles or other devices.

Side Effects of Prostanoids

Although prostanoids are useful for treating PAH and high blood pressure, they can also cause other side effects. Common side effects of prostanoids include:

• Nausea
• Vomiting
• Diarrhea
• Headache
• Nervousness/anxiety
• Jaw pain
• Cough (from inhaled forms)
• Tongue pain
• Flushing
• Low blood pressure
• Fainting due to a drop in blood pressure
• Flu-like symptoms

Using a catheter or an infusion pump can lead to swelling, pain, or bleeding at the infusion site, which can also become infected. The area must be kept clean, and devices should be monitored to make sure they are giving the correct doses.

Managing Prostanoid Side Effects

Suggestions for managing some of the side effects of prostanoids include the following:

• Eat small meals to avoid nausea and vomiting.
• Take antidiarrheal drugs.
• Treat headaches with pain medication, such as acetaminophen, ibuprofen, or prescription-strength drugs.
• Use cough preparations (but, to reduce the risk of aspiration, avoid cough drops).
• Swish your mouth with water and spit it out after using inhaled medication.
• Apply ice or a topical corticosteroid or pain cream to an infusion site.
• Try alternative therapies for pain relief, such as relaxation techniques, acupuncture, and acupressure.

Talk With Others Who Understand

On myPHteam, the social network for people with pulmonary hypertension and their loved ones, more than 46,000 members come together to ask questions, give advice, and share their stories with others who understand life with pulmonary hypertension.

Are you or a loved one living with pulmonary hypertension? Do you have any tips for managing side effects of prostanoids? Share your experience in the comments below, or start a conversation by posting on your Activities page.