• Pulmonary arterial hypertension (PAH) involves prostacyclin deficiency in the body, especially the lungs.
• A deficiency of prostacyclin can lead to narrowing of the blood vessels in the lungs and the symptoms of PAH.
• Medications that mimic prostacyclin can help to counteract a prostacyclin deficiency and improve the quality of life for people with PAH

When a person has high blood pressure of the blood vessels running from their heart to their lungs, doctors diagnose them with pulmonary arterial hypertension. PAH is one type of pulmonary hypertension.

The underlying causes of PAH are complex, but studies have shown that a molecule called prostacyclin is related to the condition. People with PAH show lower amounts of prostacyclin circulating in their bodies. This has led researchers to conclude that an imbalance between prostacyclin and other molecules may lead to PAH.

Lower amounts of prostacyclin in the body cause the blood vessels in the lungs to narrow, leading to the symptoms of PAH. Many PAH medications approved by the U.S. Food and Drug Administration (FDA) affect the prostacyclin pathway to help alleviate symptoms and slow down the disease.

Despite the health benefits of prostacyclin analogues — medications which act like the body’s own prostacyclin — these medications do come with side effects. This can limit the use of these drugs.

What Is Prostacyclin?

Injury or inflammation triggers the innermost layer of blood vessels (endothelial cells) throughout the body to make and release prostacyclin.

Prostacyclin travels from the inside layer to other parts of blood vessels, activating nearby receptors. This works similarly to putting a key into a door lock. Once prostacyclin links to these receptors, it causes the following actions:

• Decrease in inflammation
• Decrease in blood clotting
• Relaxation of the smooth muscle of blood vessels (vasodilation)
• Blocking of smooth muscle overgrowth (antiproliferation)

Proliferation of smooth muscle happens when extra cells grow in the walls of the blood vessels. This leads to high blood pressure. Prostacyclin helps counteract this.

Since people with PAH have lower amounts of prostacyclin circulating in their bodies, they do not get these benefits of prostacyclin. Instead, they experience higher levels of inflammation, smooth muscle overgrowth of their blood vessels, blood clotting, and a narrowing of blood vessels.

Prostacyclin Medications in the Treatment of Pulmonary Arterial Hypertension

For the treatment of PAH, doctors often prescribe prostacyclin analogues. These medications help to counter prostacyclin imbalance by acting as stand-ins for the body’s own prostacyclins.

Prostacyclin analogues help to decrease inflammation, block smooth muscle overgrowth, limit blood clotting, and open blood vessels. In that way, they do the same activities as natural prostacyclin in the body.

Doctors usually recommend prostacyclin analogues for people with PAH who are in a higher risk group, have more advanced PAH, or are not responding well to other therapies. This is because getting the dose right with prostacyclins can be difficult. Also, people on prostacyclins for PAH can develop a tolerance to the medication — along with unwanted side effects. Side effects of prostacyclin analogues may include:

• Headache
• Jaw pain
• Nausea
• Diarrhea
• Pain in the hands and feet
• Low blood pressure

Approved Prostacyclin Medications for PAH Treatment

Through clinical trials, the FDA has approved one prostacyclin medication (epoprostenol), two prostacyclin analogues (iloprost and treprostinil), and one prostacyclin receptor agonist (selexipag) for the treatment of PAH.

A prostacyclin receptor agonist does not try to mimic the shape of the body’s own prostacyclin — like the prostacyclin analogues do. However, a prostacyclin receptor agonist still acts like the body’s own prostacyclin and has a similar effect on the body as natural prostacyclin.

People need careful dose monitoring and adjustments by their doctor when taking any of these medications:

• Epoprostenol (sold under the brand names Flolan and Veletri) is administered intravenously.
• Ventavis (iloprost) is inhaled.
• Tyvaso (treprostinil) can be inhaled, taken orally, or given through an IV.
• Uptravi (selexipag) is available in tablets.

Other Approved Medications for PAH Treatment

Other groups of medications for the treatment of PAH include endothelin receptor antagonists and phosphodiesterase-5 (PDE-5) inhibitors.

Examples of endothelin receptor antagonists include Tracleer (bosentan) and Letairis (ambrisentan). Examples of PDE-5 inhibitors include Revatio (sildenafil) and Adcirca (tadalafil).

Limitations and Side Effects of Prostacyclin Medications

Every type of prostacyclin medication is linked to side effects, which may include any of the following:

• Head or jaw pain
• Muscle aches and joint pain
• Nausea and vomiting
• Diarrhea
• Flushing
• Anemia
• Reduced appetite
• Rash
• Overactive thyroid (for people taking selexipag)

In addition, injectable forms of prostacyclin drugs such as subcutaneous treprostinil, can cause pain at the injection site on the body.

Talk to your doctor about what side effects are possible from your PAH medications. Your doctor can help you understand what is normal and what is a cause for concern. They can explain whether side effects will diminish over time or if there are ways to lessen their severity. Tell your doctor if side effects are making it difficult for you to stick with your treatment.

Cost of Treatment

Many treatments for pulmonary arterial hypertension, including prostacyclin drugs, are expensive in the U.S. The Pulmonary Hypertension Association recommends resources that can help people afford their medications. These resources include programs offered through drug manufacturers that help people afford their prescriptions.

You can also ask your health care provider about resources to make medications more affordable.

Talk With Others Who Understand

On myPHteam, the social network for people with pulmonary hypertension and their loved ones, more than 40,000 members come together to ask questions, give advice, and share their stories.

Are you living with pulmonary arterial hypertension? Which treatments have helped you? Share your experience in the comments below, or start a conversation by posting on your Activities page.