Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.

These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle and vasodilation, which can alleviate the symptoms of PAH.

Several examples of PGI2 analogs are currently in use, each with unique properties. Epoprostenol (Flotan), for instance, is delivered through a continuous intravenous infusion due to its short half-life. This means it must be administered continuously to maintain its therapeutic effect.

Treprostinil offers more versatility in terms of administration routes. It can be given via continuous intravenous and subcutaneous infusion, inhalation, or oral delivery. This flexibility can make it a more convenient option for some patients.

Iloprost (Ventavis), on the other hand, is available as an inhaled formulation. It has shown potent effects on relaxing pulmonary circulation, making it a valuable tool in the fight against PAH.

Beraprost was the first orally available PGI2 analog. However, despite its groundbreaking delivery method, it showed no significant benefit in long-term trials.

Selexipag (Uptravi) stands out as an orally active, selective IPR agonist. It boasts a rapid absorption rate and a longer half-life than other options, making it a practical choice for many patients.

As with any medication, prostacyclin receptor agonists come with potential adverse effects. Some patients may experience myalgias, extremity pain, jaw pain, nausea, headaches, abdominal discomfort, diarrhea, flushing, dizziness, systemic hypotension, and cough.