Comparative Safety and Tolerability of Prostacyclins in Pulmonary Hypertension

Abstract Prostacyclin (PGI2) is a prostaglandin derived from arachidonic acid in the endothelium and smooth muscle which causes vasodilation, inhibits platelet aggregation, and has anti-inflammatory, anti-thrombotic and anti-proliferative effects. In pulmonary arterial hypertension (PAH), PGI2 levels and PGI2 synthase expression are reduced, contributing to the vasoconstriction and vascular smooth muscle cell proliferation seen in the disease. Based on these findings, PGI2 analogues were developed to target this pathway. Epoprostenol was the first targeted therapy available for treating PAH. Due to the short half-life of this drug, it requires administration via a continuous intravenous infusion, and therefore it carries the risks of central line infections and thrombosis. However, it remains the treatment of choice in patients with severe PAH as it has a proven survival benefit as well as improved functional class and exercise capacity. Subsequently, several other PGI2 analogues have been developed with differing modes of administration and varying degrees of efficacy. Beraprost is an oral PGI2 analogue for which a sustained efficacy has not been demonstrated. Iloprost is a nebulised PGI2 analogue that requires administration six to nine times a day and leads to improved functional class, exercise capacity and haemodynamics. There are inhaled, oral, subcutaneous and intravenous forms of treprostinil. Subcutaneous treprostinil avoids the risks of a continuou...
Source: Drug Safety - Category: Drugs & Pharmacology Source Type: research