Comparative Safety and Tolerability of Prostacyclins in XXXX .

@entity1 @entity1423 @entity120 @entity1426 @entity3009 @entity4770 @entity13992 @entity158 @entity715
UNASSIGNED: Prostacyclin ( @entity4770 ) is a @entity3009 derived from @entity1426 in the endothelium and smooth muscle which causes vasodilation, inhibits @entity1423 , and has anti-inflammatory, anti- @entity715 and anti-proliferative effects. In @entity120 ( @entity120 ), @entity4770 levels and @entity4770 synthase expression are reduced, contributing to the vasoconstriction and vascular smooth muscle cell proliferation seen in the disease. Based on these findings, @entity4770 analogues were developed to target this pathway. @entity4770 was the first targeted therapy available for treating @entity120 . 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 @entity715 . However, it remains the treatment of choice in @entity1 with severe @entity120 as it has a proven survival benefit as well as improved functional class and exercise capacity. Subsequently, several other @entity4770 analogues have been developed with differing modes of administration and varying degrees of efficacy. Beraprost is an oral @entity4770 analogue for which a sustained efficacy has not been demonstrated. Iloprost is a nebulised @entity4770 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 @entity13992 . Subcutaneous @entity13992 avoids the risks of a continuous intravenous administration; however, this drug can cause intractable @entity158 at the injection site. Selexipag is the new oral non-prostanoid IP @entity4770 receptor agonist that has shown improved haemodynamics and good tolerance in a phase  II study. Initial results of the phase  III trial are promising. Comparison of the different @entity4770 agents is limited by a lack of head-to-head clinical trials. However, the development of @entity4770 analogues has improved survival in @entity1 with @entity120 and remains the main treatment option in advanced disease. While @entity4770 analogues have good efficacy in @entity120 , they are not interchangeable, and their delivery systems have many limitations; in particular, they are associated with significant deleterious consequences. In the future, it is hoped that the elusive goal of developing an effective oral @entity4770 analogue will be achieved. This would increase the number of @entity1 who could benefit from the treatment while reducing the associated adverse events, and as a result improve the survival and quality of life for these @entity1 .
