the past 6 months; or a history of cerebrovascular events (e.g. stroke) within 3 months. Vasoconstriction IP receptor agonists are front-line drugs to treat pulmonary hypertension. Major drugs in this category include PGI2 itself (i.e. epoprostenol), iloprost, treprostinil, and beraprost with epoprostenol being favored in some studies. However, newly developed IP agonists with favorable pharmacological features such as Selexipag have been granted by the US FDA Orphan Drug status for the treatment of pulmonary hypertension. IP agonists are also to treat severe vasoconstriction in Raynaud's disease, Raynaud's disease-like syndromes, and scleroderma. Epoprostenol causes improvements in hemodynamic parameters and oxygenation in patients suffering the acute respiratory distress syndrome but due to the limited number of randomized clinical trials and lack of studies investigating mortality, its use cannot be recommended as standard of care for this disease and should be reserved for those refractory to traditional therapies. A meta-analysis of 18 clinical trials on the use of prostanoids including principally IP receptor agonists on patients with severe lower limb peripheral artery disease due to diverse causes found that these drugs may reduce the extent of limb tissue that needed to be amputated. However, the studies did not support extensive use of prostanoids in patients with critical limb ischemia as an adjunct to revascularization or as an alternative to major amputation in cases which cannot undergo revascularization. Thrombotic diseases IP receptor agonists have been used to treat Thromboangiitis obliterans, a disease involving blood clotting and inflammation of the small and medium-sized arteries and veins in the hands and feet. Genomic studies An adenine (A) to cytosine (C) synonymous substitution at base 984 (i.e. A984C) in exon 3 of PTGIR''' is the most frequent single nucleotide polymorphism (SNP) variant in a sampling of Japanese. This variant was associated with an increase in platelet activation responses in vitro and an increase in incidence of cerebral ischemia. Two other synonymous SNP variants, V53V and S328S, in PTGIR in an Italian population study were associated with enhanced platelet activation response and deep vein thrombosis. The rare SNP variant 795C of 794T in the PTGIR gene is associated with an increased incidence of Aspirin-induced asthma and a greater percentage fall in the forced expiratory volume response of airways to inhalation of an aspirin like compound (lysine-acetyl salicylic acid) in a Korean population sample. See also PTGIR'' gene (https://www.wikigenes.org/e/gene/e/5739.html) PGI2 Prostaglandin receptors Eicosanoid receptor References Further reading External links