Prostanoid therapies in the management of pulmonary arterial hypertension

Abstract

Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary artery pressure due to a high pulmonary vascular resistance state. A relative decrease in prostacyclin presence has been associated with PAH; this pathway has thus become a therapeutic target. Epoprostenol, the synthetic equivalent of prostacyclin, was first utilized as short-term or bridging therapy in the 1980s. Further refinement of its long-term use via continuous intravenous infusion followed. A randomized controlled trial by Barst et al in 1996 demonstrated functional, hemodynamic, and mortality benefits of epoprostenol use. This work was a groundbreaking achievement in the management of PAH and initiated a wave of research that markedly altered the dismal prognosis previously associated with PAH. Analogs of prostacyclin, including iloprost and treprostinil, exhibit increased stability and allow for an extended array of parenteral and non-parenteral (inhaled and oral) therapeutic options. This review further examines the pharmacology and clinical use of epoprostenol and its analogs in PAH.

Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ12‐Prostaglandin J3

“…Prostaglandins are an important class of potent lipid mediators that are involved in the regulation of many biological processes such as inflammation, pain response, and fever . Consequently, this class of compounds has found wide‐spread use as pharmaceuticals for the treatment of several diseases including pulmonary arterial hypertension and glaucoma . We recently described a dramatically short route to the prostaglandins, completing the total synthesis of PGF 2α in just seven steps (Scheme ), and its subsequent application to the concise synthesis of the related pharmaceutical analogues latanaprost and bimatoprost, and alfaprostol .…”

Riociguat in PAH and CTEPH: Strategies for Patient Management

“…Prostacyclin therapy in patients with PH is also associated with a well-established pattern of AEs, including headache and GI disturbances (nausea, vomiting, diarrhea) [36]. As these AEs are similar to those commonly associated with riociguat, patients taking both therapies should be educated on self-care and treatment strategies.…”

Pulmonary hypertension: Molecular aspects of current therapeutic intervention and future direction

“…Numerous, prostacyclin analogs such as Epoprostenol, Iloprost, Beraprost, Treprosinil, Cicaprost have been studied in the experimental and clinical investigation as promising agents for the treatment of PH. Epoprostenol was the first drug approved by the FDA in 1984 for the management of PH and considered as the first line treatment for pulmonary hypertension (LeVarge, ). Whereas, Iloprost which administered by inhalation route has more intrapulmonary selectivity and less systemic side effects.…”

“…Moreover, Iloprost also prevent the right‐to‐left cardiac shunt which allows the deoxygenated blood flow from right heart to the left heart (LeVarge, ). Beraprost was noted to inhibit the development of pulmonary hypertension through vasodilation, antiplatelet aggregation, and anti‐inflammatory effect (LeVarge., ). A recent report revealed that intratracheal administration of Beraprost nanoparticle was found to decrease the right ventricular hypertrophy (RVH), right ventricular pressure (RVP) in monocrotaline model (MCT) of rats (Akagi et al, ).…”