Brief Review of Pharmacotherapy for Pulmonary Arterial Hypertension

Pulmonary arterial hypertension affects the distal pulmonary vasculature causing intimal, medial, adventitial fibrosis, thickening and periadventitial changes leading to progressive increase in pulmonary vascular resistance and pulmonary arterial pressure [1]. Pulmonary hypertension (PH) is defined as mean pulmonary artery pressure equal to or greater than 25 mm Hg at rest. PH is classified into five major groups by the World Health Organization (WHO) based on their etiologies most recently by the 5th World symposium on Pulmonary hypertension in 2013 [2]. WHO Group I contains Pulmonary arterial hypertension (PAH) which acan be idiopathic, heritable, drug and toxin induced, associated with connective tissue disorders, HIV infection, portal hypertension, congenital heart diseases, schistosomiasis, pulmonary veno occlusive disease/ pulmonary capillary hemangiomatosis, persistent pulmonary hypertension of the newborn.Specifically, PAHis defined as the presence of mean pulmonary pressure artery greater than 25 mm Hg at rest when the pulmonary capillary wedge pressure is less than 15 mm Hg and the pulmonary vascular resistance is greater than 3 Wood units [2]. Pharmacologic intervention in pulmonary hypertension has been primarily focused on targeting the physiological pathways involved in controlling pulmonary vasoreactivity. Consequently, Group I PH or PAH is where most of this therapeutic development has occurred. Drug therapy for PAH can be classified based on their mechanisms of action into phosphodiesterase 5 (PDE-5) inhibitors, guanylate cyclase stimulators, prostacyclin analogs, prostacyclin receptor agonists, endothelin receptor antagonists [1].