title: Tadalafil for the treatment of pulmonary arterial hypertension.
abstract: Tadalafil is a selective inhibitor of phosphodiesterase type-5 (PDE-5) that was originally developed for the treatment of male erectile dysfunction and recently approved for the treatment of pulmonary arterial hypertension (PAH). The antipulmonary hypertensive effects of nitric oxide and the natriuretic peptides are mediated via increasing intracellular cGMP and enzymatic degradation by PDE-5 is the major route of cGMP inactivation in the lung. Evidence is accruing that PDE-5 activity is increased in pulmonary vascular diseases and may contribute to the pathogenesis of PAH. The longer half-life of tadalafil allows for once-daily dosing as compared with three-times daily dosing for sildenafil, the only other PDE-5 inhibitor currently approved for treatment of PAH. This article reviews the role of cGMP and PDE-5 in PAH, presents the results of recent clinical trials and discusses the role of tadalafil in the treatment of this rare but difficult-to-treat disease.
authors.affiliation: Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital, Alpert Medical School, Brown University, 593 Eddy Street, Providence, RI 02903, USA. james_klinger@brown.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Klinger
mesh_terms: D001794:Blood Pressure / Q000187:drug effects*; D002243:Carbolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000378:metabolism; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D045265:Natriuretic Peptides / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D000068581:Tadalafil; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D002243:Carbolines; D045265:Natriuretic Peptides; D058986:Phosphodiesterase 5 Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068581:Tadalafil; D006152:Cyclic GMP