title: Drug-induced pulmonary arterial hypertension: a recent outbreak.
abstract: Pulmonary arterial hypertension (PAH) is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH.
authors.affiliation: Université Paris-Sud, Le Kremlin-Bicêtre, France. david.montani@bct.aphp.fr
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.forename: Andrei
authors.initials: A
authors.lastname: Seferian
authors.forename: Laurent
authors.initials: L
authors.lastname: Savale
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D062186:Arterial Pressure / Q000187:drug effects*; D004196:Disease Outbreaks; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D012307:Risk Factors