title: Drugs induced pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a rare disorder characterized 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 appetite suppressant 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 These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market.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 arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH.
authors: Université Paris-Sud, Le Kremlin-Bicêtre, France; Hôpital Bicêtre, AP-HP, service de pneumologie, DHU Thorax Innovation, Le Kremlin-Bicêtre, France; Inserm U999, LabEx Lermit, centre chirurgical Marie-Lannelongue, Le Plessis-Robinson, France.
authors: Andrei
authors: A
authors: Seferian
authors: Marie-Camille
authors: MC
authors: Chaumais
authors: Laurent
authors: L
authors: Savale
authors: Sven
authors: S
authors: Günther
authors: Pascale
authors: P
authors: Tubert-Bitter
authors: Marc
authors: M
authors: Humbert
authors: David
authors: D
authors: Montani
mesh_terms: D000661:Amphetamine / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects; D001067:Appetite Depressants / Q000009:adverse effects; D004198:Disease Susceptibility; D065627:Familial Primary Pulmonary Hypertension; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D008168:Lung / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D012307:Risk Factors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001067:Appetite Depressants; D000661:Amphetamine