Presse Med. 2013 Aug 21. pii: S0755-4982(13)00667-2. doi: 10.1016/j.lpm.2013.07.005. [Epub ahead of print]

Drugs induced pulmonary arterial hypertension.

Seferian A, Chaumais MC, Savale L, Günther S, Tubert-Bitter P, Humbert M, Montani D.

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.

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 These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market.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.

PMID:23972547