Drug induced pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a rare disease characterized by progressive obliteration of pulmonary arterioles, increase of pressure in the pulmonary artery and pulmonary vascular resistance. These factors lead to overload of the right ventricle and its failure. PAH is among others associated with the use of some drugs. For the first time, this relationship has been observed with the use of anorexigens (aminorex, fenfluramine and benfluorex). These drugs were after withdrawn from the market for a confirmed risk of PAH developing. Amphetamines, phentermine and mazindol have also been shown as the other drugs posing a risk of PAH induction and developing. Although their direct connection with PAH induction has not been confirmed, they are considered to be dangerous. Tyrosine kinase inhibitors, especially dasatinib (a dual BCR / ABL kinase and SRC kinases inhibitor) are associated with cases of severe PAH, partially reversible after discontinuation. The cases of PAH following interferon therapy have been reported in alpha and beta interferon. Several cases of PAH following the use of essential amino acid L-tryptophan in patients suffered with the eosinophilia-myalgia syndrome have been reported, but otherwise PAH have been observed also in patients who did not have myalgia or eosinophilia. Phenylpropanolamine (indicated to decongest mucous membranes) caused the death of a seven-years-old boy.This case supported the results of the SOPHIA study with the hypothesis of the risk of PAH in phenylpropanolamine users. Antiparkinsonic drug Pergolide was also withdrawn from the market for the proven risk of val-vulopathy and due to potential association with PAH. Serotonin reuptake inhibitors (SSRIs) may also cause persisting pulmonary hypertension of newborns (PPHN). Many cases of PAH following the use of these drugs are published only as a case report, indicating individual sensitivity to the onset and development of PAH. Larger studies would be needed to confirm the relationship between the use of these drugs and PAH, which is problematic because PAH is a rare disease.