PMC:3750932 / 7023-9693 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3750932","sourcedb":"PMC","sourceid":"3750932","source_url":"http://www.ncbi.nlm.nih.gov/pmc/3750932","text":"Group 1.3 Drug- and toxin-induced PAH \nA number of risk factors for the development of PAH have been individualized in the last European Respiratory Society/ European Society of Cardiology (ERS/ESC) conjoint guidelines of PH [15] (Table 2).\nTable 2 Updated risk level of drugs and toxins known to be associated with PAH *This table was adapted from Galiè et al. [15]. Aminorex, fenfluramine derivatives and toxic rapeseed oil represent the only identified “definite” risk factors for PAH [5,16]. Souza et al. have demonstrated that this subgroup of PAH shares clinical, functional, hemodynamic, and genetic features with idiopathic PAH, suggesting that fenfluramine exposure represents a potential trigger for PAH without influencing its clinical course [17].\nTwo prospective epidemiologic investigations, the SNAP (Surveillance of North American Pulmonary Hypertension) and the SOPHIA (Surveillance of Pulmonary Hypertension in America) study, were conducted in the USA [18,19]. These investigations included retrospectively 559 and 1335 patients with PH, respectively, and confirmed the previously described association between idiopathic PAH and the use of fenfluramine. In the SNAP study, the odds ratio of developing PH was 7.5 for the use of fenfluramine more than six months of treatment [18].\nThe agent benfluorex is structurally and pharmacological related to fenfluramine and may be also considered as an anorectic agent. Frachon and co-workers [20] showed a significantly higher prevalence of unexplained valvular heart disease in patients taking benfluorex compared to controls. In addition, Savale and co-workers demonstrated recently that exposure to benfluorex is suggested to be a trigger in the development of PAH [21]. Benfluorex was withdrawn from the market in 2009.\nThe SOPHIA study examined intake of a variety of nonselective monoamine reuptake inhibitors, selective serotonin reuptake inhibitors, antidepressants and anxiolytics. No increased risk of developing PAH was observed [19].\nAmphetamine use represents a “likely” risk factor, although they are frequently used in combination with fenfluramine. A recent retrospective study suggested a relationship with the use of methamphetamine (inhaled, smoked, oral, or intravenous) and the occurrence of PAH [22]. Methamphetamine use is now considered a “very likely” risk factor for the development of PAH.\nRecently published data from the French registry of pulmonary hypertension suggested that dasatinib, a tyrosine kinsase inhibitor (TKI), may induce precapillary PAH [23]. Several cases of precapillary PH in chronic myelogenous leukemia patients treated with dasatinib have been reported.","divisions":[{"label":"Title","span":{"begin":0,"end":39}},{"label":"Table 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