Cardiac Fibrosis - Connection With Direct Serotonergic Agonist Drugs

Connection With Direct Serotonergic Agonist Drugs

Elevated prevalence of cardiac fibrosis and related valvopathies was found to be associated with use of a number of unrelated drugs following long-term statistical analysis once the drugs had been on the market for some time. The cause of this was unknown at the time, but eventually it was realised that all the implicated drugs acted as agonists at 5-HT2B receptors in the heart in addition to their intended sites of action elsewhere in the body. The precise mechanisms involved remain elusive however, as while the cardiotoxicity shows some dose-response relationship, it does not always develop, and consistent daily use over an extended period tends to be most strongly predictive of development of valvopathy. The drugs most classically associated with the condition are weight loss drugs such as fenfluramine and chlorphentermine, and anti-parkinsonian drugs such as pergolide and cabergoline, which are prescribed to be taken several times a day, often for months or years at a time. Drugs which act as 5-HT2B agonists but are used only intermittently are capable of producing the same kind of heart damage, but tend to be less likely to do so. Also while the heart valve changes can result in permanent damage and life-threatening heart problems if use of the causative drug is continued, longitudinal studies of former patients suggest that the damage will heal over time to some extent at least.

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