Valvular heart disease induced by drugs
- William H Gaasch, MD
William H Gaasch, MD
- Section Editor — Valvular Disease
- Professor of Medicine
- University of Massachusetts Medical School
- Tufts University School of Medicine
- Senior Consultant in Cardiology
- Lahey Clinic
- Gerard P Aurigemma, MD
Gerard P Aurigemma, MD
- Professor of Medicine and Radiology
- University of Massachusetts Medical School
Valvular abnormalities have been described in association with anorectic drugs and with ergot derivatives including drugs used for treatment or prophylaxis of migraine, particularly ergotamine and methysergide, and drugs used in the treatment of Parkinson disease, particularly pergolide and cabergoline . Use of 3,4-methylenedioxymethamphetamine (MDMA, also known as ecstasy) may also induce valve disease. The common pathogenetic link is increased serotonin activity.
The echocardiographic and pathologic features of the valve disease seen in patients with drug-induced valvular disease are similar to those occurring in carcinoid heart valve disease . (See "Carcinoid heart disease".)
The link between these two conditions appears to be serotonin, a neurotransmitter that is elevated in serum and plasma of most patients with carcinoid heart valve disease . As noted above, fenfluramine and dexfenfluramine augment serotonergic activity, while phentermine may contribute to the fenfluramine valvulopathy by interfering with the pulmonary clearance of serotonin.
Serotonin is also thought to play a role in the valve disease associated with ergot derivatives ergotamine , methysergide , and the dopamine agonists pergolide and cabergoline [6-8]. These drugs are structurally similar to serotonin and are thought to produce valve disease by stimulation of serotonin (5-HT 2B) receptors [6,9,10]. (See 'Parkinson disease' below.)
Serotonin stimulates fibroblast growth and fibrogenesis, which appears to underlie the valve disease seen in patients with carcinoid and anorectic drug and ergot derivative related heart valve disease. More direct evidence for a central role of serotonin comes from studies in animals:
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