Drug-Induced Valvulopathy
Drug-Induced Valvulopathy
Drug-Induced Valvulopathy
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<strong>Drug</strong>-<strong>Induced</strong><br />
<strong>Valvulopathy</strong><br />
Bryan S Judge, MD<br />
LLSA Medical Toxicology Review<br />
ACMT Spring Conference – San Juan, Puerto Rico<br />
March 28, 2009
Roth BL. <strong>Drug</strong>s and valvular heart<br />
disease. NEJM 2007;356:6-9.
Schade R, et al. Dopamine agonists and the<br />
risk of cardiac-valve regurgitation. NEJM<br />
2007;356:29-38.<br />
Cabergoline and pergolide significantly<br />
associated with cardiac-valve disease<br />
Aortic, mitral, and tricuspid valves<br />
affected<br />
Amantadine associated with an<br />
increased risk of valvular heart disease
Zanettini R, et al. Valvular heart disease and<br />
the use of dopamine agonists for Parkinson’s<br />
disease. NEJM 2007;356:39-46.<br />
Clinically significant regurgitation was<br />
discovered only in patients taking<br />
cabergoline or pergolide<br />
Rates of drug-induced valvulopathy<br />
were high<br />
<strong>Drug</strong>-induced insufficiency was evident<br />
in aortic, mitral, and tricuspid valves
Norfenfluramine<br />
Cabergoline<br />
Pergolide<br />
Methylergonovine<br />
Extracellular<br />
space<br />
5-HT 2B<br />
TGF-β<br />
Intracellular<br />
space<br />
Gαq<br />
Gβy<br />
P<br />
P<br />
βArr<br />
GTP<br />
PLC-β<br />
DAG<br />
ERK1/2<br />
P<br />
P<br />
Src-P<br />
PKC<br />
Nucleus<br />
Rb-P<br />
Left atrium<br />
Mitral valve<br />
Left atrium<br />
Mitral valve<br />
Chordae<br />
tendinae<br />
Left ventricle<br />
Proliferation<br />
Chordae<br />
tendinae<br />
Left ventricle
Take Home Points<br />
5-HT 2B receptors are<br />
abundant in human<br />
cardiac valves<br />
Several drugs are<br />
potent 5-HT 2B agonists<br />
Several studies have<br />
implicated activation of<br />
5-HT 2B receptors as a<br />
key step in initiating<br />
drug-induced<br />
valvulopathy<br />
Two recent studies have<br />
associated cabergoline<br />
and pergolide with<br />
valvular disease<br />
Avoid prescribing drugs<br />
that are potent 5-HT 2B<br />
agonists
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