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Date: | Sat, 12 Jun 2004 17:11:07 EDT |
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SCARY ARTICLE SENT TO ME BY A BASIC SCIENTIST FRIEND:
Domperidone Should Not Be Considered a No-Risk Alternative to Cisapride in
the Treatment of Gastrointestinal Motility Disorders
Benoit Drolet, MSc; Guy Rousseau, PhD; Pascal Daleau, PhD; Rene´ Cardinal,
PhD; Jacques Turgeon, PhD
Background—Several cases of QT prolongation and ventricular tachyarrhythmia
have been reported with domperidone, a gastrokinetic and antiemetic agent
available worldwide but still under investigation in the United States. Although
electrolyte disturbances such as hypokalemia could account for some of these
events, we hypothesized that domperidone
may have unsuspected electrophysiological effects predisposing some patients
to proarrhythmia.
Methods and Results—Studies were undertaken in 9 isolated guinea pig hearts,
which demonstrated reverse use–dependent prolongation of cardiac
repolarization by 100 nmol/L domperidone. Action potential duration increased 27% from
baseline with domperidone (from 11463 to 14562 ms) during pacing at a cycle length
of 250 ms, and a 9% increase (from 9762 to 10663 ms) was seen with pacing at
a cycle length of 150 ms. Experiments in human ether-a-go-go–related gene
(HERG)-transfected Chinese hamster ovary cells (n532) demonstrated a
concentration-dependent block of the rapid component (IKr) of the delayed rectifier
potassium current. The tail current decreased by 50% at 162 nmol/L domperidone.
Conclusions—Domperidone possesses cardiac electrophysiological effects
similar to those of cisapride and class III antiarrhythmic drugs. These effects are
observed at clinically relevant concentrations of the drug. Therefore,
domperidone should not be
considered a no-risk alternative to cisapride, a drug that was recently
withdrawn from the US market. (Circulation. 2000;102:1883-1885.)
Key Words: arrhythmia n ion channels n torsade de pointes n electrophysiology
n long-QT syndrome
ANYONE WHO WANTS THE FULL ARTICLE IN PDF, PLEASE EMAIL ME AND I WILL ATTACH
IT.
Nancy
Nancy E. Wight MD, IBCLC, FAAP, FABM
Neonatologist
Children's Hospital and Sharp Mary Birch Hospital for Women
Medical Director, Sharp HealthCare Lactation Services
San Diego, CA
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