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Influence of gender on drug-acquired long QT syndrome

M.-D. Drici*

Department of Pharmacology, Pasteur University Hospital, Nice and CNRS-UPR 411, Sophia Antipolis, Valbonne, France

* Correspondence: Milou-Daniel Drici, MD, PhD, Laboratoire de Pharmacologie Faculté de Médecine de Nice, Avenue de Valombrose, 06107 Nice Cedex 02, France.

Abstract

Numerous drugs from diverse classes, such as antiarrhythmics, antihistamines, gastrokinetics, antipsychotics and antibiotics, share the potential to induce a prolongation of the QT interval on the electrocardiogram and torsade de pointes ventricular arrhythmias. The underlying mechanism of these side-effects is the blocking of voltage-gated potassium channels, particularly the rapid component IKr, of the delayed rectifier IK. The risk of such drug-induced arrhythmias is far greater in women than in men. Clinical data as well as experimental studies show that, in comparison to men, the feminine gender is associated with a longer baseline QT interval, a greater response to drugs that block IKr and a greater propensity to drug-induced torsade de pointes. This is most likely the result of a specific regulation of channel expression by — and perhaps a direct non genomic effect of — sex steroids.

Key Words: Gender difference • potassium channel blockers • long QT syndrome • IKr • ventricular arrhythmia • sudden death

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