Influence of gender on drug-acquired long QT syndrome

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.