Drug-induced QT-interval prolongation: considerations for clinicians.
Drug-induced proarrhythmia is a frequently encountered clinical problem and a leading cause for withdrawal or relabeling of prescription drugs. Suppression of the rapid component of the delayed rectifier potassium current, I(Kr), represents the principal pharmacodynamic mechanism leading to heterogeneous prolongation of the ventricular action potential and prolongation of the QT interval clinically. However, the risk of proarrhythmia by QT-interval-prolonging drugs is variable and critically dependent on several factors leading to multiple reductions in the cardiac repolarization reserve. As antiarrhythmic drugs that prolong the QT interval are usually aggressively managed with continuous electrocardiogram monitoring and screening for drug interactions when administered to patients who have a high risk of sudden cardiac death, their risk of mortality is not increased. However, noncardiovascular QT-interval-prolonging drugs, which often produce less QT-interval prolongation compared with antiarrhythmic drugs, are found to be associated with increased rates of death in patients who have a markedly lower de novo risk of sudden cardiac death. Thus, it is important for clinicians, particularly pharmacists, to be cognizant of the levels of risk associated with varying degrees of QT-interval prolongation caused by drugs so that they can develop strategies to either prevent or reduce the risk of proarrhythmias.
Li
Edward C
EC
National Comprehensive Cancer Network, Fort Washington, Pennsylvania, USA.
Esterly
John S
JS
Pohl
Shaunte
S
Scott
Shane D
SD
McBride
Brian F
BF
D000200:Action Potentials / Q000502:physiology; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000150:complications; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control; D064907:Diagnostic Uses of Chemicals; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography / Q000009:adverse effects; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D004364:Pharmaceutical Preparations
D000889:Anti-Arrhythmia Agents; D064907:Diagnostic Uses of Chemicals; D004364:Pharmaceutical Preparations