Drug-Induced QT Interval Prolongation: Mechanisms, Risk Factors, Genetics and Clinical Management

Long QT syndrome (LQTS) characterized by prolongation of the QT interval, may occur as congenital or drug-induced forms. Drug-induced QTinterval prolongation (DI-QTP) is closely associated with severe ventricular arrhythmias [especially torsade de pointes (TdP)] and sudden cardiacdeath. In particular, development of DI-QTP is generally associated with multiple risk factors. Cardiac and non-cardiac drugs may cause QTinterval prolongation (QTP) and TdP. Most of the QT-prolonging drugs act by blocking the rapid component of the delayed rectifier potassiumchannel whereas a smaller number of drugs act by modifying Ca2+ and Na+ currents. In addition, pharmacokinetic drug interactions areamong the reasons of DI-QTP. The corrected QT interval (QTc) according to heart rate by Bazett’s formula is the most commonly used. Geneticsusceptibility is another important issue in predicting DI-QTP and TdP risk. Silent mutations and/or polymorphisms associated with cardiacion channels may cause a risk for DI-QTP. Firstly, for treatment, drugs that cause QTP should be stopped rapidly, electrolyte abnormalities andother pathologies should be rapidly corrected. Intravenous magnesium sulphate, overdrive pacing, isoproterenol and plasma alkalinisationvia sodium bicarbonate are the main useful treatments for DI-QTP and related TdP therapy. Class 1B antiarrhythmic drugs and intravenouspotassium are thought to may be effective in TdP.The purpose of this article is to review the underlying mechanisms of QTP, risk factors and genetics of DI-QTP, how to measurement of QTinterval and treatment of acquired LQTS.

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