Drug induced QT prolongation and torsades de pointes

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Abstract
Since the original work by Dessertenne, it has been well recognised that many conditions may cause prolonged or abnormal repolarisation (that is, QT interval prolongation and/or abnormal T or T/U wave morphology), which is associated with TdP. If TdP is rapid or prolonged, it can lead to ventricular fibrillation and sudden cardiac death (fig 1). Essentially, TdP may be caused by either congenital or acquired long QT syndrome (LQTS). In recent years, there has been considerable renewed interest in the assessment and understanding of ventricular repolarisation and TdP. There are several reasons for this. Firstly, the cloning of cardiac ion channels has improved the understanding of the role of ionic channels in mediating cardiac repolarisation, the pathophysiological mechanism of LQTS (congenital and acquired forms), and the pathogenesis of TdP. Secondly, modern molecular techniques have unravelled the mutations in genes encoding cardiac ion channels that cause long QT syndrome, although the genetic defects in about 50% of patients are still unknown. Thirdly, there has been considerable enthusiasm for the development and use of class III antiarrhythmic drugs, which prolong repolarisation and cardiac refractoriness. Unfortunately, drugs that alter repolarisation have now been recognised to increase the propensity for TdP. Finally, an increasing number of drugs, especially non-cardiac drugs, have been recognised to delay cardiac repolarisation and to share the ability with class III antiarrhythmics to cause TdP occasionally.

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