Most of the drugs that have been withdrawn from the market due to cardiotoxicity appear to affect heart function by directly interfering with well-coordinated electrical activity in the heart.The electrical activity of the heart itself results from directional and selective movement of calcium, sodium, and potassium ions across channels in the membrane of cardiomyocytes; this movement couples with the specialized cytoskeleton to produce contraction and the force necessary for the pumping action of the heart. Interfering with this well-orchestrated movement of ions across the cardiomyocyte membrane can lead to electrical arrhythmia that will ultimately affect the excitation/contraction coupling cycle of the heart and may lead to a life-threatening form of ventricular arrhythmia called Torsades de Pointes (TdP).
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