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Cellular, Molecular, and Pharmacologic Mechanisms Underlying Drug-Induced Cardiac Arrhythmogenesis

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Cardiac Safety of Noncardiac Drugs

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Abstract

Pharmacologic agents can contribute to cardiac arrhythmogenesis by altering conduction, repolarization, or automaticity, and by inducing triggered activity in the form of early or delayed afterdepolarizations. Modulation of ion channel activity by drugs contributes to the development of both passive and active cardiac arrhythmias. The mechanisms responsible for active cardiac arrhythmias are generally divided into two major categories: (1) enhanced or abnormal impulse formation, and (2) re-entry (Fig. 1). Re-entry occurs when a propagating impulse fails to die out after normal activation of the heart and persists to re-excite the heart after expiration of the refractory period. Evidence implicating re-entry as a mechanism of cardiac arrhythmias stems back to the turn of the twentieth century (1–16). The mechanisms responsible for abnormal impulse formation include enhanced automaticity and triggered activity. Automaticity can be further subdivided into normal and abnormal and triggered activity, consisting of early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs).

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  1. Masonic Medical Research Laboratory, Utica, NY, USA

    Charles Antzelevitch PhD, FACC, FAHA (Executive Director and Director of Research, Gordon K. Moe Scholar, Experimental Cardiology Program Director, Professor of Pharmacology)

  2. Upstate Medical University, Syracuse, NY

    Charles Antzelevitch PhD, FACC, FAHA (Executive Director and Director of Research, Gordon K. Moe Scholar, Experimental Cardiology Program Director, Professor of Pharmacology)

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    Joel Morganroth MD (Chief Scientist, Clinical Professor of Medicine) (Chief Scientist, Clinical Professor of Medicine)

  2. University of Pennsylvania School of Medicine, Philadelphia, PA, USA

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    Ihor Gussak MD, PhD, FACC (Vice President, Clinical Associate Professor of Medicine, Associate Editor) (Vice President, Clinical Associate Professor of Medicine, Associate Editor)

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Antzelevitch, C. (2005). Cellular, Molecular, and Pharmacologic Mechanisms Underlying Drug-Induced Cardiac Arrhythmogenesis. In: Morganroth, J., Gussak, I. (eds) Cardiac Safety of Noncardiac Drugs. Humana Press. https://doi.org/10.1007/978-1-59259-884-7_3

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