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Novel pharmacological approaches for antiarrhythmic therapy

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Abstract

Arrhythmias are caused by the perturbation of physiological impulse formation, impaired conduction, or disturbed electrical recovery. Currently available antiarrhythmic drugs—perhaps with exception of amiodarone—are not sufficiently effective and are burdened by cardiac and extracardiac side effects that may offset their therapeutic benefits. Detailed knowledge about electrical and structural remodelling may provide a better understanding of the mechanisms leading to generation and maintenance of arrhythmias especially in the setting of underlying heart disease and accompanying autonomic dysfunction. Thus, targets for new pharmacological interventions could include atrial-selective ion channels (e.g. atrial INa, IKur and IK,ACh), pathology-selective ion channels (constitutively active IK,ACh, TRP channels), ischemia-uncoupled gap junctions, proteins related to malfunctioning intracellular Ca2+ homeostasis (e.g. “leaky” ryanodine receptors, overactive Na+,Ca2+ exchanger) or risk factors for arrhythmias (“upstream” therapies). In ventricular arrhythmias implantable cardioverter-defibrillator devices rather than antiarrhythmic drugs are the safest treatment option. The domain for new approaches to drug treatment is atrial fibrillation.

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Acknowledgements

The author thanks Dobromir Dobrev and Niels Voigt for critical reading of the manuscript and helpful suggestions. The author receives financial support from Fondation Leducq (07 CVD 03, “Leducq European-North American Atrial Fibrillation Research Alliance”) and the German Federal Ministry of Education and Research (Atrial Fibrillation Competence Network, member of the steering committee; New Antiarrhythmic Drugs, Research project 03FPB00226).

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  1. Department of Pharmacology and Toxicology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Fetscherstrasse 74, 01307, Dresden, Germany

    Ursula Ravens

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Ravens, U. Novel pharmacological approaches for antiarrhythmic therapy. Naunyn-Schmied Arch Pharmacol 381, 187–193 (2010). https://doi.org/10.1007/s00210-009-0487-8

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