Modernized Classification of Cardiac Antiarrhythmic Drugs
Year: 2018
Type: review
Abstract: Background: Among his major cardiac electrophysiological contributions, Miles Vaughan Williams (1918–2016) provided a classification of antiarrhythmic drugs that remains central to their clinical use. Methods: We survey implications of subsequent discoveries concerning sarcolemmal, sarcoplasmic reticular, and cytosolic biomolecules, developing an expanded but pragmatic classification that encompasses approved and potential antiarrhythmic drugs on this centenary of his birth. Results: We first consider the range of pharmacological targets, tracking these through to cellular electrophysiological effects. We retain the original Vaughan Williams Classes I through IV but subcategorize these divisions in light of more recent developments, including the existence of Na + current components (for Class I), advances in autonomic (often G protein–mediated) signaling (for Class II), K + channel subspecies (for Class III), and novel molecular targets related to Ca 2+ homeostasis (for Class IV). We introduce new classes based on additional targets, including channels involved in automaticity, mechanically sensitive ion channels, connexins controlling electrotonic cell coupling, and molecules underlying longer-term signaling processes affecting structural remodeling. Inclusion of this widened range of targets and their physiological sequelae provides a framework for a modernized classification of established antiarrhythmic drugs based on their pharmacological targets. The revised classification allows for the existence of multiple drug targets/actions and for adverse, sometimes actually proarrhythmic, effects. The new scheme also aids classification of novel drugs under investigation. Conclusions: We emerge with a modernized classification preserving the simplicity of the original Vaughan Williams framework while aiding our understanding and clinical management of cardiac arrhythmic events and facilitating future developments in this area.
Source: Circulation
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: Regulation of cardiac automaticity and conduction in murine hearts with a cardiac-specific deletion of P21 activated kinase-1, The sodium channel β3-subunit, sodium channel clusters and cardiac arrhythmias, Age-related atrial remodelling and arrhythmogenesis in mice with atrial myocyte specific genetic deficiency of MKK4, Modulation of electrophysiology, Ca2+ handling and arrhythmic susceptibility in the atria in mice with cardiomyocyte- specific deletion of P21 activated kinase-1, Cardiac arrhythmogenesis in the PGC-1alpha -/- murine system, Investigating the molecular and cellular basis underlying Pak1 intervention in Ca2+-dependent ventricular arrhythmogenesis, Myosin VI as a novel regulator of cardiac autophagy – a potential target for the treatment of heart failure triggered by autophagic cell death
OpenAlex ID: W2896576092