Modernised classification of cardiac anti-arrhytmic drugs

Amongst his major cardiac electrophysiological contributions, Miles Vaughan Williams (1918-2016) provided a classification of anti-arrhythmic drugs that remains central to their clinical use. On this centenary of his birth we survey the implications of subsequent discoveries concerning sarcolemmal,...

Celý popis

Podrobná bibliografie
Hlavní autoři: Lei, M, Wu, L, Terrar, D, Huang, C
Médium: Journal article
Vydáno: American Heart Association 2018
_version_ 1826259317096972288
author Lei, M
Wu, L
Terrar, D
Huang, C
author_facet Lei, M
Wu, L
Terrar, D
Huang, C
author_sort Lei, M
collection OXFORD
description Amongst his major cardiac electrophysiological contributions, Miles Vaughan Williams (1918-2016) provided a classification of anti-arrhythmic drugs that remains central to their clinical use. On this centenary of his birth we survey the implications of subsequent discoveries concerning sarcolemmal, sarcoplasmic reticular and cytosolic biomolecules, to develop an expanded but pragmatic classification that encompasses approved and potential anti-arrhythmic drugs. We first consider the range of pharmacological targets, tracking these through to cellular electrophysiological effects. We retain the original Vaughan Williams classes I to IV, but subcategorise these divisions in the light of more recent developments, including existence of Na+ current components (for Class 1), advances in autonomic (often G-protein-mediated) signalling (for Class II), K+ channel subspecies (for Class III), and novel molecular targets related to Ca2+ 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 signalling processes affecting structural remodelling. Inclusion of this widened range of targets and their physiological sequelae provides a framework for a modernised classification of established anti-arrhythmic drugs based on their pharmacological targets. The revised classification allows for existence of multiple drug targets/actions and for adverse, sometimes actually pro-arrhythmic effects. The new scheme also aids classification of novel drugs under investigation. We emerge with a revised classification preserving the simplicity of the original Vaughan Williams framework whilst aiding our understanding and clinical management of cardiac arrhythmic events, and facilitating future developments in this area.
first_indexed 2024-03-06T18:47:56Z
format Journal article
id oxford-uuid:0f2d1a37-99d3-46a8-9d03-269a1dc9a6c3
institution University of Oxford
last_indexed 2024-03-06T18:47:56Z
publishDate 2018
publisher American Heart Association
record_format dspace
spelling oxford-uuid:0f2d1a37-99d3-46a8-9d03-269a1dc9a6c32022-03-26T09:49:56ZModernised classification of cardiac anti-arrhytmic drugsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0f2d1a37-99d3-46a8-9d03-269a1dc9a6c3Symplectic Elements at OxfordAmerican Heart Association2018Lei, MWu, LTerrar, DHuang, CAmongst his major cardiac electrophysiological contributions, Miles Vaughan Williams (1918-2016) provided a classification of anti-arrhythmic drugs that remains central to their clinical use. On this centenary of his birth we survey the implications of subsequent discoveries concerning sarcolemmal, sarcoplasmic reticular and cytosolic biomolecules, to develop an expanded but pragmatic classification that encompasses approved and potential anti-arrhythmic drugs. We first consider the range of pharmacological targets, tracking these through to cellular electrophysiological effects. We retain the original Vaughan Williams classes I to IV, but subcategorise these divisions in the light of more recent developments, including existence of Na+ current components (for Class 1), advances in autonomic (often G-protein-mediated) signalling (for Class II), K+ channel subspecies (for Class III), and novel molecular targets related to Ca2+ 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 signalling processes affecting structural remodelling. Inclusion of this widened range of targets and their physiological sequelae provides a framework for a modernised classification of established anti-arrhythmic drugs based on their pharmacological targets. The revised classification allows for existence of multiple drug targets/actions and for adverse, sometimes actually pro-arrhythmic effects. The new scheme also aids classification of novel drugs under investigation. We emerge with a revised classification preserving the simplicity of the original Vaughan Williams framework whilst aiding our understanding and clinical management of cardiac arrhythmic events, and facilitating future developments in this area.
spellingShingle Lei, M
Wu, L
Terrar, D
Huang, C
Modernised classification of cardiac anti-arrhytmic drugs
title Modernised classification of cardiac anti-arrhytmic drugs
title_full Modernised classification of cardiac anti-arrhytmic drugs
title_fullStr Modernised classification of cardiac anti-arrhytmic drugs
title_full_unstemmed Modernised classification of cardiac anti-arrhytmic drugs
title_short Modernised classification of cardiac anti-arrhytmic drugs
title_sort modernised classification of cardiac anti arrhytmic drugs
work_keys_str_mv AT leim modernisedclassificationofcardiacantiarrhytmicdrugs
AT wul modernisedclassificationofcardiacantiarrhytmicdrugs
AT terrard modernisedclassificationofcardiacantiarrhytmicdrugs
AT huangc modernisedclassificationofcardiacantiarrhytmicdrugs