Problems with class 3 antiarrhythmic agents: Conclusions of the past - Perspectives of the future

Research output: Contribution to journalShort survey

Abstract

The majority of the currently used antiarrhythmic drugs carry serious proarrhythmic risk at the same time. Regarding class 3 agents, their torsadogenic action, which is associated with the reverse rate-dependent mode of action of these drugs, is the most serious side-effect. This mini-review provides a mass of evidence suggesting that the reverse rate-dependent nature of class 3 antiarrhythmic drug-effects is a common feature of all cardioactive agents in human cardiac tissues, consequently, development of selective blockers of the rapid delayed rectifier K + current (I kr) without reverse rate-dependent properties has little chance to succeed. A more promising approach might be to combine prolongation of action potential duration with interventions suitable to minimize arrhythmogenesis at slow heart rates. This can likely be achieved by combining K + channel blocking drugs with blockers of plateau inward currents, such as L-type Ca 2+ current and window Na + current. This view is supported by the results obtained by either combining two distinct molecules, or by applying single drugs having intrinsically combined modes of action.

Original languageEnglish
Pages (from-to)11-18
Number of pages8
JournalCurrent Topics in Pharmacology
Volume15
Issue number2
Publication statusPublished - Dec 1 2011

Keywords

  • Action potential duration
  • Class 3 antiarrhythmic drugs
  • Combination therapy
  • Human myocardium
  • Membrane current
  • Reverse rate-dependency
  • Ventricular repolarization

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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