Classification of antiarrhythmic drugs in relation to mechanisms of arrhythmias

  • Michiel J. Janse


For more than 20 years, the classification of antiarrhythmic drugs proposed by Vaughan Williams [1] has held the field. In essence, it is based on the effects of antiarrhythmic agents on the transmembrane potentials of normal, isolated cardiac tissue. In 1972, Singh and Vaughan Williams modified the classification by introducing the calcium entry blocking effect as a fourth class of antiarrhythmic action [2], and in 1992, Vaughan Williams proposed that specific bradycardic agents constitute a fifth class [3]. A modification of the classification of Na+ channel blocking agents was provided by Harrison et al. [4], who subdivided class I actions into the classes a, b and c, mainly on the basis of the effects on action potential duration. Thus, class la agents prolonged the action potential duration, class Ib drugs shortened it, and class Ic components had little effect. Later, more sophisticated subclassifications of drugs that blocked inward currents, either carried by Na+ or Ca2+ ions, were made on the basis of the kinetics of ion channel blockade and by defining the state of the channel (i.e. resting, activated or inactivated) to which drugs bind and unbind [5–7]. An important consequence of these later modifications was the recognition of use or frequency-dependent channel blockade. Drugs with use-dependent action bind to the activated and/or inactivated channel and slowly dissociate from the channel during diastole. They therefore exert their greatest effect at rapid heart rates. The time constants for unbinding are short for class Ib drugs and long for class Ia and Ic drugs. Class Ic drugs, which have the slowest kinetics, can further be subdivided into three groups according to their saturation behaviour at rapid rates [7].


Antiarrhythmic Drug Action Potential Duration Antiarrhythmic Agent Antiarrhythmic Action Reentrant Tachycardia 
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  1. 1.
    Vaughan Williams EM. Classification of antiarrhythmic drugs. In: Sandoe E, Flensted-Jensen E, Olsen KH, editors. Cardiac Arrhythmias. Sodertalje, Sweden: Astra, 1970: 449–472.Google Scholar
  2. 2.
    Singh BN, Vaughan Williams EM. A fourth class of antidysrhythmic action? Effect of verapamil on ouabain toxicity, on atrial and ventricular intracellular potentials, and on other features of cardiac function. Cardiovasc Res 1972; 6: 109–119.PubMedCrossRefGoogle Scholar
  3. 3.
    Vaughan Williams EM. Classifying antiarrhythmic actions: by facts or speculation. J Clin Pharmacol 1992; 32: 964–977.PubMedGoogle Scholar
  4. 4.
    Harrison DC, Winkle RA, Sami M, Mason JW. Encainide: A new and potent antiarrhythmic agent. In: Harrison DC, Hall GK, editors. Cardiac Arrhythmias, a Decade of Progress. Boston: Medical Publishers 1981: 315–330.Google Scholar
  5. 5.
    Hondeghem LM, Katzung BG, Antiarrhythmic agents: the modulated receptor mechanism of action of sodium and calcium blocking drugs. Annu Rev Pharmacol Toxicol 1984; 24: 387–423.PubMedCrossRefGoogle Scholar
  6. 6.
    Starmer CF, Grant AO, Strauss HC. Mechanisms of use dependent block of sodium channels in excitable membranes by local anesthetics. Biophys J 1984; 46: 15–27.PubMedCrossRefGoogle Scholar
  7. 7.
    Weirich J, Antoni H. Differential analysis of the frequency-dependent effects of class I antiarrhythmic drugs according to periodical ligand binding: implication for antiarrhythmic and proarrhythmic activity. J Cardiovasc Pharmacol 1990; 15: 998–1009.PubMedCrossRefGoogle Scholar
  8. 8.
    Vaughan Williams EM,. Significance of classifying antiarrhythmic actions since the Cardiac Arrhythmia Suppression Trial. J Clin Pharmacol 1991; 31: 123–135.PubMedGoogle Scholar
  9. 9.
    Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. The Sicilian Gambit. A new approach to the classification of antiarrhythmic drugs based on their action on arrhythmogenic mechanisms. Circulation 1991; 84: 1831–1851; Eur Heart J 1991; 12: 1112-31.CrossRefGoogle Scholar
  10. 10.
    Waldo AL, Olshansky B, Okumura K, Henthorn RW. Current perspectives on entrainment of tachyarrhythmias. In: Brugada P, Wellens HJJ, editors. Cardiac Arrhythmias: Where to go from Here? Mount Kisco, NY: Futura, 1987: 171–189.Google Scholar
  11. 11.
    Wells JL, MacLean WAH, James TN, Waldo AL. Characterization of atrial flutter. Studies in man after open heart surgery using fixed atrial electrodes. Circulation 1979; 60: 665–673.PubMedCrossRefGoogle Scholar
  12. 12.
    Wit AL, Janse MJ. The ventricular arrhythmias of ischemia and infarction. Electrophysiol-ogical mechanisms. Mount Kisco, NY: Futura, 1993.Google Scholar
  13. 13.
    Schwartz PJ, Zaza A. The Sicilian Gambit revisited — theory and practice. Eur Heart J 1992; (Suppl F): 23–9.CrossRefGoogle Scholar

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© Springer Science+Business Media Dordrecht 1994

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  • Michiel J. Janse

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