Pharmacology of Anti-arrhythmic Agents

  • Peter S. FischbachEmail author
  • Srikant Das


Cardiac arrhythmias result from alterations in the orderly sequence of depolarization and repolarization in the heart (Chap.  2). The clinical severity of disordered cardiac activation ranges from asymptomatic palpitations to lethal arrhythmias. Clinicians have a number of therapeutic options from which to choose in an effort to suppress or eliminate the sources or structures that support the arrhythmias, as well as to convert the heart to normal rhythm if other therapies fail. While recent technological advances have led to an increase in the use of non-pharmacological strategies including transcatheter radiofrequency or cryothermal ablation, intraoperative cryoablation as well as implantable pacemakers and defibrillators, pharmacological therapy remains a valuable tool for monotherapy or as adjunctive therapy in combination with device therapy. Anti-arrhythmic medications exert direct effects on cardiac cells by inhibiting the function of specific ion channels or ion pumps or by altering the autonomic input into the heart resulting in alteration of the electrophysiologic properties of the cardiac conduction system. Additionally, several widely used cardiovascular therapies such as angiotensin-converting enzyme, hydroxy-methyl-glutaryl (HMG) Co-A reductase inhibitors, dexmedetomidine, and others also appear to exert important anti-arrhythmic effects. Physicians caring for patients with arrhythmias, therefore, must understand and appreciate the benefits and risks provided by each therapeutic agent, what is the indication for each, and how they interact.


Class IA drugs: procainamide, quinidine Class IB drugs: lidocaine, mexiletine Class IC drugs: flecainide, propafenone Class II drugs: atenolol, esmolol, nadalol, propranolol Class III drugs: amiodarone, dofetilide, dronedarone, ibutilide, ranolazine, sotalol, vernakalant Class IV drugs: diltiazem, verapamil Calcium channel blockers Potassium channel blockers Sodium channel blockers DFTs Drug/device interactions Pharmacology Vaughan Williams classification 

Suggested Reading

  1. Anonymous. The Sicilian gambit. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. Circulation. 1991;84(4):1831–51.Google Scholar
  2. Brugada J, Blom N, Sarquella-Brugada G, Blomstrom-Lundqvist C, et al. Pharmacological and non-pharmacological therapy for arrhythmias in the pediatric population: EHRA and AEPC-Arrhythmia Working Group joint consensus statement. Europace. 2013;15(9):1337–82.CrossRefPubMedGoogle Scholar
  3. Carmeliet E, Mubagwa K. Antiarrhythmic drugs and cardiac ion channels: mechanisms of action. Prog Biophys Mol Biol. 1998;70:1–72.CrossRefPubMedGoogle Scholar
  4. Cavero I, Mestre M, Guillon JM, Crumb W. Drugs that prolong QT interval as an unwanted effect: assessing their likelihood of inducing hazardous cardiac dysrhythmias. Expert Opin Pharmacother. 2000;1:947–73.CrossRefPubMedGoogle Scholar
  5. Gillis AM. Effects of antiarrhythmic drugs on QT interval dispersion—relationship to antiarrhythmic action and proarrhythmia. Prog Cardiovasc Dis. 2000;42:385–96.CrossRefPubMedGoogle Scholar
  6. Glassman AH, Bigger Jr JT. Antipsychotic drugs: prolonged QTc interval, torsades de pointes, and sudden death. Am J Psychol. 2001;158:1774–82.CrossRefGoogle Scholar
  7. Hohnloser SH. Proarrhythmia with class III antiarrhythmic drugs: types, risks, and management. Am J Cardiol. 1997;80(8A):82G–9.CrossRefPubMedGoogle Scholar
  8. Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhythmias. N Engl J Med. 2001;345:1473–82.CrossRefPubMedGoogle Scholar
  9. Link MS, Homound M, Foote CB, et al. Antiarrhythmic drug therapy for ventricular arrhythmias: current perspectives. J Cardiovasc Electrophysiol. 1996;7(7):653–70.CrossRefPubMedGoogle Scholar
  10. Nattel S, Singh BN. Evolution, mechanisms, and classification of antiarrhythmic drugs: focus on class III actions. Am J Cardiol. 1999;84(9A):11R–9.CrossRefPubMedGoogle Scholar
  11. Patel C, Yan GX, Kowey PR. Dronedarone. Circulation. 2009;120:636–44.CrossRefPubMedGoogle Scholar
  12. Roden DM, George Jr AL. The cardiac ion channels: relevance to management of arrhythmias. Annu Rev Med. 1996;47:135–48.CrossRefPubMedGoogle Scholar
  13. Schwartz PJ. Clinical applicability of molecular biology: the case of the long QT syndrome. Curr Control Trials Cardiovasc Med. 2000;1:88–91.PubMedCentralCrossRefPubMedGoogle Scholar
  14. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406.Google Scholar
  15. van der Werf C, Kannankeril PJ, Sacher F, et al. Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol. 2011;57:2244–54.PubMedCentralCrossRefPubMedGoogle Scholar
  16. Vaughan Williams EM. Significance of classifying antiarrhythmic actions since the cardiac arrhythmia suppression trial. J Clin Pharmacol. 1991;31:123.CrossRefPubMedGoogle Scholar
  17. Watanabe H, Chopra N, Laver D, et al. Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat Med. 2009;15:380.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, New York 2015

Authors and Affiliations

  1. 1.Sibley Heart Center, Children’s Healthcare of Atlanta, Department of PediatricsEmory University School of MedicineAtlantaUSA
  2. 2.Department of Pediatric Cardiology, Arkansas Children’s HospitalUniversity of Arkansas for Medical SciencesLittle RockUSA

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