Antiarrhythmic agents. II. Therapeutic considerations

D. T. Mason, A. N. DeMaria, Ezra A Amsterdam, R. Zelis, R. A. Massumi

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Clinical management of cardiac tachyarrhythmias is fundamentally founded on precise determination of their nature and the clinical condition in which they occur, together with knowledge of the mechanisms of action and pharmacodynamics of the antiarrhythmic drugs and understanding of the related electrical therapeutic modalities. The initial objective in the therapy of supraventricular tachyarrhythmias is control of ventricular rate and then restoration of normal sinus rhythm. In general, supraventricular disorders are treated with digitalis, vagal stimulation, quinidine, procainamide, propranolol and direct current electroshock. Ventricular tachyarrhythmias are managed with lignocaine, procainamide, quinidine, propranolol, phenytoin (diphenylhydantoin), bretylium, direct current electroshock and electrical pacemaker ventricular overdrive Digitalis toxicity is among the most common adverse drug reactions and may cause arrhythmias and conduction disturbances in as many as 1 of 5 patients. Particularly responsible are the electrophysiological properties of digitalis in increasing the automaticity of subsidiary pacemakers, reducing the refractory period and prolonging conduction velocity in the atria and ventricles, and delaying conduction in the atrioventricular node. Digitalis can provoke every type of cardiac arrhythmia and no specific disorder of rhythm can be considered absolutely pathognomonic of digitalis toxicity. The factors that predispose to digitalis toxicity, as well as the onset and duration of action of the agent, must be taken into account. Potassium has relatively little influence on the toxic and the contractile actions of digitalis when the cation is administered after the glycoside has been taken up by the myocardium. In contrast, alterations in serum potassium effected before treatment with digitalis may have drastic effects on the electrophysiologic and contractile actions of the glycoside; hyperkalemia reduces the binding of digitalis to the myocardium. Phenytoin, lignocaine and propranolol are effective in terminating digitalis provoked tachyarrhythmias, usually without inducing or worsening A V block. Atrial or ventricular pacing to achieve electrical overdrive of the ectopic focus may be used if standard measures fail. In complete heart block, potassium should not be administered; atropine and electrical pacing should be used. In general, antiarrhythmic agents have depressant effects on cardiac contractility which are related to dose, speed of administration, and extent of myocardial disease. In addition, these agents reduce peripheral vascular resistance. However, the negative inotropic action and vasodilator effect are usually minimal or absent in the small beginning doses used to control tachyarrhythmias. The fundamental subcellular actions of antiarrhythmic agents appear to occur as a consequence of their influence on the cardiac cell membranes and, in this manner, altered transmembrane fluxes of Na + and K + ions underlie their electrophysiological effects and changes in Ca ++ movement mediate their contractile properties.

Original languageEnglish (US)
Pages (from-to)292-317
Number of pages26
JournalDrugs
Volume5
Issue number4
StatePublished - 1973

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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    Mason, D. T., DeMaria, A. N., Amsterdam, E. A., Zelis, R., & Massumi, R. A. (1973). Antiarrhythmic agents. II. Therapeutic considerations. Drugs, 5(4), 292-317.