The clinical pharmacology and therapeutic applications of the antiarrhythmic drugs

Dean T. Mason, James F. Spann, Robert Zelis, Ezra A. Amsterdam

Research output: Contribution to journalReview article

19 Scopus citations

Abstract

The mechanisms of action and therapeutic applications of the commonly employed and new antiarrhythmic agents are best understood by consideration of the basic electrophysiologic properties of heart muscle affected by these drugs. Thus, each of these agents depresses disorders of impulse formation by reducing diastolic depolarization and thereby diminishing automaticity and inhibits disorders of impulse conduction by altering conduction velocity and refractory period and thereby disrupting re-entry mechanisms. Accompanying these antiarrhythmic actions, quinidine, procaine amide (Pronestyl), propranolol (Inderal), and potassium worsen: atrioventricular block; whereas lidocaine (Xylocaine) usually does not influence nodal conduction velocity, and diphenylhydantoin accelerates this property in the atrioventricular node. Quinidine and procaine amide directly prolong refractory period; in contrast, lidocaine, diphenylhydantoin, and propranolol directly reduce this period. Quinidine and procaine amide are useful in most types of supraventricular and ventricular tachyarrhythmias. Propranolol is particularly effective against supraventricular arrhythmias; however, lidocaine is only moderately effective in disorders of atrial rhythm but markedly suppresses ventricular tachyarrhythmias. Diphenylhydantoin (Dilantin) and bretylium (Darcnthin) are most beneficial in terminating disorders of ventricular rhythm and, in the case of bretylium, particularly those due to re-entry mechanisms. Diphenylhydantoin, propranolol, and lidocaine possess electrophysiologic properties that are particularly salutary in the treatment of digitalis toxicity. In general, antiarrhythmic agents have depressant effects on cardiac contractility which are related to dose, speed of administration, and extent of myocardial disease. In contrast, bretylium possesses positive isotropic actions, and potassium within normal serum concentrations has no effect oft contractile state. It is suggested that the fundamental subcellular actions of antiarrhythtnie agents occur as a consequence of their binding to the cell membrane; in this manner, altered transmembrane fluxes of sodium and potassium ions underlie the elect rophysiologic effects, and those of calcinin ions underlie the contractile properties of these agents. From these observations, the thorough understanding of basic and applied pharmacology of the antiarrhythmic agents provides for their more judicious use in patients.

Original languageEnglish (US)
Pages (from-to)460-480
Number of pages21
JournalClinical Pharmacology & Therapeutics
Volume11
Issue number4
DOIs
StatePublished - Jan 1 1970

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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