• Clinical science

Antiarrhythmic drugs

Abstract

Antiarrhythmic drugs are classified into 5 classes based on their electrophysiological effect on the myocardium. The original classification system, which was developed by Vaughn Williams in 1970, consisted of four classes. The fifth class was added to accommodate new antiarrhythmic drugs developed since 1970. Antiarrhythmic drugs are used to prevent recurrent arrhythmias and restore sinus rhythm in patients presenting with cardiac arrhythmias. Antiarrhythmic drugs do not improve the survival of patients with non-life-threatening arrhythmias and may increase mortality, particularly in patients with structural heart disease. They are associated with severe adverse effects, primarily due to the proarrhythmic effect they exert on the myocardium. Intravenous administration should, therefore, be monitored with ECG. Several drugs classed as antiarrhythmics, including beta blockers, calcium channel blockers, amiodarone, cardiac glycosides, and lidocaine, also have other medical uses. These are discussed separately in the corresponding learning cards.

Overview

Classes of antiarrhythmic drugs

Class Drug group Main mechanism of action Examples Use Adverse Effects
Class I antiarrhythmic drugs Class IA antiarrhythmics
  • Fast sodium channel blockers
  • Inhibit conduction velocity (negative dromotropy), particularly in depolarized tissue (e.g., during tachycardia):
  • Membrane stabilizers
  • Separated into 3 subgroups based upon their effects on the Na+ channel and the AP duration
Class IB antiarrhythmics
  • Weak blockade of Na+ channels (fast association/dissociation)
  • Shorten AP duration (left shift) → slow ERP
  • Strongest effect on ischemic myocardium
  • VT (especially post-MI)
Class IC antiarrhythmics
  • Strong blockade of Na+ channels (slow association/dissociation) → QRS prolongation
  • No to minimal effect on AP duration (no shift) → ERP unaffected
  • Proarrhythmia: contraindicated post-MI!
Class II antiarrhythmic drugs
  • Inhibit β-adrenergic activation of adenylate cyclase → cAMP ↓ Ca2+
  • Decrease slope of phase 4 in pacemaker cells, leading to a slower conduction velocity
Class III antiarrhythmic drugs
  • Inhibit potassium delayed rectifier currents
  • Prolongs AP duration (Reverse use-dependence) and effective refractory period (ERP)
  • No effect on conduction velocity
Class IV antiarrhythmic drugs
Class V antiarrhythmic drugs
  • Variable mechanisms
  • See section on “Other antiarrhythmic drugs” below for details.
  • See section on “Other antiarrhythmic drugs” below for details.
  • All antiarrhythmic drugs are also potentially proarrhythmic! Intravenous administration should be done with ECG monitoring!

References:[2][3][4][5][6][7][8][9]

Other antiarrhythmic drugs

Adenosine (drug)

  • Mechanism of action: transient AV node block
  • Administration:
    • Rapid bolus IV (very short half-life: < 10 seconds)
    • May be administered repeatedly if previous dose was unsuccessful
    • Warn patients of unpleasant feeling that can follow administration. They may be feel a sense of impending doom.
  • Indications:
  • Adverse Effects:
  • Contraindications
    • Pre-excitation syndrome: antidromic AVRT including Wolf-Parkinson-White syndrome
    • AV block
    • Asthma

Digoxin

  • Mechanism of action: Inhibition of Na+/K+-ATPases → higher intracellular Na+ concentration → reduced efficacy of Na+/Ca2+ exchangers higher intracellular Ca2+ concentration → increased contractility, decreased heart rate
  • Indications: tachyarrhythmias (e.g., AFib)
  • See cardiac glycosides for details.

Magnesium sulfate

If-channel blocker

References:[3][4][10][11][12][13][14][15][16]