Medicine & USMLE

Class 1A Antiarrhythmics

Antiarrhythmic Drugs (New)
  1. Adenosine
  2. Class 3 Antiarrhythmics - Dofetilide & Ibutilide
  3. Class 1A Antiarrhythmics
  4. Class 1B Antiarrhythmics
  5. Class 1C Antiarrhythmics
  6. Class 2 Antiarrhythmics
  7. Sotalol
  8. Class 3 Antiarrhythmics - Amiodarone
  9. Class 4 Antiarrhythmics
  10. Digoxin


The class 1A antiarrhythmics include quinidine, procainamide, and disopyramide.

Moving to mechanisms, Class 1A drugs primarily act on non-nodal tissue, where they moderately block sodium channels and also block potassium channels. The blockade of sodium channels leads to a moderate decrease in the slope of the phase 0 upstroke, as well as slowed conduction in heart cells. The blocking of potassium channels leads to an increase in the length of the ERP, a prolonged AP duration, and a prolonged QT interval.

Clinically, these drugs are used to treat arrhythmias including ventricular arrhythmias and A-Fib, where they are used for rhythm control. These drugs are also used to treat reentry arrhythmias, as well as premature heartbeats.

Moving onto the drug-specific side effects, procainamide can cause drug-induced lupus, quinidine can cause cinchonism, and disopyramide can cause heart failure. Side effects that can be seen with all Class 1A drugs include Torsades de Pointes and thrombocytopenia.

Key Points

  • Class 1A Antiarrhythmics
    • Drug Names
      • Quinidine
      • Procainamide
      • Disopyramide
    • Mechanism
      • Primarily acts on non-nodal cardiomyocytes
        • Phase 0 upstroke is mediated by Ca2+ in nodal tissue, which is less affected by sodium channel blockade
        • This explains why these drugs are more used for rhythm control than rate control
      • Moderately Blocks Sodium (Na+) channels
        • Moderate prolongation of phase 0 depolarization
        • Intermediate binding strength among Class 1 AAs, since binding affinity for Na+ receptor is 1C > 1A > 1B
        • Leads to intermediate use dependence
          • Use-dependence is a phenomena in which higher rates of depolarization (e.g. high HR) and long dissociation time (e.g. strong binding affinity) lead to accumulated blockade of sodium channel blockade (e.g. compounding effect over several cardiac cycles). This leads to slowing of conduction speed out of proportion to the prolongation of the refractory period.
      • Block Potassium (K+) channels
        • Blockade of repolarizing rectifier potassium channels is unique to Class 1A (not seen with 1B or 1C)
          • Especially seen at lower doses, where drug preferentially binds to K+ channels over Na+ channels
      • Increases length of ERP
      • Prolongs AP duration
      • Prolongs QT interval
        • Due to K+ channel blockade described above, causing phase 3 repolarization prolongation
        • Increases risk of early after-depolarizations and Torsades de Pointes
    • Clinical Use
      • Treats atrial fibrillation
        • Used primarily for rhythm control
      • Treats premature heartbeats (ectopic arrhythmias)
        • e.g. PACs and PVCs
      • Treats reentrant arrhythmias
      • Treats ventricular arrhythmias
    • Side Effects
      • Cinchonism (quinidine)
        • Tinnitus and headache
      • Drug-induced lupus (procainamide)
        • Also known as SLE-like syndrome
        • Especially common in slow acetylators
        • Occurs in up to 20% of patients taking procainamide, with a notably lack of anti-dsDNA antibodies and rapid reversal after stopping the drug
      • Heart failure (disopyramide)
      • Thrombocytopenia
      • Torsades de Pointes
        • Due to QT prolongation above
        • All patients monitored during first 24 hours in hospital