Medicine & USMLE

Class IA Antiarrhythmics

Cardiovascular Pharm (Old)
  1. Adenosine
  2. Magnesium
  3. Nitroprusside
  4. Nitrates
  5. Ivabradine
  6. Digoxin/Digitalis
  7. Class IA Antiarrhythmics
  8. Class IB Antiarrhythmics
  9. Class IC Antiarrhythmics
  10. Class II Antiarrhythmics
  11. Class III Antiarrhythmics - Amiodarone
  12. Class III Antiarrythmics - Sotalol
  13. Class III Antiarrhythmics - Ibutilide, Dofetilide
  14. Class IV Antiarrhythmics - Verapamil, Diltiazem
  15. HMG-CoA Reductase Inhibitors (Statins)
  16. Ezetimibe
  17. Fibrates
  18. PCSK9 Inhibitors (Alirocumab, Evolocumab)
  19. Fish Oil and Omega-3s
  20. Milrinone
  21. Aliskiren
  22. Hydralazine
  23. Ranolazine
  24. Sacubitril


Quinidine, procainamide, and disopyramide are Class IA antiarrhythmics. Class IA antiarrhythmics work by blocking both sodium and potassium channels in the heart. In non-nodal cardiomyocytes, they both decrease the slope of the sodium upstroke and lengthen the potassium repolarization. This mechanism makes Class IA drugs clinically useful for both atrial and ventricular arrhythmias.

However, because Class IA antiarrhythmics prolong the QT interval, patients are at an increased risk for developing Torsades de pointes, a dangerous arrhythmia that can result in sudden cardiac death. Procainamide additionally comes with the potential of causing drug-induced lupus, a syndrome which is reversible once the drug is stopped.

Key Points

  • Class 1A Antiarrhythmics
    • Drugs
      • Quinidine
      • Procainamide
      • Disopyramide
    • Mechanism
      • Block Sodium (Na+) channels
        • Prolong phase 0 depolarization in non-nodal cardiomyocytes (rhythm control)
          • Phase 0 upstroke is mediated by Ca2+ in nodal tissue, which is less affected by sodium channel blockade (less effective for rate control)
        • Intermediate binding affinity among Class 1 AAs
          • 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
        • 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
        • Prolong phase 3 repolarization by blocking rectifier potassium channels
        • Increases AP duration and effective refractory period (ERP)
          • Prolonged QT creates risk for early after-depolarizations and Torsades de Pointes
      • May block Ca2+ channels to an extent
    • Clinical Use
      • Atrial and Ventricular Tachyarrhythmias
        • Used for reentrant and ectopic SVTs  and ventricular tachycardias
    • Adverse Effects
      • Long QT (Torsades de Pointes risk)
        • Due to K+ channel blockade described above
        • All patients monitored during first 24 hours in hospital
      • Drug-induced lupus (procainamide)
        • 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
      • Cinchonism (quinidine)
        • Tinnitus and headache
      • Heart Failure (Disopyramide)
      • Thrombocytopenia