Medicine & USMLE

Class IV Antiarrhythmics - Verapamil, Diltiazem

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


Class 4 antiarrhythmics include the drugs verapamil and diltiazem, and these drugs function primarily by blocking Calcium channels at the heart. This calcium channel blockade mainly affects nodal tissue in the SA and AV nodes, suppressing their phase 0 upstroke and action potentials. The overall clinical effect is a slowing of the heart rate and AV nodal conduction, which is extremely useful for treatment of supraventricular tachycardias like atrial fibrillation. In this context, Class 4 antiarrhythmics work as rate control drugs - slowing down the rate of the heart to allow the ventricles time to fill without correcting the aberrant heart rhythm. Side effects of these drugs include constipation, bradycardia, and hyperprolactinemia.

Key Points

  • Class 4 Antiarrhythmics
    • Drugs
      • Verapamil
      • Diltiazem
    • Mechanism
      • Block Calcium (Ca2+) channels
        • Decrease SA/AV nodal activity (rate control)
          • Reduces slope of phase 0 depolarization at nodal tissue, which is dependent on voltage-gated L-type calcium channels
          • Reduces HR (negative chronotropy) and AV conduction velocity (negative dromotropy) to increase PR interval
          • Increase effective refractory period (ERP)
        • Minor negative inotropic effect
          • Due to calcium channel blockade, but this is rarely clinically significant
    • Clinical Use
      • Ventricular rate control
        • Supraventricular arrhythmias
          • Atrial fibrillation/flutter
          • Paroxysmal SVT
      • Historically used for hypertension
        • Historical use case; non-DHP calcium channel blockers are not currently used for hypertension due to chronotropic suppression, which can cause bradycardia especially when combined with beta-blockers
    • Adverse Effects
      • Constipation
        • Mechanism unclear, but thought to be related to inhibition of enteric nervous system in sigmoid colon
      • Hyperprolactinemia
        • May decrease CNS dopamine signaling, which normally inhibits prolactin release by anterior pituitary gland
      • Cardiovascular Depression (e.g. bradycardia, AV block)
        • Due to nodal depression described above
      • Gingival Hyperplasia (verapamil)
        • Mechanism unknown
      • May worsen left ventricular heart failure
        • Via small negative inotropic effect described above
      • Flushing and edema also seen