Medicine & USMLE

Class 4 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 4 antiarrhythmics include the drug names verapamil and diltiazem.

The Class 4 antiarrhythmics work as calcium channel blockers, specifically by blocking voltage-dependent L-type calcium channels. They belong to the non-dihydropyridine group of calcium channel blockers.

Blocking calcium channels works primarily on nodal tissue to cause a slow rise in the AP. This slows pacing by the SA node and slows conduction by the AV node. In addition, these drugs can prolong repolarization at the AV node, and increase the length of the ERP. The slowing of the AV node manifests as an increased PR interval on EKGs.

Clinically, these drugs are used to treat arrhythmias, including SVT and A-Fib, where they are used primarily for rate control. They are also used to treat atrial flutter and AV nodal arrhythmias. These drugs may be less commonly used to treat angina and hypertension.

Side effects of the Class 4 antiarrhythmics include cardiovascular depression, constipation, flushing, hyperprolactinemia, edema, gingival hyperplasia, and heart block.

Key Points

  • Class 4 Antiarrhythmics
    • Drug Names
      • Verapamil
      • Diltiazem
    • Clinical Use
      • Treats SVT
        • Treats A-Fib (Atrial Fibrillation)
          • Used for ventricular rate control
        • Treats Atrial Flutter
        • Treats AV Nodal Arrhythmias
      • Treats Chest Pain (Angina)
        • Less commonly used than the DHP calcium channel blockers (e.g. nifedipine, nicardipine)
      • Lowers Blood Pressure (Treats Hypertension)
        • These drugs are not preferred agents for treating hypertension compared to the DHP calcium channel blockers (e.g. amlodipine) due to their negative chronotropic effects (e.g. slows heart rate)
    • Mechanism
      • Non-Dihydropyridine Calcium Channel Blocker
        • Blocks Voltage-Dependent (L-type) Calcium Channels
        • Slows SA node pacemaker function
          • Reduced calcium influx slows depolarization in nodal action potential for SA pacemaker function
        • Slows AV node conduction
          • Reduced calcium influx slows depolarization in nodal action potential for AV conduction function
      • Prolongs repolarization (esp. at AV node)
      • ↑ PR interval
        • Manifestation of slowed AV conduction (negative dromotropy) seen on EKG
      • ↑ ERP
      • Slow Rise of AP
        • Reduces slope of both phase 0 and phase 4 depolarization in the nodal action potential
      • Minor negative inotropic effect
        • Due to calcium channel blockade, but this is rarely clinically significant
    • Side Effects
      • Constipation
        • Mechanism unclear, but thought to be related to inhibition of enteric nervous system in sigmoid colon
      • Flushing
      • Edema
      • Cardiovascular Depression (e.g. bradycardia, AV block)
        • Due to nodal depression described above
      • Hyperprolactinemia
        • May decrease CNS dopamine signaling, which normally inhibits prolactin release by anterior pituitary gland
      • Gingival Hyperplasia (verapamil)
        • Mechanism unknown