Chapter 8  ·  Module 5

Class IV Agents and Other Nodal Modulators

Verapamil, diltiazem, adenosine, digoxin, and magnesium sulfate

Class IV Agents — Non-Dihydropyridine Calcium Channel Blockers

Class IV

Verapamil

  • Blocks L-type calcium channels in nodal tissue
  • Slows atrioventricular node; prolongs PR interval
  • Indications: atrioventricular nodal reentrant tachycardia / atrioventricular reentrant tachycardia termination (second-line to adenosine); rate control in atrial fibrillation; fascicular ventricular tachycardia
  • More negative inotropy than diltiazem
  • Avoid in heart failure with reduced ejection fraction, wide-complex tachycardia of unknown origin, Wolff-Parkinson-White

Class IV

Diltiazem

  • Same atrioventricular nodal blocking mechanism as verapamil
  • Substantially less negative inotropic effect
  • Preferred for sustained atrial fibrillation rate control (continuous infusion possible)
  • Better tolerated with borderline left ventricular function
  • Same contraindications as verapamil: heart failure with reduced ejection fraction, Wolff-Parkinson-White, wide-complex tachycardia

Adenosine and Magnesium Sulfate

Unclassified

Adenosine

  • A1 receptor agonist → transient atrioventricular nodal block (10 to 20 seconds)
  • Half-life under 10 seconds; rapid bolus required
  • First-line for atrioventricular nodal reentrant tachycardia / atrioventricular reentrant tachycardia; diagnostic tool in wide-complex tachycardia
  • Adverse effects: flushing, chest tightness, dyspnea (transient and universal)
  • Contraindicated in Wolff-Parkinson-White with atrial fibrillation and severe asthma
  • Methylxanthines (caffeine, theophylline) block effect; dipyridamole potentiates

Electrolyte Agent

Magnesium Sulfate

  • Suppresses early afterdepolarizations by blocking calcium current
  • First-line for torsades de pointes regardless of serum magnesium level
  • Adjunct in digoxin toxicity (give slowly to avoid worsening atrioventricular block)
  • Empiric use in refractory ventricular fibrillation
  • Toxicity: loss of deep tendon reflexes → respiratory paralysis
  • Antidote: calcium gluconate

Digoxin

Cardiac Glycoside

Mechanism and Indications

  • Inhibits sodium-potassium pump → raises intracellular calcium → positive inotropy
  • Atrioventricular nodal slowing via vagotonic mechanism (ineffective during exercise)
  • Atrial fibrillation rate control adjunct (not monotherapy); heart failure with reduced ejection fraction (reduces hospitalizations, not mortality)
  • Renally eliminated; dose reduction in renal impairment
  • Key interactions: amiodarone, verapamil, quinidine all raise digoxin levels

Cardiac Glycoside

Toxicity Recognition

  • Precipitated by hypokalemia, hypomagnesemia, renal impairment, advanced age
  • Non-cardiac: nausea, vomiting, yellow-green visual disturbances (xanthopsia)
  • Cardiac: bradyarrhythmias, atrioventricular block, bidirectional ventricular tachycardia (severe)
  • Treatment: stop digoxin; correct hypokalemia; avoid calcium
  • Digoxin-specific antibody fragments (Digibind/DigiFab) for life-threatening toxicity

Critical Rule — Wolff-Parkinson-White Syndrome with Atrial Fibrillation

Adenosine, verapamil, diltiazem, digoxin, and beta-blockers are ALL contraindicated in pre-excited atrial fibrillation or flutter in Wolff-Parkinson-White syndrome. Blocking the atrioventricular node redirects all conduction through the accessory pathway, which can conduct atrial fibrillation at 200 to 300 beats per minute and degenerate into ventricular fibrillation. Treatment: intravenous procainamide or electrical cardioversion only.