21. ANTIARRHYTHMIC AGENTS

Cardiac arrhythmias are disturbances in the normal rhythm of the heart caused by altered impulse generation or conduction. Common contributors include ischemia, hypertension, electrolyte imbalance, hyperthyroidism, and drug toxicity. Antiarrhythmic drugs work by modifying ion fluxes (Na⁺, K⁺, Ca²⁺) during the cardiac action potential to restore or control rhythm.

Cardiac Action Potential — Quick Recap

• Phase 0 – Rapid depolarization (Na⁺ influx)
• Phase 1–2 – Early repolarization and plateau (K⁺ efflux, Ca²⁺ influx)
• Phase 3 – Repolarization (K⁺ efflux)
• Phase 4 – Resting potential (ionic gradients maintained by pumps)

Vaughan–Williams Classification

Antiarrhythmics are grouped into four classes based on primary electrophysiologic action:

Class I — Sodium Channel Blockers

These drugs slow phase-0 depolarization by blocking fast Na⁺ channels. They are subdivided by effect on action potential duration (APD):

• IA — increase APD (e.g., quinidine, procainamide, disopyramide). Useful for supraventricular and some ventricular arrhythmias; may widen QRS and prolong QT.
• IB — decrease APD (e.g., lidocaine, phenytoin, mexiletine). Preferential for ischemic ventricular tissue; lidocaine is used IV for acute ventricular arrhythmias.
• IC — marked Na⁺ block with little APD change (e.g., flecainide, lorcainide). Potent slowing of conduction; used for refractory ventricular arrhythmias (careful in structural heart disease).

Class II — β-Adrenergic Blockers

Beta-blockers (propranolol, atenolol, esmolol) reduce sympathetic stimulation, slow phase-4 depolarization, decrease heart rate and contractility, and are effective for tachyarrhythmias driven by adrenergic tone. They also indirectly reduce Ca²⁺ entry.

Class III — Potassium Channel Blockers

These agents prolong repolarization (phase-3), increasing APD and the effective refractory period (ERP). Examples include amiodarone and sotalol. Amiodarone has multi-channel effects (K⁺, Na⁺, Ca²⁺) plus α/β-blocking actions and is a broad-spectrum antiarrhythmic used for many life-threatening arrhythmias.

Class IV — Calcium Channel Blockers

L-type Ca²⁺ channel blockers (verapamil, diltiazem) slow AV nodal conduction and reduce automaticity. They are especially useful in supraventricular tachycardias and rate control in atrial fibrillation.

Clinical Uses — Practical Points

• Supraventricular arrhythmias (e.g., atrial fibrillation/flutter): rate control with β-blockers or CCBs; rhythm control may use class I or III drugs.
• Ventricular arrhythmias: acute therapy often uses IV lidocaine or amiodarone; chronic suppression may use class I or III agents depending on underlying heart disease.
• Digitalis-induced arrhythmias: phenytoin or lidocaine can be effective.
• Sotalol combines β-blockade and K⁺ channel blockade — useful but may prolong QT (torsades risk).

Adverse Effects & Cautions

• Proarrhythmia — many antiarrhythmics can cause or worsen arrhythmias (e.g., QT prolongation → torsades with IA/III agents).
• β-blockers: bradycardia, bronchospasm (nonselective agents), fatigue.
• Amiodarone: pulmonary fibrosis, thyroid dysfunction, hepatic toxicity, skin photosensitivity; complex drug interactions.
• Class IC drugs: contraindicated in structural heart disease or post-MI due to proarrhythmic risk.

Summary Table

Detailed Notes:

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