Antiarrhythmic agents

Introduction

Antiarrhythmic agents are a class of drugs used to manage cardiac arrhythmias—abnormalities in the heart’s electrical rhythm. Arrhythmias range from benign palpitations to life-threatening conditions such as ventricular fibrillation. The goal of antiarrhythmic therapy is to restore normal sinus rhythm, control heart rate, suppress ectopic activity, and prevent recurrence of arrhythmias.

These drugs act on various ion channels, receptors, or nodal conduction pathways within the heart. The classification most widely used is the Vaughan Williams Classification, which divides antiarrhythmics into five main classes (I–V) based on their mechanism of action. However, overlap exists, as many agents possess mixed actions.

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Classification of Antiarrhythmic Agents

Vaughan Williams System

1. Class I: Sodium Channel Blockers

   • Subdivided into IA, IB, and IC.

   • Reduce phase 0 depolarization, slow conduction.

2. Class II: Beta-Adrenergic Blockers

   • Reduce sympathetic activity.

   • Decrease automaticity and conduction velocity.

3. Class III: Potassium Channel Blockers

   • Prolong repolarization (phase 3).

   • Increase action potential duration.

4. Class IV: Calcium Channel Blockers

   • Block L-type calcium channels.

   • Slow conduction through the AV node.

5. Class V: Miscellaneous Agents

   • Adenosine, Digoxin, Magnesium sulfate.

   • Act through unique mechanisms not fitting into Classes I–IV.

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Class I: Sodium Channel Blockers

Class IA (Moderate Na+ Blockers)

• Mechanism: Block fast sodium channels, slow depolarization, prolong repolarization (increase QT interval).

• Examples: Quinidine, Procainamide, Disopyramide.

Uses: Atrial fibrillation, supraventricular tachycardia (SVT), ventricular tachycardia.

Doses:

• Quinidine: 200–400 mg PO every 6 hours.

• Procainamide: 1–4 g/day PO divided q6h, or IV loading 15 mg/kg.

• Disopyramide: 400–600 mg/day PO divided q6–8h.

Adverse Effects: QT prolongation, torsades de pointes, hypotension, lupus-like syndrome (procainamide).

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Class IB (Weak Na+ Blockers)

• Mechanism: Shorten repolarization, decrease action potential duration.

• Examples: Lidocaine, Mexiletine.

Uses: Ventricular arrhythmias, particularly post-MI or during digitalis toxicity.

Doses:

• Lidocaine: 1–1.5 mg/kg IV bolus, followed by infusion 1–4 mg/min.

• Mexiletine: 200–400 mg PO every 8 hours.

Adverse Effects: CNS toxicity (tremor, seizures), hypotension, bradycardia.

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Class IC (Strong Na+ Blockers)

• Mechanism: Marked slowing of phase 0 depolarization, minimal effect on repolarization.

• Examples: Flecainide, Propafenone.

Uses: Supraventricular arrhythmias, atrial fibrillation, ventricular tachycardia (without structural heart disease).

Doses:

• Flecainide: 50–150 mg PO twice daily.

• Propafenone: 150–300 mg PO every 8 hours.

Adverse Effects: Proarrhythmia, blurred vision, dizziness.
Contraindication: Structural heart disease, post-MI (increased mortality).

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Class II: Beta-Adrenergic Blockers

• Mechanism: Inhibit β1-receptors, decrease SA node automaticity, slow AV conduction, reduce myocardial oxygen demand.

• Examples: Propranolol, Metoprolol, Atenolol, Esmolol.

Uses: Rate control in atrial fibrillation, supraventricular tachycardia, prevention of ventricular arrhythmias, post-MI mortality reduction.

Doses:

• Propranolol: 10–40 mg PO every 6–8 hours.

• Metoprolol: 25–100 mg PO twice daily, or IV 5 mg every 5 min × 3 doses.

• Atenolol: 50–100 mg PO once daily.

• Esmolol: 500 mcg/kg IV bolus, then 50–200 mcg/kg/min infusion.

Adverse Effects: Bradycardia, hypotension, bronchospasm, fatigue, depression.

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Class III: Potassium Channel Blockers

• Mechanism: Prolong repolarization, increase action potential duration and refractory period.

• Examples: Amiodarone, Sotalol, Dofetilide, Ibutilide.

Uses: Atrial fibrillation, atrial flutter, ventricular tachycardia, ventricular fibrillation.

Doses:

• Amiodarone: 200–400 mg PO daily (maintenance); IV loading: 150 mg over 10 min, then infusion 1 mg/min.

• Sotalol: 80–160 mg PO twice daily.

• Dofetilide: 500 mcg PO twice daily (adjust for renal function).

• Ibutilide: 1 mg IV over 10 minutes, may repeat.

Adverse Effects:

• Amiodarone: pulmonary fibrosis, thyroid dysfunction, corneal deposits, skin discoloration.

• Sotalol: torsades de pointes, bradycardia.

• Dofetilide/Ibutilide: QT prolongation, torsades risk.

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Class IV: Calcium Channel Blockers

• Mechanism: Block L-type calcium channels, prolong AV nodal conduction, reduce heart rate.

• Examples: Verapamil, Diltiazem.

Uses: Supraventricular tachycardias (PSVT), rate control in atrial fibrillation/flutter.

Doses:

• Verapamil: 120–240 mg/day PO divided doses, or IV 2.5–5 mg over 2 minutes.

• Diltiazem: 120–360 mg/day PO, or IV 0.25 mg/kg bolus, then infusion 5–15 mg/hr.

Adverse Effects: Bradycardia, hypotension, constipation (verapamil), heart block.
Contraindications: Severe heart failure, WPW syndrome with AF.

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Class V: Miscellaneous Agents

Adenosine

• Mechanism: Activates adenosine receptors, increases K+ efflux, transiently blocks AV node conduction.

• Uses: Acute termination of paroxysmal supraventricular tachycardia (PSVT).

• Dose: 6 mg IV rapid bolus, followed by 12 mg if needed.

• Adverse Effects: Flushing, chest pain, dyspnea, bronchospasm.

Digoxin

• Mechanism: Inhibits Na+/K+ ATPase, increases vagal tone, slows AV conduction.

• Uses: Rate control in atrial fibrillation/flutter (especially with heart failure).

• Dose: 0.125–0.25 mg PO daily.

• Adverse Effects: Arrhythmias, nausea, visual disturbances (“yellow vision”).

Magnesium sulfate

• Mechanism: Stabilizes cardiac cell membranes, suppresses early afterdepolarizations.

• Uses: Torsades de pointes, digitalis-induced arrhythmias.

• Dose: 1–2 g IV over 15 minutes.

• Adverse Effects: Hypotension, bradycardia (with rapid infusion).

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Adverse Effects of Antiarrhythmic Therapy

• Proarrhythmia: All classes may paradoxically worsen arrhythmias.

• Organ-specific toxicities:

  • Amiodarone → thyroid, lung, liver toxicity.

  • Procainamide → lupus-like syndrome.

  • Quinidine → cinchonism (tinnitus, headache, blurred vision).

• Electrolyte imbalance: Hypokalemia and hypomagnesemia increase arrhythmia risk.

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Contraindications

• Structural heart disease: Class IC agents contraindicated.

• Severe bradycardia/AV block: Avoid beta-blockers, calcium channel blockers, digoxin.

• QT prolongation history: Avoid Class IA and Class III drugs (torsades risk).

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Drug Interactions

• Amiodarone: Inhibits CYP450, increasing levels of warfarin, digoxin, phenytoin.

• Beta-blockers + Calcium channel blockers: Additive bradycardia and AV block.

• Digoxin: Toxicity potentiated by hypokalemia (with diuretics).

• Class IA/III + other QT-prolonging drugs: Increased torsades risk.

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Clinical Efficacy and Limitations

Antiarrhythmic agents remain essential but challenging therapies due to:

• Narrow therapeutic index.

• High risk of adverse and proarrhythmic effects.

• Need for individualized therapy guided by arrhythmia type, comorbidities, and monitoring.

In many cases, non-pharmacological strategies (catheter ablation, implantable cardioverter-defibrillators) are increasingly favored due to superior long-term safety and efficacy.