Antiarrhythmic Drugs

Antiarrhythmic drugs suppress abnormal impulse formation or conduction. Effective treatment needs the rhythm diagnosed, the cause treated, and electrolytes corrected, and definitive options such as ablation or an implantable defibrillator often replace long-term drugs. All antiarrhythmics can cause arrhythmia.

Classification. Class I sodium channel blockers (IA quinidine, procainamide, disopyramide; IB lidocaine, mexiletine; IC flecainide, propafenone). Class II beta blockers. Class III potassium channel blockers (amiodarone, sotalol, dofetilide, ibutilide, dronedarone). Class IV calcium channel blockers (verapamil, diltiazem). Others: adenosine, digoxin, magnesium and atropine.

Mechanism. Class I slows phase 0 depolarisation and conduction, with use dependence. Class II reduces sympathetic effects. Class III prolongs repolarisation and refractoriness. Class IV slows nodal conduction. Adenosine briefly blocks the atrioventricular node.

Proarrhythmia. Class I drugs raise mortality after myocardial infarction and in structural heart disease. Class III drugs prolong QT and cause torsades de pointes. Hypokalaemia and hypomagnesaemia increase risk.

Pharmacokinetics. Amiodarone has a half-life of weeks with many interactions. Sotalol is renally cleared. Flecainide and propafenone depend on CYP2D6.

• Class I: sodium channel blockade; avoid in structural heart disease.
• Class II: rate control and ischaemia protection.
• Class III: amiodarone has broad activity; sotalol and dofetilide need QT monitoring.
• Class IV: rate control with preserved ejection fraction.
• Adenosine: terminates nodal re-entry tachycardia.
• Magnesium: torsades de pointes.

• Supraventricular tachycardia (narrow complex): vagal manoeuvres, then adenosine 6 mg rapid intravenous bolus, then 12 mg, then 12 mg (3 mg if given by central line, on dipyridamole or carbamazepine, or in a heart transplant recipient). Then verapamil, diltiazem or a beta blocker if not terminated.
• Atrial fibrillation: rate control with beta blocker, diltiazem or verapamil, with digoxin or amiodarone as add-on. For rhythm control, cardioversion, flecainide in a structurally normal heart, or amiodarone 300 mg intravenously over 1 hour then 900 mg over 24 hours. Anticoagulate by stroke risk. In rheumatic mitral stenosis, use warfarin rather than direct oral anticoagulants.
• Stable ventricular tachycardia: amiodarone 300 mg intravenously, or procainamide, or lidocaine 1 to 1.5 mg/kg.
• Cardiac arrest with ventricular fibrillation or pulseless tachycardia: amiodarone 300 mg after the third shock and 150 mg after the fifth, or lidocaine 1 to 1.5 mg/kg as an alternative.
• Torsades de pointes: magnesium sulphate 2 g intravenously over 10 minutes, correct potassium to over 4.5 mmol/L, stop QT-prolonging drugs, and use overdrive pacing or isoprenaline for recurrent bradycardia-dependent episodes.
• Bradycardia: atropine 500 micrograms intravenously, repeated to 3 mg.
• Selection: match to rhythm and heart structure. Class IC drugs only with a structurally normal heart, and avoid class I and dronedarone in reduced ejection fraction.

Contraindications. Class-specific: structural heart disease and coronary disease (class IC), long QT (class IA and III), heart failure (class I, dronedarone, non-dihydropyridine calcium channel blockers), conduction disease without a pacemaker, and Brugada syndrome (class I).

Adverse effects. Proarrhythmia, bradycardia, heart block, hypotension, negative inotropy and drug-specific organ toxicity (amiodarone: thyroid, lung, liver, eye, skin).

Interactions. QT-prolonging drugs, CYP2D6 and CYP3A4 inhibitors, digoxin, warfarin and beta blockers. Amiodarone raises levels of many drugs.

Monitoring. Electrocardiogram for QRS and QTc at baseline and after dose changes, potassium and magnesium, kidney and liver function, and thyroid function with amiodarone. Stop or reduce when QTc exceeds 500 ms or increases by over 60 ms.

Referral and escalation. Refer for ablation or defibrillator assessment when drugs fail or when the rhythm is life threatening.

Special groups. Pregnancy: use digoxin, beta blockers, verapamil or flecainide as needed, and avoid amiodarone. Older adults: lower doses and more sensitivity to bradycardia. Kidney disease: adjust sotalol, dofetilide and procainamide. Hepatic disease: adjust amiodarone and lidocaine.