Anti-Arrhythmics

An arrhythmia is an abnormal cardiac rhythm. Arrhythmias arise from defects in impulse generation (SA node automaticity) or impulse conduction. Impulse generation defects include enhanced automaticity (latent pacemakers firing ectopically due to increased Na+ permeability) and triggered activity: early after-depolarisations (EADs — abnormally prolonged AP allows Na+ channels to recover before full repolarisation; causes torsades de pointes) and delayed after-depolarisations (DADs — cellular Ca2+ overload activates inward Na+ current; seen with digoxin toxicity).

Impulse conduction defects include heart block (loss of SA control due to impaired conduction; manifests as 1st, 2nd, or 3rd degree block) and re-entry (unidirectional block allows AP to travel retrogradely through damaged tissue; requires balance between conduction velocity and refractory period; major cause of ventricular tachycardia and fibrillation).

Atrial fibrillation (AF) — causes include IHD, hypertension, heart failure, hyperthyroidism, diabetes, old age, alcohol. AF → hypokinetic atria → blood stasis → thrombus → ischaemic stroke risk. Treatment targets: rate control, rhythm control, and stroke prevention (anticoagulation).

The Vaughan Williams (VW) classification categorises anti-arrhythmic drugs by their electrophysiological effects. It does not include all clinically used agents (e.g. digoxin, adenosine, atropine are outside this system).

Class I — sodium channel blockers: block fast Na+ channels in a use-dependent manner (more effective at higher heart rates where channels are more frequently in open/inactivated states). Reduce phase 0 slope and peak; decrease conduction velocity in non-nodal tissue. Examples: lignocaine (lignocaine may be used for polymorphic VT), flecainide (chemical cardioversion). ADR: can induce arrhythmias by slowing conduction.

Class II — beta-blockers (e.g. metoprolol, propranolol): block cardiac beta-adrenergic receptors; diminish SA nodal phase 4 depolarisation; reduce automaticity; slow AV node conduction (negative dromotropy); lengthen effective refractory period (ERP). Indications: rate control in AF (first-line), SVTs and VTs from sympathetic excess, prevention of recurrent tachycardias, decrease mortality post-MI. Contraindications: AV block, sinus node dysfunction, wide complex tachycardia. ADRs: bronchospasm (non-selective blockers), bradycardia, AV block, decreased contractility, CNS effects (metoprolol crosses BBB). Withdrawal must be gradual (over minimum 2 weeks) to avoid rebound angina/MI.

Class III — potassium channel blockers (e.g. amiodarone): reduce K+ efflux during phase 3 repolarisation; prolong AP duration; substantially prolong ERP; decrease re-entry risk. Amiodarone has multiple mechanisms: blocks K+ channels (phase 3), Na+ channels (phase 0), Ca2+ channels (SA/AV nodes), and has beta-blocking properties. Effective against a wide range of arrhythmias including SVT and VT; also used for rate control in AF. Amiodarone may prolong the QT interval (risk of torsades de pointes). ADRs: thyroid dysfunction (iodine-rich), pulmonary toxicity, corneal microdeposits, photosensitivity, hepatotoxicity. Contraindicated with drugs cleared via P-glycoprotein and with beta-blockers (profound heart block).

Class IV — calcium channel blockers (diltiazem, verapamil — not dihydropyridines): inhibit L-type and T-type Ca2+ channels; decrease SA node rate and AV conduction velocity; lengthen refractory period. Indications: rate control in AF, supraventricular arrhythmias only. Contraindications: combined with beta-blockers (profound cardiac depression), heart failure.

Non-VW drugs — Digoxin: two mechanisms. (1) Inhibits Na+/K+-ATPase → increased intracellular Na+ → inhibits Na+/Ca2+ exchanger → increased intracellular Ca2+ → positive inotropy. (2) Increases vagal (ACh) activity → reduces SA firing rate and AV conduction velocity → rate control in AF. Very narrow therapeutic index (therapeutic 0.5-0.9 ng/mL; toxic 2.5 ng/mL). Toxicity: facilitates ectopic pacemaker activity; can cause AF. Interactions: diuretic-induced hypokalaemia (K+ competes with digoxin for Na+/K+-ATPase binding site) increases toxicity; diltiazem, quinidine, verapamil reduce digoxin clearance via P-gp. Treatment of digoxin toxicity: withhold digoxin; correct K+; lidocaine; atropine; Fab antibody fragments.