Antiarrhythmic Drugs

Vaughan Williams classification

Classified by mechanism, not by clinical use — which is why several drugs sit awkwardly in it and four important agents sit outside it entirely.

Class	Mechanism	Effect on the action potential	Examples
I — membrane stabilisers	Block fast Na⁺ channels	↓ rate of rise of phase 0 → slower conduction; ↑ depolarisation threshold	See subclasses below
Ia	Moderate Na⁺ block, also K⁺ block	Prolongs AP duration and QT	Quinidine, procainamide, disopyramide
Ib	Weak, fast-dissociating Na⁺ block	Shortens AP duration. Selective for ischaemic/depolarised tissue	Lidocaine, mexiletine, phenytoin
Ic	Strong Na⁺ block, slow dissociation	Little change in AP duration but marked conduction slowing	Flecainide, propafenone
II — beta blockers	Block β₁ adrenoceptors	↓ Phase 4 slope in nodal tissue → ↓ automaticity, ↓ AV conduction	Metoprolol, bisoprolol, esmolol, atenolol
III — K⁺ channel blockers	Block outward K⁺ current	Slow repolarisation → prolonged AP duration, prolonged refractory period, prolonged QT	Amiodarone, sotalol, bretylium, ibutilide
IV — calcium channel blockers	Block L-type Ca²⁺ channels	↓ Phase 0 in nodal tissue (which is Ca²⁺-dependent) → ↓ spontaneous depolarisation and AV conduction	Verapamil, diltiazem

Adenosine — transient AV nodal block via A₁ receptors. Half-life under 10 seconds. Potentiated by dipyridamole, antagonised by theophylline; may cause bronchospasm.
Digoxin — Na⁺/K⁺ ATPase inhibition plus a strong vagotonic effect on the AV node.
Magnesium — the treatment of choice in torsades de pointes.
Atropine — antimuscarinic, used for bradycardia.

A more useful grouping in practice than the class numbers.

Supraventricular	Both	Ventricular
Adenosine Verapamil Digoxin Beta blockers	Amiodarone Disopyramide Flecainide Procainamide Propafenone Quinidine Sotalol	Lidocaine Mexiletine Bretylium Moricizine Phenytoin Tocainide

Amiodarone is the all-rounder — effective in both supraventricular and ventricular arrhythmias, and the drug given after the third shock in a shockable cardiac arrest (300 mg).
Adenosine is diagnostic as well as therapeutic: it terminates re-entrant SVT and unmasks the underlying rhythm in atrial flutter.
Never give verapamil in a broad-complex tachycardia of uncertain origin — if it is VT, the result can be catastrophic hypotension.
Avoid AV nodal blockers (digoxin, verapamil, adenosine) in AF with WPW — blocking the node promotes conduction down the accessory pathway.

Nominally class III, but it has properties of all four classes.
Very long half-life — 20 to 100 days, owing to extensive tissue distribution. Effects and interactions persist long after stopping.
Toxicity: pulmonary fibrosis, thyroid dysfunction (both hyper- and hypo-, as it is iodine-rich), hepatitis, corneal microdeposits, slate-grey skin discoloration, photosensitivity, peripheral neuropathy.
Causes hypotension if given rapidly IV — partly the drug, partly the solvent. Give centrally where possible; it is a peripheral vein irritant.
Interactions: potentiates warfarin and digoxin — both need dose reduction.
Porphyria: unsafe.

Precipitated by: hypokalaemia (the big one), hypercalcaemia, hypomagnesaemia, renal impairment, age, and amiodarone.
Features: nausea and vomiting, confusion, xanthopsia (yellow-green vision), and arrhythmias — classically bradycardia with ectopics, or atrial tachycardia with block.
The reverse-tick ST depression is a sign of digoxin effect, not toxicity.
Contraindicated in VF, and in AF with WPW. Treat significant toxicity with digoxin-specific antibody fragments.