PharmacologyTier 1Medical Sciences concept

Vaughan Williams antiarrhythmic drug classification (Na, K, Ca channel, beta-blockade)

Core concept

Classification is by which phase of the cardiac action potential the drug acts on

Class	Target	Action potential effect
I	Fast Na channel	dec phase 0 upstroke -> dec conduction velocity, inc QRS
II	Beta-adrenoceptor	dec phase 4 slope in SA/AV node -> dec rate, dec AV conduction
III	K channel (IKr)	Prolong phase 3 repolarisation -> inc APD, inc QT
IV	L-type Ca channel	dec phase 0 in nodal tissue -> dec AV conduction
V/other	Various	Digoxin, adenosine, magnesium, ivabradine

Class I subdivides by binding kinetics - how fast the drug dissociates from the Na channel

Subclass	Dissociation	Effect	Drugs
Ia	Intermediate	dec conduction + inc APD/QT	Quinidine, procainamide, disopyramide
Ib	Fast	dec APD; selective for ischaemic/depolarised tissue	Lidocaine, mexiletine, phenytoin
Ic	Slow	Marked dec conduction, no APD change	Flecainide, propafenone

Mnemonic: "Double Quarter Pounder, Lettuce Mayo Please, Fries Please" - Ia disopyramide/quinidine/procainamide, Ib lidocaine/mexiletine/phenytoin, Ic flecainide/propafenone

Use-dependence - class I blockade increases at faster heart rates (channel more often open) -> effective against tachycardia
- Contrast class III reverse use-dependence - greatest effect at slow rates -> pro-arrhythmic (torsades) during bradycardia
Amiodarone is all four classes at once - Na, beta, K and Ca blockade
- t-half ~50 days, Vd ~60 L/kg; loading required
- Thyroid (both hypo and hyper), pulmonary fibrosis, hepatitis, corneal microdeposits, blue-grey skin, optic neuropathy, peripheral neuropathy
- Prolongs QT markedly but rarely causes torsades
- Inhibits CYP3A4, CYP2C9 and P-gp -> warfarin and digoxin doses must be reduced
Flecainide is contraindicated in structural heart disease and ischaemia (CAST trial - inc mortality)
- Safe in structurally normal hearts: "pill in the pocket" for paroxysmal AF
- Must be given with an AV nodal blocker - it slows atrial flutter to a rate the AV node can conduct 1:1
Sotalol - class III plus non-selective beta-blockade; renal clearance, inpatient initiation, torsades risk
Dronedarone - amiodarone analogue without iodine; contraindicated in permanent AF and in heart failure (inc mortality)
Class II and IV act on nodal tissue -> rate control in AF/flutter, termination of AVNRT

The classification predicts the danger
- Class Ic -> proarrhythmia in ischaemic or structurally abnormal hearts
- Class III -> torsades, especially with hypokalaemia and bradycardia
- Class II/IV -> bradycardia, heart block; avoid combining verapamil with a beta-blocker IV
Rate vs rhythm control in AF - rate control (beta-blocker, verapamil/diltiazem, digoxin) unless symptomatic despite rate control, HF, or early AF, where early rhythm control improves outcomes (EAST-AFNET 4)
Amiodarone needs baseline and 6-monthly TFTs and LFTs, annual CXR/lung function, and eye review - the monitoring burden is examinable
Adenosine, magnesium and digoxin sit outside the classification and are often the answer for that reason
Antiarrhythmic drugs treat symptoms; ICDs treat mortality in ventricular arrhythmia with structural disease

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