Bit · Pharm/Tox
Antiarrhythmics — Vaughan-Williams Classification (I, II, III, IV)
Four classes of antiarrhythmic. Each blocks a different ion channel or receptor. NBME tests the channel + the toxicity, every time.
Mechanism
The Vaughan-Williams system organizes antiarrhythmics by primary mechanism:
- Class I — Na⁺ channel blockers (slow phase 0 depolarization in non-nodal myocytes). Subdivided IA, IB, IC by binding kinetics and QT effect.
- Class II — β-blockers. Slow SA/AV nodal conduction (rate control).
- Class III — K⁺ channel blockers (prolong phase 3 repolarization, prolong QT, prolong refractoriness).
- Class IV — non-dihydropyridine Ca²⁺ channel blockers. Slow SA/AV nodal conduction (rate control).
Outliers: adenosine (transient AV block; first-line for SVT termination), digoxin (vagal tone + Na/K-ATPase inhibition), magnesium (torsades).
Differentiator Table
| Class | Mechanism | Drugs | Use | Key toxicity |
|---|---|---|---|---|
| IA | Na⁺ channel block (moderate); ↑ AP duration | Quinidine, Procainamide, Disopyramide | Atrial + ventricular arrhythmias | ↑ QT → torsades. Quinidine: cinchonism. Procainamide: drug-induced lupus (anti-histone) |
| IB | Na⁺ channel block (fast on/off); ↓ AP duration | Lidocaine, Mexiletine | Ventricular arrhythmias post-MI; digoxin toxicity | CNS toxicity (confusion, seizures) |
| IC | Na⁺ channel block (slow on/off); no effect on AP duration | Flecainide, Propafenone | Atrial fibrillation in structurally NORMAL heart | Proarrhythmic in structural heart disease (CAST trial); AVOID in CAD |
| II | β-blockers | Metoprolol, esmolol, propranolol | Rate control, post-MI, HFrEF | Bradycardia, AV block, bronchospasm, masks hypoglycemia |
| III | K⁺ channel block | Amiodarone, Sotalol, Dofetilide, Ibutilide | Atrial + ventricular | Amiodarone: PULMONARY FIBROSIS, hepatotoxicity, hypo- or hyperthyroidism, blue-grey skin, corneal deposits. Sotalol: torsades. |
| IV | Non-DHP Ca²⁺ channel blockers | Verapamil, Diltiazem | Rate control in AF, SVT | Constipation (verapamil), AV block, ↓ contractility (avoid in HFrEF) |
| Other | Adenosine | First-line for SVT termination | Causes 5–15 sec asystole; sense of impending doom | |
| Other | Digoxin | Vagal tone + Na/K-ATPase inhibition; chronic AF rate control | Yellow vision, scooped ST, hyperkalemia in toxicity | |
| Other | Magnesium | Stabilizes membranes | Torsades de pointes; refractory VF |
The Pivot
Three questions:
- What channel does it block? Na⁺ → Class I. β → Class II. K⁺ → Class III. Ca²⁺ → Class IV.
- Within Class I — what does it do to QT? Lengthens → IA (torsades risk). Shortens → IB. No change → IC.
- Match to toxicity: pulmonary fibrosis + thyroid + skin → amiodarone. Lupus → procainamide. Cinchonism → quinidine.
NBME-Style Stem
A 62-year-old man with paroxysmal atrial fibrillation and chronic obstructive pulmonary disease is treated long-term with an antiarrhythmic. He develops progressive dyspnea, a non-productive cough, and bilateral interstitial infiltrates on chest x-ray. Which of the following drugs is most likely responsible?
Concept Anchor
Four classes, four channels, four predictable toxicity profiles. The drug's chemistry tells you the side effect — amiodarone's iodine touches the thyroid and skin, procainamide creates anti-histone antibodies, IB's CNS penetration drives seizures.