Table of Contents · 11 sections
- 1. Vaughan Williams classification principles
- 2. Class I — sodium channel blockers
- 3. Class II — β-blockers
- 4. Class III — potassium channel blockers
- 5. Class IV — calcium antagonists (nondihydropyridine)
- 6. Unclassified agents
- 7. Clinical scenarios
- 8. Proarrhythmic effect
- 9. Adverse effects of key drugs
- 10. Therapy monitoring
- 11. FAQ
In a nutshell. Antiarrhythmic drugs (AADs) are divided according to the Vaughan Williams classification into 4 classes based on their site of action: Class I — Na⁺ channel blockers (Ia, Ib, Ic), Class II — β-blockers, Class III — K⁺ channel blockers (amiodarone, sotalol), Class IV — Ca²⁺ channel blockers (verapamil, diltiazem). Class I and III drugs can cause proarrhythmia (QT prolongation, torsades). First-line therapy for most arrhythmias today is β-blockers and amiodarone; catheter ablation is increasingly replacing long-term AAD therapy.
1. Vaughan Williams classification principles
Proposed in 1970, updated by Harrison in 1981. Drugs are categorized by their dominant electrophysiological effect:
- Class I — Fast Na⁺ channel blockade (phase 0 of the action potential).
- Class II — β-adrenergic blockade (↓ sympathetic tone).
- Class III — K⁺ channel blockade (↑ action potential duration, refractoriness).
- Class IV — L-type Ca²⁺ channel blockade (phase 0 of the action potential in the sinus and AV nodes).
Many drugs possess mixed properties (e.g., amiodarone exhibits effects from all 4 classes). The modern Sicilian Gambit classification accounts for multiple effects, but Vaughan Williams remains dominant in clinical practice.
2. Class I — sodium channel blockers
| Subclass | Effect on action potential | Drugs | Indication |
|---|---|---|---|
| Ia | Moderate phase 0 slowing, ↑ action potential duration | Quinidine, procainamide, disopyramide | Supraventricular and ventricular arrhythmias |
| Ib | Mild phase 0 slowing, ↓ action potential duration | Lidocaine, mexiletine | Ventricular arrhythmias (especially in ischemia) |
| Ic | Marked phase 0 slowing, no effect on action potential duration | Propafenone, flecainide, ethacizine | Termination of atrial fibrillation, AV re-entrant tachycardias; "pill-in-pocket" approach |
Class Ic considerations
- Contraindicated in structural heart disease (per the CAST trial — increased mortality in post-MI patients).
- Used in a "pill-in-pocket" strategy: propafenone 450–600 mg single dose for an atrial fibrillation paroxysm in patients without structural heart disease.
3. Class II — β-blockers
- Metoprolol, bisoprolol, atenolol, propranolol, esmolol (ultra-short-acting, IV).
- Mechanism: suppression of sinus node automaticity, slowing of AV conduction, ↓ catecholamine release.
- Indications: sinus tachycardia, atrial flutter/fibrillation (rate control), AV re-entrant tachycardias, premature ventricular contractions (PVCs), ventricular tachycardia, post-MI prevention.
- Contraindications: AV block ≥ grade II, bradycardia < 50 bpm, bronchospasm (for non-selective agents).
4. Class III — potassium channel blockers
| Drug | Features |
|---|---|
| Amiodarone | Universal — blocks Na⁺, K⁺, Ca²⁺ channels and β-receptors; minimal proarrhythmic risk; however — thyroid, pulmonary, and hepatic toxicity, photosensitivity, corneal deposits |
| Dronedarone | Amiodarone analogue without iodine; lower toxicity, but lower efficacy as well; contraindicated in decompensated heart failure and permanent atrial fibrillation |
| Sotalol | K⁺ channel blocker + β-blocker; caution — QT prolongation and torsades de pointes, monitor magnesium and potassium levels |
| Ibutilide, dofetilide | IV termination of atrial fibrillation/flutter; risk of torsades de pointes; rarely available in Russia |
| Bretylium | Resuscitation in ventricular fibrillation, obsolete since the introduction of amiodarone |
5. Class IV — calcium antagonists (nondihydropyridine)
- Verapamil, diltiazem.
- Blockade of L-type Ca²⁺ channels in the sinus and AV nodes → ↓ automaticity, ↓ AV conduction.
- Indications: paroxysmal supraventricular tachycardia (SVT), rate control in atrial fibrillation/flutter in patients without heart failure.
- Contraindications: ejection fraction < 40% and WPW syndrome with atrial fibrillation (AV nodal block leads to preferential conduction via the accessory pathway → ventricular fibrillation).
6. Unclassified agents
- Adenosine — IV bolus 6–12 mg; instant and transient AV nodal blockade; drug of choice for SVT termination.
- Digoxin — rate control in atrial fibrillation in patients with heart failure; via slowed AV conduction (vagal effect).
- Magnesium sulfate — for torsades de pointes and hypomagnesemic arrhythmias.
- Atropine — for bradycardia and AV block.
- Ivabradine — sinus node If-channel inhibitor; for sinus tachycardia with a contraindication to β-blockers.
7. Clinical scenarios
Atrial fibrillation
- Rhythm control: propafenone (without structural heart disease), amiodarone (any structure), sotalol. Catheter ablation — when drug therapy is ineffective.
- Rate control: β-blockers or non-dihydropyridine CCBs; in heart failure — β-blockers + digoxin.
Ventricular arrhythmias
- VT in myocardial infarction — IV amiodarone, lidocaine.
- VF — defibrillation + amiodarone 300 mg bolus.
- For long-term prevention in patients with EF < 35% — ICD (implantable cardioverter-defibrillator).
SVT (AVNRT, WPW)
- Acute termination: vagal maneuvers → IV adenosine → β-blockers or verapamil.
- Prevention: radiofrequency ablation — method of choice.
Torsades de pointes
- Magnesium sulfate 2 g IV.
- Elimination of the cause (drugs that prolong the QT interval).
- Temporary cardiac pacing for overdrive pacing.
8. Proarrhythmic effect
All Class I and III antiarrhythmic drugs can cause new arrhythmias:
- Ic — monomorphic VT (especially with structural heart disease).
- Ia and III — QT prolongation → torsades de pointes.
- Risk factors: hypokalemia, hypomagnesemia, bradycardia, female sex, combination with other QT-prolonging drugs (macrolides, fluoroquinolones, antipsychotics).
9. Side Effects of Key Drugs
- Amiodarone: hyper-/hypothyroidism, pulmonary fibrosis, hepatitis, photosensitivity, corneal deposits, polyneuropathy.
- Sotalol: bradycardia, QT prolongation, bronchospasm.
- Propafenone: bitter taste in the mouth, worsening of CHF, QRS prolongation.
- Verapamil: constipation, edema, hypotension.
- Digoxin: narrow therapeutic window, digitalis toxicity (xanthopsia, nausea, arrhythmias).
10. Therapy Monitoring
- Serial ECG — QRS, QT, PR.
- Amiodarone: TSH, ALT, chest X-ray / pulmonary function tests every 6 months.
- Digoxin: serum level (0.5–0.9 ng/mL in heart failure), K⁺, Mg²⁺.
- Sotalol: Mg²⁺, K⁺, QT interval.
11. FAQ
Why did the CAST trial change the approach to antiarrhythmics?
CAST (1989) demonstrated that flecainide and encainide in post-MI patients reduce the frequency of VES, but increase mortality. Since then, Class Ic drugs are contraindicated in structural heart disease.
How does amiodarone differ from dronedarone?
Amiodarone contains iodine, is more effective, but more toxic; dronedarone is iodine-free, safer for the thyroid gland, but less effective and contraindicated in NYHA class II–IV CHF.
When is verapamil contraindicated in AF?
In WPW syndrome with antegrade conduction via the accessory pathway: verapamil blocks the AV node, and impulses travel via the accessory pathway → risk of ventricular fibrillation.
Why magnesium in torsades de pointes?
It stabilizes the cardiomyocyte membrane, even with normal blood Mg levels. First-line drug for polymorphic VT with prolonged QT.
Will ablation replace drug therapy?
Partially — in paroxysmal AF, AVNRT, WPW, and typical atrial flutter, ablation outperforms AAAs. However, in persistent AF and VT associated with cardiomyopathies, drugs remain the mainstay.
See also: Myocardial Infarction · CHF · Anticoagulants · β-blockers · Pharmacology Catalog · Clinical Scales