Which anti arrhythmic drugs cause arrhythmia

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I now have comprehensive information from multiple authoritative textbooks. Here is the full answer:

Antiarrhythmic Drugs That Cause Arrhythmia (Proarrhythmia)

The paradoxical ability of antiarrhythmic drugs to cause or worsen arrhythmias is called proarrhythmia. It occurs in 5-10% of patients on antiarrhythmic agents, and the risk rises significantly with heart failure, reduced LV function, digitalis/diuretic use, bradycardia, and pre-existing QT prolongation. (Braunwald's Heart Disease)

Proarrhythmia can manifest as:

Increased frequency of a pre-existing arrhythmia
Sustaining of a previously non-sustained arrhythmia (even making it incessant)
Development of a completely new arrhythmia

Class IA - Sodium Channel Blockers (Intermediate Dissociation)

These drugs prolong the QT interval via IKr blockade (reverse use dependence - worse at slow heart rates), predisposing to Early Afterdepolarizations (EADs) and Torsades de Pointes (TdP).

Drug	Proarrhythmic Effect
Quinidine	QT prolongation, TdP ("quinidine syncope"); most notorious for this class; also reflexly accelerates AV conduction, which can convert AF flutter to 1:1 conduction
Procainamide	QT prolongation and TdP (via active N-acetyl metabolite NAPA); lupus-like syndrome with chronic use
Disopyramide	QT prolongation, TdP; strong negative inotrope - can precipitate VF in patients with poor LV function

Class IB - Sodium Channel Blockers (Fast Dissociation)

Least proarrhythmic of the Class I drugs; act preferentially on diseased/ischemic tissue.

Drug	Proarrhythmic Effect
Lidocaine	At toxic doses, can cause seizures and paradoxically worsen conduction; rare ventricular arrhythmias
Mexiletine	Minimal proarrhythmic risk; may worsen conduction disturbances
Phenytoin	Generally low risk; occasionally worsens conduction

Class IC - Sodium Channel Blockers (Slow Dissociation) - HIGHEST RISK

These are the most proarrhythmic of all antiarrhythmic agents. They markedly slow conduction and are particularly dangerous in structural heart disease.

Drug	Proarrhythmic Effect
Flecainide	Can cause new or worsened ventricular arrhythmias in 5-30% of patients with pre-existing sustained VT; can convert AF to a slow atrial flutter with paradoxical 1:1 AV conduction (risk of very fast ventricular rate); incessant VT
Encainide	Similar to flecainide (no longer available in most countries)
Propafenone	Similar proarrhythmic profile to flecainide

The CAST Trial - A Landmark Warning

The Cardiac Arrhythmia Suppression Trial (CAST) demonstrated a 2-3x increase in mortality when post-MI patients with ventricular arrhythmias were treated with flecainide, encainide, or moricizine. This established that suppressing PVCs with Class IC drugs does not improve survival and may be fatal in patients with coronary artery disease. - (Pfenninger and Fowler's Procedures for Primary Care; Braunwald's Heart Disease)

Class II - Beta Blockers

Generally anti-proarrhythmic in most contexts. However:

Can cause bradycardia, AV block, and asystole in susceptible patients
May precipitate ventricular arrhythmias via bradycardia-dependent QT prolongation in patients already at risk

Class III - Potassium Channel Blockers (K⁺ Channel Blockers)

These drugs prolong repolarization and the QT interval. The risk of TdP is a class effect.

Drug	Proarrhythmic Effect
Sotalol	~3% risk of excessive QT prolongation and TdP; risk amplified by hypokalemia, bradycardia, and female sex
Dofetilide	~3% risk of TdP; must be initiated only in hospital with QTc monitoring; avoid with other QT-prolonging drugs
Ibutilide	4-8% risk of TdP; used for pharmacologic cardioversion of AF/AFL - (Washington Manual; Sabiston Textbook)
Amiodarone	Despite the longest QT prolongation, has the lowest TdP risk of Class III agents (likely due to additional Class I, II, and IV effects); however, it can cause incessant VT at high doses
Dronedarone	Increased mortality in permanent AF (PALLAS trial); proarrhythmic in structural heart disease

Class IV - Calcium Channel Blockers

Verapamil / Diltiazem: Can cause severe bradycardia, sinus arrest, or AV block; verapamil in WPW syndrome with AF can dramatically accelerate conduction down the accessory pathway, precipitating VF

Digoxin (Cardiac Glycoside)

"In digoxin toxicity, almost any cardiac arrhythmia may be observed, with the exception of rapidly conducted atrial arrhythmias." - Tintinalli's Emergency Medicine

The most common arrhythmias are PVCs and bradycardic rhythms
Can cause bidirectional VT (pathognomonic), AF with slow ventricular response, junctional tachycardia, AV block
Risk is amplified by hypokalemia, hypomagnesemia, and renal failure
Treatment of choice for life-threatening toxicity: Digoxin-specific Fab antibody fragments

Key Risk Factors for Proarrhythmia

Structural heart disease / reduced EF (especially post-MI)
Female sex (women have longer baseline QTc; sex hormones modify ion channels)
Hypokalemia and hypomagnesemia
Bradycardia (slower rate = more QT prolongation)
Pre-existing QT prolongation
Concomitant QT-prolonging drugs (antibiotics like moxifloxacin/erythromycin, antipsychotics, etc.)
Heart failure and digitalis/diuretic use

Quick Reference Summary

Class	Drug	Proarrhythmia Type
IA	Quinidine, Procainamide, Disopyramide	TdP (QT prolongation)
IB	Lidocaine	Minimal - only at toxic doses
IC	Flecainide, Propafenone	Incessant VT, VF (use-dependent Na⁺ block); fatal in CAD
III	Sotalol, Dofetilide, Ibutilide	TdP (QT prolongation)
III	Amiodarone	Incessant VT (rarely TdP despite QT prolongation)
IV	Verapamil	VF in WPW; severe bradycardia/AV block
Misc	Digoxin	Any arrhythmia - PVCs, bidirectional VT, AV blocks

Sources: Braunwald's Heart Disease; Goodman & Gilman's Pharmacological Basis of Therapeutics; Harrison's Principles of Internal Medicine 22E (2025); Katzung's Basic and Clinical Pharmacology 16th Ed; Tintinalli's Emergency Medicine

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