Group I antiarrhythmics

Generic and Brand Names

Subclass IA

• Quinidine — Quinidex, Cardioquin

• Procainamide — Pronestyl

• Disopyramide — Norpace

Subclass IB

• Lidocaine — Xylocaine

• Mexiletine — Mexitil

• Phenytoin — Dilantin (off-label for arrhythmias)

Subclass IC

• Flecainide — Tambocor

• Propafenone — Rythmol

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Class

• Vaughan Williams Class I antiarrhythmics

• Sodium channel blockers — inhibit phase 0 depolarization in fast-response cardiac tissues (atria, ventricles, His–Purkinje system)

• Subclassified based on effects on action potential duration (APD) and conduction velocity

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Mechanism of Action

All Class I agents

• Block fast sodium channels → slow conduction velocity

• Decrease phase 0 slope in ventricular muscle fibers

• Subclass-specific effects on APD:

  • IA: Moderate Na⁺ channel block + K⁺ channel block → slows conduction, prolongs APD and QT interval

  • IB: Weak Na⁺ channel block → minimal conduction slowing, shortens APD (especially in ischemic tissue)

  • IC: Strong Na⁺ channel block → marked conduction slowing, minimal change in APD

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Indications

IA

• Atrial fibrillation/flutter (conversion and maintenance)

• Supraventricular tachycardia

• Ventricular tachycardia prevention/termination

IB

• Acute ventricular arrhythmias (especially post-MI or during cardiac surgery)

• Digitalis-induced ventricular arrhythmias (phenytoin)

IC

• Supraventricular arrhythmias (e.g., AF in structurally normal hearts)

• Ventricular arrhythmias in absence of significant structural heart disease

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Dosage and Administration

Quinidine

• Oral: 200–400 mg every 6–8 h
  Procainamide

• IV: 15–18 mg/kg over 25–30 min, then 1–4 mg/min infusion
  Disopyramide

• Oral: 100–150 mg every 6 h (IR) or 200–300 mg twice daily (CR)

Lidocaine

• IV bolus: 1–1.5 mg/kg; repeat 0.5–0.75 mg/kg q5–10min; infusion 1–4 mg/min
  Mexiletine

• Oral: 200–300 mg every 8 h
  Phenytoin (arrhythmia use)

• IV: 15 mg/kg at ≤50 mg/min

Flecainide

• Oral: 50–150 mg every 12 h
  Propafenone

• Oral: 150–300 mg every 8 h (IR) or 225–425 mg every 12 h (ER)

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Monitoring

• ECG: QRS duration, QT interval, PR interval (drug-specific)

• Blood pressure

• Serum drug levels (quinidine, procainamide, lidocaine, flecainide)

• Electrolytes (esp. potassium, magnesium)

• Renal/hepatic function

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Contraindications

• Significant structural heart disease (esp. IC agents)

• AV block without pacemaker

• Cardiogenic shock

• Prolonged QT (avoid IA in long QT syndrome)

• Post-MI prophylaxis (IC agents increase mortality)

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Precautions

• Proarrhythmia risk — torsades de pointes (esp. IA), ventricular arrhythmias (IC)

• Adjust dose in renal/hepatic impairment

• Avoid IC in patients with ischemic heart disease or LV dysfunction (CAST trial findings)

• Quinidine: risk of cinchonism; Procainamide: lupus-like syndrome with chronic use

• Lidocaine: CNS toxicity at high levels (seizures, confusion)

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Adverse Effects

IA

• Quinidine: GI upset, cinchonism (tinnitus, headache, vision changes), hypotension, torsades de pointes

• Procainamide: Hypotension (IV), lupus-like syndrome, torsades

• Disopyramide: Anticholinergic effects (dry mouth, urinary retention), negative inotropy

IB

• Lidocaine: CNS effects (confusion, tremor, seizures), hypotension

• Mexiletine: GI upset, CNS symptoms (dizziness, tremor)

• Phenytoin: Nystagmus, ataxia, gingival hyperplasia (chronic use)

IC

• Flecainide: Proarrhythmia in structural heart disease, visual disturbances, dizziness

• Propafenone: Metallic taste, bradycardia, mild beta-blockade effects

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Drug Interactions

• CYP inhibitors/inducers affecting metabolism (esp. flecainide, propafenone, quinidine)

• Additive proarrhythmia with other QT-prolonging agents

• Quinidine: Inhibits P-gp → increases digoxin levels

• Amiodarone increases levels of flecainide, propafenone

• Lidocaine clearance reduced by beta-blockers, cimetidine

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Overdose

• Severe conduction disturbances, hypotension, ventricular arrhythmias, cardiac arrest

• Management: Supportive care, sodium bicarbonate for QRS widening, magnesium for torsades, pacing/defibrillation if needed

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Patient Counselling

• Take at same times daily; do not double doses if missed

• Report palpitations, dizziness, syncope immediately

• Maintain electrolyte balance (adequate potassium, magnesium)

• Avoid sudden discontinuation without medical advice

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Comparison Table — Class I Subclasses

Feature	IA	IB	IC
Na⁺ Channel Block	Moderate	Weak	Strong
APD Effect	Prolongs	Shortens	Minimal change
ERP Effect	Prolongs	Shortens	Minimal change
Conduction Velocity	↓	Slight ↓	Marked ↓
Main Uses	Atrial + ventricular arrhythmias	Ventricular arrhythmias (esp. post-MI)	SVT, ventricular arrhythmias without structural heart disease
Torsades Risk	High	Low	Low–moderate
Unique Notes	Also block K⁺ channels	Preferential action in ischemic tissue	Avoid in structural heart disease, post-MI