Class I antiarrhythmics (sodium channel blockers)

Mechanism of Action - The Sodium Block Party

• Primary Action: Blocks voltage-gated Na+ channels, primarily during Phase 0 of the cardiac action potential.
• Consequence: ↓ the slope and amplitude of Phase 0 depolarization, which slows the conduction velocity in the atria, ventricles, and His-Purkinje system.

• State-Dependent Blockade: Drugs bind more avidly to open or inactivated channels than to resting channels.

⭐ Use-Dependence: The clinical effect is magnified in rapidly depolarizing tissue. This means the drug is more effective when it's needed most-during a tachycardia.

Class IA Agents - Prolonging the Potential

• Agents: Quinidine, Procainamide, Disopyramide.
  • 📌 Mnemonic: Queen Proclaims Diso's pyramid.
• Mechanism: Moderately block voltage-gated Na⁺ channels (Phase 0) and K⁺ channels.
  • Prolongs action potential duration (APD) and effective refractory period (ERP).
  • Slows conduction velocity and increases the threshold for excitability.
• Clinical Use: Atrial & ventricular tachyarrhythmias (e.g., SVT, VT).

• Adverse Effects:
  • All: Can cause Torsades de Pointes (due to ↑QT interval), cinchonism (headache, tinnitus).
  • Quinidine: Thrombocytopenia.
  • Procainamide: Drug-induced lupus (anti-histone antibodies).
  • Disopyramide: Strong anticholinergic effects, exacerbates heart failure.

⭐ Exam Favorite: Procainamide is associated with a reversible, drug-induced lupus erythematosus (SLE)-like syndrome.

Class IB Agents - Ischemia's Enemy

• Mechanism: Weak Na⁺ channel blockers with rapid dissociation. Selectively target ischemic and depolarized Purkinje/ventricular tissue.
  • Shortens Phase 3 repolarization, leading to a ↓ in action potential duration.
• Agents: Lidocaine (IV), Mexiletine (oral).
• Clinical Use: Acute ventricular arrhythmias, especially post-MI. Also used for digitalis-induced arrhythmias.
• Adverse Effects: Primarily CNS stimulation/depression (paresthesias, tremor, convulsions). Cardiovascular toxicity is less common.
• 📌 Mnemonic: "I'd Buy Liddy's Mexican Tacos" → IB, Lidocaine, Mexiletine, Tachycardia (ventricular).

⭐ High-Yield: Class IB agents exhibit state-dependent binding, with highest affinity for the inactivated Na⁺ channel state common in depolarized, ischemic tissue, making them ideal for post-MI arrhythmias.

Class IC Agents - The Risky Rhythm-Killers

• Agents: Flecainide, Propafenone
• Mechanism: Strongest Na+ channel blockade. Markedly slows Phase 0 depolarization, leading to a significant ↓ in conduction velocity.
  • Prolongs the QRS duration significantly.
  • Minimal effect on action potential duration or QT interval.
• Clinical Use: Atrial fibrillation/flutter (especially "pill-in-the-pocket" approach), refractory ventricular arrhythmias in structurally normal hearts.
• Adverse Effects:
  • ⚠️ High proarrhythmic potential, especially in ischemic or structural heart disease.
  • CNS effects (dizziness, visual disturbances).

⭐ CAST Trial Finding: Increased mortality was observed in post-myocardial infarction patients treated with flecainide/encainide. This restricts Class IC use to patients without structural heart disease.

📌 Mnemonic: "Can I Please Fry?" (Class IC, Propafenone, Flecainide).

High‑Yield Points - ⚡ Biggest Takeaways

• Class I drugs block voltage-gated Na+ channels, decreasing the slope of phase 0 depolarization and slowing conduction.
• They exhibit use-dependence, preferentially binding to open or inactivated channels over resting channels.
• Class IA (e.g., Quinidine) prolongs AP duration and the QT interval, risking Torsades de Pointes.
• Class IB (e.g., Lidocaine) shortens AP duration and is ideal for ischemic or depolarized tissue.
• Class IC (e.g., Flecainide) is strongly proarrhythmic post-MI and contraindicated in structural heart disease.
• Procainamide is associated with drug-induced lupus (anti-histone antibodies).