Class 1A Antiarrhythmic Agents: Na+ Channel Blockers

Class I: Na+ Channel Blockers

Class 1A: Antiarrhythmic

• Block fast Na+ channels (↓ INa) in open or activated state
• Also block K+ channel, prolonging repolarization and action potential duration
• Effective refractory period is increased
• Drugs:
  • Quinidine • Causes muscarinic receptor blockade, increasing HR and AV conduction • May cause vasodilation via alpha block with possible reflex tachycardia • Orally effective, with wide clinical use in many arrhythmias • Adverse effects: cinchonism, hypotension, prolongation of QRS and QT interval, and torsade
  • Procainamide • Less muscarinic receptor block • Metabolized to N-acetyl procainamide (NAPA), an active metabolite • Adverse effects: systemic lupus erythematosus (SLE)-like syndrome, hematotoxicity, and CV effects (torsade)

Class 1B

• Block fast Na+ channels (↓ INa) in inactivated channels
• Preference for tissues partly depolarized (slow conduction in hypoxic and ischemic tissues)
• Increased threshold for excitation and less excitability of hypoxic heart muscle
• Decreased APD due to block of slow Na+ “window” currents
• Increased diastole and extended time for recovery
• Drugs and uses:
  • Lidocaine • Used in post-MI, open-heart surgery, and digoxin toxicity for ventricular arrhythmias only • Side effects: CNS toxicity, seizures • IV use due to first-pass metabolism
  • Mexiletine • Same uses as lidocaine • Oral formulations

Class 1C

• Block fast Na+ channels (↓ INa) in His-Purkinje tissue
• No effect on APD
• No ANS effects
• Drug:
  • Flecainide • Limited use due to proarrhythmogenic effects, leading to increased sudden death post-MI and in VT

Class II: Beta Blockers

• Prevent β-receptor activation, which normally increases cAMP
• Decrease SA and AV nodal activity
• Decrease slope of phase 4 of AP in pacemakers
• Drugs:
  • Propranolol (nonselective) and cardioselective drugs (acebutolol and esmolol)
  • Uses: • Prophylaxis post-MI and in supraventricular tachyarrhythmias (SVTs) • Esmolol (IV) used in acute SVTs

Class III: K+ Channel Blockers

• Decrease IK (delayed rectifier current), slowing phase 3 (repolarization) of AP
• Increase APD and ERP, especially in Purkinje and ventricular fibers
• Drugs:
  • Amiodarone • Mimics classes I, II, III, and IV • Increases APD and ERP in all cardiac tissues • Uses: any arrhythmias • t1/2 >80 days • Binds extensively to tissues (large Vd and multiple effects) • Side effects: pulmonary fibrosis, blue pigmentation of the skin, phototoxicity, corneal deposits, hepatic necrosis, and thyroid dysfunction
  • Sotalol • Decreases IK, slowing phase III • Nonselective beta blocker: β1 blockade, leading to decreased HR, decreased AV conduction • Uses: life-threatening ventricular arrhythmia • Side effects: torsade

Class IV: Ca2+ Channel Blockers

• Block slow cardiac Ca2+ channels
• Decrease phase 0, decrease phase 4
• Decrease SA, decrease AV nodal activity
• Drugs:
  • Verapamil and diltiazem • Prototype Ca2+-channel blockers • Uses: supraventricular tachycardias • Side effects: constipation, dizziness, flushing, hypotension, AV block • Drug interaction: additive AV block with β-blockers, digoxin; verapamil displaces digoxin from tissue-binding sites

Treatment of Torsade

• Correct hypokalemia
• Correct hypomagnesemia