Class 1A Antiarrhythmic Agents: Na+ Channel Blockers

Study Notes

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

Description

This quiz covers the mechanisms of action of Class 1A antiarrhythmic agents, specifically their blockade of fast Na+ channels and effects on the cardiac action potential. Learn about the pharmacological effects of quinidine and its clinical implications.