Learning Objective
By the end of this activity, learners should be able to:
- Classify Class I antiarrhythmic drugs based on their effects on action potential duration.
- Describe the mechanism of action of Class IA, IB, and IC Na+ channel blockers.
- Identify key pharmacological effects, clinical uses, and adverse effects of Quinidine, Procainamide, Lidocaine, Mexiletine, and Flecainide.
- Differentiate antiarrhythmic from proarrhythmic drug effects for USMLE Step 1.
Class I Antiarrhythmic Drugs: Na+ Channel Blockers
Class IA
- Block fast Na+ channels (↓ INa)
- Preferential binding to open (activated) state – state-dependent blockade
- Also block K+ channels → prolong repolarization
- ↑ Action Potential Duration (APD)
- ↑ Effective Refractory Period (ERP)
Drugs: Quinidine
- Muscarinic receptor blockade → ↑ HR and AV conduction
- Alpha blockade → vasodilation and reflex tachycardia
- Orally effective
- Requires digitalization in atrial fibrillation
- Adverse Effects: Cinchonism (GI upset, tinnitus, visual disturbance), hypotension
- Prolonged QRS and QT → risk of torsades de pointes
- Displaces digoxin from tissue binding sites → ↑ toxicity
Procainamide
- Minimal muscarinic receptor blockade
- Metabolized by N-acetyltransferase → NAPA (active metabolite)
- Adverse Effects: SLE-like syndrome (↑ in slow acetylators)
- Hematotoxicity: agranulocytosis, thrombocytopenia
- Risk of torsades de pointes
Activity
Class IB
- Block inactivated Na+ channels
- Preferential action in ischemic or depolarized tissues
- ↓ Action Potential Duration
- ↑ Threshold for excitation
- Useful in ventricular arrhythmias
Drugs: Lidocaine
- Used in ventricular arrhythmias post-MI
- Effective in digoxin toxicity
- Administered IV due to first-pass metabolism
- Adverse Effect: CNS toxicity (seizures)
- The least cardiotoxic among conventional antiarrhythmics
Mexiletine
- Oral analogue of lidocaine
- Same clinical uses as lidocaine
Activity
Class IC
- Block fast Na+ channels (His-Purkinje system)
- No significant effect on APD
- No autonomic nervous system effects
Drug: Flecainide
- Potent Na+ channel blockade
- Limited use due to proarrhythmic risk
- ↑ Risk of sudden death post-MI
- Not used prophylactically in ventricular tachycardia
Exam Tip
Distinguish between antiarrhythmic effects (suppression of abnormal rhythm) and proarrhythmic effects (drug-induced arrhythmias such as torsades de pointes).
