7.2 Antiarrhythmics
Antiarrhythmic drugs modify cardiac electrophysiology to treat abnormal heart rhythms. The Vaughan Williams classification organizes these drugs by their primary mechanism of action on cardiac ion channels.
Cardiac Action Potential Review
Phase 0: Rapid depolarization (Na⁺ influx)
Phase 1: Early repolarization (transient K⁺ outward)
Phase 2: Plateau (Ca²⁺ in, K⁺ out balanced)
Phase 3: Repolarization (K⁺ efflux)
Phase 4: Resting potential (Na⁺/K⁺-ATPase)
SA/AV node: Phase 0 via Ca²⁺ (not Na⁺), slower upstroke, automaticity
Class I: Sodium Channel Blockers
Class IA - Moderate Na⁺ Block + K⁺ Block
Drugs: Quinidine, Procainamide, Disopyramide
Effects: ↓ Phase 0 slope, ↑ AP duration (K⁺ block), ↑ QRS, ↑ QT
Uses: Atrial and ventricular arrhythmias (rarely used now)
Toxicity: QT prolongation → Torsades de pointes, cinchonism (quinidine), lupus-like (procainamide)
Class IB - Weak Na⁺ Block
Drugs: Lidocaine, Mexiletine
Effects: Minimal ↓ Phase 0, ↓ AP duration (↑ K⁺ channels), minimal QRS/QT change
Preferentially bind inactivated Na⁺ channels → fast on/off kinetics
Uses: Ventricular arrhythmias (especially post-MI), NOT atrial
Lidocaine: IV only (high first-pass metabolism), CNS side effects (seizures at toxic levels)
Class IC - Strong Na⁺ Block
Drugs: Flecainide, Propafenone
Effects: Marked ↓ Phase 0, minimal AP duration change, marked ↑ QRS
Slow conduction velocity significantly
Uses: Atrial fibrillation/flutter, SVT (structurally normal hearts only)
Contraindicated: CAD, heart failure (CAST trial—↑ mortality)
Class II: Beta-Blockers
Mechanism
Block β₁-adrenergic receptors → ↓ cAMP → ↓ Ca²⁺ influx
↓ SA node automaticity, ↓ AV node conduction, ↓ contractility
↑ PR interval, ↓ HR
Examples & Uses
Metoprolol, esmolol, propranolol
Uses: SVT, atrial fibrillation (rate control), ventricular arrhythmias from ischemia/catecholamines
Post-MI mortality benefit
Esmolol: ultra-short-acting (β₁-selective), IV for acute rate control
Side Effects
Bradycardia, AV block, hypotension, bronchospasm, fatigue
Avoid in severe bradycardia, AV block, decompensated heart failure, asthma
Class III: Potassium Channel Blockers
Mechanism
Block K⁺ channels → ↓ Phase 3 repolarization
↑ Action potential duration, ↑ refractory period, ↑ QT interval
Amiodarone
Most effective antiarrhythmic—multiple mechanisms (K⁺, Na⁺, Ca²⁺, α/β blockade)
Uses: Refractory atrial/ventricular arrhythmias, V-fib/V-tach (ACLS), rate control
Long half-life (~50 days), extensive tissue accumulation
Toxicity: Pulmonary fibrosis (5-15%, can be fatal), thyroid dysfunction (hypo/hyper), hepatotoxicity, corneal deposits, blue-gray skin discoloration
Many drug interactions (CYP450 inhibitor)
Sotalol
K⁺ channel blocker + non-selective β-blocker (Class II + III)
Uses: Atrial fibrillation, ventricular tachycardia
Risk: QT prolongation → Torsades de pointes (dose-related)
Monitor QT interval, adjust for renal function
Dofetilide, Ibutilide
Dofetilide: Pure K⁺ channel blocker, atrial fibrillation conversion/maintenance
Requires in-hospital initiation (QT monitoring)
Ibutilide: IV for acute AFib/flutter conversion
Both: Torsades risk (monitor QT, electrolytes)
Class IV: Calcium Channel Blockers
Mechanism
Block L-type Ca²⁺ channels in SA/AV nodes
↓ Phase 0 slope (SA/AV), ↓ Phase 2 (plateau), ↓ automaticity, ↓ conduction velocity
↑ PR interval, ↓ HR
Verapamil & Diltiazem
Non-dihydropyridine CCBs (cardiac-selective)
Uses: SVT (acute termination), atrial fibrillation/flutter (rate control)
NOT for V-tach (dangerous—may worsen)
Side effects: Bradycardia, AV block, hypotension, constipation (verapamil)
Avoid with β-blockers (additive cardiac depression)
Other Antiarrhythmics
Adenosine
A₁ receptor agonist → ↑ K⁺ efflux, ↓ cAMP
Transiently blocks AV node (~10 seconds)
Use: First-line for acute SVT (PSVT) termination
Extremely short t½ (<10s)—rapid IV push
Side effects: Flushing, dyspnea, chest discomfort (transient)
Contraindicated in WPW with AFib (can precipitate V-fib)
Digoxin
Na⁺/K⁺-ATPase inhibitor → ↑ intracellular Ca²⁺
↑ Vagal tone → ↓ AV conduction, ↓ HR
Use: Atrial fibrillation rate control (less effective than β-blockers/CCBs)
Heart failure with reduced EF (↑ contractility)
Toxicity: Narrow therapeutic index, GI upset, visual changes (yellow halos), arrhythmias (PACs, AV block, V-tach)
Risk factors: Hypokalemia, hypomagnesemia, renal dysfunction
Magnesium Sulfate
Treatment of choice for Torsades de pointes
Stabilizes cardiac membranes, ↓ Ca²⁺ influx
Also used in pre-eclampsia/eclampsia
Atropine
Muscarinic antagonist → blocks vagal effects
↑ SA automaticity, ↑ AV conduction
Use: Symptomatic bradycardia (first-line in ACLS)
Torsades de Pointes
Polymorphic V-Tach Associated with QT Prolongation
Causes: Class IA, Class III (sotalol, dofetilide), hypokalemia, hypomagnesemia, congenital long QT
Risk factors: Female, bradycardia, structural heart disease, electrolyte abnormalities
ECG: "Twisting of the points" - QRS complexes twist around isoelectric line
Treatment: Magnesium sulfate (even if Mg²⁺ normal), correct electrolytes, stop offending drugs, temporary pacing (↑ HR shortens QT)
Can degenerate to V-fib → cardiac arrest