STEPTRACKERPHARMACOLOGY + PHYSIOLOGY | CARDIOVASCULAR | HIGH-YIELD REVIEW

Antiarrhythmics I — Classes I & II

Class I drugs block sodium channels and are sorted by how tightly they bind; class II drugs are β-blockers acting on the nodes. Read each against the action potential.

FOCUS ON
Class I = Na⁺ channel blockers (↓ phase 0 slope); use-dependent — work better at faster rates. IA (quinidine, procainamide, disopyramide): moderate Na⁺ block + K⁺ block → ↑ AP duration, ↑ QRS and QT; atrial and ventricular arrhythmias, WPW (procainamide). Adverse: quinidine — cinchonism (tinnitus, headache), thrombocytopenia, torsades; procainamide — drug-induced lupus; disopyramide — anticholinergic, HF. IB (lidocaine, mexiletine): weak, fast-dissociating; shorten AP; prefer ischemic/depolarized tissue → post-MI ventricular arrhythmias, digoxin toxicity. Adverse: CNS (seizures, paresthesias). IC (flecainide, propafenone): strong, slow dissociation; ↑ QRS, AP duration unchanged; SVT, AF in structurally normal hearts; proarrhythmic post-MI. Class II (β-blockers): ↓ cAMP → ↓ phase 4 slope in SA/AV nodes, ↑ PR; rate control, post-MI.
CLASS · DRUGS
ECG / AP EFFECT
USES
TOXICITY
IA — quinidine
↓ Phase 0, ↑ AP duration, ↑ ERP; ↑ QRS, ↑ QT; antimuscarinic
AF, ventricular arrhythmias, malaria (IV)
Cinchonism, diarrhea, thrombocytopenia, torsades
IA — procainamide
Same; active metabolite NAPA (class III)
WPW with AF, stable wide-complex tachycardia
Drug-induced lupus (anti-histone, slow acetylators), agranulocytosis, torsades
IA — disopyramide
Same + strong negative inotrope
Hypertrophic cardiomyopathy obstruction (off-label)
Anticholinergic effects, HF
IB — lidocaine
↓ AP duration; binds inactivated channels in depolarized tissue
Ventricular arrhythmias after MI, digoxin-induced arrhythmias
CNS stimulation then depression, seizures; IV only (first pass)
IB — mexiletine · phenytoin
Oral IB
Ventricular arrhythmias, long QT 3
GI upset, tremor, ataxia
IC — flecainide · propafenone
Marked ↓ phase 0; ↑ QRS; no AP-duration change; ↑ ERP in AV node and accessory pathway
AF and SVT in structurally normal hearts ("pill in pocket")
Proarrhythmic after MI or with structural disease (↑ mortality in trials)
Use dependence
Class I binds open/inactivated channels
More block at fast rates
IC strongest, IB weakest at normal rates
Class II — β-blockers
↓ Phase 4 slope (SA, AV nodes), ↑ PR, ↑ AV refractoriness
Rate control in AF/flutter, SVT, post-MI, long QT, catecholaminergic VT
Bradycardia, AV block, bronchospasm, masked hypoglycemia
Esmolol
IV, minutes
Acute rate control, perioperative SVT
Hypotension
Hyperkalemia effect
Depolarized myocytes
↑ Class I toxicity
Hypokalemia ↑ class IA/III torsades risk
Na⁺ channel overdose (TCA, cocaine, IC)
Wide QRS
—
Sodium bicarbonate

Mechanism — why lidocaine targets ischemic tissue

Ischemia depolarizes myocytes
→
More Na⁺ channels inactivated
→
IB binds inactivated channels
→
Selective suppression of ectopyNormal tissue spared

Class I subgroups

SUBCLASS
Na⁺ BLOCK
AP DURATION
QRS
IA
Moderate
↑
↑
IB
Weak
↓
—
IC
Strong
—
↑↑

How it's tested

COMMON CONFUSIONIA prolongs QT (K⁺ block too); IC widens QRS without changing QT much; IB barely changes either.
THE TRAPFlecainide after an MI increased deaths (CAST trial) — never give IC drugs with structural heart disease.
YOUR APPROACHLocate the arrhythmia (atrial, ventricular, nodal) → check structural heart disease → choose class → check QT and conduction.

If you see… think…

Tinnitus, headache, diarrhea on an antiarrhythmic → quinidine (cinchonism)
Positive anti-histone antibodies on an antiarrhythmic → procainamide
Ventricular ectopy in acute MI, IV drug → lidocaine
Seizure after IV antiarrhythmic → lidocaine toxicity
AF in a young person with a normal heart, pill in pocket → flecainide or propafenone
Flecainide in post-MI patient → ↑ mortality
Use-dependent block → class I (strongest IC)
Class II effect on ECG → ↑ PR interval
WPW with AF, stable → procainamide (avoid AV nodal blockers)
Wide QRS from Na⁺ channel overdose → sodium bicarbonate