STEPTRACKERPHARMACOLOGY | CARDIOVASCULAR | HIGH-YIELD REVIEW

Antiarrhythmics II — Classes III, IV & Others

Potassium-channel blockers lengthen repolarization; calcium-channel blockers slow the AV node. A few unclassified drugs — adenosine, magnesium, digoxin — fill specific gaps.

FOCUS ON

Class III = K⁺ channel blockers → ↑ AP duration, ↑ ERP, ↑ QT. Amiodarone (also class I, II, IV effects): AF, VT/VF; toxicity — pulmonary fibrosis, hypo- or hyperthyroidism (iodine), hepatotoxicity, corneal deposits, optic neuropathy, blue-gray skin, photosensitivity, bradycardia; huge Vd, long t½; monitor PFTs, TFTs, LFTs; inhibits CYP (↑ warfarin, digoxin). Sotalol (also β-blocker), dofetilide, ibutilide: torsades risk; dronedarone: no iodine, avoid in HF. Torsades is rare with amiodarone despite ↑ QT. Class IV (verapamil, diltiazem): ↓ AV conduction (↑ PR) — SVT, rate control; avoid in WPW and HFrEF. Adenosine: A1 → ↑ K⁺ out, ↓ Ca²⁺ in AV node → terminates AV-nodal reentrant SVT; t½ seconds; flushing, chest pain, dyspnea, sense of doom; blocked by theophylline/caffeine, potentiated by dipyridamole. Magnesium: torsades. Digoxin: rate control.

DRUG

ACTION

USES

TOXICITY · MONITOR

Amiodarone

K⁺ block (plus Na⁺, β, Ca²⁺ effects) → ↑ AP duration, ↑ QT

AF (rhythm or rate), VT, VF arrest

Lungs, thyroid, liver, eyes, skin, nerves · PFTs, TFTs, LFTs

Dronedarone

Amiodarone analog without iodine

AF maintenance

Contraindicated in HF (↑ mortality), permanent AF

Sotalol

K⁺ block + nonselective β-block

AF, ventricular arrhythmias

Torsades (dose by renal function), bradycardia

Dofetilide · ibutilide

Pure IKr block

AF/flutter conversion and maintenance

Torsades — start in hospital with QT monitoring

Verapamil · diltiazem

L-type Ca²⁺ block in SA and AV nodes → ↓ phase 0 and 4 there, ↑ PR

SVT, AF/flutter rate control, angina, HTN

Bradycardia, AV block, constipation, HF worsening; ↑ digoxin level

Adenosine

A1 (Gi) in AV node → K⁺ efflux, hyperpolarization

Terminate AVNRT/AVRT; unmask flutter waves

Flushing, chest tightness, bronchospasm, brief asystole

Magnesium sulfate

Stabilizes membrane; blocks Ca²⁺ currents

Torsades de pointes, digoxin toxicity arrhythmias

Hypotension, ↓ reflexes

Digoxin

↑ Vagal tone → slows AV node

AF rate control in HF

Toxicity: atrial tachycardia with block, bidirectional VT

Atropine

M2 block

Symptomatic sinus bradycardia, nodal block

Ineffective in infranodal block → pace

Ivabradine

If block in SA node

Inappropriate sinus tachycardia, HF

Phosphenes

Torsades triggers

Class IA, III, macrolides, fluoroquinolones, antipsychotics, methadone, ondansetron, TCAs

Worse with ↓ K⁺, ↓ Mg²⁺, bradycardia, female sex

Treat: IV Mg²⁺, correct K⁺, overdrive pacing or isoproterenol

Picture it — where each class acts on the action potential

Ventricular myocytePhase 0 is the Na⁺ upstroke that class I drugs slow; the plateau is held by Ca²⁺ entry; phase 3 repolarization by K⁺ efflux is lengthened by class III drugs, which shows as a longer QT.

SA and AV nodal cellNo fast Na⁺ upstroke: phase 0 is carried by Ca²⁺ (slowed by class IV). The spontaneous phase 4 rise (funny current) is flattened by β-blockers and ivabradine; adenosine hyperpolarizes the cell through K⁺ efflux.

Schematic diagrams, not to scale.

Mechanism — adenosine at the AV node

Adenosine → A1 receptor

→

↑ K⁺ efflux, ↓ Ca²⁺ entry

→

Transient AV block

→

Reentry circuit through AV node breaks

Give as a rapid IV push near the heart — red cells and endothelium clear it in seconds.

The four classes

CLASS

TARGET

ECG

Na⁺ channel

↑ QRS (IA/IC)

β receptor

↑ PR

III

K⁺ channel

↑ QT

Ca²⁺ channel (nodes)

↑ PR

How it's tested

COMMON CONFUSIONAmiodarone causes either hypothyroidism (Wolff-Chaikoff) or hyperthyroidism (Jod-Basedow or thyroiditis) — check TFTs before and during.

THE TRAPIn WPW with AF, AV nodal blockers (adenosine, verapamil, digoxin, β-blockers) push impulses down the accessory pathway → VF. Use procainamide or cardioversion.

YOUR APPROACHRegular narrow-complex tachycardia → vagal maneuver → adenosine. Rate control → β-blocker/CCB. Rhythm control → depends on structural disease.

If you see… think…

Pulmonary fibrosis, thyroid change, blue-gray skin → amiodarone

Sense of impending doom, flushing, brief asystole → adenosine

Adenosine less effective in a coffee drinker → caffeine blocks adenosine receptors

Polymorphic VT with long QT → IV magnesium

Antiarrhythmic causing constipation → verapamil

β-blocker that also prolongs QT → sotalol

Amiodarone analog contraindicated in HF → dronedarone

WPW with AF, hemodynamically stable → procainamide (not nodal blockers)

INR rises after amiodarone started → CYP2C9 inhibition

Class with greatest PR prolongation → II and IV