Antiarrhythmics by Vaughan-Williams class
Verified · Oct 2026Each Vaughan-Williams class blocks a different current of the cardiac action potential, so each moves a different part of the ECG and carries a different signature toxicity. This page lines them up across the four class pages that hold them.
Where each class acts on the action potential
In a ventricular myocyte, phase 0 is the upstroke through voltage-gated sodium channels, phase 2 is the plateau of potassium leaving against calcium entering, and phase 3 is repolarization by outward potassium current. Pacemaker cells instead drift upward in phase 4 and fire with a calcium-driven phase 0.
The classes map onto those currents. Class I drugs block sodium channels and lower the phase 0 slope; class II β-blockers lower cAMP and slow SA-node pacing; class III potassium-channel blockers delay phase 3 repolarization and lengthen the refractory period; class IV calcium-channel blockers slow SA-node pacing and AV-node conduction and lengthen the PR interval.
Several drugs do not fit one box. Amiodarone has properties of all four classes, sotalol has class II and class III actions, and adenosine and digoxin slow AV-node conduction through other mechanisms.
Comparison
The classes compared
| Class | Target | Action potential and ECG | Key drugs | Signature toxicity | Key interaction |
|---|---|---|---|---|---|
| Class Ia | Fast Na⁺ channels — moderate block | Slower phase 0, longer action potential; wider QRS, longer QTc | Quinidine, procainamide, disopyramide | Torsades (the most QT-prolonging Na⁺ blockers); procainamide lupus-like syndrome, quinidine cinchonism, disopyramide anticholinergic effects | Quinidine slows digoxin elimination (levels up to doubled) and inhibits CYP2D6 |
| Class Ib | Fast Na⁺ channels — weakest block | Shorter action potential; little QRS or QT change | Lidocaine, mexiletine | Lidocaine CNS toxicity (seizures); mexiletine GI distress and tremor | β-blockers raise lidocaine levels by lowering hepatic blood flow |
| Class Ic | Fast Na⁺ channels — strongest block | Much slower phase 0, duration unchanged; wider QRS, little QT change | Flecainide, propafenone | Proarrhythmia — more deaths after MI in CAST; flecainide can turn AF into flutter with 1:1 conduction | Flecainide is given with a β-blocker or calcium-channel blocker |
| Class II | β-adrenergic receptors (↓ cAMP) | Slower SA-node pacing; longer AV refractory period and PR interval | β-blockers; sotalol has class II and III actions | Severe bradycardia, AV block; bronchospasm in asthma | With verapamil or diltiazem: additive slowing of rate and AV conduction, including reports of complete heart block |
| Class III | K⁺ channels (IKr for dofetilide, ibutilide, sotalol) | Longer phase 3 and refractory period; longer QT | Amiodarone, sotalol, dofetilide | Torsades de pointes (sotalol worst at slow rates); amiodarone pulmonary, hepatic and thyroid toxicity | Amiodarone raises digoxin levels and potentiates warfarin |
| Class IV | L-type Ca²⁺ channels | Lower slope of nodal phases 0 and 4; slower AV-node conduction; longer PR | Verapamil, diltiazem | Bradycardia, AV block, severe hypotension; constipation | Chronic verapamil raises digoxin levels; additive AV effects with β-blockers |
| Adenosine | Adenosine receptors in the AV node | Slower AV-node conduction; interrupts AV-node re-entry | Adenosine (half-life under 10 seconds) | Short-lasting heart block, up to third-degree | Antagonized by methylxanthines (caffeine, theophylline); potentiated by dipyridamole |
| Digoxin | Na⁺/K⁺-ATPase inhibition plus indirect parasympathetic stimulation | Slower SA- and AV-node conduction; longer AV refractory period | Digoxin | Almost any arrhythmia at toxic levels; nausea, vomiting, yellow-green vision; worse with hypokalemia | Amiodarone, verapamil and quinidine raise digoxin levels (P-glycoprotein) |
IV magnesium, which is not one of the four classes, is the first-line drug for torsades de pointes (its exact mechanism is unknown). Amiodarone shows properties of all four classes.
High-yield
Practice questions
Q1A 70-year-old woman with atrial fibrillation takes digoxin for rate control. Another drug is added for better rate control. Ten days later she has nausea, vomiting and yellow-tinted vision, and her digoxin level is high. The added drug lengthens her PR interval by slowing AV-node conduction through L-type calcium channels.
Which drug was most likely added?
- A.Verapamil
- B.Metoprolol
- C.Dofetilide
- D.Adenosine
- E.Flecainide
Show answer
A. Verapamil — Verapamil is a class IV L-type calcium-channel blocker that slows SA-node pacing and AV-node conduction and lengthens the PR interval. Chronic verapamil can raise serum digoxin levels by 50% to 75% in the first week and cause digitalis toxicity; nausea, vomiting and yellow or green-tinted vision are typical of digoxin toxicity. Metoprolol slows AV conduction through β-receptors, not calcium channels; dofetilide blocks the rapid potassium current (IKr), and flecainide is a class Ic sodium-channel blocker.
Q2A 28-year-old man with recurrent paroxysmal supraventricular tachycardia drinks large amounts of coffee and takes theophylline for asthma. A rapid IV push of a drug that slows AV-node conduction fails to end his tachycardia at the usual dose.
What best explains the poor response?
- A.Theophylline induces the metabolism of the drug
- B.The drug has a half-life of several hours
- C.Caffeine blocks AV-node sodium channels
- D.Methylxanthines competitively antagonize adenosine
- E.The tachycardia is atrial flutter with 1:1 conduction
Show answer
D. Methylxanthines competitively antagonize adenosine — Adenosine slows conduction through the AV node and can interrupt re-entry there, restoring sinus rhythm in PSVT. It is antagonized competitively by methylxanthines such as caffeine and theophylline. Its half-life is under 10 seconds, which is why it is given as a rapid bolus.
Q3A 66-year-old man starts a drug for atrial fibrillation that also blocks β-receptors. On a night when his heart rate falls to 42/min, he develops a polymorphic ventricular tachycardia with a twisting QRS axis; his QTc is markedly prolonged.
Which mechanism best explains this arrhythmia?
- A.Sodium-channel block that widens the QRS
- B.Na⁺/K⁺-ATPase inhibition causing afterdepolarizations
- C.L-type calcium-channel block in the AV node
- D.Adenosine-receptor activation in the AV node
- E.Potassium-channel block that prolongs repolarization, maximal at slow heart rates
Show answer
E. Potassium-channel block that prolongs repolarization, maximal at slow heart rates — Sotalol has class II and class III actions. Its potassium-channel block prolongs repolarization and the QT interval, and it shows reverse use dependence — the blocking effect is greatest when the heart rate is slow, raising the risk of QT prolongation and torsades de pointes in bradycardia. Inhibiting the delayed rectifier potassium current prolongs repolarization, and an ectopic beat in that window (R-on-T) can trigger torsades. IV magnesium is the first-line drug.
Q4A 58-year-old man had a myocardial infarction 6 months ago and now has frequent asymptomatic premature ventricular contractions. A drug is proposed that markedly blocks sodium channels and widens the QRS without changing the QT interval much.
Why should this class be avoided?
- A.It causes a lupus-like syndrome
- B.It increased death and cardiac arrest after myocardial infarction in CAST
- C.It causes pulmonary fibrosis
- D.It shortens the action potential and is ineffective
- E.It is contraindicated with digoxin
Show answer
B. It increased death and cardiac arrest after myocardial infarction in CAST — This describes class Ic (flecainide, propafenone): marked sodium-channel block with a wider QRS and little QT effect. In CAST, encainide or flecainide after myocardial infarction increased death or cardiac arrest (7.7% vs 3.0% on placebo), and class Ic drugs are contraindicated after myocardial infarction. The lupus-like syndrome belongs to procainamide (Ia) and pulmonary toxicity to amiodarone (III). Class Ic conserves action-potential duration; it is class Ib that reduces it. Digoxin is not a contraindication either: propafenone’s label does not list it among the contraindications, though propafenone may increase digoxin levels.
Sources
- Antiarrhythmic Medications — Vaughan-Williams classes, adenosine — StatPearls (NCBI)
- PACERONE (amiodarone) — toxicities, digoxin and warfarin interactions (FDA label) — FDA / DailyMed
- Cardiac Glycoside and Digoxin Toxicity — arrhythmias, electrolytes, P-glycoprotein interactions — StatPearls (NCBI)
- Quinidine gluconate ER — pharmacokinetics, CYP2D6, digoxin (FDA label) — FDA / DailyMed
- Lidocaine HCl and 5% dextrose injection — CNS toxicity, clearance with β-blockers (FDA label) — FDA / DailyMed
- Verapamil HCl ER — adverse reactions, β-blocker and digoxin interactions (FDA label) — FDA / DailyMed
- Torsade de Pointes — mechanism, magnesium — StatPearls (NCBI)
- Propranolol — bradycardia, AV block, bronchospasm — StatPearls (NCBI)
- Mexiletine — class I subgroups, use dependence — StatPearls (NCBI)
- Sotalol — class II and III actions, reverse use dependence — StatPearls (NCBI)
- Procainamide HCl injection — lupus-like syndrome (FDA label) — FDA / DailyMed
- Adenosine injection — AV-node effects, half-life, methylxanthines, heart block (FDA label) — FDA / DailyMed
- Mexiletine HCl capsules — GI distress, tremor (FDA label) — FDA / DailyMed
- Selective Beta-1 Blockers — AV-nodal refractory period and PR interval — StatPearls (NCBI)
- Digoxin — toxicity signs, interactions — StatPearls (NCBI)
- Propafenone HCl tablets — contraindications, digoxin interaction (FDA label) — FDA / DailyMed
- Flecainide — use-dependent block, 1:1 flutter, toxicity and sodium bicarbonate — StatPearls (NCBI)
- Physiology, Cardiac — myocyte and pacemaker action potentials — StatPearls (NCBI)
- Norpace (disopyramide) — FDA label — FDA / DailyMed
- Beta Blockers — receptor subtypes, selective vs non-selective agents, α1 blockade, CNS effects — StatPearls (NCBI)
- Cardizem (diltiazem) — bioavailability, half-life, desacetyl metabolite (FDA label) — FDA / DailyMed
- Long QT Syndrome — KCNQ1, IKr (KCNH2) block by drugs — StatPearls (NCBI)
- Amiodarone — tissue distribution, thyroid, corneal deposits, pulmonary toxicity — StatPearls (NCBI)
- Calcium Channel Blockers — L-type channels, subclasses, CYP3A4 first pass, overdose management — StatPearls (NCBI)
- Adenosine — rapid IV push with saline flush, very short half-life — StatPearls (NCBI)
- Flecainide acetate tablets — FDA label — FDA / DailyMed
- Lanoxin (digoxin) tablets — mechanism, P-glycoprotein interactions, pharmacokinetics, overdosage (FDA label) — FDA / DailyMed
- Cardiac Glycosides — nursing considerations (apical pulse, potassium) — Open RN — Nursing Pharmacology
- Procainamide — NAPA, lupus, overdose — StatPearls (NCBI)
- Toprol-XL (metoprolol succinate) — clinical pharmacology, CYP2D6, overdosage (FDA label) — FDA / DailyMed
- Open RN Nursing Pharmacology — Ch. 4 Autonomic Nervous System (metoprolol & propranolol: apical pulse < 60 hold, masked hypoglycemia, taper) — Open RN (NCBI Bookshelf)
- BETAPACE / BETAPACE AF (sotalol) — FDA label — FDA / DailyMed
- Digoxin Immune Fab — indications and monitoring — StatPearls (NCBI)
- Metoprolol — mechanism, IV use and ECG monitoring, withdrawal syndrome, contraindications — StatPearls (NCBI)
Each class page compared lists its full sources; this page reuses facts verified there.
By LearnDrugs
Educational summary for medical students. Always verify against current prescribing information and guidelines. Not medical advice.