Antiarrhythmic drugs
The drugs that slow a fast heart, restore sinus rhythm or prevent attacks, from flecainide and amiodarone to adenosine and digoxin; how each class changes the cardiac action potential, which drug suits which arrhythmia and which heart, and why every one of them can also cause arrhythmias.
- 12 min read
- 5 questions
- Checked 26 Oct 2026
Contents6 sections
At a glance
- Antiarrhythmic drugs act on the ion channels of heart cells, or on the autonomic nerves to the heart, to slow the rate, restore sinus rhythm or prevent attacks.
- The Vaughan Williams classes are I, sodium channel blockers; II, beta-blockers; III, potassium channel blockers that prolong the action potential; and IV, calcium channel blockers. Adenosine, digoxin, magnesium and atropine stand outside them.
- Every antiarrhythmic drug can also cause arrhythmias: class Ic drugs in a scarred heart, and class Ia and III drugs through a long QT interval and torsades de pointes.
- Apart from beta-blockers, they relieve symptoms but do not prolong life, so the choice rests on safety: class Ic drugs only for a structurally normal heart, amiodarone when the heart is diseased.
- Amiodarone works in most arrhythmias but harms the thyroid, lungs, liver, skin, eyes and nerves, so it needs monitoring.
- Digoxin toxicity is brought on by low potassium, kidney impairment and interacting drugs, and causes nausea, disturbed vision, confusion and almost any arrhythmia.
Definition and overview
Antiarrhythmic drugs treat the tachycardias and some bradycardias described in supraventricular arrhythmias, ventricular arrhythmias and conduction disturbances. They are grouped by their main effect on the cardiac action potential, the Vaughan Williams classification:
| Class | Drugs | Main action | ECG effect | Main uses |
|---|---|---|---|---|
| Ia | quinidine, procainamide, disopyramide | moderate sodium channel block, and potassium channel block | wider QRS, longer QT | pre-excited atrial fibrillation (procainamide), Brugada syndrome (quinidine); now rarely used |
| Ib | lidocaine, mexiletine | weak sodium channel block, mainly in depolarised, ischaemic tissue | little change | ventricular tachycardia in ischaemia, long QT type 3 (mexiletine) |
| Ic | flecainide, propafenone | strong sodium channel block, slowing conduction | wider QRS, longer PR | atrial fibrillation and supraventricular tachycardia in a normal heart, catecholaminergic ventricular tachycardia |
| II | beta-blockers: bisoprolol, metoprolol, propranolol, nadolol, esmolol | block the effect of adrenaline and noradrenaline on the nodes and the ventricles | slower rate, longer PR | rate control, prevention of supraventricular and ventricular tachycardia, long QT syndrome, after myocardial infarction |
| III | amiodarone, dronedarone, sotalol, dofetilide, ibutilide | block potassium channels, prolonging repolarisation and the refractory period | longer QT | atrial fibrillation and flutter, ventricular tachycardia |
| IV | verapamil and diltiazem | block L-type calcium channels in the sinus and atrioventricular nodes | slower rate, longer PR | ending and preventing supraventricular tachycardia, rate control, fascicular ventricular tachycardia |
| Other | adenosine, digoxin, magnesium, atropine, vernakalant, ivabradine | see below |
Many drugs have actions of more than one class: amiodarone has all four, sotalol is a beta-blocker as well as a class III drug, and propafenone also blocks beta-receptors. A modernised classification adds classes for newer targets, such as class 0 for ivabradine, which blocks the funny current of the sinus node, but the four classic classes remain the teaching framework.
Etiology and pathophysiology
The action potential and where each class acts
- 1
Phase 4, diastolic depolarisation
In the sinus and atrioventricular nodes the membrane drifts up towards threshold through the funny current and calcium channels; this sets the heart rate. Beta-blockers, calcium channel blockers and ivabradine slow it, and adrenaline speeds it. - 2
Phase 0, the upstroke
In atrial and ventricular muscle and the conduction fibres, sodium channels open and depolarise the cell fast, which sets the speed of conduction. Class I drugs block them. In the nodes the upstroke depends on calcium, which is why verapamil and diltiazem slow conduction through the atrioventricular node. - 3
Phase 2, the plateau
Calcium entry holds the cell depolarised and triggers contraction. Class IV drugs reduce it, which also weakens contraction. - 4
Phase 3, repolarisation
Potassium currents return the cell to rest. Class III drugs block them, prolonging the action potential, the refractory period and the QT interval.
Re-entry, the mechanism of most tachycardias, needs a circuit in which the impulse always finds tissue that has recovered. Drugs break it either by slowing conduction until the impulse blocks (class I) or by prolonging the refractory period so the impulse meets refractory tissue (class III). Drugs that slow the atrioventricular node end tachycardias that use the node: adenosine for a few seconds, which also unmasks flutter waves, and classes II and IV for longer. Classes II and IV and digoxin also slow the ventricular response to atrial fibrillation and flutter.
Class Ic drugs bind more at fast rates (use dependence), so their effect, and their toxicity, grow during exercise and tachycardia.
Proarrhythmia
The same effects that stop one arrhythmia can start another:
- Slowed conduction by class I drugs creates new re-entry in scarred ventricles, causing ventricular tachycardia that is hard to stop. This is why they increased deaths after myocardial infarction.
- Flecainide and propafenone can slow atrial flutter enough for the atrioventricular node to conduct every wave, giving a ventricular rate near 200 or more. They are therefore given with a beta-blocker or a rate-limiting calcium channel blocker.
- Prolonged repolarisation by class Ia and III drugs allows early afterdepolarisations and torsades de pointes, especially with bradycardia, low potassium or magnesium, kidney impairment, female sex and other QT-prolonging drugs. Amiodarone prolongs the QT but rarely causes torsades.
- Drugs that slow the nodes cause bradycardia and heart block, and in pre-excited atrial fibrillation they can speed conduction over the accessory pathway.
- Class I drugs (especially disopyramide and flecainide), class IV drugs and some class III drugs (dronedarone) weaken contraction and can worsen heart failure.
Clinical features
Adverse effects
| Drug | Main adverse effects | Interactions and cautions |
|---|---|---|
| Flecainide, propafenone | ventricular tachycardia in structural heart disease, 1:1 atrial flutter, dizziness, blurred vision; propafenone also a metallic taste and bronchospasm | avoided with coronary disease, heart failure or significant hypertrophy, Brugada syndrome, and severe kidney impairment for flecainide; not used alone to convert flutter; QRS widening of more than about a quarter means a lower dose |
| Lidocaine | confusion, paraesthesia around the mouth, seizures at high levels | lower doses in heart and liver failure |
| Beta-blockers | fatigue, bradycardia, cold extremities, bronchospasm, erectile dysfunction | asthma; not combined with intravenous verapamil |
| Amiodarone | hypo- and hyperthyroidism, lung inflammation and fibrosis, liver injury, photosensitivity and a blue-grey skin, corneal microdeposits, rarely optic neuropathy, peripheral neuropathy, bradycardia; phlebitis when given into a peripheral vein | raises the levels of warfarin, digoxin, some statins and some direct anticoagulants, so their doses are reduced; severe bradycardia with sofosbuvir-based hepatitis C treatment; not intravenously in pre-excited atrial fibrillation; very long half-life, about 50 days |
| Dronedarone | gastrointestinal upset, liver injury, raised creatinine | avoided in heart failure with a reduced ejection fraction or recent decompensation, and in permanent atrial fibrillation, where it increased deaths and events; the European licence excludes any current or past heart failure or left ventricular dysfunction; not with dabigatran, strong CYP3A4 inhibitors, other QT-prolonging drugs, a QTc of 500 ms or more or severe kidney impairment; it raises digoxin levels |
| Sotalol | torsades de pointes, bradycardia, the effects of a beta-blocker | cleared by the kidney; dose lowered or avoided in kidney impairment and with a long QT |
| Verapamil, diltiazem | bradycardia, heart block, hypotension, worsening heart failure, constipation (verapamil), ankle oedema | avoided with a reduced ejection fraction, in pre-excited atrial fibrillation and in ventricular tachycardia; raise digoxin levels |
| Digoxin | toxicity: nausea, vomiting, confusion, yellow-green vision, and arrhythmias | toxicity more likely with kidney impairment, low potassium or magnesium, high calcium, old age, amiodarone, verapamil and some macrolides |
| Adenosine | flushing, chest tightness, breathlessness, a sense of doom, all lasting seconds; bronchospasm; transient atrial fibrillation in up to about 1 in 10, dangerous with an accessory pathway | avoided in asthma and bronchospastic lung disease, second- or third-degree block or sick sinus syndrome without a pacemaker, and long QT; not with dipyridamole, which increases its effect, as does a transplanted heart; its effect is reduced by theophylline and caffeine |
Digoxin toxicity
Digoxin toxicity causes nausea, loss of appetite, vomiting, confusion, blurred or yellow-green vision, and arrhythmias: ventricular ectopics and bigeminy, atrial tachycardia with block, junctional rhythms, atrioventricular block and, in severe cases, ventricular tachycardia, including the bidirectional form. The sagging ST depression on the ECG, the reverse tick, shows that the patient takes digoxin, not that it is toxic. Treatment is to stop digoxin, correct potassium and magnesium, and give digoxin-specific antibody fragments for life-threatening arrhythmias, severe hyperkalaemia or very high levels.
Diagnosis and management
Choosing a drug
| Situation | Drugs |
|---|---|
| Rate control in atrial fibrillation or flutter | a beta-blocker, diltiazem or verapamil (ejection fraction above 40 per cent), digoxin, alone or combined; amiodarone in the critically ill |
| Rhythm control in atrial fibrillation | flecainide or propafenone in a heart without significant structural disease; dronedarone; sotalol with QT monitoring; amiodarone in heart failure with a reduced ejection fraction |
| Drug cardioversion of recent atrial fibrillation | intravenous flecainide or propafenone; vernakalant, an atrial-selective blocker of potassium and sodium channels, not given with a systolic pressure below 100 mmHg, an acute coronary syndrome within a month, severe heart failure, a long QT or severe aortic stenosis; or amiodarone when there is structural heart disease; a single oral dose of flecainide or propafenone carried by the patient (the pill in the pocket) |
| Ending a regular narrow-complex tachycardia | after vagal manoeuvres, adenosine; verapamil or diltiazem; a beta-blocker; synchronised cardioversion if unstable |
| Preventing paroxysmal supraventricular tachycardia | a beta-blocker, verapamil or diltiazem; flecainide or propafenone in a normal heart |
| Pre-excited atrial fibrillation | ibutilide, procainamide or flecainide; no adenosine, verapamil, diltiazem, beta-blockers, digoxin or intravenous amiodarone |
| Ventricular tachycardia, acute | amiodarone, procainamide, lidocaine; a beta-blocker or verapamil in idiopathic types |
| Preventing ventricular tachycardia | a beta-blocker, amiodarone, sotalol; usually alongside a defibrillator |
| Torsades de pointes | magnesium sulfate |
| Symptomatic bradycardia | atropine, then isoprenaline or adrenaline as a bridge to pacing |
| Long QT syndrome and catecholaminergic ventricular tachycardia | nadolol or propranolol; flecainide added in catecholaminergic tachycardia, mexiletine in long QT type 3 |
The safety of the drug in that heart decides the choice more than its strength. In a structurally normal heart the risk of proarrhythmia is low and class Ic drugs are effective. In heart failure with a reduced ejection fraction, amiodarone is the drug; in coronary or valvular disease or a mildly reduced ejection fraction, amiodarone or dronedarone; sotalol only in selected patients with close QT monitoring. For many arrhythmias, catheter ablation is more effective than any drug and is offered early.
Doses of the most used drugs
| Drug | Typical use and dose |
|---|---|
| Adenosine | 6 mg as a rapid intravenous bolus with a saline flush, then 12 mg, then 18 mg if needed |
| Amiodarone | intravenously 300 mg over 20 to 60 minutes, then 900 mg over 24 hours, through a central vein when possible; in cardiac arrest 300 mg as a bolus. Orally 200 mg three times daily for a week, twice daily for a week, then 200 mg daily or less |
| Flecainide | 50 to 150 mg twice daily by mouth; intravenously 2 mg/kg over 10 minutes; pill in the pocket 200 mg, or 300 mg over 70 kg |
| Verapamil | 5 to 10 mg intravenously over 2 to 3 minutes |
| Digoxin | a loading dose over 24 hours for rapid rate control, then usually 62.5 to 250 micrograms daily, lower in older people and kidney impairment |
| Atropine | 0.5 to 1 mg intravenously, repeated to a maximum of 3 mg |
| Magnesium sulfate | 2 g (8 mmol) intravenously over 10 to 15 minutes |
Doses vary with the patient, the kidney function and local guidance, so they are checked against a formulary before prescribing.
Rules for safe use
- The arrhythmia is documented on an ECG before a drug is started, and reversible causes are treated first: thyrotoxicosis, electrolytes, ischaemia, alcohol.
- One drug at a time where possible, at the lowest effective dose.
- Drugs that slow the node are not combined carelessly: intravenous verapamil after an intravenous beta-blocker can cause asystole.
- Interactions are checked, especially with warfarin, digoxin and other QT-prolonging drugs.
- Patients taking an antiarrhythmic drug for atrial fibrillation still need anticoagulation according to their stroke risk.
Epidemiology
Beta-blockers are by far the most widely used drugs with an antiarrhythmic action, because they are also given for hypertension, angina, heart failure and after infarction. Of the specific antiarrhythmic drugs, amiodarone remains widely used despite its toxicity. Use of the others has fallen as catheter ablation has grown. Drugs are the commonest cause of an acquired long QT interval. Thyroid problems develop in about 15 to 20 per cent of patients on long-term amiodarone, hypothyroidism more often in iodine-replete regions and hyperthyroidism in iodine-deficient ones, and lung toxicity in a few per cent. Digoxin toxicity is mainly a problem of older people with declining kidney function.
Prognosis
Large trials have shaped how these drugs are used. Flecainide and encainide, given after myocardial infarction to suppress ventricular ectopics, more than doubled deaths compared with placebo (about 8 against 3.5 per cent). In heart failure, amiodarone did not improve survival, while a defibrillator did. Dronedarone reduced the combination of cardiovascular admission or death in patients with paroxysmal or persistent atrial fibrillation, mainly through fewer admissions, without a clear effect on overall deaths, but increased deaths in severe heart failure and cardiovascular events in permanent atrial fibrillation. Digoxin reduced heart failure admissions but not deaths. Beta-blockers are the exception: they reduce deaths after myocardial infarction and in heart failure.
So, apart from beta-blockers, antiarrhythmic drugs relieve symptoms and prevent recurrences but do not prolong life, and a defibrillator, not a drug, protects against sudden death. Most adverse effects resolve when the drug is stopped, but amiodarone lung toxicity can be fatal, and its effects persist for months because of its long half-life.
Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.
1Flecainide is being considered to keep sinus rhythm in four patients with paroxysmal atrial fibrillation. In which patient must it not be used?
2A patient is starting long-term amiodarone. Which monitoring is needed?
3An 84-year-old taking digoxin and furosemide has nausea, confusion and yellow-tinged vision. Her potassium is 2.9 mmol/L and her creatinine has risen. What is the most likely explanation?
4Three days after starting sotalol for atrial fibrillation, a patient's QTc is 540 ms. What should be done?
5Which pair of drugs belongs to class III, which prolong the action potential by blocking potassium channels?
Linked topicsThe concepts this topic shares, and the topics they tie it to.
See on the mapCardiac conduction
The same drug classes seen from the bedside: which to choose for which rhythm.
- The resting membrane potentialPhysiologyNot written yetThe ion gradients and channels behind every cardiac action potential.
- Antiarrhythmic drugsPharmacologyNot written yetGrouped by what they block: sodium channels (I), β-receptors (II), potassium channels (III), calcium channels (IV).
- Calcium channel blockersPharmacologyNot written yetVerapamil and diltiazem slow conduction through the AV node; the dihydropyridines hardly do.
- Drugs for the treatment of heart failurePharmacologyNot written yetDigoxin slows conduction through the AV node.
- Local anaestheticsPharmacologyNot written yetLidocaine, a local anaesthetic, is also a class Ib antiarrhythmic: both effects come from blocking sodium channels.
- Conductive disturbances. Treatment of conductive disturbancesCardiovascular diseasesSinoatrial and AV blocks slow or drop beats; a single bundle branch block widens the QRS instead.
- Rhythm abnormalities: supraventricular arrhythmiasCardiovascular diseasesFast rhythms that start above the ventricles, such as atrial fibrillation.
- Rhythm abnormalities: ventricular arrhythmiasCardiovascular diseasesFast rhythms from the ventricles, which can turn into ventricular fibrillation.