Antiarrhythmic drugs

Last updated: January 31, 2025

Summary

Antiarrhythmic drugs are used to prevent recurrent arrhythmias and restore sinus rhythm in patients with cardiac arrhythmias. These drugs are classified based on their electrophysiological effect on the myocardium. Antiarrhythmic drugs do not improve the survival of patients with non-life-threatening arrhythmias and may increase mortality, particularly in patients with structural heart disease. They are associated with severe adverse effects, primarily due to their proarrhythmic effects on the myocardium. Patients who have received an intravenous antiarrhythmic should be monitored closely with serial ECGs. Several classes of antiarrhythmics, including beta blockers, calcium channel blockers, amiodarone, cardiac glycosides, and lidocaine, also have other medical uses, which are discussed in their respective articles.

Overview

Classes of antiarrhythmic drugs ^[1]^[2]
Class		Drug group	Mechanism of action		Examples	Use	Adverse effects
Class I antiarrhythmics	Class IA antiarrhythmics	Fast sodium channel blockers	Reduce or even block conduction (negative dromotropy), particularly in depolarized tissue (e.g., during tachycardia) State-dependent: the faster the heart rate (e.g., tachycardia), the greater the effect Shorter diastole Sodium channels spend less time in resting state Decreases the slope of phase 0 depolarization Stabilize membrane Categorized into 3 subgroups based upon their effects on the Na⁺ channel and the action potential (AP) duration	Moderate blockage of Na⁺ channels (intermediate association/dissociation) Prolong action potential (AP) duration (right shift) Slow conduction velocity Prolong effective refractory period (ERP) in ventricular APs Weak blockade of the K⁺ channel	Quinidine Procainamide Disopyramide Ajmaline	Paroxysmal supraventricular tachycardia (PSVT): AVNRT and AVRT Ectopic SVTs Antidromic AVRT and WPW (procainamide) Atrial fibrillation (AFib) and atrial flutter Ventricular arrhythmias	QT prolongation → torsade de pointes (TdP) Cinchonism: headache, hearing/vision loss, tinnitus, psychosis and cognitive impairment, associated with quinidine use Thrombocytopenia Procainamide Drug-induced lupus erythematosus (reversible) Drug fever Disopyramide Heart failure Anticholinergic effects
	Class IB antiarrhythmics			Weak blockade of Na⁺ channels (fast association/dissociation) Shorten AP duration Slow conduction velocity No effect on or slight prolongation of ERP Strongest effect on ischemic or depolarized cardiac Purkinje cells and ventricular myocardium	Lidocaine Mexiletine Phenytoin	Ventricular arrhythmias (especially following myocardial infarction) Digitalis-induced cardiac arrhythmias	CNS: possible depression or excitation Dizziness, nausea Seizures Cardiovascular: AV conduction block, ventricular extrasystoles
	Class IC antiarrhythmics			Strong blockage of Na⁺ channels (slow association/dissociation) → QRS prolongation No to minimal effect on AP duration (no shift) Slow conduction velocity Extend duration of effective refractory period in both AV node and accessory tracts ERP unaffected in cardiac Purkinje cells and ventricular myocardium	Flecainide Propafenone	PSVT AFib (cardioversion) Atrial flutter Last resort in refractory VT	Proarrhythmogenic: contraindicated following myocardial infarction Possible QT prolongation due to increased QRS duration ^[3]
Class II antiarrhythmic drugs		Beta blockers	Inhibit β-adrenergic activation of adenylate cyclase → ↓ cAMP → ↓ Ca²⁺ → ↓ SA node and AV node activity Prolong AV node repolarization (AV node is highly sensitive to beta blockers) → prolongation of PR interval Decrease slope of phase 4 in cardiac pacemaker cells → suppression of aberrant pacemakers Slow conduction velocity		Metoprolol Esmolol (short acting) Propranolol Atenolol Timolol Carvedilol Sotalol	AFib (rate control) Atrial flutter PSVT Premature ventricular contractions Ventricular arrhythmias Atrial premature beats ^[4]	AV block, bradycardia, heart failure Exacerbation of asthma, COPD Sedation, CNS depression, sleep alterations Impotence Hypoglycemia (can mask symptoms of hypoglycemia) Hyperkalemia Dyslipidemia (metoprolol) Propanolol: may intensify vasospams in patients with preexisting vasospastic angina Avoid in patients with concurrent cocaine use or pheochromocytoma. Unopposed α₁agonism → ↑ blood pressure, coronary and systemic vasoconstriction Except for labetalol and carvedilol, which are nonselective α- and β-antagonists
Class III antiarrhythmic drugs		Potassium channel blockers	Inhibit delayed rectifier potassium currents Prolong QT interval Prolong AP duration (reverse use dependence) and ERP No effect on conduction velocity		Amiodarone (has class I, II, III, and IV properties; lipophilic) Dronedarone Sotalol Bretylium Ibutilide Dofetilide	AFib (cardioversion and rhythm control) Atrial flutter Sotalol and amiodarone can be used to treat: Supraventricular arrhythmias Ventricular arrhythmias, e.g., tachycardia	QT prolongation → TdP Amiodarone Cardiovascular May cause heart failure, heart block, bradycardia, hypotension Lowest risk of ventricular arrhythmia compared to other drugs in its class ^[5] Pulmonary fibrosis Thyroid dysfunction (hypo- or hyperthyroidism) due to high iodine content Liver dysfunction Neurologic side effects (e.g., peripheral neuropathy) Can act as a hapten → bluish-gray deposits in cornea and skin → photosensitivity → photodermatitis Constipation Sotalol: see “Beta blocker adverse effects”
Class IV antiarrhythmic drugs		Calcium channel blockers	Inhibit slow calcium channels Decrease slope of phase 0 and 4 → slower conduction velocity → increased ERP Prolong AV node repolarization Prolong PR interval		Verapamil Diltiazem Nifedipine	AFib (rate control) Atrial flutter Prophylaxis of nodal arrhythmias, e.g., PSVT Multifocal atrial tachycardia Hypertension (nifedipine)	Verapamil AV block Bradycardia Depression of sinus node Heart failure Constipation Flushing Edema Nifedipine Headache Flushing Pitting edema Reflex tachycardia Diltiazem: adverse effects similar to those of both verapamil and nifedipine, but less prominent
Class V antiarrhythmic drugs		Variable mechanisms	Activates G_i protein → ↓ cAMP → deactivation of L-type Ca²⁺ channels → ↓ Ca²⁺ and ↑ K⁺ efflux → transient AV node block Very short acting (∼ 15 sec)		Adenosine (drug)	Diagnosis and termination of certain forms of PSVT (e.g., AVNRT and orthodromic AVRT)	Chest pain Flushing Hypotension Bronchospasm Sense of impending doom Effect weakened by adenosine receptor antagonists (e.g., theophylline, caffeine)
			Decreases calcium influx → prevents early afterdepolarizations (EADs)		Magnesium sulfate	TdP Digoxin toxicity	Hypotension Asystole Drowsiness Flushing Loss of reflexes Respiratory depression
			Inhibits Na⁺/K⁺-ATPases → higher intracellular Na⁺ concentration → reduced efficacy of Na⁺/Ca²⁺ exchangers → higher intracellular Ca²⁺ concentration → increased contractility and decreased heart rate		Digoxin	AFib Atrial flutter Chronic systolic heart failure	Nausea, vomiting Abdominal pain Blurry vision with a yellow tint and halos
			Selectively inhibits I_fchannel in the pacemaker cells of the SA node → prolongs slow depolarization (phase 4) → slows heart rate		Ivabradine	Chronic stable coronary heart disease in patients who cannot tolerate beta blockers Chronic HFrEF	Vision changes: luminous phenomena (enhanced visual brightness) Bradycardia Hypertension

All antiarrhythmic drugs are also potentially proarrhythmic! Intravenous administration should only be performed with continuous cardiac monitoring!

“I am Ambivalent about the QUEEn PROofreading my DISsertation”: Class IA antiarrhythmic drugs are QUEEnidine, PROcainamide, DISopyramide.
“LInDO MEXIco Is the Best”: LIDOcaine and MEXIletine are class IB antiarrhythmic drugs.
“I Can't Fail, Please”: Class IC antiarrhythmics are Flecainide, Propafenone.
“I Am Sober, Doctor, for III days”: Ibutilide, Amiodarone, Sotalol, and Dofetilide are class III antiarrhythmic drugs.

Diltiazem and Verapamil Diminish conduction Velocity.

Class IB antiarrhythmic drugs work Best after myocardial infarction; class IC antiarrhythmic drugs are Contraindicated.

Overview of antiarrhythmic drug classes Cardiac action potentials Action potentials of pacemaker cells in the sinus node Action potential and ion flux in myocardial contractile cells

References:^[6]^[7]^[8]

Other antiarrhythmic drugs

Adenosine (drug) ^[1]

Mechanism of action: activates G_i protein → inhibition of adenylate cyclase → ↓ cAMP → deactivation of L-type Ca²⁺ channels and activation of K⁺ channels → ↓ Ca²⁺ and ↑ K⁺ efflux → hyperpolarization → transient AV node block (short-acting, ∼ 15 seconds) → acute termination of supraventricular tachycardia
Indications
- Diagnosis and termination of certain forms of paroxysmal supraventricular tachycardias; (e.g., AVNRT and orthodromic AVRT) ^[9]
- Diagnosis of underlying AFib in supraventricular tachyarrhythmias
- Pharmacological stress test in myocardial perfusion scintigraphy ^[10]
Administration
- Rapid bolus IV (very short half-life: < 10 seconds) ^[11]
- May be administered repeatedly if the previous dose was unsuccessful
Adverse effects ^[12]
- Chest pain, flushing, hypotension, bronchospasm
- Sense of impending doom
- AV block, asystole
Contraindications to adenosine
- Pre-excitation syndromes: antidromic AVRT, WPW
- AV block
- Asthma
Interactions: Theophylline and caffeine weaken the effects of adenosine because they are adenosine receptor antagonists.

Avoid adenosine in patients with suspected pre-excitation tachycardia (e.g., WPW), because it may exacerbate the tachycardia via accessory pathway routes.

Digoxin

Mechanism of action: inhibits Na⁺/K⁺-ATPases → higher intracellular Na⁺ concentration → reduced efficacy of Na⁺/Ca²⁺ exchangers → higher intracellular Ca²⁺ concentration → increased contractility, decreased heart rate
Indications
- AFib
- Atrial flutter
- Chronic systolic heart failure
Adverse effects: See “Cardiac glycoside poisoning”.

Magnesium sulfate ^[1]^[13]

Mechanism of action: decreases calcium influx → prevents early afterdepolarizations (EADs)
Indications
- Torsade-de-pointes
- Refractory ventricular tachyarrhythmias (e.g., polymorphic VT)
- Digoxin intoxication
- Eclampsia
- Constipation
- Tocolysis
Adverse effects
- Hypotension
- Asystole
- Drowsiness
- Flush
- Loss of reflexes
- Respiratory depression

Ivabradine ^[14]

Mechanism of action: selectively inhibits I_fchannel in the pacemaker cells of the SA node → prolongs slow depolarization (phase 4) → slows heart rate
Indications: symptomatic stable coronary heart disease and congestive heart failure (NYHA II-IV) in patients who cannot tolerate beta blockers
Adverse effects
- Vision changes: luminous phenomena (enhanced visual brightness)
- Bradycardia
- Hypertension

IVabradine slows depolarization in phase IV.

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