Mechanism of Action of Antiarrhythmic Drugs

Introduction

Antiarrhythmic drugs are medications used to treat irregular heart rhythms (arrhythmias). These drugs work by modifying the electrical activity of the heart to restore or maintain a normal rhythm.

The heart’s electrical activity is primarily governed by ion channels, which regulate the flow of sodium (Na⁺), potassium (K⁺), and calcium (Ca²⁺) in and out of cardiac cells. Different antiarrhythmic drugs target different ion channels or receptors to modify the heart's rhythm.

Classification of Antiarrhythmic Drugs (Vaughan-Williams Classification)

The most common classification of antiarrhythmic drugs is the Vaughan-Williams classification, which divides these drugs into five major classes:

Class I: Sodium Channel Blockers

• Mechanism: Block sodium (Na⁺) channels, reducing the speed of impulse conduction in the heart.
• Subclasses:
  • Class IA (e.g., quinidine, procainamide, disopyramide) – moderate Na⁺ channel block, prolong repolarization.
  • Class IB (e.g., lidocaine, mexiletine) – weak Na⁺ channel block, shorten repolarization.
  • Class IC (e.g., flecainide, propafenone) – strong Na⁺ channel block, with minimal effect on repolarization.

Class II: Beta-Blockers

• Mechanism: Block beta-adrenergic receptors, reducing the effects of adrenaline on the heart. This slows heart rate and conduction through the AV node.
• Examples: Propranolol, metoprolol, atenolol, esmolol.

Class III: Potassium Channel Blockers

• Mechanism: Block K⁺ channels, prolonging repolarization and increasing the duration of the action potential, which helps stabilize heart rhythms.
• Examples: Amiodarone, sotalol, dofetilide, ibutilide.

Class IV: Calcium Channel Blockers

• Mechanism: Block calcium (Ca²⁺) channels, decreasing AV nodal conduction and reducing heart rate in arrhythmias.
• Examples: Verapamil, diltiazem.

Class V: Miscellaneous Agents

• Mechanism: Include drugs that work through unique mechanisms that do not fit into the Vaughan-Williams classification.
• Examples:
  • Adenosine – Slows conduction through the AV node, commonly used for supraventricular tachycardia.
  • Digoxin – Inhibits the sodium-potassium ATPase pump, increasing intracellular calcium and enhancing parasympathetic tone, which slows heart rate.

Clinical Uses

• Atrial fibrillation (AFib): Commonly treated with Class II (beta-blockers), Class III (amiodarone), or Class IV (calcium channel blockers).
• Ventricular arrhythmias: Often treated with Class I (sodium channel blockers) or Class III (K⁺ channel blockers like amiodarone).
• Supraventricular tachycardia (SVT): Typically treated with adenosine or calcium channel blockers.

Conclusion

Understanding the mechanism of action of antiarrhythmic drugs is essential for their appropriate clinical use. These medications influence cardiac ion channels and autonomic receptors to help restore normal heart rhythm.

Source recommendations

1. European Society of Cardiology Guidelines on the management of atrial fibrillation

1. https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Atrial-Fibrillation
2. https://academic.oup.com/eurheartj/article/45/36/3314/7738779
3. https://www.escardio.org/static-file/Escardio/Guidelines/Documents/ehaa612.pdf
4. https://academic.oup.com/eurheartj/article/42/5/373/5899003
5. https://pubmed.ncbi.nlm.nih.gov/32860505/

2. American Heart Association Guidelines for the management of patients with ventricular arrhythmias

1. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000549
2. https://pubmed.ncbi.nlm.nih.gov/29097320/
3. https://www.sciencedirect.com/science/article/pii/S2405500X22010945
4. https://pubmed.ncbi.nlm.nih.gov/29084733/
5. https://www.hrsonline.org/guidance/clinical-resources/2017-ahaacchrs-guideline-management-patients-ventricular-arrhythmias-and-prevention-sudden-cardiac