How do Class 1 antiarrhythmic medications work?

From the Guidelines

Class 1 antiarrhythmic medications work primarily by blocking sodium channels in cardiac cells, which helps to suppress abnormal heart rhythms by slowing the conduction of electrical impulses through the heart. These drugs reduce the rate of rise of the action potential in cardiac cells, slowing the speed at which electrical signals travel through the heart tissue, and can interrupt and prevent the circular patterns of electrical activity that cause many arrhythmias. Common examples of Class 1 antiarrhythmic medications include:

• Quinidine
• Procainamide
• Disopyramide (Class 1A)
• Lidocaine
• Mexiletine (Class 1B)
• Flecainide
• Propafenone (Class 1C) These medications are typically used to treat atrial and ventricular arrhythmias, but must be used cautiously as they can sometimes worsen arrhythmias or cause new ones, especially in patients with structural heart disease, as noted in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. The specific choice of drug, dosage, and administration route depends on the type of arrhythmia being treated and the patient's overall cardiac health, and a cardiologist should always be consulted for proper management of these medications. It is also important to consider the potential risks and benefits of each medication, including the risk of proarrhythmia, and to monitor patients closely for adverse effects, as recommended in the 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation 1.

From the FDA Drug Label

In cardiac muscle and in Purkinje fibers, quinidine depresses the rapid inward depolarizing sodium current, thereby slowing phase-0 depolarization and reducing the amplitude of the action potential without affecting the resting potential. Propafenone reduces the fast inward current carried by sodium ions. The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential

Class 1 antiarrhythmic medications work by depressing the rapid inward depolarizing sodium current, thereby slowing phase-0 depolarization and reducing the amplitude of the action potential. This action slows conduction and reduces automaticity in the heart.

• Key effects include:
  • Slowing of conduction
  • Reduction of automaticity
  • Prolongation of the effective refractory period
  • Reduction of the amplitude of the action potential 2 3 3

From the Research

Mechanism of Action

• Class 1 antiarrhythmic medications work by inhibiting sodium channels, which slows myocardial conduction and interrupts or prevents reentrant arrhythmia 4, 5, 6, 7, 8
• They act by depressing the fast inward depolarizing sodium current, thereby slowing the rate of the rise of the action potential (phase 0) 5, 6, 7
• This category is further divided into subclasses (IA, IB, and IC) according to the degree of potency as sodium channel inhibitors, and the individual effects of the drug on action potential, conduction velocity, and repolarization 5, 7

Effects on the Heart

• Class 1 antiarrhythmic drugs can slow conduction and convert regions of unidirectional block to bidirectional block, thereby preventing reentrant arrhythmias 8
• They can also lengthen repolarization and refractoriness, although this is more characteristic of Class III antiarrhythmic agents 5, 8
• The use of Class 1 antiarrhythmic drugs can be limited by their proarrhythmic effects and the risk of ventricular tachyarrhythmia, particularly in patients with structural heart disease 4

Examples of Class 1 Antiarrhythmic Drugs

• Quinidine, procainamide, disopyramide, lidocaine, tocainide, mexiletine, flecainide, amiodarone, encainide, and lorcainide are all examples of Class 1 antiarrhythmic drugs 5, 6
• These drugs can be used to treat a variety of arrhythmias, including atrial fibrillation, although their use must be carefully considered due to the potential risks and side effects 4, 5, 6, 7, 8