Antiarrhythmics Overview

Antiarrhythmics are used in the treatment of ventricular, junctional, and atrial arrhythmias.  They perform these functions by interacting with a variety of receptor sites and electrolyte channels.  

Class I antiarrhythmics act on sodium channels primarily – some medications in class I also affect other channels and receptors.

Class II antiarrhythmics are drugs that we’ve already reviewed in the autonomic section, beta-blockers.

Class III antiarrhythmics work primarily on potassium channels, but like class I drugs, some drugs in this class also affect other channels and receptors.

Class IV antiarrhythmics are calcium channel blockers, which were previously reviewed in the cardiology section.  

Arrhythmias

An arrhythmia is a condition where the heart contracts in an abnormal or irregular rhythm.  

Common types of arrhythmias that are treated by drugs in these classes include: 

Atrial arrhythmias – most commonly, atrial fibrillation and atrial flutter 

AV junctional arrhythmias, which originate around the AV node and most commonly include AV nodal reentry tachycardia and supraventricular tachycardia

Ventricular arrhythmias include both polymorphic and monomorphic ventricular tachycardia as well as ventricular fibrillation.  

Causes of arrhythmias: 

• Increased automaticity: the pacemaker function of the SA node is usurped by another area of the heart which shows abnormally increased automaticity, which can induce an arrhythmia.  

• Impulse conduction disorders: impulses are not carried through the cardiac tissue as normally expected. Typically, conduction travels through the AV node then splits to each ventricle to induce contraction. Blockage of these conduction pathways can occur, which results from myocardial injury or a physiologic block from a prolonged refractory period.

 

Electrophysiology Basics

Signals for cardiac conduction travel through the myocardium by depolarization of the cardiac action potential.

The action potential is broken into phases that correlate with openings and closings of ion channels including sodium, potassium, and calcium ion channels.  

The baseline action potential is driven by the sodium-potassium ATPase pump that exchanges 3 sodium ions for two potassium ions.  In addition, highly permeable potassium channels contribute to the electrochemical gradient that create the action potential.  

Above is a schematic of the baseline/normal action potential.  The action potential is broken into 5 total phases, numbered 0-4. Phase 4 is the baseline action potential driven by the sodium-potassium ATPase pump and the highly permeable potassium channels.  Depolarization begins in phase 0 with opening of voltage-gated sodium channels with a rapid rise of the membrane potential.  Transient opening of potassium channels along with closing of sodium channels occurs in phase 1, which is brief.  In phase 2, potassium efflux continues along with calcium influx via voltage-gated L-type calcium channels, which open in phase 2.  In phase 3, calcium channels close and efflux of potassium through potassium efflux channels continues as the voltage returns to phase 4 levels.  

Antiarrhythmic Drug Classes

There are four (some consider that there are five) classes of antiarrhythmic drugs.

Class I: Sodium channel blockers

Class II: Beta blockers

Class III: Potassium channel blockers

Class IV: Calcium channel blockers

Class V: “Other” antiarrhythmics – like digoxin and adenosine.

Class I

Class I refers to drugs with primarily sodium channel blocking effects, which slows phase 0 of the action potential.  

There are 3 subclasses of class I:

• Class IA: Class IA drugs also incorporate class III and class IV effects. Classe III effects are potassium channel inhibition, and class IV effects are calcium channel blockade.  These medications prolong repolarization and lengthen the QTc and QRS intervals.  Overall the action potential duration increases and conduction slows.  

• Class IB: Class IB medications shorten action potential phases through sodium channel blockade both in phase 0 and in phase 3 through sustained late sodium channel blockade.  

• Class IC: Class IC medications prolong the QRS interval through slowing of phase 0 but do not prolong the total duration of the action potential.

 

Class II

Class II antiarrhythmics are beta blockers. Beta blockers decrease phase 4 depolarization, which reduces automaticity, prolong AV conduction (slowing HR), and reduces contractility.  

Class III

Class III antiarrhythmics have potassium channel blocking effects, which prolongs action potential duration by decreasing outward potassium flow.  

Class IV

Class IV medications are calcium channel blockers. These medications prevent repolarization until the drug dissociates from calcium channels, which results in decreased phase 4 depolarization. Class IV drugs more strongly affect the SA and AV nodes, which slows heart rate.  Calcium channel blockers are used primarily for treatment of supraventricular arrhythmias.