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Antiarrhythmic drugs

This category includes:

Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress fast rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation.
While the use of antiarrhythmic agents to suppress atrial arrhythmias (atrial fibrillation and atrial flutter) is still in practice, it is unclear whether suppression of atrial arrhythmias will prolong life 1,2.
In the past, it was believed that supression of the potentially dangerous ventricular arrhythmias, ventricular tachycardia and ventricular fibrillation would prolong life, but it was found in large clinical trials that suppression of these arrhythmias would paradoxically increase mortality 3,4.
In individuals with atrial fibrillation, antiarrhythmics are still used to suppress arrhythmias. This is often done to relieve the symptoms that may be associated with the loss of the atrial component to ventricular filling (atrial kick) that is due to atrial fibrillation or flutter.
In individuals with ventricular arrhythmias, antiarrhythmic agents are often still in use to suppress arrhythmias. In this case, the patient may have frequent arrhythmic events or at high risk for ventricular arrhythmias. Antiarrhythmic agents may be considered the first-line therapy in the prevention of sudden death in certain forms of structural heart disease, and failure of these agents to suppress arrhythmias may lead to implantation of an implantable cardioverter-defibrillator (ICD).
The use of antiarrhythmic agents in this population may be in conjunction with an ICD. In this case, the ICD is used to prevent sudden death due to ventricular fibrillation, while the antiarrhythmic agent(s) are used to suppress ventricular tachyarrhythmias so that the ICD doesn't shock the patient frequently.

The cardiac action potential

The antiarrhythmic agents are classified based on what portion of the action potential they directly affect, and which ion channels of the cardiac myocyte they interact with.
Antiarrhythmic classes
There are five main classes (Vaughan Williams-classification) of antiarrhythmic agents:
Class I agents interfere with the Na+ channel.
Class II agents are anti-sympathetic agents. All agents in this class are beta blockers.
Class III agents affect K+ influx
Class IV agents affect the AV node.
Class V agents work by other or unknown mechanisms.

Class I agents
The class I antiarrhythmic agenst interfere with the Na+ channel. Class I agents are grouped by what affect they have on the Na+ channel, and what affect they have on the cardiac action potential.

Class Ia agents

Class Ia agent decreasing Vmax, thereby increasing action potential duration.

Class Ia agents block the fast sodium channel. Blocking this channel depresses the phase 0 depolarization (reduces Vmax). This prolongs the action potential duration by slowing conduction. Agents in this class also cause decreased conductivity and increase refractoriness.
Indications for Class Ia agents are supraventricular tachycardia, ventricular tachycardia, symptomatic ventricular premature beats, and prevention of ventricular fibrillation.
Class Ia agents include quinidine, procainamide, disopyramide, and moricizine.

Class Ib agents

Effect of class Ib antiarrhythmic agents on the cardiac action potential.

Class Ib antiarrhythmic agents are sodium channel blockers. Class Ib agents have fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. Class Ib agents shorten the action potential duration and reduce refractoriness. These agents will decrease Vmax in partially depolarized cells with fast response action potentials. They either do not change the action potential duration, or they may decrease the action potential duration.
Class Ib agents are indicated for the treatment of ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation.
Class Ib agents include lidocaine, mexilitine, tocainide, and phenytoin.

Class Ic agents

Effect of class Ic antiarrhythmic agent on cardiac action potential.

Class Ic antiarrhythmic agents markedly depress the phase 0 repolarization (decreasing Vmax). They decrease conductivity, but have a minimal effect on the action potential duration.
Class Ic agents are indicated for life-threatening ventricular tachycardiac or ventricular fibrillation, and for the treatment of refractory supraventricular tachycardia (ie: atrial fibrillation).
Class Ic agents include flecainide and propafenone.

Class II agents
Class II agents are conventional beta blockers. They act by slowing conduction through the AV node.
Class II agents include esmolol, propranolol, and metoprolol.


Class III agents

Effect of class III antiarrhythmic agent on cardiac action potential.

Class III agents predominantly block the potassium channels, thereby prolonging repolarization5. Since these agents do not affect the sodium channel, conduction velocity is not decreased. The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias (The re-entrant rhythm is more like to interact with tissue that has become refractory).
Class III antiarrhythmic agents exhibit reverse use dependent prolongation of the action potential duration (Reverse use-dependance)5. This means that the refractoriness of the ventricular myocyte increases at lower heart rates. This increases the susceptability of the myocardium to early after-depolarizations (EADs) at low heart rates. At low heart rates, class III antiarrhythmic agents may paradoxically be more arrhythmogenic.
Class III agents include amiodarone, sotalol, dofetilide, ibutilide, and bretylium.
Amiodarone is indicated for the treatment of refractory VT or VF, particularly in the setting of acute ischemia. Sotalol is indicated for the treatment of atrial or ventricular tachyarrhythmias, and AV re-entrant arrhythmias.

Class IV agents
Class IV agents are slow calcium channel blockers. They decrease conduction through the AV node.
Clas IV agents include verapamil and diltiazem.

Class V agents
Class V agents include adenosine and digoxin.

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