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Back to Cardiology Drug index
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.
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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
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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.
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Class Ib agents
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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.
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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.
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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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