Antiarrhythmic agent

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The cardiac action potential

Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress abnormal rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation. Many attempts have been made to classify anti-arrhythmic agents. The problem arises from the fact that many of the antiarrhythmic agents have multiple modes of action, making any classification imprecise.
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1 Singh Vaughan Williams classification 1.1 Overview table 1.2 Class I agents 1.3 Class II agents 1.4 Class III agents 1.5 Class IV agents 1.6 Other agents ("Class V") 2 Sicilian Gambit classification 3 See also 4 References

[edit]Singh

Vaughan Williams classification

The Singh Vaughan Williams classification, introduced in 1970 based on the seminal work of Bramah N. Singh in his doctoral thesis at Oxford where Vaughan Williams was his advisor and on subsequent work by Singh and

his colleagues in the United States, is one of the most widely used classification schemes for antiarrhythmic agents. This scheme classifies a drug based on the primary mechanism of its antiarrhythmic effect. However, its dependence on primary mechanism is one of the limitations of the Singh-VW classification, since many antiarrhythmic agents have multiple action mechanisms. Amiodarone, for example, has effects consistent with all of the first four classes. Another limitation is the lack of consideration within the Singh-VW classification system for the effects of drug metabolites. Procainamidea class Ia agent whose metabolite N-acetyl procainamide (NAPA) has a class III actionis one such example. A historical limitation was that drugs such as digoxinand adenosine important antiarrhythmic agents had no place at all in the VW classification system. This has since been rectified by the inclusion of class V.[citation needed] With regards to management of atrial fibrillation, Class I and III are used in rhythm control as medical cardioversion agents whilst Class II and IV are used as rate control agents. There are five main classes in the Singh Vaughan Williams classification of antiarrhythmic agents:

Class I agents interfere with the sodium (Na+) channel. Class II agents are anti-sympathetic nervous system agents. Most agents in this class are beta

blockers.

Class III agents affect potassium (K+) efflux. Class IV agents affect calcium channels and the AV node. Class V agents work by other or unknown mechanisms.

[edit]Overview Class

table
Examples Mechanism Clinical uses [1] Ventricular arrhythmias prevention of

Known as

fastchannel blockersAffect QRS complex Quinidine (Na+) channel block Procainamide (intermediate association/dissociation) Disopyramide
+

paroxysmal recurrent atrial fibrillation (triggered by vagal overactivity) procainamide in Wolff-

Ia

Parkinson-White syndrome Ib- Do not affect QRS complex Lidocaine Phenytoin (Na ) channel block (fast association/dissociation) treatment and prevention

during and immediately after myocardial infarction, though

this practice is now discouraged Mexiletine Tocainide atrial fibrillation prevents paroxysmal atrial given the increased risk of asystole ventricular tachycardia

fibrillation Ic Flecainide Propafenone Moricizine contraindicated immediately post-myocardial infarction. II Betablockers III Propranolol Esmolol Timolol Metoprolol Atenolol Bisoprolol Amiodarone Sotalol Ibutilide Dofetilide Dronedarone E-4031 K+ channel blocker Sotalol is also a beta blocker[2]Amiodarone has Class I, II, and III activity In Wolff-Parkinson-White beta blocking Propranolol also shows some class I action decrease myocardial (Na ) channel block (slow association/dissociation)
+

treats recurrent

tachyarrhythmias of abnormal conduction system.

infarction mortality prevent recurrence

of tachyarrhythmias

syndrome (sotalol:) ventricular

tachycardias and atrial fibrillation (Ibutilide:) atrial

flutter and atrial fibrillation prevent recurrence

IV

slowchannel blockers

Verapamil Ca2+ channel blocker Diltiazem

of paroxysmal supraventricular tachycardia reduce ventricular rate in

patients with atrial fibrillation V Adenosine Work by other or unknown Used in supraventricular arrhythmias, mechanisms (Direct nodal especially in Heart Failure with Atrial

Digoxin Magnesium inhibition).

Sulfate [edit]Class

Fibrillation, contraindicated in ventricular arrhythmias. Or in the case of Magnesium Sulfate, used in Torsades de Pointes.

I agents

The class I antiarrhythmic agents interfere with the sodium channel. Class I agents are grouped by what effect they have on the Na+ channel, and what effect they have on cardiac action potentials. Class I agents are called Membrane Stabilizing agents. The 'stabilizing' word is used to describe the decrease of excitogenicity of the plasma membrane which is brought about by these agents. (Also noteworthy is that a few class II agents like propranolol also have a membrane stabilizing effect.) Class I agents are divided into three groups (Ia, Ib and Ic) based upon their effect on the length of the action potential.[3][4]

Ia lengthens the action potential (right shift) Ib shortens the action potential (left shift) Ic does not significantly affect the action potential (no shift)

Class Ia

Class Ib

Class Ic

There is a popular mnemonic to remember the class I agents:

Class Ia Disopyramide, Quinidine, Procainamide Double Quarter Pounder

Class Ib Lidocaine, Mexiletine, Tocainide

Lettuce, Mayo, Tomato

Class Ic Moricizine, Flecainide, Propafenone [edit]Class

More Fries Please. (note there are two "M"s in the mnemonic, but morcizine and more can clarify which is which)

II agents

Class II agents are conventional beta blockers. They act by blocking the effects of catecholamines at the 1adrenergic receptors, thereby decreasing sympathetic activity on the heart. These agents are particularly useful in the treatment of supraventricular tachycardias. They decrease conduction through the AV node. Class II agents include atenolol, esmolol, propranolol, and metoprolol.

[edit]Class

III agents

Class III

Class III agents predominantly block the potassium channels, thereby prolonging repolarization.[5] 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 less likely to interact with tissue that has become refractory). Drugs include:amiodarone, ibutilide, sotalol, dofetilide, and dronedarone.

[edit]Class

IV agents

Class IV agents are slow calcium channel blockers. They decrease conduction through the AV node, and shorten phase two (the plateau) of the cardiac action potential. They thus reduce the contractility of the heart, so may be inappropriate in heart failure. However, in contrast to beta blockers, they allow the body to retain adrenergic control of heart rate and contractility.

Class IV agents include verapamil and diltiazem.

[edit]Other

agents ("Class V")

Since the development of the original Vaughan-Williams classification system, additional agents have been used that don't fit cleanly into categories I through IV. Some sources use the term "Class V".[6] However, they are more frequently identified by their precise mechanism. Agents include:

Digoxin, which decreases conduction of electrical impulses through the AV node and increases vagal

activity via its central action on the central nervous system.

Adenosine[7] Magnesium sulfate,[8] which has been used for torsades de pointes.[9][10]

[edit]Sicilian

Gambit classification

Another approach, known as the "Sicilian Gambit", placed a greater approach on the underlying mechanism. [11]
[12][13]

It presents the drugs on two axes, instead of one, and is presented in tabular form. On the Y axis, each drug is listed, in approximately the Vaughan Williams order. On the X axis, the channels, receptors, pumps, and clinical effects are listed for each drug, with the results listed in a grid. It is therefore not a true classification in that it does not aggregate drugs into categories.[14]

[edit]See

also