Antiarrhythmic drugs are a group of pharmaceuticals that are used to suppress fast rhythms of the heart such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation.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).
Vaughn-Williams Classification
The Vaughn-Williams classification of antiarrhythmic therapy takes into account some of this approach. It is a somewhat confusing mechanism of memorizing antiarrhythmics and we will spend little time discussing the classification system itself. It is based on the cellular properties of the normal his-Purkinje cells. Classification of drugs is dependent upon the ion currents responsible for depolarization and repolarization as well as the beta-adrenergic receptors. Its advantages are that it is a physiologically based system and highlights the beneficial and deleterious effects of the specific drugs. Unfortunately, its disadvantages are that all cells are not normal. Therefore in addition to this, all cells in the heart are not his-purkinje in origin and therefore have different dysrhythmia profiles.
The Vaughn-Williams classification as I stated before divides antiarrhythmics based on certain ion channels they affect. Class I antiarrhythmics are sodium channel blockers and have direct membrane action upon the sodium channel. Class II antiarrhythmics are the beta-blockers and affect the heart by sympatholysis (beta blocking). Class III antiarrhythmics prolong repolarization by affecting the potassium channels and Class IV antiarrhythmics are calcium channel blockers. In addition to these classes other antiarrhythmics would include purinergic agonists and the digitalis glycosides, which do not fall in any of the above classifications.
There are five main classes in the 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.
The class I antiarrhythmic agents interfere with the sodium channel and they are also called Membrane Stabilizing agents.Class II agents are conventional beta blockers. They act by blocking the effects of catecholamines at the β1-adrenergic receptors, thereby decreasing sympathetic activity on the heart.Class III agents predominantly block the potassium channels, thereby prolonging repolarization.Class IV agents are slow calcium channel blockers. They decrease conduction through the AV node, and shorten the plateau phase of the cardiac action potential.
Antiarrhythmic therapy has progressed over the past years from a concept of empiric arrhythmia diagnosis; that is, diagnosis solely of the appearance of the electrograms on the surface ECG with interventions aimed at making the ECG and the patient appear more “normal”, to a more scientific approach to current electrophysiology.
In current pediatric and adult cardiology practices, an attempt is made at understanding the pathophysiologic diagnosis ( the what and how) of the arrhythmia. This allows the cardiologist to evaluate mechanisms and components of the arrhythmia in order to evaluate vulnerable parameters and target the arrhythmia on a subcellular level. Ultimately this intervention leads to, for the most part, making the ECG and the patient appear more “normal”!
A simple example of this would be the diagnosis and treatment of AV node reentry tachycardia.
The diagnosis of this arrhythmia can be made on a surface electrocardiogram. However, when a Pediatric Cardiologist evaluates this more closely, the AV node reentry circuit that is responsible for this tachycardia is secondary to an anatomic fast and slow pathway within the AV node. The AV node slow conduction pathway provides a retrograde circuit making this much like other types of reentry tachycardia. The vulnerable perimeter in this case would be the AV nodal action potential. On a subcellular level, the L-type calcium channel is prominent within the AV node. Therefore, interventions could be aimed at interfering with this channel either directly with a calcium channel blocker or indirectly with a beta-blocker. In either case, the clinical outcome would be the same and that is returning the patient to sinus rhythm.
by
Dr.Akshaya Srikanth
Pharm.D India
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