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20-September-2008 09:55:47 - Antiarrhythmic agent 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.12 In the past, it was believed that following myocardial infarction heart attack, suppression of ventricular arrhythmias would prolong life. However, large clinical trials found that suppression of these arrhythmias would paradoxically increase mortality,34 which may happen due to the proarrhythmic effect these drugs may have CAST trial. 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 be 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 cardiac action potential The cardiac action potential Many attempts have been made to classify antiarrhythmic agents. The problem arises from the fact that many of the antiarrhythmic agents have multiple modes of action, making any classification imprecise. Contents 1 Vaughan Williams antiarrhythmic 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 Class V agents 2 Other classification approaches 3 Trials 4 Mnemonics 5 See also 6 References Vaughan Williams antiarrhythmic classification The Vaughan Williams classification, introduced in 1970,5 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 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 VW classification system for the effects of drug metabolites. Procainamide-a class Ia agent whose metabolite N-acetyl procainamide NAPA has a class III action-is one such example. A historical limitation was that drugs such as digoxin and 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 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. Overview table Class Examples Mechanism Clinical uses 6 Ia Quinidine Procainamide Disopyramide Na+ channel block intermediate association/dissociation Ventricular arrhythmias prevention of paroxysmal recurrent atrial fibrillation triggered by vagal overactivity, procainamide in Wolff-Parkinson-White syndrome Ib Lidocaine Phenytoin Mexiletine Na+ channel block fast association/dissociation treatment and prevention during and immediately after myocardial infarction, though this practice is now discouraged given the increased risk of asystole ventricular tachycardia atrial fibrillation Ic Flecainide Propafenone Moricizine Na+ channel block slow association/dissociation prevents paroxysmal atrial fibrillation treats recurrent tachyarrhythmias of abnormal conduction system. II Propranolol Esmolol timolol metoprolol sotalol atenolol beta blocking decrease myocardial infarction mortality prevent recurrence of tachyarrhythmias III Amiodarone Sotalol Ibutilide Dofetilide K+ channel blocker Sotalol is also a beta blocker7 In Wolff-Parkinson-White syndrome sotalol: ventricular tachycardias and atrial fibrillation nibentan: atrial flutter and atrial fibrillation IV verapamil diltiazem Ca2+ channel block prevent recurrence of paroxysmal supraventricular tachycardia reduce ventricular rate in patients with atrial fibrillation Class I agents Class Ia agent decreasing Vmax, thereby increasing action potential duration. Class Ia agent decreasing Vmax, thereby increasing action potential duration. Effect of class Ib antiarrhythmic agents on the cardiac action potential. Effect of class Ib antiarrhythmic agents on the cardiac action potential. Effect of class Ic antiarrhythmic agent on cardiac action potential. Effect of class Ic antiarrhythmic agent on cardiac action potential. Effect of class III antiarrhythmic agent on cardiac action potential. Effect of class III antiarrhythmic agent on cardiac action potential. 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 1 agents are called Membrane Stabilizing agents. The 'stabilizing' is the word 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 2 agents like propranolol also have a membrane stabilizing effect. Class II 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. 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. Class III agents Class III agents predominantly block the potassium channels, thereby prolonging repolarization.8 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. 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. Class V agents Class V agents include digoxin and adenosine. Digoxin increases vagal activity via its central action on the central nervous system, thus decreasing the conduction of electrical impulses through the AV node. It should be noted that Class V agents are not part of the original Vaughan-Williams classification system. Other classification approaches Another approach, known as the Sicilian Gambit, placed a greater approach on the underlying mechanism.91011 Trials The Cardiac Arrhythmia Suppression Trial CAST trial 12 was a medical study that demonstrated that some class 1 anti-arrhythemic drugs were not helpful to people suffering from ventricular premature depolarization. Specifically, for populations of recent heart attack survivors, the study observed lower mortality in a control population than in populations treated with encainide, flecainide or moricizine all class 1c drugs. Class Ic and all other class I drugs shoud be avoided in patients with significant coronary artery disease, left ventiricular dysfunction or other forms of significant structural heart disease. Mnemonics Mnemonic for Class I-IV agents: SoBe PoCa SOBE as in South Beach or the drink, POCA as in Polka Also - remembering that of all anti-arrhythmics some block potassium channels can help you: Class I Some = S = Sodium Class II Block = B =Beta blockers Class III Potassium = Potassium channel blockers Class IV Channels = C =Calcium channel blockers Sodium channel blockers, Beta blockers, Potassium channel blockers, Calcium channel blockers To remember the Class I agents: Class IA Double Quarter Pounder Disopyramide, Quinidine, Procainamide, Class IB Lettuce, Tomato, Mayo Lidocaine, Tocainide, Mexilitine, Class IC More Fries Please Moricizine, Flecainide, Propafenone. To remember the Class III agents: A Big Dog Is Scary Amiodarone, Bretylium, Dofetilide, Ibutilide, Sotalol. Dr. Hrometz 2008, Ohio Northern University To remember calcium channel blockers: Calcium channel blockers are Very Nice Drugs verapamil, nifedipine, diltiazem See also Action potential Cardiac action potential Electrocardiogram Plasma membrane Stabilization References ^ Wyse D, Waldo A, DiMarco J, Domanski M, Rosenberg Y, Schron E, Kellen J, Greene H, Mickel M, Dalquist J, Corley S 2002. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 347 23: 1825-33. PMID 12466506. ^ Nichol G, McAlister F, Pham B, Laupacis A, Shea B, Green M, Tang A, Wells G 2002. Meta-analysis of randomised controlled trials of the effectiveness of antiarrhythmic agents at promoting sinus rhythm in patients with atrial fibrillation. Heart 87 6: 535-43. doi:10.1136/heart.87.6.535. PMID 12010934. ^ Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression Trial CAST Investigators 1989. N Engl J Med 321 6: 406-12. PMID 2473403. ^ Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. The Cardiac Arrhythmia Suppression Trial II Investigators 1992. N Engl J Med 327 4: 227-33. PMID 1377359. ^ Vaughan Williams EM. Classification of anti-arrhythmic drugs. In: Symposium on Cardiac Arrhythmias, Sandfte E, Flensted-Jensen E, Olesen KH eds. Sweden, AB ASTRA, Södertälje, 1970;449-472. ^ Unless else specified in boxes, then ref is: Rang, H. P. 2003. Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. ^ Kulmatycki KM, Abouchehade K, Sattari S, Jamali F May 2001. Drug-disease interactions: reduced beta-adrenergic and potassium channel antagonist activities of sotalol in the presence of acute and chronic inflammatory conditions in the rat. Br. J. Pharmacol. 133 2: 286-94. doi:10.1038/sj.bjp.0704067. PMID 11350865. PMC:1572777. ^ Lenz TL, Hilleman DE, Department of Cardiology, Creighton University, Omaha, Nebraska. Dofetilide, a New Class III Antiarrhythmic Agent. Pharmacotherapy 207:776-786, 2000. Medline abstract ^ The 'Sicilian Gambit'. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. The Task Force of the Working Group on Arrhythmias of the European Society of Cardiology October 1991. Eur. Heart J. 12 10: 1112-31. PMID 1723682. ^ Vaughan Williams EM November 1992. Classifying antiarrhythmic actions: by facts or speculation. J Clin Pharmacol 32 11: 964-77. PMID 1474169. ^ Milestones in the Evolution of the Study of Arrhythmias. Retrieved on 2008-07-31. ^ Entry on Clinical Trials.gov v d e Antiarrhythmic agents C01B class I Na+ channel blockers class Ia Phase 0 Ajmaline Disopyramide Prajmaline Procainamide Quinidine Sparteine class Ib Phase 3 Aprindine Lidocaine Mexiletine Tocainide class Ic Phase 0 Encainide Flecainide Lorcainide Moricizine Propafenone class II Phase 4, beta blockers Propranolol Metoprolol Nadolol Atenolol Acebutolol Pindolol class III Phase 3, K+ channel blockers Amiodarone Bretylium tosylate Bunaftine Dofetilide Ibutilide Nifekalant Sotalol class IV Phase 4, Ca2+ channel blockers Verapamil Diltiazem class V other A1 agonist Adenosine muscarinic antagonist Atropine cardiac glycoside Digoxin v d e Major drug groups Gastrointestinal tract/metabolism A stomach acid Antacids, H2 antagonists, Proton pump inhibitors Antiemetics Laxatives Antidiarrhoeals/Antipropulsives Anti-obesity drugs Anti-diabetics Vitamins Dietary minerals Blood and blood forming organs B Antithrombotics Anticoagulants, Antiplatelets, Thrombolytics Antihemorrhagics Cardiovascular system C cardiac therapy/antianginals Cardiac glycosides, Antiarrhythmics, Cardiac stimulant Antihypertensives Diuretics Vasodilators Beta blockers renin-angiotensin system ACE inhibitors, Angiotensin II receptor antagonists, Renin inhibitors Antihyperlipidemics Skin D Emollients Cicatrizant Antipruritics Reproductive system G Hormonal contraception Fertility agents SERMs Sex hormones Endocrine system H Corticosteroids Sex hormones Thyroid hormones Antithyroid agent Infections and infestations J, P Antibiotics Antivirals Vaccines Antifungals Antiparasitic Antiprotozoals, Anthelmintics Malignant and immune disease L Anticancer agents Immunostimulators Immunosuppressants Muscles, bones, and joints M Anabolic steroids Anti-inflammatories NSAID Antirheumatics Corticosteroids Muscle relaxants Brain and nervous system N Anesthetics General, Local Analgesics Anticonvulsants Mood stabilizers Psycholeptic Anxiolytics, Antipsychotics, Hypnotics/Sedatives Psychoanaleptic Antidepressants, Stimulants/Psychostimulants Respiratory system R Bronchodilators Decongestants H1 antagonists Other ATC V Antidotes Contrast media Radiopharmaceuticals Dressing Retrieved from http://en..org/wiki/Antiarrhythmic_agent Categories: Antiarrhythmic agents | Cardiac electrophysiologyHidden categories: All articles with statements | Articles with statements since September 2007 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Català Deutsch Español Français Hrvatski Magyar 日本語 Polski Português This page was last modified on 19 August 2008, at 12:2
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