II. SELECTION OF AN ANTIARRHYTHMIC DRUG Selection of a drug in a complicated arrhythmia is

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II. SELECTION OF AN ANTIARRHYTHMIC DRUG Selection of a drug in a complicated arrhythmia is often difficult because of the lack of knowledge regarding the exact mechanism of the arrhythmia. In some cases, certain agents will be excluded by the existence of contraindications to their use. Choice of an agent may be aided or narrowed by testing the candidate drugs with programmed electrical stimulation (PES) in the clinical electrophysiology laboratory, or with prolonged (48 hr) Holter monitoring; by knowledge of prior efficacy of a drug in that patient; by presence of nodal dysfunction; and by presence of congestive heart failure. The drugs available are commonly classified into 4 groups. These groups are discussed be- low and listed in the following tables: Group IA: Group IB: Group IC: Groups II, III, and IV: Miscellaneous agents (amiodarone, digoxin, phenytoin): (PgDn key for more text) 1. Sodium channel blockers (Group I). Quinidine and its congeners have a local anesthetic-like action on ventricular muscle and on the rapid conduction system. Conduction is slowed and ectopic pacemaker discharge rate is reduced. * Group IA agents (eg, quinidine, see ) produce a dose- dependent prolongation of the QRS duration, reflecting slowing of intraventricular conduction even in normal myocardium. They also increase the QTc duration. * Group IB agents (lidocaine, etc ) produce little ECG effect; their action on normal myocardium is minimal, but they have significant effects on abnormal tissue, especially in the conducting system and the ventricular myocardium. * Group IC drugs (flecainide, encainide, ) are potent depressants of conduction and prolong the QRS and PR interval but have little effect on QTc duration. (PgDn key for more text) 2. Sympathetic nervous system blockers (Group II). Propranolol and other beta blockers act by this mechanism and, to a lesser extent, through sodium channel blockade. Some of the effect of bretylium probably results from this mechanism. Esmolol is an new ultra-short-acting beta blocker that has been used successfully to reduce heart rate and suppress arrhythmias during cardiac surgery. The ECG effects of the beta-adrenoceptor blocking agents are not dramatic but often include sinus rate slowing and PR prolongation. 3. Drugs that prolong of the action potential (Group III). Drugs in this class, eg, bretylium, probably block potassium channels in myocardial cells in addition to other effects. Quinidine and amiodarone also significantly prolong the action potential. This action is reflected in the ECG by QTc prolongation. Sotalol and clofilium are investigative group III drugs. 4. Calcium channel blockers (Group IV). The calcium channel blockers reduce pacemaker activity and conduction in the SA and AV nodes, and significantly prolong AV nodal refractoriness. The ECG manifestations include PR prolongation. (PgDn key for more text) Major indications for selected drugs (see also ): * Isolated atrial premature depolarizations: seldom require therapy. If associated with symptoms, Group IA agents or beta-blockers may be used. * Paroxysmal supraventricular tachycardia (including sinus node reentry, atrial reentry, AV nodal reentry, or atrioventricular tachycardia involving a bypass tract): - Acute therapy: vagal maneuvers (eg,carotid sinus massage); IV verapamil; IV adenosine (investigational); IV propranolol (if calcium channel blocker has not been used); IV procainamide; direct current countershock - Chronic maintenance therapy: Digoxin, beta-blockers, calcium channel blockers, group IA agents, flecainide, or amiodarone have all been used. Diltiazem (investigational use) may be useful. Digoxin is contraindicated in WPW syndrome. If drugs are ineffective or not tolerated, surgical procedures, antitachycardia pacing, or catheter ablation procedures may be considered. (PgDn key for more text) * Atrial flutter or fibrillation: - Acute therapy: IV digoxin, IV verapamil, IV beta-blockers, or DC countershock. Digoxin and verapamil are contraindicated in patients with WPW syndrome and atrial fibrillation. These patients should be treated with IV procainamide and DC shock. - Maintenance therapy: Group IA drugs, or amiodarone (investigational). Diltiazem (investigational use) may be useful in ventricular rate control. Consider surgery for patients with WPW syndrome and fibrillation. * Ventricular premature depolarizations: quinidine, procainamide, disopyramide, lidocaine, mexiletine, tocainide, propranolol, acebutolol, flecainide, (amiodarone, unlabelled) * Unsustained ventricular tachycardia: quinidine, procainamide, disopyramide, lidocaine, mexiletine, tocainide, flecainide, (amiodarone, unlabelled) (PgDn key for more text) * Sustained ventricular tachycardia and recurrent ventricular fibrillation: - Acute therapy: DC countershock, IV lidocaine, IV procainamide, IV bretylium, (or IV amiodarone, investigational) - Chronic therapy: Drug selection should be guided by programmed stimulation electrophysiologic testing. For refractory cases, consider cardiac electrosurgery, catheter ablation procedures, or insertion of automatic internal cardioverter defibrillator. * Drug or hormone-related arrhythmias: may be caused by any Group IA antiarrhythmic agent (pattern may be polymorphous ventricular tachycardia or torsade de pointes), digitalis excess, catecholamine excess, or thyrotoxicosis. Therapy includes prompt cessation of the causative agent, IV lidocaine, IV phenytoin, or beta-blockers in the case of thyrotoxicosis. Resistant cases may require IV magnesium and cardiac pacing. (PgDn key for more text) Drugs of Special Importance * Quinidine is the prototype antiarrhythmic and still perhaps the single most useful drug for oral therapy of cardiac arrhythmias. Procainamide and disopyramide have similar efficacy profiles but are less well tolerated in chronic oral therapy than quinidine. * Lidocaine is one of the most useful agents for the rapid control of life-threatening arrhythmias, especially those associated with myocardial infarction and digitalis intoxication. It has the lowest toxicity of all the antiarrhythmic drugs but it must be used parenterally. Tocainide and mexiletine are orally active drugs with similar actions. * Amiodarone is one of the most efficacious of all the antiarrhythmic agents, but it is also one of the most toxic. It is therefore reserved for use only when other agents fail. Flecainide is less toxic overall than amiodarone but is more proarrhythmic and has a much more restricted spectrum of action. * Verapamil is considered the drug of choice for acute management of narrow QRS supraventricular tachycardia. (Home key to return to top of file)

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