Atrial fibrillation antiarrhythmics

QuinidJne. Quinidine, an alkaloid obtained from cinchona bark (Sinchona sp.), is the dextrorotatory stereoisomer of quinine [130-95-0] (see Alkaloids). The first use of quinidine for the treatment of atrial fibrillation was reported in 1918 (12). The sulfate, gluconate, and polygalacturonate salts are used in clinical practice. The dmg is given mainly by the oral (po) route, rarely by the intravenous (iv) route of adniinistration. It is the most frequentiy prescribed po antiarrhythmic agent in the United States. The clinical uses of quinidine include suppression of atrial and ventricular extrasystoles and serious ventricular arrhythmias (1 3). 

Verapamil. Verapamil hydrochloride (see Table 1) is a synthetic papaverine [58-74-2] C2qH2 N04, derivative that was originally studied as a smooth muscle relaxant. It was later found to have properties of a new class of dmgs that inhibited transmembrane calcium movements. It is a (+),(—) racemic mixture. The (+)-isomer has local anesthetic properties and may exert effects on the fast sodium channel and slow phase 0 depolarization of the action potential. The (—)-isomer affects the slow calcium channel. Verapamil is an effective antiarrhythmic agent for supraventricular AV nodal reentrant arrhythmias (V1-2) and for controlling the ventricular response to atrial fibrillation (1,2,71—73). 

The uses of the antiarrhythmic drug are given in the Summaiy Drug Table Antiarrhythmic Drug3. In general these drugp are used to prevent and treat cardiac arrhythmias, such as premature ventricular contractions (PVCs), ventricular tachycardia (VT), premature atrial contractions (PACs), paroxysmal atrial tachycardia (PAT), atrial fibrillation, and atrial flutter. Some of the antiarrhythmic dru are used for other... 

FIGURE 6-2. Algorithm for the treatment of acute (top portion) paroxysmal supraventricular tachycardia and chronic prevention of recurrences (bottom portion). Note For empiric bridge therapy prior to radiofrequency ablation procedures, calcium channel blockers (or other atrioventricular [AV] nodal blockers) should not be used if the patient has AV reentry with an accessory pathway. (AAD, antiarrhythmic drugs AF, atrial fibrillation AP, accessory pathway AVN, atrioventricular nodal AVNRT, atrioventricular nodal reentrant tachycardia AVRT, atrioventricular reentrant tachycardia DCC, direct-current cardioversion ECG, electrocardiographic monitoring EPS, electrophysiologic studies PRN, as needed VT, ventricular tachycardia.)... 

Procainamide is an effective antiarrhythmic agent when given in sufficient doses at relatively short (3-4 hours) dosage intervals. Procainamide is useful in the treatment of premature atrial contractions, paroxysmal atrial tachycardia, and atrial fibrillation of recent onset. Procainamide is only moderately effective in converting atrial flutter or chronic atrial fibrillation to sinus rhythm, although it has... 

The antiarrhythmic actions and uses of diltiazem (Cardizem see Chapter 19) are similar to those of verapamil. Diltiazem is effective in controlling the ventricular rate in patients with atrial flutter or atrial fibrillation. The pharmacology of diltiazem is discussed in detail in Chapter 19. 

In the USA, amiodarone is approved for oral and intravenous use to treat serious ventricular arrhythmias. However, the drug is also highly effective for the treatment of supraventricular arrhythmias such as atrial fibrillation. As a result of its broad spectrum of antiarrhythmic action, it is very extensively used for a wide variety of arrhythmias. Amiodarone has unusual pharmacokinetics and important extracardiac adverse effects. Dronedarone, an analog that lacks iodine atoms, is under investigation. 

Dronedarone doubled the interval between episodes of atrial fibrillation recurrence in patients with paroxysmal or persistent atrial fibrillation. It is the first antiarrhythmic drug to demonstrate a reduction in mortality or hospitalization in patients with atrial fibrillation. 

The limited success of highly specific drugs that target single ion channels and the efficacy of multi-ion channel blockers such as amiodarone has shifted the emphasis in antiarrhythmic drug development to the multi-ion channel blockers class of drugs. Vernakalant is an investigational multi-channel blocker that was developed for the treatment of atrial fibrillation. 

The margin between efficacy and toxicity is particularly narrow for antiarrhythmic drugs. Risks and benefits must be carefully considered (see Antiarrhythmic Drug-Use Principles Applied to Atrial Fibrillation). 

Antiarrhythmic Drug-Use Principles Applied to Atrial Fibrillation... 

Marcus GM, Sung RJ. Antiarrhythmic agents in facilitating electrical cardioversion of atrial fibrillation and promoting maintenance of sinus rhythm. Cardiology. 2001 95 1-8. 

Nattel S, Kneller J, Zou R, Leon LJ. Mechanisms of termination of atrial fibrillation by Class I antiarrhythmic drugs evidence from clinical, experimental, and mathematical modeling studies. J Cardiovasc Electro-physiol 2 003 14(suppl) S133—S139. 

Ohmura K, Kobayashi Y, Miyauchi Y, et al. Electrocardiographic and electrophysiological characteristics of atrial fibrillation organized into atrial flutter by oral administration of class I antiarrhythmic agents. Pacing Clin Electrophysiol. 2003 26 692-702. 

Tsikouris JP, Cox CD. A review of class III antiarrhythmic agents for atrial fibrillation maintenance of normal sinus rhythm. Pharmacotherapy. 2001 21 1514-1529. 

Tikosyn Dofetilide 125, 250, 500 (jig Capsule Maintenance of normal sinus rhythm and conversion of atrial fibrillation/ flutter Cardiac ion channel blocker/ antiarrhythmic drug MCC, corn starch, silicon dioxide, magnesium stearate Pfizer... 

Keywords Antiarrhythmic Atrial fibrillation I-g UI potassium current Kvl.5 channel... 

FIGURE 6-1. Algorithm for the treatment of atrial fibrillation (AF) and atrial flutter. °lf AF <48 hours, anticoagulation prior to cardioversion is unnecessary may consider transesophageal echocardiogram (TEE) if patient has risk factors for stroke. Ablation may be considered for patients who fail or do not tolerate one antiarrhythmic drug (AAD). Chronic antithrombotic therapy should be considered in all patients with AF and risk factors for stroke regardless of whether or not they remain in sinus rhythm. (BB, 8-blocker CCB, calcium channel blocker p.e., verapamil or diltiazem] DCC, direct-current cardioversion.)... 

Flecainide slows conduction in all cardiac cells including the anomalous pathways responsible for the Wolff-Parkinson-White (WPW) syndrome. Together with encainide and moricizine, it underwent clinical trials to establish if suppression of asymptomatic premature beats with antiarrhythmic drugs would reduce the risk of death from arrhythmia after myocardial infarction. The study was terminated after preliminary analysis of 1727 patients revealed that mortality in the groups treated with flecainide or encainide was 7.7% compared with 3.0% in controls. The most likely explanation for the result was the induction of lethal ventricular arrhythmias possibly due to ischaemia by flecainide and encainide, i.e. a proarrhythmic effect. In the light of these findings the indications for flecainide are restricted to patients with no evidence of structural heart disease. The most common indication, indeed where it is the drug of choice, is atrioventricular re-entrant tachycardia, such as AV nodal tachycardia or in the tachycardias associated with the WPW syndrome or similar conditions with anomalous pathways. This should be as a prelude to definitive treatment with radiofrequency ablation. Flecainide may also be useful in patients with paroxysmal atrial fibrillation. 

Digoxin retains a unique role as a positively inotropic antiarrhythmic, being most useful in slowing atrioventricular conduction in atrial fibrillation. 

Northridge D 1996 Frusemide or nitrates for acute heart failure [see comments] Lancet 347 667-668 Peters N S et al 2002 Atrial fibrillation strategies to control, combat and cure. Lancet 359 593-603 Pitt B et al 2000 Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure randomised trial — the Losartan Heart Failure Survival Study ELITE II. [see comments] Lancet 355 1582-1587 Podrid P J 1999 Redefining the role of antiarrhythmic drugs. New England Journal of Medicine 340 1910-1912... 

Kosior D, Karpinski G, Wretowski D, Stolaiz P, Stawicki S, Rabczenko D, Torbicki A, Opolski G. Sequential prophylactic antiarrhythmic therapy for maintenance of sinus rhythm after cardioversion of persistent atrial fibrillation—one year follow-up. Kardiol Pol 2002 56 361-7. 

The Research Group for Antiarrhythmic Drug Therapy. Cost-Effectiveness of antiarrhythmic drugs for prevention of thromboembolism in patients with paroxysmal atrial fibrillation. Jpn Circ J 2001 65(9) 765-8. 

Flaker GC, Blackshear JL, McBride R, Kronmal RA, Halperin JL, Hart RG. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. J Am CoU Cardiol 1992 20(3) 527-32. 

Crijns HJ, Kingma JH, Gosselink AT, Dalrymple HW, De Langen CD, Lie K. Sequential bilateral bundle branch block during dofetilide, a new class III antiarrhythmic agent, in a patient with atrial fibrillation. J Cardiovasc Electrophysiol 1993 4(4) 459-66. 

Suttorp MJ, Polak PE, van t Hof A, Rasmussen HS, Dunsehnan PH, Kingma JH. Efficacy and safety of a new selective class III antiarrhythmic agent dofetilide in paroxysmal atrial fibrillation or atrial flutter. Am J Cardiol 1992 69(4) 417-19. 

Frost L, Mortensen PE, Tingleff J, Platon ES, Christiansen EH, Christiansen N. Efficacy and safety of dofetilide, a new class III antiarrhythmic agent, in acute termination of atrial fibrillation or flutter after coronary artery bypass surgery. Dofetilide Post-CABG Study Group. Int J Cardiol 1997 58(2) 135 0. 

Falk RH, Poliak A, Singh SN, Friedrich T. Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. Intravenous Dofetilide Investigators. J Am CoU Cardiol 1997 29(2) 385-90. 

Schumacher B, Jung W, Lewalter T, Vahlhaus C, Wolpert C, Luderitz B. Radiofrequency ablation of atrial flutter due to administration of class IC antiarrhythmic drugs for atrial fibrillation. Am J Cardiol 1999 83(5) 710-13. 

Valderrabano M, Singh BN. Electrophysiologic and Antiarrhythmic Effects of Propafenone Focus on Atrial Fibrillation. J Cardiovasc Pharmacol Ther 1999 4(3) 183-98. 

Amman EM, Beamer AD, Cantillon C, McGowan N, Friedman PL. Therapy of refractory symptomatic atrial fibrillation and atrial flutter a staged care approach with new antiarrhythmic drugs. J Am Coll Cardiol 1990 15(3) 698-707. 

Jazwinska-Tarnawska E, Orzechowska-Juzwenko K, Niewinski P, Rzemislawska Z, Loboz-Grudzien K, Dmochowska-Perz M, Slawin J. The influence of CYP2D6 polymorphism on the antiarrhythmic efficacy of propafenone in patients with paroxysmal atrial fibrillation during 3 months propafenone prophylactic treatment. Int J Clin Pharmacol Ther 2001 39(7) 288-92. 

HPI DD is a 67-year-old woman who presents to the clinic complaining of headache, dizziness, and "buzzing in her ears." She states that her symptoms have been present for about 4 days. One week prior, the patient was discharged from the hospital for atrial fibrillation Rate control was achieved and she was converted to normal sinus rhythm (NSR). She was placed on a new antiarrhythmic medication to prevent further episodes of AF. PMH Episodic AF, cirrhosis,... 

Indications Atrial fibrillation Category Antiarrhythmic class I c Half-life 7-22 hours... 

Indications Atrial fibrillation and flutter Category Antiarrhythmic class III Half-life 2-12 hours... 

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