Quinidine atrial fibrillation

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). 

Qninidine exhibits all of the pharmacological properties of qninine, including antimalar-ial, fever-redncing, and other properties. Quinidine is used in varions forms of arrhythmia for preventing tachycardia and atrial fibrillation, and particularly for preventing ciliary fibrillation, paroxysmal snpraventricnlar tachycardia, extrasystole, and ventricular tachycardia. However, it is a toxic drug and is nsed relatively rarely. 

Primary indications for the use of quinidine include (1) abolition of premature complexes that have an atrial, A-V junctional, or ventricular origin (2) restoration of normal sinus rhythm in atrial flutter and atrial fibrillation after controlling the ventricular rate with digitahs (3) maintenance of normal sinus rhythm after electrical conversion of atrial arrhythmias (4) prophylaxis against arrhythmias associated with electrical countershock (5) termination of ventricular tachycardia and (6) suppression of repetitive tachycardia associated with Wolff-Parkinson-White (WPW) syndrome. 

Although quinidine often is successful in producing normal sinus rhythm, its administration in the presence of a rapid atrial rate (flutter and possibly atrial fibrillation) can lead to a further and dangerous increase in the ventricular rate secondary to inhibition of basal vagal tone upon the A-V node. For this reason, digitalis should be used before quinidine when one is attempting to convert atrial flutter or atrial fibrillation to normal sinus rhythm... 

Lau CP, Chow MS, Tse HF, Tang MO, Fan C. Control of paroxysmal atrial fibrillation recurrence using combined administration of propafenone and quinidine. Am J Cardiol 2000 86 1327-1332. 

Quinine is a cinchona alkaloid that acts rapidly against all four species of Plasmodium. It is used to treat protozoal infections and leg cramps, and as a bitter and flavoring agent. However, the drug is not used prophylactically for malaria. Quinines are contraindicated in patients with a history of hypersensitivity to quinine or quinidine. They should not be used in the presence of hemolysis and should be used with caution in patients with atrial fibrillation, cardiac conduction defects, or heart block. Quinine administration in myasthenia gravis may aggravate the disease, hence it should be avoided. Quinine can be used in pregnancy.37 Intravenous infusion of quinine should be slow, and the patient should be monitored for cardiotoxicity.38 Cinchonism, which is characterized by tinnitus, GI disturbances, and impaired vision may occur with therapeutic doses of quinine.39... 

Juul-Moller S, Edvardsson N, Rehnqvist-Ahlberg N. Sotalol versus quinidine for the maintenance of sinus rhythm after direct current conversion of atrial fibrillation. Circulation 1990 82(6) 1932-9. 

Quinidine has been added to propafenone with the intention of inhibiting propafenone metabolism via CYP2D6 in the hope of improving outcome (8). Of 60 patients with paroxysmal atrial fibrillation given propafenone 300-450 mg/day for 8 weeks there were 19 refractory cases, who were then randomized double-blind to receive either a higher dose of propafenone (450-675 mg/day) or the standard dose of propafenone with extra low-dose quinidine (150 mg/day), each for 8 weeks, with subsequent crossover to the alternative. Patients who even then were not adequately controlled were given the standard dose of propafenone plus a standard dose of quinidine (600 mg/day) for a further 8 weeks. The plasma propafenone concentrations during the four phases were as follows ... 

The beneficial effects were related to these plasma concentrations, as were the time to the first bout of atrial fibrillation, the frequency of bouts of atrial fibrillation, and the time between episodes. However, when atrial fibrillation occurred there was no difference in the ventricular rate in the different groups. Adverse effects necessitated drug withdrawal in four patients one had heart failure and two had gastrointestinal symptoms. These effects were not dose-related, although there were too few occurrences for a definitive conclusion. The authors suggested that this stepwise approach, with increasing doses of propafenone and increasing doses of quinidine could be beneficial in the treatment of paroxysmal atrial fibrillation. 

A placebo-controUed study of the use of propafenone 450-600 mg orally, either alone or in combination with digoxin, has been carried out in 176 patients with atrial fibrillation a further 70 patients were given digitalis plus quinidine (12). There were no significant differences across the groups in terms of percentage conversion to sinus rhjThm,... 

A 56-year-old man who took quinidine 324 mg five times daily for prevention of paroxysmal atrial fibrillation developed a syndrome similar to polymyalgia rheumatica which settled on drug withdrawal (60). 

C Diltiazem. Quinidine can be used to maintain normal sinus rhythm (NSR) after cardioversion of atrial fibrillation. Metoprolol is commonly used to control ventricular rate before conversion to NSR. However, this patient has two contraindications (COPD and diabetes) for beta-blocker use. Unlike diltiazem, amlodipine and nimodipine do not block AV nodal conduction therefore, they would be ineffective at rate control. 

Quinidine, the d-isomer of quinine, has been used in horses since 1924 (Roos 1924) and has a wide variety of properties. It is currently the drug of choice for the treatment of atrial fibrillation (AF) in horses but can be used for the treatment of a variety of re-entrant and ectopic arrhythmias. Quinidine affects heart rate, cardiac rhythm and vascular tone by a range of mechanisms and also produces a variety of non-cardiac effects. In addition to the class la activity, which prolongs the effective refractory period, the drug is vagolytic as a result of its antimuscarinic properties. 

Figure 12.2 Electrocardiograms from a horse undergoing treatment for atrial fibrillation, (a, b) Base-apex (a) and modified base-apex (b) electrocardiograms after treatment with quinidine sulfate (330mg/kg). Ventricular tachycardia, (torsades de pointes) occurred after 40 h. (c) The horse was treated with five bolus doses of magnesium sulfate, together with intravenous propanoloi, which resulted in conversion to normal sinus rhythm with QRS prolongation, (d) Twenty-four hours after conversion, the electrocardiogram showed normal sinus rhythm without QRS prolongation.

Quinidine gluconate Acute-onset atrial fibrillation ventricular tachycardia 2.2 mg/kg i.v. every 10 min 12 mg/kg total... 

Quinidine sulfate Atrial fibrillation 2.2 mg/kg by nasogastric tube every 2 h for six doses... 

Muir W W 1995 The haemodynamic effects of milrinone HCI In halothane anaesthetized horses. Equine Veterinary Journal Supplement 19 108-113 Muir W W, Mcguirk S M 1985 Pheirmacology and pharmacokinetics of drugs used to treat cardiac disease in horses. Veterinary Clinics of North America Equine Practice 1 335-352 Muir W W D, Mcguirk S 1987 Cardiovascular drugs. Their pharmacology and use In horses. Veterinary Clinics of North America Equine Practice 3 37-57 Muir W W D, Reed S M, Mcguirk S M 1990 Treatment of atrial fibrillation in horses by intravenous administration of quinidine. Journal of the American Veterinary Medical Association 197 1607-1610... 

Neff C A, Davis L E, Baggot J D 1972 A comparative study of the pharmacokinetics of quinidine. American Journal of Veterinary Research 33 1521-1525 Ohmura H, Nukada T, Mizuno Y et al 2000 Safe and efficacious dosage of flecainide acetate for treating equine atrial fibrillation. Journal of Veterinary Medical Science 62 711-715... 

Quinidine is used to treat and control atrial fibrillation and atrial flutter. Quinidine is also approved to treat premature ventricular contractions and to treat paroxysmal atrial tachycardia or paroxysmal atrioventricular junctional rhythm. It may also be used to treat malaria, although quinine is preferred. 

Disopyramide, proprietary name Norpace, is used for maintenance of sinus rhythm in patients with atrial flutter and atrial fibrillation and for prevention of ventricular tachycardia and fibrillation. The mechanism of action of disopyramide is similar to that of quinidine, and the drug can be used as replacement therapy for quinidine when quinidine side effects are intolerable. 

Procainamide, proprietary name Pronestyl, is used for therapy of PVCs, ventricular tachycardia, atrial fibrillation, and paroxysmal atrial tachycardia. Its mechanism of action is similar to that of quinidine in that it increases the threshold membrane potential by blocking potassium outflow, reducing excitability and contraction velocity in Purkinje s fibers and ventricular muscle. 

Example A 70-kg patient with poor LV function (i.e., CHE) and frequent paroxysmal episodes of atrial fibrillation is to be treated with oral quinidine. A straight line drawn between 1 on the conditions bar and 70 kg on the weight bar will intersect near the center arrow on the box. Directly above the point of intersection are the medium dosage ranges quinidine sulfate can be initiated at 1200 mg/ day or 300 mg every 6 hours in this patient. (From Bauman JL, Schoen MD, Hoon TJ. Practical optimisation of antiarrhythmic drug therapy using pharmacokinetic principles. Clin Pharmacokinet 1991 20 151-166, with permission.)... 

Alternatives to amiodarone include the type Ic drugs (e.g., fle-cainide and propafenone) and the type III blockers (e.g., sotalol and dofetilide). Because of the risk of pro arrhythmia, the type Ic drugs should be reserved for those without heart disease (i.e., lone atrial fibrillation). Sotalol has been shown to be at least as effective as quinidine in preventing recurrences of atrial fibrillation." However, treatment with either quinidine or sotalol is associated with a similar incidence of torsade de pointes. Since this form of proarrhythmia occurs primarily with higher doses of sotalol (quinidine usually causes torsade de pointes at low or therapeutic concentrations), it may be predicted more easily and therefore avoided. Nonetheless, it is possible that sotalol increases mortality in patients with atrial fibrillation similar to quinidine, and this requires further study." ... 

The newest type III agent, dofetihde, is effective in preventing recurrences of atrial fibrillation" but has not been compared directly with amiodarone. In a large multicenter trial," dofetihde (dose adjusted for renal function and QT interval) was more effective than placebo in maintaining sinus rhythm (about 40% to 60% at 1 year). Like sotalol and quinidine, dofetilide has significant potential to cause torsade de pointes (in a dose-related fashion), and because of this, we believe that dofetilide should not be considered first-line therapy for recurrent atrial fibrillation at this time. 

Southworth MR, Zarembski D, Viana M, Bauman JL. Comparison of sotalol versus quinidine for maintenance of normal sinus rhythm in patients with chronic atrial fibrillation. Am J Cardiol 1999 83 1629-1632. 

In addition to use in heart failure, the vagomimetic properties of digoxin may be used prophy-lactically in supraventricular tachyarrhythmias (SVTs), including atrial Fibrillation, and for slow-ing the increase in AV conduction caused by quinidine. 

Here I will mention only one example. Disturbances of cardiac rhythm are an important medical problem. Quinidine, the d-isomer of quinine, is one of the most effective agents available for the treatment of cardiac arrhythmias. The discovery that quinine, and subsequently quinidine, could be used to treat certain arrhythmias must be attributed to luck. A patient of Wenckebach, a famous Viennese physician, noted in 1912 that when he took quinine for his malaria it also caused his rapid, irregular pulse to become slower and more regular. In 1918 Frey compared several cinchana alkaloids and found that quinidine was more effective in treating atrial fibrillation than quinine. Subsequently, quinidine was found to be effective against many other cardiac arrhythmias. 

Quinidine is used mainly in the therapy of atrial fibrillation and certain other cardiac arrhythmias. Its pharmacological actions, especially cardiac activities, as well as its toxic reactions and therapeutic uses, are adequately illustrated in a recent edition of The Pharmacological Basis of Therapeutics by Goodman and Gilman (54). 

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