Chronic and Acute Effects of Dronedarone on the Action Potential of Rabbit Atrial Muscle Preparations: Comparison With Amiodarone

Sun, Wei; Sarma, J. S. M.; Singh, Bramah N.

doi:10.1097/00005344-200205000-00008

Cited by 101 publications

(74 citation statements)

References 34 publications

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“…The most consistent effect is usedependent inhibition of maximum upstroke velocity, both after acute and sustained administration. Acute administration of 0.1 to 10 mol/L of dronedarone decreased action potential duration in rabbit papillary muscle, 22 rabbit atrial muscle, 37 and the canine papillary muscle preparation, 25 with no effect on guinea pig ventricular myocytes. 24 On the other hand, sustained administration of drug increased action potential duration in rabbit papillary muscles 22 and rabbit atrial muscles.…”

Section: Electrophysiological Properties Of Dronedarone In Vitro Expementioning

confidence: 91%

“…24 On the other hand, sustained administration of drug increased action potential duration in rabbit papillary muscles 22 and rabbit atrial muscles. 37 The action potential duration of dog papillary muscle remained unchanged. 25 In canine left ventricular Purkinje fibers, 10 mol/L of dronedarone reduced the incidence of early and delayed afterdepolarizations evoked by dofetilide and ouabain, respectively.…”

Section: Electrophysiological Properties Of Dronedarone In Vitro Expementioning

confidence: 97%

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Dronedarone

2009

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Abstract-Amiodarone is the most effective antiarrhythmic drug for maintaining sinus rhythm for patients with atrial fibrillation. Extra-cardiac side effects have been a limiting factor, especially during chronic use, and may offset its benefits. Dronedarone is a noniodinated benzofuran derivative of amiodarone that has been developed for the treatment of atrial fibrillation and atrial flutter. Similar to amiodarone, dronedarone is a potent blocker of multiple ion currents, including the rapidly activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine activated potassium current, peak sodium current, and L-type calcium current, and exhibits antiadrenergic effects. It has been studied for maintenance of sinus rhythm and control of ventricular response during episodes of atrial fibrillation. Dronedarone reduces mortality and morbidity in patients with high-risk atrial fibrillation, but may be unsafe in those with severe heart failure. This article will review evidence of safety and effectiveness of dronedarone in patients with atrial fibrillation. Key Words: amiodarone Ⅲ arrhythmia Ⅲ atrial fibrillations Ⅲ dronedarone A trial fibrillation (AF) is the most common arrhythmia in clinical practice and a usual cause for hospitalization and consultation. 1,2 It is an epidemic. It is projected that by 2050, more than 15 million people will contract AF in the United States alone. 2,3 Nearly 1 in every 10 persons aged 80 years and older has AF, 1,4,5 predisposing them to stroke, heart failure, and death. 6,7 A recent report from Centers for Medicare and Medicaid Services suggested that AF accounted for 1 765 304 hospitalizations in 1999. 8 The cost of medical care for patients with AF is almost 5 times higher than the care of patients without AF. 9,10 Despite improvements in primary and secondary prevention of ischemic heart disease and hypertension, the US age-adjusted death rate due to AF increased from 27.6 in 1980 to 69.8 per 100 000 in 1998. 2,11 Current therapy for AF is multidimensional and complicated. 12 There is some consensus on the benefits of anticoagulation in patients with AF, but debate continues about the relative value of rate versus rhythm control. Recent clinical trials have failed to demonstrate superiority of sinus rhythm maintenance, 13-18 but antiarrhythmic therapy is important for patients with severe symptoms. Conventional antiarrhythmic drugs have limited efficacy and safety. In fact, data suggest that the benefit of restoring and maintaining sinus rhythm in AF may be offset by significant cardiac and extracardiac side effects of currently used drugs. 19 -21 Improvement in the current approach to AF is clearly necessary. This review focuses on dronedarone, a new antiarrhythmic drug for AF suppression (Figure 1). Electrophysiological Properties of Dronedarone In Vitro ExperimentsIn vitro electrophysiological properties of dronedarone and its comparison with amiodarone are summarized in Table...

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Section: Electrophysiological Properties Of Dronedarone In Vitro Expementioning

confidence: 91%

Section: Electrophysiological Properties Of Dronedarone In Vitro Expementioning

confidence: 97%

Dronedarone

2009

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“…32 It was also found that dronedarone produced less prolongation of ventricular repolarization than amiodarone during long-term treatment of canines. The lack of APD prolongation with short term administration in animal models may relate to the balanced influence on depolarizing and repolarizing currents.…”

Section: Evidence From Animal Studiesmentioning

confidence: 96%

Dronedarone in the management of atrial fibrillation

Saleem¹,

Bharani²,

Chetty³

et al. 2010

OAEM

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Atrial fibrillation is the most common type of tachyarrhythmia caused by multiple re-entrant wave forms within the atria and bombarding the atrioventricular node several times making it beat in a rapid, disorganized fashion termed "fibrillation". In atrial fibrillation, atria beat more than 300 times per minute. The arrhythmatous condition needs to be controlled, as humans cannot withstand this rapid and chaotic beating of the heart. New investigational drugs like Dronedarone ® are being used. Dronedarone is the most recent antiarrhythmic drugs. It was approved by US-FDA on July 2nd 2009 and is available in the USA as Multaq tablets (400 mg). Dronedarone falls under the category of multiple ion channel blocker. It mainly targets the repolarization currents, making them less active and hence prolonging the action potential duration (APD). Dronedarone also exhibits antiadrenergic activity, thus reducing the pace of the pacemaker. Dronedarone has been proven to be a safer and efficacious AAD, evidenced by both animal and human studies. These studies showed that there was prolongation of the APD and absence of QT interval prolongation with long term administration of the drug. Also there was reduced thyroid hormone receptor expression. Dronedarone is significantly safer and effective in maintaining the sinus rhythm and reducing the ventricular proarrhythmias, justifying it for the long term treatment of atrial fibrillation compared to other antiarrhythmic drugs.

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“…46 Dronedarone is a benzofuran derivative with an electropharmacologic profile resembling that of amiodarone but with different relative effects on individual ion channels. [47][48][49][50] The structural changes made to amiodarone to produce dronedarone include the removal of iodine and the addition of a methane-sulfonyl group.…”

Section: Ranolazine+drondedaronementioning

confidence: 99%