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Journal of Managed Care Pharmacy : JMCP Oct 2006Amiodarone (Cordarone, Pacerone) is a powerful antiarrhythmic that is effective in converting atrial fibrillation (AF) to sinus rhythm and superior to sotalol in...
Amiodarone (Cordarone, Pacerone) is a powerful antiarrhythmic that is effective in converting atrial fibrillation (AF) to sinus rhythm and superior to sotalol in maintaining sinus rhythm. In 665 patients who were receiving anticoagulants and had persistent AF, Singh et al. found a median time to recurrence of AF of 487 days in the amiodarone group versus 74 days in the sotalol group and 6 days in the placebo group, with improved quality of life and improved exercise performance in the amiodarone group.1 In this study known as the Sotalol Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T), spontaneous conversion occurred in 72.1% of amiodarone patients, 24.2% for sotalol, and 0.8% for placebo. However, the use of amiodarone in AF is not approved by the U.S. Food and Drug Administration (FDA). The unlabeled (off-label) uses of amiodarone include conversion of atrial fibrillation and maintenance of sinus rhythm, and treatment of supraventricular tachycardia.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Humans; Safety Management; United States
PubMed: 17269848
DOI: 10.18553/jmcp.2006.12.8.687 -
Journal of Pharmacy & Pharmaceutical... 2014Carica papaya has been traditionally used worldwide in folk medicine to treat a wide range of ailments in humans, including the management of obesity and digestive...
PURPOSE
Carica papaya has been traditionally used worldwide in folk medicine to treat a wide range of ailments in humans, including the management of obesity and digestive disorders. However, scientific information about its potential to interact with conventional drugs is lacking. Thus, this work aimed to investigate the interference of a standardized C. papaya extract (GMP certificate) on the systemic exposure to amiodarone (a narrow therapeutic index drug) in rats.
METHODS
In the first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of C. papaya (1230 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.); in the second study, rats were pre-treated for 14 days with C. papaya (1230 mg/kg/day, p.o.) and received amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the herbal extract vehicle. Blood samples were collected before dosing and at 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h following amiodarone administration; in addition, at 24 h post-dose, blood and tissues (heart, liver, kidneys and lungs) were also harvested. Thereafter, the concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were determined in plasma and tissue samples employing a high-performance liquid chromatography-diode array detection method previously developed and validated.
RESULTS
In both studies was observed a delay in attaining the maximum plasma concentrations of amiodarone (tmax) in the rats treated with the extract. Nevertheless, it must be highlighted the marked increase (60-70%) of the extent of amiodarone systemic exposure (as assessed by AUC0-t and AUC0-∞) in the rats pre-treated with C. papaya comparatively with the control (vehicle) group.
CONCLUSIONS
The results herein found suggest an herb-drug interaction between C. papaya extract and amiodarone, which clearly increase the drug bioavailability. To reliably assess the clinical impact of these findings appropriate human studies should be conducted.
Topics: Administration, Oral; Amiodarone; Animals; Biological Availability; Carica; Fruit; Herb-Drug Interactions; Injections, Intravenous; Male; Plant Extracts; Rats; Rats, Wistar
PubMed: 25224345
DOI: 10.18433/j3559n -
Journal of the American College of... Apr 1995This study assessed the safety and efficacy of combined flecainide and amiodarone therapy in controlling refractory tachyarrhythmias in infants.
OBJECTIVES
This study assessed the safety and efficacy of combined flecainide and amiodarone therapy in controlling refractory tachyarrhythmias in infants.
BACKGROUND
Single-drug as well as standard combination medical therapy for tachyarrhythmias in infants sometimes fails. In those cases, one may consider interventional therapy. However, this option may carry a high risk of morbidity and mortality in infants. The natural history of tachyarrhythmias in infants often favors eventual resolution and reinforces the importance of selecting an effective medical regimen.
METHODS
We performed a retrospective analysis of nine infants (median age 2 months) who received combined flecainide and amiodarone therapy for attempted control of refractory tachyarrhythmias. Trough serum drug levels of flecainide were monitored, and 24-h ambulatory electrocardiographic monitoring was used to determine efficacy of therapy.
RESULTS
Single-drug treatment with flecainide or amiodarone failed in all of the infants studied. An average of four drugs failed (range one to six) before administration of combined flecainide and amiodarone therapy. During combined therapy, the flecainide dose was 70 to 110 mg/m2 per day, and that for amiodarone was 7.5 to 13.5 mg/kg per day for a mean (+/- SD) of 9 +/- 2 days to load and 5 to 12 mg/kg per day as maintenance. Successful control of tachyarrhythmias was demonstrated in seven (78%) of nine infants (95% confidence interval 46% to 99%) (three of three with congenital junctional ectopic tachycardia, three of three with supraventricular tachycardia and one of three with ventricular tachycardia). During combined therapy, flecainide trough levels ranged from 350 to 731 ng/ml. Corrected QT intervals varied from 0.440 to 0.488 ms. No proarrhythmia occurred. None of the infants required a pacemaker, and all had normal left ventricular dimensions and fractional shortening by echocardiography. Eight of nine infants had a structurally normal heart. One infant had surgical correction of an atrioventricular septal defect.
CONCLUSIONS
Combination therapy with flecainide and amiodarone appears to be safe and effective in controlling refractory tachyarrhythmias in infants. The combination of flecainide and amiodarone may obviate the need for early interventional therapy or may allow delay until the child is older.
Topics: Amiodarone; Drug Therapy, Combination; Electrocardiography, Ambulatory; Female; Flecainide; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Retrospective Studies; Tachycardia, Supraventricular; Tachycardia, Ventricular; Time Factors
PubMed: 7897134
DOI: 10.1016/0735-1097(94)00513-p -
CMAJ : Canadian Medical Association... Oct 2012
Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Humans; Lung Diseases; Male; Tachycardia, Ventricular; Tomography, X-Ray Computed
PubMed: 22529166
DOI: 10.1503/cmaj.111763 -
American Journal of Physiology.... Sep 2021Drug-induced liver injury is an emerging form of acute and chronic liver disease that may manifest as fatty liver. Amiodarone (AMD), a widely used antiarrhythmic drug,...
Drug-induced liver injury is an emerging form of acute and chronic liver disease that may manifest as fatty liver. Amiodarone (AMD), a widely used antiarrhythmic drug, can cause hepatic injury and steatosis by a variety of mechanisms, not all completely understood. We hypothesized that repetitive AMD administration may induce hepatic lipotoxicity not only via effects on the liver but also via effects on adipose tissue. Indeed, repetitive AMD administration induced endoplasmic reticulum (ER) stress in both liver and adipose tissue. In adipose tissue, AMD reduced lipogenesis and increased lipolysis. Moreover, AMD treatment induced ER stress and ER stress-dependent lipolysis in 3T3L1 adipocytes in vitro. In the liver, AMD caused increased expression of genes encoding proteins involved in fatty acid (FA) uptake and transfer (, , and ), and resulted in increased hepatic accumulation of free FAs, but not of triacylglycerols. In line with this, there was increased expression of hepatic de novo FA synthesis genes. However, AMD significantly reduced the expression of the desaturase and elongase , detected at mRNA and protein levels. Accordingly, the FA profile of hepatic total lipids revealed increased accumulation of palmitate, an SCD1 and ELOVL6 substrate, and reduced levels of palmitoleate and -vaccenate, products of the enzymes. In addition, AMD-treated mice displayed increased hepatic apoptosis. The studies show that repetitive AMD induces ER stress and aggravates lipolysis in adipose tissue while inducing a lipotoxic hepatic lipid environment, suggesting that AMD-induced liver damage is due to compound insult to liver and adipose tissue. AMD chronic administration induces hepatic lipid accumulation by several mechanisms, including induction of hepatic ER stress, impairment of β-oxidation, and inhibition of triacylglycerol secretion. Our study shows that repetitive AMD treatment induces not only hepatic ER stress but also adipose tissue ER stress and lipolysis and hepatic accumulation of free fatty acids and enrichment of palmitate in the total lipids. Understanding the toxicity mechanisms of AMD would help devise ways to limit liver damage.
Topics: Adipocytes; Adipose Tissue; Amiodarone; Animals; Endoplasmic Reticulum Stress; Fatty Acid-Binding Proteins; Fatty Acids; Fatty Acids, Nonesterified; Fatty Liver; Lipid Metabolism; Lipogenesis; Lipolysis; Liver; Liver Diseases; Mice; Triglycerides
PubMed: 34259586
DOI: 10.1152/ajpgi.00458.2020 -
Annals of Thoracic and Cardiovascular... Dec 2021The aim of this study was to evaluate the efficacy of the multichannel-blocker dronedarone for postoperative new onset atrial fibrillation (POAF) as compared to...
PURPOSE
The aim of this study was to evaluate the efficacy of the multichannel-blocker dronedarone for postoperative new onset atrial fibrillation (POAF) as compared to amiodarone.
METHODS
Out of 990 patients who underwent cardiothoracic surgery between March 2011 and March 2012, 166 patients who developed POAF and treated with amiodarone or dronedarone were enrolled in this study.
RESULTS
Eighty-nine patients were treated with amiodarone and 77 patients were treated with dronedarone at discharge. Seventy-five percent of patients with dronedarone were treated initially with intravenous amiodarone but quickly converted to oral dronedarone as soon as the mechanical ventilation was weaned off. The rate of conversion in sinus rhythm was not influenced by the resulting amiodarone-to-dronedarone crossover as compared to oral dronedarone only (p <0.247 at the ICU and p <0.640 at the normal care unit). At hospital discharge sinus rhythm was documented in 44% of the amiodarone patients and 99% of the dronedarone patients (p <0.001). The maintenance of sinus rhythm was demonstrated in 82% of the amiodarone patients versus 81% of the dronedarone patients at 6-month follow-up (p <0.804).
CONCLUSIONS
Our data demonstrated the higher conversion rate to sinus rhythm in the early phase in the dronedarone group despite a comparable conversion rate in the mid-term phase compared to amiodarone.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Surgical Procedures; Dronedarone; Humans; Treatment Outcome
PubMed: 34276001
DOI: 10.5761/atcs.oa.21-00070 -
Indian Heart Journal 2012Atrial fibrillation (AF) is the most common of the serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality. Available drug therapy... (Review)
Review
Atrial fibrillation (AF) is the most common of the serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality. Available drug therapy for AF has modest efficacy and is associated with the risk of life-threatening pro-arrhythmic complications. Dronedarone is a newer therapeutic agent with a structural resemblance to amiodarone and a better side effect profile. It is a multichannel blocker with antiadrenergic properties and has been evaluated in both rate and rhythm control strategies in the management of AF. In this review, we discuss the current role of dronedarone in the contemporary management of AF.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Dronedarone; Heart Failure; Humans; Treatment Outcome
PubMed: 22572497
DOI: 10.1016/S0019-4832(12)60058-3 -
Turkish Journal of Medical Sciences Oct 2018Background/aim: Esmolol and amiodarone are two most commonly used antiarrhythmic drugs in coronary artery bypass grafting (CABG) surgery. Nevertheless, blockade of...
Background/aim: Esmolol and amiodarone are two most commonly used antiarrhythmic drugs in coronary artery bypass grafting (CABG) surgery. Nevertheless, blockade of beta-2 receptors by increasing doses raise concerns about possible vasospasms. We studied the vasoactive effects of amiodarone and esmolol on left internal mammary artery (LIMA), radial artery (RA), and saphenous vein (SV) grafts. Materials and methods: After determining the presence of functional smooth muscle and endothelial layers, the responses of submaximally preconstricted graft samples were recorded in a tissue bath system. A total of 96 graft samples from 40 patients were used: 16 LIMA, 16 RA, and 16 SV grafts for each drug. Esmolol and amiodarone were added to reservoirs separately, starting from a concentration of 10-8 M until a concentration of 10-4 M. Results: Although both drugs caused vasodilatation, amiodarone exhibited a more potent vasodilatory effect than esmolol (P < 0.0001 for LIMA, P = 0.0128 for RA, and P < 0.0001 for SV). The vasodilatation rates with esmolol were 48.99 ± 2.28% in LIMA, 49.77 ± 3.03% in RA, and 41.90 ± 4.05% in SV grafts and with amiodarone they were 71.65 ± 5.18% in LIMA, 58.61 ± 5.87% in RA, and 65.07 ± 4.09% in SV grafts. Conclusion: This in vitro study revealed that even increasing doses of both drugs induce vasodilatation of CABG grafts, with amiodarone having a more potent vasodilatory effect than esmolol.
Topics: Aged; Aged, 80 and over; Amiodarone; Coronary Artery Bypass; Coronary Vessels; Female; Humans; Male; Middle Aged; Propanolamines; Vasodilation
PubMed: 30384577
DOI: 10.3906/sag-1802-124 -
Journal of the American College of... Jul 1986The time to onset of action of amiodarone is often long in patients treated for arrhythmias; one reason might be a slow entry of the drug into the target organ, the...
The time to onset of action of amiodarone is often long in patients treated for arrhythmias; one reason might be a slow entry of the drug into the target organ, the heart. Amiodarone and desethylamiodarone, its active metabolite, were measured in the plasma, atrial tissue and pericardial fat of patients undergoing cardiac surgery. Two groups were studied: patients treated with amiodarone for less than 28 days (short-term group) and those treated for 28 days or more (long-term group). Plasma levels of amiodarone in the two groups were not different, whereas levels of desethylamiodarone were significantly higher in the long-term group. Average concentrations of amiodarone in the atrium were higher with longer treatment periods (30.2 +/- 5.6 versus 13.2 +/- 2.5 micrograms/g wet weight of tissue); the same was true for desethylamiodarone (40.3 +/- 7.7 versus 15.7 +/- 3.7 micrograms/g). Amiodarone concentrations in fat were also significantly higher in the long-term than in the short-term group. Atrium/plasma concentration ratios of desethylamiodarone were higher than those of amiodarone, whereas fat plasma concentration ratios of desethylamiodarone were lower. In conclusion, the equilibration of amiodarone and desethylamiodarone concentrations between myocardium and plasma appears to occur slowly in patients undergoing long-term treatment with amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adipose Tissue; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Surgical Procedures; Heart Atria; Humans; Kinetics; Middle Aged; Myocardium; Time Factors
PubMed: 3711518
DOI: 10.1016/s0735-1097(86)80114-0 -
Journal of the American Veterinary... Feb 2017
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Electric Countershock; Horse Diseases; Horses
PubMed: 28117639
DOI: 10.2460/javma.250.3.278