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PloS One 2013Apamin sensitive potassium current (I KAS), carried by the type 2 small conductance Ca(2+)-activated potassium (SK2) channels, plays an important role in post-shock...
BACKGROUND
Apamin sensitive potassium current (I KAS), carried by the type 2 small conductance Ca(2+)-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles.
OBJECTIVE
To test the hypothesis that amiodarone inhibits I KAS in human embryonic kidney 293 (HEK-293) cells.
METHODS
We used the patch-clamp technique to study I KAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration.
RESULTS
Amiodarone inhibited IKAS in a dose-dependent manner (IC50, 2.67 ± 0.25 µM with 1 µM intrapipette Ca(2+)). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6 ± 3.1% of IKAS induced with 1 µM intrapipette Ca(2+) (n = 3). IKAS inhibition by amiodarone was not voltage-dependent, but was Ca(2+)-dependent: 30 µM amiodarone inhibited 81.5±1.9% of I KAS induced with 1 µM Ca(2+) (n = 4), and 16.4±4.9% with 250 nM Ca(2+) (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca(2+) dependent inhibition of I KAS.
CONCLUSION
Both amiodarone and desethylamiodarone inhibit I KAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca(2+) concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles.
Topics: Amiodarone; Anti-Arrhythmia Agents; Apamin; Calcium; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Intracellular Space; Patch-Clamp Techniques; Small-Conductance Calcium-Activated Potassium Channels; Ventricular Fibrillation
PubMed: 23922993
DOI: 10.1371/journal.pone.0070450 -
BioMed Research International 2020Amiodarone and propafenone are commonly used to maintain sinus rhythm in patients with atrial fibrillation (AF). However, it is not known which one is better in reducing... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
Amiodarone and propafenone are commonly used to maintain sinus rhythm in patients with atrial fibrillation (AF). However, it is not known which one is better in reducing early recurrence (ER) during the blanking period (the first three months after catheter ablation).
OBJECTIVE
To compare the efficacy and safety of amiodarone and propafenone in reducing ER during the blanking period after radiofrequency catheter ablation (RFCA) in AF patients.
MATERIALS AND METHODS
A total of 694 patients who underwent their first RFCA between May 2014 and May 2018 were enrolled in this retrospective study. Subsequently, 202 patients were excluded according to the exclusion criteria. The remaining 492 patients were divided into two groups based on the choice of antiarrhythmic drugs (AADs) (amiodarone or propafenone) in the blanking period. The primary outcomes were incidence of ER and AAD-associated adverse effects during the blanking period after RFCA. Propensity score matching (PSM) analyses were used to compare the outcomes of the two groups while controlling for confounders.
RESULTS
Among the 492 patients who took AADs in the blanking period (187 amiodarone and 305 propafenone), PSM selected 135 unique pairs of patients with similar characteristics. Amiodarone was associated with a lower ER incidence rate (23.7% versus 48.9%, < 0.001) and a similar rate of AAD-associated adverse effects (2.1% versus 1.5%, = 0.652). Treatment with amiodarone in the blanking period was significantly associated with a lower ER incidence rate compared to treatment with propafenone (HR = 0.416, 95% CI 0.272-0.637, < 0.001).
CONCLUSIONS
Compared with propafenone, amiodarone was associated with a lower ER incidence rate, and they had similar rates of AAD-associated adverse effects. Treatment with amiodarone in the blanking period was shown to be more effective in reducing ER than propafenone.
Topics: Aged; Amiodarone; Atrial Fibrillation; Catheter Ablation; Female; Humans; Male; Middle Aged; Propafenone; Recurrence
PubMed: 32685445
DOI: 10.1155/2020/1835181 -
PLoS Neglected Tropical Diseases Aug 2018Chagas disease is a neglected chronic condition caused by Trypanosoma cruzi, with high prevalence and burden in Latin America. Ventricular arrhythmias are common in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chagas disease is a neglected chronic condition caused by Trypanosoma cruzi, with high prevalence and burden in Latin America. Ventricular arrhythmias are common in patients with Chagas cardiomyopathy, and amiodarone has been widely used for this purpose. The aim of our study was to assess the effect of amiodarone in patients with Chagas cardiomyopathy.
METHODOLOGY
We searched MEDLINE, Embase and LILACS up to January 2018. Data from randomized and observational studies evaluating amiodarone use in Chagas cardiomyopathy were included. Two reviewers selected the studies, extracted data and assessed risk of bias. Overall quality of evidence was accessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
PRINCIPAL FINDINGS
We included 9 studies (3 before-after studies, 5 case series and 1 randomized controlled trial). Two studies with a total of 38 patients had the full dataset, allowing individual patient data (IPD) analysis. In 24-hour Holter, amiodarone reduced the number of ventricular tachycardia episodes in 99.9% (95%CI 99.8%-100%), ventricular premature beats in 93.1% (95%CI 82%-97.4%) and the incidence of ventricular couplets in 79% (RR 0.21, 95%CI 0.11-0.39). Studies not included in the IPD analysis showed a reduction of ventricular premature beats (5 studies), ventricular tachycardia (6 studies) and ventricular couplets (1 study). We pooled the incidence of adverse side effects with random effects meta-analysis; amiodarone was associated with corneal microdeposits (61.1%, 95%CI 19.0-91.3, 5 studies), gastrointestinal events (16.1%, 95%CI 6.61-34.2, 3 studies), sinus bradycardia (12.7%, 95%CI 3.71-35.5, 6 studies), dermatological events (10.6%, 95%CI 4.77-21.9, 3 studies) and drug discontinuation (7.68%, 95%CI 4.17-13.7, 5 studies). Quality of evidence ranged from moderate to very low.
CONCLUSIONS
Amiodarone is effective in reducing ventricular arrhythmias, but there is no evidence for hard endpoints (sudden death, hospitalization). Although our findings support the use of amiodarone, it is important to balance the potential benefits and harms at the individual level for decision-making.
Topics: Amiodarone; Arrhythmias, Cardiac; Chagas Cardiomyopathy
PubMed: 30125291
DOI: 10.1371/journal.pntd.0006742 -
Ugeskrift For Laeger 2014Amiodarone is associated with multiple side effects among which a substantial number of patients are suffering from amiodarone-induced thyroid disease. In this review we... (Review)
Review
Amiodarone is associated with multiple side effects among which a substantial number of patients are suffering from amiodarone-induced thyroid disease. In this review we present difficulties in diagnosing, sub typing and treating amiodarone-induced thyroid disease and give views on the future of this drug and one of the alternatives, dronedarone. Amiodarone holds a place in modern medicine due to its unique antiarrhythmic effects and associated thyroid diseases requires collaboration between cardiologists and endocrinologists due to the complexity hereof.
Topics: Amiodarone; Anti-Arrhythmia Agents; Dronedarone; Drug Prescriptions; Humans; Hypothyroidism; Risk Factors; Thyrotoxicosis
PubMed: 25293567
DOI: No ID Found -
British Journal of Pharmacology Jul 2022The aim of the present study was to study the antiarrhythmic effects and cellular mechanisms of desethylamiodarone (DEA), the main metabolite of amiodarone (AMIO),...
BACKGROUND AND PURPOSE
The aim of the present study was to study the antiarrhythmic effects and cellular mechanisms of desethylamiodarone (DEA), the main metabolite of amiodarone (AMIO), following acute and chronic 4-week oral treatments (25-50 mg·kg ·day ).
EXPERIMENTAL APPROACH
The antiarrhythmic effects of acute iv. (10 mg·kg ) and chronic oral (4 weeks, 25 mg·kg ·day ) administration of DEA were assessed in carbachol and tachypacing-induced dog atrial fibrillation models. Action potentials were recorded from atrial and right ventricular tissue following acute (10 μM) and chronic (p.o. 4 weeks, 50 mg·kg ·day ) DEA application using the conventional microelectrode technique. Ionic currents were measured by the whole cell configuration of the patch clamp technique in isolated left ventricular myocytes. Pharmacokinetic studies were performed following a single intravenous dose (25 mg·kg ) of AMIO and DEA intravenously and orally. In chronic (91-day) toxicological investigations, DEA and AMIO were administered in the oral dose of 25 mg·kg ·day ).
KEY RESULTS
DEA exerted marked antiarrhythmic effects in both canine atrial fibrillation models. Both acute and chronic DEA administration prolonged action potential duration in atrial and ventricular muscle without any changes detected in Purkinje fibres. DEA decreased the amplitude of several outward potassium currents such as I , I , I , I , and I , while the I and late I inward currents were also significantly depressed. Better drug bioavailability and higher volume of distribution for DEA were observed compared to AMIO. No neutropenia and less severe pulmonary fibrosis was found following DEA compared to that of AMIO administration.
CONCLUSION AND IMPLICATIONS
Chronic DEA treatment in animal experiments has marked antiarrhythmic and electrophysiological effects with better pharmacokinetics and lower toxicity than its parent compound. These results suggest that the active metabolite, DEA, should be considered for clinical trials as a possible new, more favourable option for the treatment of cardiac arrhythmias including atrial fibrillation.
Topics: Action Potentials; Amiodarone; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Dogs; Heart Atria; Myocytes, Cardiac
PubMed: 35106755
DOI: 10.1111/bph.15812 -
Health Technology Assessment... Oct 2010This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of dronedarone for the treatment of atrial... (Review)
Review
This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of dronedarone for the treatment of atrial fibrillation (AF) or atrial flutter based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The population considered in the submission were adult clinically stable patients with a recent history of or current non-permanent AF. Comparators were the current available anti-arrhythmic drugs: class 1c agents (flecainide and propafenone), sotalol and amiodarone. Outcomes were AF recurrence, all-cause mortality, stroke, treatment discontinuations (due to any cause or due to adverse events) and serious adverse events. The main evidence came from four phase III randomised controlled trials, direct and indirect meta-analyses from a systematic review, and a synthesis of the direct and indirect evidence using a mixed-treatment comparison. Overall, the results from the different synthesis approaches showed that the odds of AF recurrence appeared statistically significantly lower with dronedarone and other anti-arrhythmic drugs than with non-active control, and that the odds of AF recurrence are statistically significantly higher for dronedarone than for amiodarone. However, the results for outcomes of all-cause mortality, stroke and treatment discontinuations and serious adverse events were all uncertain. A discrete event simulation model was used to evaluate dronedarone versus antiarrhythmic drugs and standard therapy alone. The incremental cost-effectiveness ratio of dronedarone was relatively robust and less than 20,000 pounds per quality-adjusted life-year. Exploratory work undertaken by the ERG identified that the main drivers of cost-effectiveness were the benefits assigned to dronedarone for all-cause mortality and stroke. Dronedarone is not cost-effective relative to its comparators when the only effect of treatment is a reduction in AF recurrences. In conclusion, uncertainties remain in the clinical effectiveness and cost-effectiveness of dronedarone. In particular, the clinical evidence for the major drivers of cost-effectiveness (all-cause mortality and stroke), and consequently the additional benefits attributed in the economic model to dronedarone compared to other anti-arrhythmic drugs are highly uncertain. The final guidance, issued by NICE on 25 August 2010, states that: Dronedarone is recommended as an option for the treatment of non-permanent atrial fibrillation only in people: whose atrial fibrillation is not controlled by first-line therapy (usually including beta-blockers), that is, as a second-line treatment option, and who have at least one of the following cardiovascular risk factors: - hypertension requiring drugs of at least two different classes, diabetes mellitus, previous transient ischaemic attack, stroke or systemic embolism, left atrial diameter of 50 mm or greater, left ventricular ejection fraction less than 40% (noting that the summary of product characteristics [SPC] does not recommend dronedarone for people with left ventricular ejection fraction less than 35% because of limited experience of using it in this group) or age 70 years or older, and who do not have unstable New York Heart Association (NYHA) class III or IV heart failure. Furthermore, 'People who do not meet the criteria above who are currently receiving dronedarone should have the option to continue treatment until they and their clinicians consider it appropriate to stop'.
Topics: Adult; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Dronedarone; Humans; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 21047492
DOI: 10.3310/hta14suppl2/08 -
The Journal of Thoracic and... Jul 2019Atrial fibrillation (AF) is a common complication after esophagectomy and is associated with symptoms, hemodynamic instability, prolonged hospital stay, and an increased...
OBJECTIVES
Atrial fibrillation (AF) is a common complication after esophagectomy and is associated with symptoms, hemodynamic instability, prolonged hospital stay, and an increased incidence of mortality. Our objective was to determine the efficacy and safety of intravenous amiodarone for prophylaxis of postesophagectomy AF.
METHODS
In this retrospective cohort study, 309 patients who underwent esophagectomy formed the initial cohort. Following propensity score-matching, 110 patients who received prophylactic amiodarone 43.75 mg/hour via continuous intravenous infusion over 96 hours (total dose, 4200 mg) were matched to a control group of patients who did not undergo amiodarone prophylaxis (n = 110). The propensity score was obtained using a multivariate logistic regression model with amiodarone as the variable and the following covariates: age, sex, surgical approach, history of neoadjuvant chemotherapy and/or radiation, chronic obstructive pulmonary disease, heart failure, cardiovascular disease, alcohol use (>7 drinks/week), preadmission β-blockers discontinued during hospitalization, preoperative use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, preoperative use of corticosteroids, postoperative use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, postoperative use of corticosteroids, postoperative use of statins, and preoperative Charlson comorbidity index.
RESULTS
The incidence of AF requiring treatment due to rapid ventricular rate and symptoms was lower in the amiodarone group (17 out of 110 [15.5%] vs 32 out of 110 [29.1%]; odds ratio, 0.45; 95% confidence interval, 0.23-0.86; P = .015). There were no significant differences between the groups in median postoperative length of hospital stay, incidence of pulmonary complications, or mortality. The incidences of hypotension requiring treatment (42.7% vs 21.8%; P = .001), bradycardia (8.2% vs 0.0%; P = .002), and corrected QT interval prolongation (10.9% vs 0.0%; P ≤ .0001) were significantly higher in the amiodarone group.
CONCLUSIONS
Prophylactic intravenous amiodarone is associated with a reduction in the incidence of AF following esophagectomy, but is not associated with shorter postoperative length of hospital stay. Intravenous amiodarone for prophylaxis of postesophagectomy AF is associated with hypotension, bradycardia, and corrected QT interval prolongation.
Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Case-Control Studies; Chemoprevention; Esophagectomy; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Propensity Score; Retrospective Studies
PubMed: 30853230
DOI: 10.1016/j.jtcvs.2019.01.095 -
Journal of the American College of... Jul 2002The goal of this study was to evaluate the effects of acute and chronic amiodarone on activation patterns during ventricular fibrillation (VF), ventricular effective...
OBJECTIVES
The goal of this study was to evaluate the effects of acute and chronic amiodarone on activation patterns during ventricular fibrillation (VF), ventricular effective refractory period (VERP) and defibrillation threshold (DFT).
BACKGROUND
Acute and chronic amiodarone may act through different mechanisms.
METHODS
The VERP, VF activation patterns and DFT were determined in 24 dogs. Twelve dogs received acute intravenous amiodarone (10 mg/kg, n = 6) or saline (n = 6), and 12 dogs received chronic oral amiodarone (20 mg/kg/day, n = 6) or placebo (n = 6). Epicardial VF activation patterns were recorded with 504 electrodes. Quantitative descriptors of VF were calculated.
RESULTS
The DFT was unchanged by acute or chronic amiodarone. Although chronic amiodarone significantly extended the VERP, acute amiodarone did not. In the mapped region, acute and chronic amiodarone decreased the number of VF wavefronts by 42% and 60%. Acute amiodarone decreased conduction block by 22%, while chronic amiodarone increased block by 41% but decreased wave fractionation by 50%. Both chronic and acute amiodarone increased the size of the core of re-entrant circuits and decreased the incidence of re-entry by 44% and 57%; however, chronic amiodarone increased wavelength, while acute amiodarone did not.
CONCLUSIONS
Neither acute nor chronic amiodarone change the DFT. While both acute and chronic amiodarone decrease the number of wavefronts, decrease the incidence of re-entry and increase the size of re-entrant cores in the mapped region during VF, they achieve these antiarrhythmic effects through different electrophysiologic mechanisms. Chronic amiodarone prolonged the VF cycle length and slowed conduction velocity, indicating it increased the wavelength and/or the excitable gap.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Dogs; Electric Countershock; Research Design; Ventricular Fibrillation
PubMed: 12106947
DOI: 10.1016/s0735-1097(02)01942-3 -
Postgraduate Medical Journal Mar 1985A dose-dependent cutaneous leukocytoclastic vasculitis developed in a 34 year old man who was given amiodarone for supraventricular tachycardias resistant to other...
A dose-dependent cutaneous leukocytoclastic vasculitis developed in a 34 year old man who was given amiodarone for supraventricular tachycardias resistant to other drugs. This adverse reaction disappeared within 2 weeks after discontinuation of amiodarone despite its very long half-life of 52 days in this patient. During previous treatment periods with amiodarone, the patient had experienced photosensitivity and dose-dependent polyserositis. Since high doses of amiodarone have been recently proposed for the treatment of resistant cardiac arrhythmias, dose-dependent adverse effects as described here may be encountered with increasing frequency.
Topics: Adult; Amiodarone; Benzofurans; Humans; Male; Necrosis; Photosensitivity Disorders; Serositis; Tachycardia; Vasculitis, Leukocytoclastic, Cutaneous
PubMed: 3983058
DOI: 10.1136/pgmj.61.713.245 -
Internal Medicine (Tokyo, Japan) Jan 2018We describe a case of amiodarone-induced thyrotoxicosis (AIT) with cardiopulmonary arrest (CPA) in a 49-year-old woman. The patient had been treated with amiodarone for...
We describe a case of amiodarone-induced thyrotoxicosis (AIT) with cardiopulmonary arrest (CPA) in a 49-year-old woman. The patient had been treated with amiodarone for non-sustained ventricular tachycardia. Two weeks prior to her admission, she developed thyrotoxicosis and prednisolone (PSL, 30 mg daily) was administered with the continuation of amiodarone. However, she was admitted to our hospital for CPA. We performed total thyroidectomy to control her thyrotoxicosis and the pathological findings were consistent with type 2 AIT. She gradually improved and was discharged on day 84. This case demonstrates the importance of considering immediate total thyroidectomy for patients with uncontrollable AIT.
Topics: Amiodarone; Anti-Arrhythmia Agents; Female; Heart Arrest; Humans; Middle Aged; Tachycardia, Ventricular; Thyroidectomy; Thyrotoxicosis; Treatment Outcome
PubMed: 29033440
DOI: 10.2169/internalmedicine.9177-17