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Ugeskrift For Laeger Jun 2014Amiodarone is an effective antiarrhythmic drug for supra-ven-tri-cular and ventricular arrhythmias. A majority of patients treated with amiodarone suffer from mild... (Review)
Review
Amiodarone is an effective antiarrhythmic drug for supra-ven-tri-cular and ventricular arrhythmias. A majority of patients treated with amiodarone suffer from mild adverse events, however, serious life-threatening adverse events caused by amiodarone are also seen. This review describes the pharmacology, interac-tions, side and adverse effects of amiodarone and highlights the importance of a systematic interdisciplinary follow-up protocol for outpatients treated with amiodarone.
Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Drug Interactions; Drug Monitoring; Humans; Lung; Thyroid Gland
PubMed: 25352080
DOI: No ID Found -
Herzschrittmachertherapie &... Sep 2017Amiodarone has multiple and complex electrophysiological effects that render it a very effective antiarrhythmic drug for the treatment of both, supraventricular and... (Review)
Review
Amiodarone has multiple and complex electrophysiological effects that render it a very effective antiarrhythmic drug for the treatment of both, supraventricular and ventricular arrhythmias. Proarrhythmic effects of amiodarone in patients with structural heart disease are rare. However, extracardiac adverse effects occurring in association with amiodarone treatment are frequent and feared. These adverse effects have usually been related to total amiodarone exposure (i. e., dose and duration of treatment). Parallel to a more frequent use of lower amiodarone maintenance doses (100-200 mg/day), the incidence of severe unwanted extracardiac side effects has decreased. High-dose maintenance regiments (daily dose ≥300 mg) are usually obsolete. This paper discusses recommendations regarding the monitoring of cardiac and extracardiac side effects of amiodarone. They need to be regarded by physicians using amiodarone to ensure long-term safety of amiodarone therapy.
Topics: Amiodarone; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Electrocardiography; Heart Conduction System; Humans; Long-Term Care; Tachycardia, Supraventricular; Tachycardia, Ventricular
PubMed: 28643175
DOI: 10.1007/s00399-017-0516-0 -
Schweizerische Medizinische... Dec 1988The extraordinary antiarrhythmic efficacy of amiodarone has been well documented in the last few years. Parallel investigations of the electrophysiologic influence of... (Review)
Review
The extraordinary antiarrhythmic efficacy of amiodarone has been well documented in the last few years. Parallel investigations of the electrophysiologic influence of this iodinated benzofuran derivative on myocardial tissue showed that repolarizing as well as depolarizing currents are inhibited. However, the detailed electrochemical aspects of these effects are only partly understood. Likewise, ideas on causes of the differences in hemodynamic and electrophysiologic actions of oral and intravenous amiodarone are still speculative. An understanding of the actions of amiodarone is particularly difficult to achieve because of the unique pharmacokinetics of the drug: it resides in extra-plasmatic compartments for months after discontinuation of treatment, a fact which explains, for example, the lack of an established dose/response relationship. Replacement of amiodarone by another antiarrhythmic drug in the same patient may be problematic, because pharmacokinetic and pharmacodynamic interactions of residual amiodarone with the new antiarrhythmic drug are to be expected. Therefore, amiodarone should be prescribed only in cases where other treatment has failed. This is also advisable in view of the long list of amiodarone-induced adverse reactions. Determinations of plasma concentrations of amiodarone and desethylamiodarone may be useful in some instances, but must never replace clinical evaluation of antiarrhythmic drug efficacy. Although the incidence of some amiodarone-induced adverse reactions increases with dosage and serum drug level, dose-independent factors may play a role in the rare but serious pulmonary and hepatic side effects.
Topics: Amiodarone; Drug Interactions; Heart Conduction System; Hemodynamics; Humans; Liver
PubMed: 3065934
DOI: No ID Found -
Journal of the American College of... Apr 1984Interest in amiodarone has increased because of its remarkable efficacy as an antiarrhythmic agent. The purpose of this report is to review what is known about the... (Review)
Review
Interest in amiodarone has increased because of its remarkable efficacy as an antiarrhythmic agent. The purpose of this report is to review what is known about the electrophysiologic actions, hemodynamic effects, pharmacokinetics, alterations of thyroid function, response to treatment of supraventricular and ventricular tachyarrhythmias and adverse effects of amiodarone. Understanding the actions of amiodarone and its metabolism will provide more intelligent use of the drug and minimize the development of side effects. The mechanism by which amiodarone suppresses cardiac arrhythmias is not known and may relate to prolongation of refractoriness in all cardiac tissues, suppression of automaticity in some fibers, minimal slowing of conduction in fast channel-dependent tissue, or to interactions with the autonomic nervous system, alterations in thyroid metabolism or other factors. Amiodarone exerts definite but fairly minor negative inotropic effects that may be offset by its vasodilator actions. Amiodarone has a reduced clearance rate, large volume of distribution, low bioavailability and a long half-life that may last 2 months in patients receiving short-term therapy. Therapeutic serum concentrations range between 1.0 and 3.5 micrograms/ml. The drug suppresses recurrences of cardiac tachyarrhythmias in a high percent of patients, in the range of 80% or more for most supraventricular tachycardias and in about 66% of patients with ventricular tachyarrhythmias, sometimes requiring addition of a second antiarrhythmic agent. Side effects, particularly when high doses are used, may limit amiodarone's usefulness and include skin, corneal, thyroid, pulmonary, neurologic, gastrointestinal and hepatic dysfunction. Aggravation of cardiac arrhythmias occurs but serious arrhythmias are caused in less than 5% of patients. Amiodarone affects the metabolism of many other drugs and care must be used to reduce doses of agents combined with amiodarone.
Topics: Administration, Oral; Amiodarone; Animals; Arrhythmias, Cardiac; Atrioventricular Node; Benzofurans; Biological Availability; Drug Interactions; Electrophysiology; Eye Diseases; Half-Life; Heart Conduction System; Humans; Injections, Intravenous; Kinetics; Lung Diseases; Metabolic Clearance Rate; Photosensitivity Disorders; Purkinje Fibers; Tachycardia; Thyroid Diseases; Wolff-Parkinson-White Syndrome
PubMed: 6368644
DOI: 10.1016/s0735-1097(84)80367-8 -
Medicina 2012Amiodarone is a structural analogue of thyroid hormone, and some of its anti-arrhythmic actions and toxicity are attributable to its interaction with nuclear receptors... (Review)
Review
Amiodarone is a structural analogue of thyroid hormone, and some of its anti-arrhythmic actions and toxicity are attributable to its interaction with nuclear receptors of thyroid hormones. Being highly lipophilic, amiodarone is concentrated in many tissues and is eliminated, consequently, very slowly. It is preferably employed to manage life-threatening arrhythmias, including ventricular fibrillation and unstable ventricular tachycardia. Other indications include atrial fibrillation and flutter, severe congestive heart failure, prevention of atrial fibrillation recurrence, and even in emergency medical situations to prevent sudden cardiac death. The aim of this review is to provide an updated approach on amiodarone and its influence on thyroid physiology and to discuss and analyze in depth its potential and not infrequent thyroidal adverse effects such as hypothyroidism and thyrotoxicosis.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Dronedarone; Humans; Hypothyroidism; Iodine; Thyroid Gland; Thyrotoxicosis
PubMed: 22257461
DOI: No ID Found -
Expert Opinion on Investigational Drugs Apr 2004Of the antiarrhythmic drugs in current use, amiodarone is one of the most effective and is associated with a comparatively low risk of drug-induced pro-arrhythmia,... (Review)
Review
Of the antiarrhythmic drugs in current use, amiodarone is one of the most effective and is associated with a comparatively low risk of drug-induced pro-arrhythmia, probably due to its multiple pharmacological actions on cardiac ion channels and receptors. However, amiodarone is associated with significant extra-cardiac side effects and this has driven development of amiodarone analogues. These analogues include short acting analogues (e.g., AT-2001) with similar acute effects to amiodarone, the thyroid receptor antagonist KB-130015 and dronedarone. Dronedarone, (SR-33589; Sanofi-Synthelabo), is a non-iodinated amiodarone derivative that inhibits Na +, K + and Ca 2+ currents. It is a potent inhibitor of the acetylcholine-activated K + current from atrial and sinoatrial nodal tissue, and inhibits the rapid delayed rectifier more potently than slow and inward rectifier K + currents and inhibits L-type calcium current. Dronedarone is an antagonist at alpha- and beta-adrenoceptors and unlike amiodarone, has little effect at thyroid receptors. Dronedarone is more potent than amiodarone in inhibiting arrhythmias and death in animal models of ischaemia- and reperfusion-induced arrhythmias. In the Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE) clinical trial, dronedarone 800 mg/day appeared to be effective and safe for the prevention of atrial fibrillation relapses after cardioversion. The Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease (ANDROMEDA) trial was stopped due to a potential increased risk of death in the dronedarone group. Trials of dronedarone in the maintenance of sinus rhythm in patients with atrial fibrillation and a safety and tolerability study in patients with an implantable cardioverter defibrillator are ongoing. Further experimental and clinical studies are required before we have a definitive answer to whether dronedarone has advantages over amiodarone and other amiodarone analogues.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Dronedarone; Drug Evaluation, Preclinical; Humans
PubMed: 15102590
DOI: 10.1517/13543784.13.4.415 -
The Annals of Pharmacotherapy Oct 2001To delineate amiodarone's role in the new American Heart Association guidelines for ventricular tachyarrhythmias, review the literature that supports the use of... (Review)
Review
OBJECTIVE
To delineate amiodarone's role in the new American Heart Association guidelines for ventricular tachyarrhythmias, review the literature that supports the use of amiodarone in ventricular tachyarrhythmias, describe the pharmaceutical properties of amiodarone and elucidate their clinical implications, and discuss the dosing, preparation, and administration of amiodarone.
DATA SOURCES
A search of MEDLINE (1966-October 2000) database and EMBASE Drugs and Pharmacology database (1980-October 2000) was performed. References from published articles and tertiary references were used to gather additional data.
DATA EXTRACTION
All articles were screened, and pertinent studies were identified and evaluated.
DATA SYNTHESIS
Recent trials have demonstrated amiodarone's usefulness in the setting of ventricular tachyarrhythmias. Based on these investigations and contrary to past guidelines, amiodarone is included in the 2000 advanced cardiovascular life support guidelines as a possible agent for hemodynamically stable monomorphic ventricular tachycardia (VT), non-QT prolonged polymorphic VT, and ventricular fibrillation (VF)/pulseless VT. Although not specifically evaluated in the setting of hemodynamically stable monomorphic VT and non-QT prolonged polymorphic VT, investigations by the intravenous Amiodarone Multicenter Trial Group and other clinical trials make amiodarone an acceptable choice for these arrythmia categories. The results of the ARREST (Resuscitation of Refractory Sustained Ventricular Tachyarrhythmias) trial prove amiodarone to be the antiarrhythmic of choice for VF/pulseless VT.
CONCLUSIONS
Amiodarone is classified as a IIb therapeutic intervention for all three arrhythmia categories, which makes it an acceptable, safe, and useful agent with fair to good evidence to support its use. In addition, amiodarone requires careful preparation and delivery to achieve safe and effective outcomes.
Topics: Administration, Oral; American Heart Association; Amiodarone; Anti-Arrhythmia Agents; Cardiopulmonary Resuscitation; Humans; Infusions, Intravenous; Life Support Care; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Tachycardia, Ventricular; United States
PubMed: 11675855
DOI: 10.1345/aph.10407 -
Deutsche Medizinische Wochenschrift... Apr 2010Amiodarone treatment affects thyroid status in about the half of patients. Amiodarone causes a wide spectrum of effects on the thyroid function including hypothyroidism... (Review)
Review
Amiodarone treatment affects thyroid status in about the half of patients. Amiodarone causes a wide spectrum of effects on the thyroid function including hypothyroidism and thyreotoxicosis. Amiodaron-induced thyroid dysfunction is the most reason for discontinuation of amiodaron therapy. In this report we describe amiodaron-induced thyroid dysfunction and the diagnostic and therapeutic challenges in such patients.
Topics: Amiodarone; Anti-Arrhythmia Agents; Drug Interactions; Follow-Up Studies; Half-Life; Humans; Hyperthyroidism; Hypothyroidism; Long-Term Care; Metabolic Clearance Rate; Tachycardia, Supraventricular; Tachycardia, Ventricular; Thyroid Function Tests; Thyroid Gland; Thyrotoxicosis
PubMed: 20391312
DOI: 10.1055/s-0030-1251935 -
Internal and Emergency Medicine Dec 2014Nowadays, amiodarone is the most commonly used antidysrhythmic drug in clinical practice. It is highly effective in the management of recurrent ventricular dysrhythmias,...
Nowadays, amiodarone is the most commonly used antidysrhythmic drug in clinical practice. It is highly effective in the management of recurrent ventricular dysrhythmias, paroxysmal supraventricular dysrhythmias, including atrial fibrillation and flutter, and in the maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation. Moreover, it has the added benefit of being well tolerated in patients with both normal and impaired left ventricular systolic function. Despite amiodarone's potent antidysrhythmic actions, its use is hampered by numerous adverse effects on various organs, including the thyroid. Adverse effects are becoming more prevalent given the increasing incidence of dysrhythmias and wider amiodarone use. Thus, physicians and patients should both be aware of the potential thyroid-specific sequelae. However, amiodarone is likely to remain a significant problem for endocrinologists as concerns exist over the use of the new alternative antiarrhythmic agent, dronedarone, especially in patients with heart failure and left ventricular dysfunction because of the risk of hepatic injury and increased mortality. The final diagnostic and therapeutic approaches must be discussed among the patient, the general practitioner, the cardiologist, and the endocrinologist.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Heart Failure; Humans; Hypothyroidism; Thyroid Gland; Thyrotoxicosis
PubMed: 25348560
DOI: 10.1007/s11739-014-1140-1 -
Deutsche Medizinische Wochenschrift... Jan 1990
Review
Topics: Amiodarone; Dose-Response Relationship, Drug; Half-Life; Heart; Humans; Time Factors
PubMed: 2404728
DOI: 10.1055/s-2008-1064978