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Kardiologia Polska 2011
Review
Topics: Amiodarone; Anti-Arrhythmia Agents; Dronedarone; Humans; Thyroid Gland; Treatment Outcome
PubMed: 21594842
DOI: No ID Found -
Journal of Clinical Pharmacology May 1989Amiodarone is a unique class III antiarrhythmic drug with several unusual pharmacokinetic, pharmacodynamic, and toxicological actions which are quite distinct from those... (Review)
Review
Amiodarone is a unique class III antiarrhythmic drug with several unusual pharmacokinetic, pharmacodynamic, and toxicological actions which are quite distinct from those of the standard antiarrhythmic drugs. Extensive animal and clinical studies have demonstrated that amiodarone and its major metabolite, desethylamiodarone, both produce a marked increase in the duration of transmembrane action potential, which may be related to their antiarrhythmic as well as clinical electrophysiological activity. Unlike most other cardiovascular drugs, it has been recognized for more than 20 years that optimal antiarrhythmic effects may take several days to weeks after onset of oral therapy. Amiodarone is highly lipid soluble and exhibits at least three separate compartments of drug distribution, with a long elimination half-life of 14-120 days after chronic therapy. The pharmacokinetic profile of desethylamiodarone is qualitatively similar to that of amiodarone, but its elimination half-life is even longer and its tissue distribution may be slightly different. Although there may not be any correlation between serum drug levels and clinical toxicity of amiodarone during long-term therapy, recent animal as well as clinical data suggest that multilamellar intracellular inclusions can be dissociated from cell death or clinical toxicity. Thus, it is possible that amiodarone toxicity can be minimized with low doses or low serum drug concentrations. The metabolite(s) of amiodarone may play a major role in its pharmacological and toxicological actions.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Humans; Inclusion Bodies
PubMed: 2544634
DOI: 10.1002/j.1552-4604.1989.tb03352.x -
Pacing and Clinical Electrophysiology :... Nov 1983The purpose of the present report is to review the available pharmacokinetic information on amiodarone with an emphasis on our own experience in monitoring serum...
The purpose of the present report is to review the available pharmacokinetic information on amiodarone with an emphasis on our own experience in monitoring serum amiodarone concentrations. We have found that 400 mg should be the maximal maintenance dose; if that treatment fails, careful addition of other antiarrhythmic agents is preferable over an increase in amiodarone dosage. Serum concentrations below 2.5 mg/L will significantly improve amiodarone's benefit-to-risk ratio.
Topics: Amiodarone; Animals; Benzofurans; Biological Availability; Cardiac Pacing, Artificial; Chromatography, High Pressure Liquid; Dogs; Half-Life; Humans; Kinetics; Rats; Tachycardia
PubMed: 6196742
DOI: 10.1111/j.1540-8159.1983.tb04475.x -
Pediatric Cardiology 1994Amiodarone, a class III antiarrhythmic agent, prolongs action potential duration and refractoriness of all cardiac structures. The drug is more rapidly metabolized in... (Review)
Review
Amiodarone, a class III antiarrhythmic agent, prolongs action potential duration and refractoriness of all cardiac structures. The drug is more rapidly metabolized in pediatric patients than in adults, but its kinetics are still unique compared with other drugs. Due to the unusual pharmacokinetic characteristics of amiodarone, treatment has to be started by administering loading doses, and there is a significant delay both in the achievement of the full anti-arrhythmic effect and in the development of side effects. Amiodarone is a highly effective agent in pediatric patients with automatic and reentrant supraventricular tachycardia as well as in refractory atrial flutter. Efficacy in ventricular tachycardia has been shown to be variable depending on the underlying anatomical substrate. The incidence of side effects is lower than that observed in adult studies with similar duration of therapy but their incidence is still significant. Amiodarone treatment is associated with a significant risk of proarrhythmic effects, requiring hospitalization of the patient during the loading period.
Topics: Amiodarone; Arrhythmias, Cardiac; Atrial Flutter; Child; Child, Preschool; Electrophysiology; Humans; Tachycardia, Supraventricular; Tachycardia, Ventricular
PubMed: 8047495
DOI: 10.1007/BF00796325 -
Drugs 1991Amiodarone is a class III antiarrhythmic drug with sympatholytic properties, which prolongs the refractory period of all cardiac tissues, depresses sinus node... (Review)
Review
Amiodarone is a class III antiarrhythmic drug with sympatholytic properties, which prolongs the refractory period of all cardiac tissues, depresses sinus node automaticity and atrioventricular nodal conduction. It is active on all cardiac arrhythmias, its use being limited by the risk of side effects, mainly extracardiac, which are dependent upon dosage and duration of treatment. The use of an oral loading dose of intravenous infusion to rapidly obtain an efficacious blood concentration may minimise the delay in onset of drug action. Amiodarone progressively accumulates in cardiac muscle and is eliminated slowly, allowing drug free periods (2 days a week) on long term therapy. Pharmacokinetic interaction with digoxin, class I antiarrhythmic drugs and warfarin must be considered during combination therapy, as well as the potentiation of electrophysiological effects when amiodarone is co-administered with combined calcium antagonists and beta-blockers.
Topics: Administration, Oral; Amiodarone; Arrhythmias, Cardiac; Contraindications; Death, Sudden; Electrocardiography; Half-Life; Humans; Infusions, Intravenous
PubMed: 1711970
DOI: 10.2165/00003495-199100412-00009 -
Heart & Lung : the Journal of Critical... Nov 1987
Review
Topics: Absorption; Amiodarone; Arrhythmias, Cardiac; Drug Interactions; Europe; Humans; Time Factors
PubMed: 3316126
DOI: No ID Found -
Proceedings of the Society For... Sep 1996The effectiveness of amiodarone in the treatment of cardiac arrhythmias is limited due to the development of pulmonary toxicity. Although the biochemical and morphologic... (Review)
Review
The effectiveness of amiodarone in the treatment of cardiac arrhythmias is limited due to the development of pulmonary toxicity. Although the biochemical and morphologic characteristics associated with amiodarone-induced pulmonary toxicity (AIPT) are well-defined, the mechanisms underlying this disorder remain unknown. This review focuses on proposed mechanisms of AIPT, in particular (i) direct cellular damage; (ii) the role of phospholipidosis; (iii) the correlation between drug burden and toxicity; (iv) the role of the immune system; (v) the generation of oxidants; (vi) changes in membrane properties; and (vii) miscellaneous biochemical considerations. Additional discussion of the role of amiodarone's primary metabolite, desethylamiodarone, in AIPT and the involvement of preexisting lung dysfunction in the susceptibility to AIPT is included. With a clearer understanding of the possible contributions of these mechanisms to AIPT, it may be possible to develop strategies to alleviate toxicity and prolong the usefulness of amiodarone in the treatment of cardiac arrhythmias.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Cell Membrane; Humans; Immune System; Lung; Oxidation-Reduction; Phospholipids
PubMed: 8751986
DOI: 10.3181/00379727-212-44019 -
Anesthesiology Apr 1997Intravenous amiodarone is a potentially valuable therapy for perioperative patients experiencing life-threatening ventricular arrhythmias refractory to conventional... (Review)
Review
Intravenous amiodarone is a potentially valuable therapy for perioperative patients experiencing life-threatening ventricular arrhythmias refractory to conventional antiarrhythmic agents perioperatively. Its potential for hemodynamic and pulmonary toxicity perioperatively suggests that it should remain an alternative therapy rather than a first-line option. However, because of its impressive efficacy in nonsurgical trials, its role in perioperative arrhythmia management will dramatically expand if clinical studies become available that clarify its safety in surgical populations.
Topics: Administration, Oral; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Hemodynamics; Humans; Injections, Intravenous; Lung; Surgical Procedures, Operative
PubMed: 9105242
DOI: 10.1097/00000542-199704000-00028 -
Amiodarone's major metabolite, desethylamiodarone, induces apoptosis in human cervical cancer cells.Canadian Journal of Physiology and... Oct 2018Previously, we found that desethylamiodarone (DEA) may have therapeutic potentiality in bladder cancer. In this study, we determined its effects on human cervical cancer...
Previously, we found that desethylamiodarone (DEA) may have therapeutic potentiality in bladder cancer. In this study, we determined its effects on human cervical cancer cells (HeLa). Cell viability was evaluated by Muse Cell Count & Viability Assay; cell apoptosis was detected by Muse Annexin V & Dead Cell Assay. Cell cycle was flow cytometrically determined by Muse Cell Cycle Kit and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33342 staining. The changes in the expression levels of apoptosis-related proteins in the HeLa cells were assessed by immunoblot. Our results showed that DEA significantly inhibited the proliferation and viability of HeLa cells and induced apoptosis in vitro in dose-dependent and also in cell cycle-dependent manner because DEA induced G0/G1 phase arrest in the HeLa cell line. We found that DEA treatment downregulated the expression of phospho-Akt and phospho-Bad. In addition, DEA could downregulate expression of Bcl-2, upregulate Bax, and induce cytochrome c release. Our results indicate that DEA might have significance as an anti-tumor agent against human cervical cancer.
Topics: Amiodarone; Apoptosis; Cell Cycle Checkpoints; Female; HeLa Cells; Humans; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Uterine Cervical Neoplasms
PubMed: 29847733
DOI: 10.1139/cjpp-2018-0113 -
Duodecim; Laaketieteellinen... 1998
Review
Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Competence; Drug Interactions; Heart; Humans; Myocardium
PubMed: 11717746
DOI: No ID Found