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Annals of the New York Academy of... 1984
Review
Topics: Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Heart Ventricles; Humans; Infusions, Parenteral; Kinetics; Recurrence; Tachycardia; Ventricular Fibrillation
PubMed: 6378011
DOI: 10.1111/j.1749-6632.1984.tb20779.x -
The Medical Letter on Drugs and... May 1986
Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Heart Diseases; Heart Ventricles; Humans; Kinetics; Pulmonary Fibrosis
PubMed: 3702807
DOI: No ID Found -
Critical Care Nurse 1986
Topics: Amiodarone; Arrhythmias, Cardiac; Hemodynamics; Humans
PubMed: 3641704
DOI: No ID Found -
Cardiology Journal 2008Class III drugs prolong the QT interval by blocking mainly the delayed rectifier rapid potassium outward current (IKr), with little effect on depolarization. This K(+)... (Review)
Review
Class III drugs prolong the QT interval by blocking mainly the delayed rectifier rapid potassium outward current (IKr), with little effect on depolarization. This K(+) channel in encoded by the human ether-a-go-go-related gene (hERG). Inhibition of hERG potassium currents by class III antiarrhythmic drugs causes lengthening of cardiac action potential, which produces a beneficial antiarrhythmic effect. Excessive prolongation of the action potential may lead to acquired long QT syndrome, which is associated with a risk of "torsade de pointes". Class III agents can block all types of potassium channels: IKs, IKr, IKur and IK1. The main representing class III agent is amiodarone. It is the gold standard in the prevention of recurrence of atrial fibrillation. Although it is highly effective in treating many arrhythmias, large number of adverse effects limits its clinical use. Dronedarone is a synthetic amiodarone analogue, iodine-free compound, with fewer adverse effects, and shares amiodarone's multichannel blocking effects, inhibiting transmembrane Na+, IKs, IKur, IK1, and slow Ca(++)L-type calcium currents. The main new generation class III drugs are: dofetilide, dronedarone, azimilide, and ibutilide. Oral dofetilide did not increase mortality in patients with a recent myocardial infarction or congestive heart failure. It is an alternative for the pharmacological conversion of atrial fibrillation and flutter. Azimilide blocks both rapid and slow potassium channels components. Azimilide is not a methanesulfonanilide compound. Trecitilide, tedisamil, ersentilide, ambasilide, chromanol and sematilide are class III miscellaneous agents. Old mixed agents are sotalol and bretylium. The present article reviews the main trials accomplished with these drugs.
Topics: Action Potentials; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Humans; Long QT Syndrome
PubMed: 18651412
DOI: No ID Found -
Journal of Clinical Pharmacology May 1989
Topics: Amiodarone; Humans
PubMed: 2738174
DOI: 10.1002/j.1552-4604.1989.tb03348.x -
Der Hautarzt; Zeitschrift Fur... Dec 1996Amiodarone can occasionally lead to a slate-coloured pigmentation in chronically UV-expose skin. A 63 year old patient presented with a pruritic bluish-purple...
Amiodarone can occasionally lead to a slate-coloured pigmentation in chronically UV-expose skin. A 63 year old patient presented with a pruritic bluish-purple pigmentation of the face 2 years after taking 400 mg of amiodarone daily for 2 years. During the 24 months after the dose was reduced to 200 mg daily, the pigmentation remained unchanged. Amiodarone pigmentation is caused by the UV-induced accumulation of lipofuscin in dermal macrophages, depending on both the daily dose and the duration of therapy. In the differential diagnosis, pigmentation caused by other drugs is the main consideration. Cessation of therapy eventually leads to complete normalization of skin colour.
Topics: Amiodarone; Anti-Arrhythmia Agents; Drug Eruptions; Female; Humans; Lipofuscin; Long-Term Care; Middle Aged; Photosensitivity Disorders; Pigmentation Disorders; Recurrence; Tachycardia, Supraventricular
PubMed: 9081941
DOI: 10.1007/s001050050534 -
The Annals of Pharmacotherapy Apr 2007To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of dronedarone for the treatment of atrial fibrillation. (Review)
Review
OBJECTIVE
To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of dronedarone for the treatment of atrial fibrillation.
DATA SOURCES
A literature search was conducted using the search terms dronedarone, SR 33589, atrial fibrillation, and antiarrhythmic medication in MEDLINE (1966-February 2007), International Pharmaceutical Abstracts (1970-February 2007), and EMBASE (1990-February 2007). References from the identified trials and selected review articles were evaluated. Additional information, including abstracts and posters, was obtained from Sanofi-Aventis.
STUDY SELECTION AND DATA EXTRACTION
Published studies and meeting abstracts evaluating the effects of dronedarone in humans and animals were reviewed.
DATA SYNTHESIS
Dronedarone is a novel antiarrhythmic medication to treat atrial fibrillation. Dronedarone has a multifaceted mechanism of action similar to that of amiodarone. Dronedarone works by blocking potassium, sodium, and calcium channels and exhibits antiadrenergic properties. The drug has been evaluated at doses of 400, 600, and 800 mg twice daily. It prolonged the time to atrial fibrillation recurrence to 60-158 days compared with 5-59 days with placebo and decreased heart rate during atrial fibrillation by 12-25 beats/min in clinical trials. Major adverse events include gastrointestinal side effects and risk of proarrhythmia. Dronedarone may increase the risk of mortality in patients with congestive heart failure.
CONCLUSIONS
Dronedarone is a new antiarrhythmic agent for the treatment of atrial fibrillation. Further studies are needed to better define dronedarone's safety profile and place in therapy.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Biological Availability; Clinical Trials as Topic; Dronedarone; Drug Interactions; Half-Life; Humans
PubMed: 17389667
DOI: 10.1345/aph.1H524 -
Clinical Pharmacology and Therapeutics Apr 1982Amiodarone serum kinetics after single oral doses and after long-term therapy were investigated in patients with ventricular tachyarrhythmias. When amiodarone was given...
Amiodarone serum kinetics after single oral doses and after long-term therapy were investigated in patients with ventricular tachyarrhythmias. When amiodarone was given as a single oral dose (1400 to 1800 mg, n = 6), serum levels of amiodarone and its metabolite, measured by high-performance liquid chromatography, correlated (r = 0.69, P less than 0.01). Peak concentrations (amiodarone, 3 to 14 microgram/ml; metabolite, 0.7 microgram/ml) were attained in 4.9 +/- 1.2 hr. Using computer fits to the data, amiodarone mean elimination rate constant and half-life (t 1/2 e) were 0.128 +/- 0.063 hr-1 and 7.2 +/- 5.0 hr. In 12 patients given a mean dose of 1327 +/- 338 mg/day of amiodarone for 4.1 +/- 2.3 wk, mean serum amiodarone level was 3.84 +/- 2.92 microgram/ml (range 0.92 to 11.99); in three patients simultaneous determination of concentrations of amiodarone and its metabolite revealed that concentration of the latter was about 50% of that of the parent drug during long-term therapy. In four patients on maintenance therapy (400 to 800 mg/day, serum level 1.08 +/- 1.3 microgram/ml) drug was discontinued and serum amiodarone levels were determined serially. Serum drug disappearance followed a single exponential function with an elimination rate constant of 0.030 +/- 0.012 day-1 and t 1/2 e of 29 +/- 19 days. Our kinetic data are consistent with the long therapeutic amiodarone t 1/2 noted in the treatment of cardiac arrhythmias.
Topics: Administration, Oral; Adult; Aged; Amiodarone; Benzofurans; Half-Life; Humans; Kinetics; Male; Middle Aged
PubMed: 7060325
DOI: 10.1038/clpt.1982.57 -
Clinical Cardiology Jul 1987Amiodarone is a new antiarrhythmic drug approved for therapy of life-threatening ventricular tachycardia and ventricular fibrillation refractory to previous... (Review)
Review
Amiodarone is a new antiarrhythmic drug approved for therapy of life-threatening ventricular tachycardia and ventricular fibrillation refractory to previous antiarrhythmic therapy. The drug is poorly absorbed and avidly binds to all adipose tissue within the body. As a result of its unique pharmacologic properties, a 1-2 month period of loading with a high dose is required before therapeutic and steady state tissue concentrations are achieved. Therefore, there is a delay in the onset of antiarrhythmic effects of the drug and evaluation of efficacy using either noninvasive or invasive techniques should be performed 1-2 months after the initiation of therapy. It has been reported that suppression of runs of ventricular tachycardia (VT) documented on ambulatory monitor correlates with long-term efficacy. When invasive electrophysiologic (EP) studies are used, continued inducibility does not predict recurrence. Other important factors from the EP test include the rate of the induced VT and prolongation of the refractory period. Another problem related to amiodarone's pharmacologic properties is the occurrence of side effects which generally develop after weeks to months of drug therapy. Moreover, the incidence of toxicity increases over time. Although most side effects are unrelated to dose or blood level, it is possible that they correlate with the cumulative dose administered or total period of drug exposure. Amiodarone causes side effects which involve many organ systems. Most side effects are minor and cause no or only minor symptoms. Serious side effects, primarily cardiac, pulmonary, neurologic and thyroid, occur in about 18% of patients and often requires drug discontinuation. Therefore, use of amiodarone requires careful and continuous follow-up and monitoring for efficacy and toxicity.
Topics: Amiodarone; Follow-Up Studies; Humans; Tachycardia; Ventricular Fibrillation
PubMed: 3078154
DOI: No ID Found -
Progress in Cardiovascular Diseases 1989
Review
Topics: Amiodarone; Animals; Electrophysiology; History, 20th Century; Humans
PubMed: 2642623
DOI: 10.1016/0033-0620(89)90033-9