Hepatotoxicity Associated with Amiodarone Therapy

Flaharty, Kristen K.; Chase, Sandra L.; Yaghsezian, Harout; Rubin, Raphael

doi:10.1002/j.1875-9114.1989.tb04102.x

Cited by 23 publications

(13 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…If this were the case, induction of CYP3A4, the main cytochrome P450 isozyme responsible for amiodarone deethylation (Fabre et al, 1993), may be a risk factor for hepatotoxicity associated with amiodarone. Although a high dosage and/or high plasma levels of amiodarone are considered to represent risk factors for hepatotoxicity associated with this drug (Pollak et al, 1990;Bravo et al, 2005), induction of CYP3A4 has so far not been reported to be a risk factor for amiodarone-associated liver injury (Rigas et al, 1986;Flaharty et al, 1989;Lewis et al, 1989). Since CYP3A4 inducers (e.g., antiepileptics such as phenytoin, phenobarbital and carbamazepine as well as rifampicin) are used quite frequently and since hepatotoxicity associated with amiodarone is potentially fatal (Lewis et al, 1989), this question is clinically important and should therefore be investigated and answered.…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular Toxicity and Pharmacological Effect of Amiodarone and Amiodarone Derivatives

Waldhauser

Török

et al. 2006

J Pharmacol Exp Ther

105

View full text Add to dashboard Cite

The aim of this work was to compare hepatocellular toxicity and pharmacological activity of amiodarone (2-n-butyl-3-[3,5 diiodo-4-diethylaminoethoxybenzoyl]-benzofuran; B2-O-Et-Ndiethyl) and of eight amiodarone derivatives. Three amiodarone metabolites were studied, namely, mono-N-desethylamioda- A concentration-dependent increase in lactate dehydrogenase leakage from HepG2 cells and isolated rat hepatocytes was observed in the presence of amiodarone and of most analogs, confirming their hepatocellular toxicity. Using freshly isolated rat liver mitochondria, amiodarone and most analogs showed a dose-dependent toxicity on the respiratory chain and on ␤-oxidation, significantly reducing the respiratory control ratio and oxidation of palmitate, respectively. The reactive oxygen species concentration in hepatocytes increased time-dependently, and apoptotic/necrotic cell populations were identified using flow cytometry and annexin V/propidium iodide staining. The effect of the three least toxic amiodarone analogs on the human ether-a-go-go-related gene (hERG) channel was compared with amiodarone. Amiodarone, B2-O-acetate, and B2-O-Et-N-dipropyl (each 10 M) significantly reduced the hERG tail current amplitude, whereas 10 M B2-O-Et displayed no detectable effect on hERG outward potassium currents. In conclusion, three amiodarone analogs (B2-O-Et-N-dipropyl, B2-O-acetate, and B2-O-Et) showed a lower hepatocellular toxicity profile than amiodarone, and two of these analogs (B2-O-Et-Ndipropyl and B2-O-acetate) retained hERG channel interaction capacity, suggesting that amiodarone analogs with class III antiarrhythmic activity and lower hepatic toxicity could be developed.

show abstract

Section: Discussionmentioning

confidence: 99%

Hepatocellular Toxicity and Pharmacological Effect of Amiodarone and Amiodarone Derivatives

Waldhauser

Török

et al. 2006

J Pharmacol Exp Ther

105

View full text Add to dashboard Cite

show abstract

“…The incidence of amiodarone induced hypothyroidism ranges from 2-20% of patients [3,19], while the incidence of amiodarone induced hyperthyroidism is approximately 3% in areas where the diet is sufficient with iodine and 20% in those with an iodine deficient diet [3,19]. Asymptomatic increases in liver transaminases (5-15%) or hepatotoxicity (0.28%) reported as hepatomegaly, jaundice, cirrhosis or chronic hepatitis may occur [16,20]. Peripheral neuropathy can be induced by chronic administration of amiodarone with an incidence of 0.3% annually [4,21].…”

Section: Dronedarone Safety Comparison To Amiodaronementioning

confidence: 96%

“…Toxicity associated with amiodarone may be related to phospholipidosis (formation of drug-lipid complexes in lysosomes), iodine content in the chemical structure, and its long half-life [3,4,16]. Amiodarone can adversely affect the cardiovascular system as well as numerous non-cardiovascular organ systems including dermatologic, gastrointestinal, endocrine, hepatic, neurologic, ophthalmologic and pulmonary [2][3][4]16].…”

Section: Dronedarone Safety Comparison To Amiodaronementioning

confidence: 99%

Dronedarone: A Safety Comparison to Amiodarone

Clem¹,

Farver²,

Fischer³

et al. 2010

CDS

View full text Add to dashboard Cite

Dronedarone is an oral Class III antiarrhythmic agent which was recently approved by the US Food and Drug Administration for use in nonpermanent atrial fibrillation. Structurally similar to amiodarone, dronedarone is a benzofuran derivative but it lacks the iodine moiety attached to amiodarone. Based upon the investigational clinical trials to date, it appears that dronedarone has an established efficacy when compared to placebo along with exhibiting a minimal adverse effect profile. The efficacy of dronedarone will need to be further evaluated in comparison trials with established antiarrhythmics for atrial fibrillation. The adverse profile of dronedarone appears to be substantially safer in comparison to amiodarone, although there is still little data available. The adverse effect profile of amiodarone necessitates close and extensive monitoring. Although a risk of pulmonary toxicity was identified in animals, long term studies in humans are needed to determine the significance of this adverse effect with dronedarone. One noted effect of dronedarone is an isolated increase in serum creatinine levels, and the clinical relevance of this effect needs further evaluation. Based on supporting evidence, the use of dronedarone is contraindicated in advanced or decompensated heart failure. Some clinically significant dronedarone drug interactions have been identified. Although the potential differences between dronedarone and amiodarone have been evaluated there have been no direct comparison trials published to date. This article reviews the chemistry, antiarrhythmic effects, pharmacokinetics, efficacy, adverse effects and drug interactions of dronedarone.

show abstract

“…Most individuals administered amiodarone on a chronic basis will experience at least one side effect [Vanerven & Schalij, 2010], Decrease heart rate and increase incidence of heart block, interstitial lung disease, Some individuals developed pulmonary fibrosis after a week of treatment, Amiodarone is structurally similar to thyroxin, which contributes to the effects of amiodarone on thyroid function, both under and over activity of the thyroid may occur on amiodarone treatment [Batcher, et al 1989], Corneal micro-deposits, Corneal verticillata, Abnormal liver enzyme results are common in patients on amiodarone. [Flaharty, et al 1989] According to the numerous drug interactions and adverse effects caused by amiodarone, this research investigates the effect of a novel antidysrhythmic drug, vernakalant, on reperfusion dysthymia in rats in comparison with amiodarone, standard broad spectrum antidysrhythmic drug.…”

Section: Amiodaronementioning

confidence: 99%

Study the Effects of Vernakalant on Ischemic-Reperfusion Dysrhythmias in Experimental Animals in Comparison with Amiodarone

Fa¹

2018

TIJMD

View full text Add to dashboard Cite

Cardiac dysrhythmia is a term for any of large heterogeneous group of conditions in which there is abnormal electrical activity in the heart. Dysrhythmias may be life threatening medical emergencies that can result in cardiac arrest and sudden death; it may predispose the patient to potentially life threatening stroke and embolism. The pathogenesis of cardiac dysrhythmia involves crossing of electrolytes through different ions channels on the cellular level that may be dysrhythmogenic. In this study, ischemic-reperfusion dysrhythmia were performed in experimental animals, ischemia of the myocardium results in release of ischemic metabolites and slowing impulse propagation while reperfusion results in increase late inward Na current (INaL) which amplifies Na + influx and intracellular Na + concentration leading finally to calcium overload. The enhancement of Na + and Ca2 + concentration causes electrophysiological instability, formation of free oxygen radicle and liberation of platelet activating factor. Seeking for novel antidysrhythmogenic agents having ions channels inhibiting properties, this work aims to investigate the effects of vernakalant, antidysrhythmic drug with atrial selective and multichannel blocking effect on ischemia-reperfusion dysrhythmia in experimental animals in comparison with amiodarone as a standard antidysrhythmic medication.

show abstract

Hepatotoxicity Associated with Amiodarone Therapy

Cited by 23 publications

References 24 publications

Hepatocellular Toxicity and Pharmacological Effect of Amiodarone and Amiodarone Derivatives

Hepatocellular Toxicity and Pharmacological Effect of Amiodarone and Amiodarone Derivatives

Dronedarone: A Safety Comparison to Amiodarone

Study the Effects of Vernakalant on Ischemic-Reperfusion Dysrhythmias in Experimental Animals in Comparison with Amiodarone

Contact Info

Product

Resources

About