Hepatotoxicity amiodarone

Jain D, Bowlus CL, Anderson JM, Robert ME. Granular cells as a marker of early amiodarone hepatotoxicity. J Clin Gastroenterol 2000 31(3) 241-3. 

Sastri SV, Diaz-Arias AA, Marshall JB. Can pancreatitis be associated with amiodarone hepatotoxicity J Clin Gastroenterol 1990 12(l) 70-3. 

Amiodarone IV Hypotension, sinus bradycardia Oral Blue-grey skin discoloration, photosensitivity, corneal microdeposits, pulmonary fibrosis, hepatotoxicity, sinus bradycardia, hypo- or hyperthyroidism, AV block... 

Chronic oral therapy with amiodarone is associated with several side effects, including pulmonary toxicity (fibrosis and probably immunologically mediated pneumonitis), hepatotoxicity, thyroid gland dysfunction, corneal microdeposits, blue-grey skin discoloration and neurological disturbances. 

Cardiac side effects Torsade de pointes (<0.5%), severe bradycardia (one-year risk of bradycardia 2.4% on amiodarone vs. 0.8% on placebo). Non-cardiac side effects Pulmonary toxicity I % per year with fatal cases discontinue and treat symptomatically, hepatotoxicity... 

Echinacea 1. Hepatotoxic drugs, e.g. anabolic steroids 2. amiodarone 3. Methotrexate 4. Ketoconazole Risk of additive hepatotoxicity Use of echinacea for over 8 weeks can cause hepatotoxicity Be aware and use drugs with a potential to cause hypertonicity cautiously, monitoring clinically and biochemically for any early signs of hepatic dysfunction... 

The authors proposed that the granular macrophages represented an early marker of amiodarone-induced hepatotoxicity. Their unusual color was attributed to the deposition of a combination of phospholipid, lipofuscin, and bile breakdown products. 

FIGURE 5.4B PCA scores plot from analysis of Fischer Rat urines after application of data filtering methods to remove the influence of chloroquine-indueed hepatotoxicity from the data set to focus on the biochemical consequences of phospholipidosis. Vehicle control rats (f), rats dosed with amiodarone (fa) and rats dosed with chloroquine (fc). 

Ricuarte B, Guirguis A, Taylor HC, Zabri ie D. Simvastatin-amiodarone interaction result-ii in rhabdcmyolysis, azotemia, and possible hepatotoxicity. Ann Pharmacother (2006) 40, 753-7. 

A 90-year-old man with paroxysmal atrial fibrillation who took low-dose amiodarone for 18 months developed signs and symptoms consistent with neurotoxicity and hepatotoxicity in association with hyperammonemia on withdrawal of the medication and treatment of the hyperammonemia, his symptoms rapidly improved and resolved. 

Amiodarone- or desethylamiodarone-induced hepatotoxicity was prevented by DL-a-tocopherol acetate as shown in primary culture of rat hepatocytes (Ruch et al. 1991). However, several other antioxidants of diverse nature (Cu,Zn-superoxide dis-mutase, catalase, N,ivr-diphenylphenylenediamine, butylated hydroxytoluene, and N-acetylcysteine)... 

Liver In a Bayesian approach, linking information from clinical trials with hepato-toxidty from published case reports, the maximum number of expected cases of hepatotoxicity in patients taking amiodarone or placebo was calculated using a Poisson distribution [41 ]. The calculated odds ratio was used as a prior for the subsequent quantification of the likelihood of amiodarone-induced hepatotoxicity in individuals. The prior odds of amiodarone-induced hepatotoxicity was 0.48. The Bayesian model combined information about the latency period and the period of remission, together with analytical parameters that properly defined the toxicity... 

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