Hepatotoxicity autoimmune

Tienilic acid- and dihydralazine-induced hepatitis are associated with antibodies against Cyp 2C9 [53] and Cyp 1A2 [54, 55], respectively. These are also the same cytochrome P450s that are responsible for the formation of reactive metabolites of these two drags. Anticonvulsant hepatotoxicity is associated with antibodies against rodent Cyp 3 A and related human enzymes such as thromboxane synthase [56, 57], It is interesting to note that cytochromes P450 are often the target of autoantibodies in idiopathic autoimmune hepatitis [58],... 

Minocycline is associated with a relatively high incidence of hepatotoxicity. In many cases it is quite distinct from minocycline-induced lupus, occurs earlier in the course of treatment (about 1 month), and the mechanism is unknown [62], However, in some cases the liver toxicity merges with the lupus-like syndrome, occurring after about a year of therapy, and is associated with ANA. This form is indistinguishable from idiopathic autoimmune hepatitis [63], and antibodies against Cyp 3A6 and Cyp 2C4 have been reported [64], Diclofenac has also been reported to cause hepatitis with autoimmune features such as ANA [65],... 

Furst, S.M., Chen, M. and Gandolfi, A.J., Use of halothane as a model for investigating chemical-induced autoimmune hepatotoxicity, Drug Info. J., 30, 301, 1996. 

Fig. 8.23 Structure of tienilic acid (A) and an isomeric variant (B) which cause hepatotoxicity by autoimmune and direct mechanisms respectively, following conversion to sulphoxide metabolites and resultant electrophilic carbon atoms.

Hepatotoxicity Penicillamine has been associated with a mild elevation of hepatic enzymes that usually returns to normal even with continuation of the drug. Autoimmune syndromes Autoimmune syndromes that may be caused by penicillamine include polymyositis, diffuse alveolitis and dermatomyositis, Goodpasture s syndrome, myasthenic syndrome, pemphigus, and obliterative bronchiolitis. 

Hepatotoxicity Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis, have been reported rarely in postmarketing data in patients receiving infliximab. Autoimmune hepatitis has been diagnosed in some of... 

Azathioprine can be administered both orally and intravenously. It is well absorbed orally and after its rapid conversion to 6-mercaptopurine it is inactivated by xanthine oxidase which converts 6-mercaptopurine to 6-thiouric acid. This final metabolite is then excreted in the urine. In combination with the xanthine oxidase inhibitor allopurinol dose adjustments of azathioprine are needed. Renal disease also raises 6-mercaptopurine concentrations and can make dose adjustments necessary. Azathioprine is still used in organ transplantation programs and for the management of several autoimmune diseases. Its adverse effects include nausea, vomiting, diarrhea and, more seriously, bone marrow suppression and hepatotoxicity. Azathioprine is not thought to cause fetal malformation. 

Hochman JA, Woodard SA, Cohen MB. Eixacerbation of autoimmune hepatitis another hepatotoxic effect of pemoline therapy. Pediatrics 1998 101(1 Pt l) 106-8. 

Barriault C, Audet M, Yousef IM, Tuchweber B (1995) Effect of agents which modify reticuloendothelial function on acute phalloidin-induced lethality and hepatotoxic-ity in mice. Toxicol Appl Pharmacol 131 206-215 Bate CA, Taverne J, Playfair JH (1989) Soluble malarial antigens are toxic and induce the production of tumor necrosis factor in vivo. Immunol 66 600-605 Bathal PS, Powell LW, Mackay IR (1982) Apoptosis in autoimmune chronic active Hepatitis (CAH). Hepatol 2 154-155... 

LeCluyse EL, Alexandre E, Hamilton GA, Viollon-Abadie C, Coon DJ, Jolley S, Richert L (2005) Isolation and culture of primary human hepatocytes. Methods Mol Biol 290 207-229 Lecoeur S, Andre C, Beaune PH (1996) Tienilic acid-induced autoimmune hepatitis anti-liver and-kidney microsomal type 2 autoantibodies recognize a three-site conformational epitope on cytochrome P4502C9. Mol Pharmacol 50 326-333 Lee WM (2003) Drug-induced hepatotoxicity. N Engl J Med 349 474-485 Lee WM, Senior JR (2005) Recognizing drug-induced liver injury ctnrent problems, possible solutions. Toxicol Pathol 33 155-164... 

Major Applications Detergent, hair dyes, prevention of colorectal cancer, treating inflanunatory bowel disease, autoimmune disorders, gastrointestinal inflanunation, chemokine-mediated diseases, mucosal tissue disorder, sleep disorders, rectoanal tenesmus, ulcerative colitis Safety/Toxicity Hepatotoxicity, cytotoxicity, - nephrotocicity, risk of renal disease, " safety in pregnancy, side effects ... 

Liver Halothane hepatitis has again been described [2 ]. Susceptibility factors are increasing age, female sex, obesity, autoimmune disease, and previous exposure to hepatotoxic drugs such as isoniazid or rifampicin. 

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