Hepatitis diclofenac

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],... 

Scully, L.J., Clarke, D., and Barr, R.J., Diclofenac induced hepatitis. 3 cases with features of autoimmune chronic active hepatitis, Dig. Dis. Sci., 38, 744, 1993. 

Diclofenac undergoes hepatic methylation and oxidation, creating (6 metabolites that are all susceptible to conjugation by glucuronidation and sulfation. A major metabolite of diclofenac is considered to be its hydroxylated derivative,... 

Acyl glucuronide Diclofenac Glucuronosyl transferase Hepatic toxicity... 

Tang W, Steams RA, Wang RW, et al. Roles of human hepatic cytochrome P450s 2C9 and 3A4 in the metabolic activation of diclofenac. Chem Res Toxicol 1999 12 192-199. 

Diclofenac is contraindicated in those with a history of hypersensitivity to aspirin or another NSAID, severe heart failure, patients with previous or active peptic ulceration, or porphyria. It should be avoided in pregnancy. It should be used with caution in patients with allergic disorders, renal, hepatic and cardiac impairment, the elderly, in lactation and in those with coagulation defects. 

Idiosyncratic toxicity Metabolic abnormality No No Weeks-months Any Increased liver enzymes, hepatitis, jaundice Diclofenac Ketoconazole... 

Lill JS, O Sullivan T, Bauer LA, et al. (2000) Pharmacokinetics of diclofenac sodium in chronic active hepatitis and alcoholic cirrhosis. J Clin Pharmacol 40 250-257. 

Hackstein, H., Mohl, W., Piischel, W., Stallmach, A., Zeitz, M. Acute cholestatic hepatitis associated with diclofenac. Z. Gastroenterol. 1998 36 385-389... 

Iveson TJ, Ryley NG, Kelly PM, Trowell JM, McGee JO, Chapman RW. Diclofenac associated hepatitis. J Hepatol 1990 10(l) 85-9. 

Mazeika PK, Ford MJ. Chronic active hepatitis associated with diclofenac sodium therapy. Br J Chn Pract 1989 43(3) 125-6. 

Jones AL, Latham T, Shallcross TM, Simpson KJ. Fulminant hepatic failure due to diclofenac treated successfully by orthotopic liver transplantation. Transplant Proc 1998 30(1) 192. ... 

Diggory P, Golding RL, Lancaster R. Renal and hepatic impairment in association with diclofenac administration. Postgrad Med J 1989 65(765) 507-8. 

Lonazolac, an arylacetic acid derivative, causes adverse effects like those of other NSAIDs. Gastrointestinal disturbances are followed in frequency by nervous system and skin reactions. The extent of gastrointestinal blood loss is similar to that with diclofenac (1). Cholestatic hepatitis has also been reported (SEDA-8, 106). 

ADRAC. Diclofenac sodium aud hepatic injury. Aust Adv Drug React Bull 1986 June. 

Zweerszeilmaker, W.M., Horbach, G.J. and Witkamp, R.F. (1997). Differential Inhibitory Effects of Phenytoin, Diclofenac, Phenylbutazone and a Series of Sulfonamides on Hepatic Cytochrome P4502c Activity in Vitro, and Correlation with Some Molecular Descriptors in the Dwarf Goat (caprus hircus aegagrus). Xenobiotica, 27, 769-780. 

Figure 15-4 In silico subtraction method for mechanistic study to compare the hepatic gene expression profile induced by compound X to other compounds that induce hepatic APR secondary to inflammation at sites other than the liver. In the proposed simple model, compound X-induced gene expression change has two components. One is vasculitis specific the other is acute phase response (APR) specific. By subtracting the APR specific component, we might select candidate genes that are specifically associated with the hepatic vascular lesion Diclofenac known to induce APR without triggering vasculitis in liver is used to subtract genes activated by hepatic APR from the compound X response.

Kretz-Rommel, A. Boelsterli, U.A. "Mechanism of Covalent Adduct Formation of Diclofenac to Rat Hepatic Microsomal Proteins. Retention of the Glucuronic Acid Moiety in the Adduct, Drug Metab Dispos. 22, 956-961 (1994). 

Coxibs and NSAIDs uncommonly cause drug-induced hepatitis the two NSAIDs most frequently implicated are diclofenac and sulin-dac. Patient monitoring should include periodic liver enzymes (aspartate aminotransferase and alanine aminotransferase), with cessation of therapy if these values exceed two to three times the normal range. 

Relationship of polymorphism in CYP2C9 to genetic susceptibility to diclofenac-induced hepatitis. Pharmacogenetics 10, 511-518. 

For reasons that are unclear, drug-induced liver injury affects females more than males Females accounted for approximately 79% of all reactions to acetaminophen and 73% of all idiosyncratic drug-induced reactions (88). Females exhibit increased risk of hepatic injury from drugs such as atorvastatin, nitrofurantoin, methyidopa, and diclofenac. 

Although the reasons are unknown, hepatic drug reactions are more common in females. Females are more susceptible to acetaminophen, halothane, nitrofurantoin, diclofenac, and sulindac. 

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