Phenytoin hepatotoxicity

Parker, William A.; Shearer, Cameron A.

doi:10.1212/wnl.29.2.175

Cited by 68 publications

(39 citation statements)

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“…Liver involvement ranges from mild elevations in transaminases to fulminant hepatic necrosis. In many cases ofliterature (10)(11)(12)(13), the large majority of patients resolved with withdrawal of the drug although severe cases of hepatitis may be lifethreatening (14). In our case, the prognosis was good, because we observed a dramatic and complete recovery in symptoms and laboratory results after withdrawal of the drug associated with corticosteroid treatment.…”

Section: Discvssionmentioning

confidence: 48%

Carbamazepine-Induced Hypersensitivity Syndrome in a Child with Epilepsy

Verrotti

Feliciani

Morresi³

et al. 2000

Int J Immunopathol Pharmacol

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Carbamazepine is an effective anticonvulsant and is considered the drug of first choice for the treatment of partial and secondarily generalized seizures. Although carbamazepine is well tolerated, many side effects have been reported in the literature. The majority of these adverse effects are transient and do not lead to the discontinuation of the therapy.We present a case of a female child, aged 11 years and 6 months, who showed an anticonvulsant hypersensitivity syndrome induced by carbamazepine. This syndrome is a rare, potentially life-threatening adverse drug reaction. The patient developed a cutaneous nonpruritic rash, associated with high fever, diffuse lymphadenopathy, and arthralgias on the knees and the ankles with local signs of arthritis. Laboratory examination showed a lymphocytosis, mild thrombocytopenia, marked eosinophilia, and high transaminases.Corticosteroid therapy (betametasone 0,5 mg x 3 day) was started and carbamazepine was gradually withdrawn changing to valproic acid, with complete control of the seizures. The fever and the rash reduced gradually, beginning from the face and then disappearing completely after 10 days. Laboratory results showed a clear improvement: after 7 days the patient showed a complete normalization of the above parameters, except for transaminases. The complete normalization of these enzymes was observed after 2 weeks from the disappearance of the skin rash.Carbamazepine (CBZ) is an effective anticonvulsant that has shown clinical efficacy in partial and secondary generalized seizures; it is an iminostilbine with a tricyclic structure (l, 2).CBZ is effective in affective disorders and trigeminal neuralgia, but its principal use is in the therapy of epilepsy; this drug is used for the treatment of partial elementary, partial complex, secondarily generalized and tonic-clonic seizures (3). A major advantage of carbamazepine is in its low potential for producing adverse behavioral and cognitive side effects (4).Although CBZ is well tolerated and global patient evaluation shows good results, many side effects have been reported in the literature. The majority of the adverse effects of CBZ includes nausea, drowsiness, vertigo, ataxia, blurred vision, diplopia. Very few patients require discontinuation of CBZ because of these side effects; Adverse reactions are most frequently transient and do not lead to discontinuation of therapy.Idiosyncratic reactions, including skin problems, have been frequently described and vary from 25% to 50% (5-9).Among the dermatologic manifestations, rashes are the most frequent finding. Their severity is generally mild and the discontinuation of the treatment solves these cutaneous features. Among the severe skin reactions (l0) anticonvulsant hypersensitivity syndrome (ARS) is a very rare

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Section: Discvssionmentioning

confidence: 48%

Carbamazepine-Induced Hypersensitivity Syndrome in a Child with Epilepsy

Verrotti

Feliciani

Morresi³

et al. 2000

Int J Immunopathol Pharmacol

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“…Hypersensitive hepatitis has been found in a few cases (Parker and Shearer, 1979). Jacobsen et al (1976) performed liver biopsies in 11 patients on long-term therapy with PHT.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Phenytoin on Serum and Organ Concentrations of Zinc and Copper in Cat

et al. 1985

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The effects of phenytoin (PHT) on zinc (Zn) and copper (Cu) concentrations in serum and different organs have been studied in cats. Five cats were treated with PHT 5 mg/kg body weight each day. Increased serum concentrations of Zn and Cu were found after 12 weeks of treatment. Increased Zn concentrations were found in the kidney and increased Cu concentrations in the liver and kidney. There wee signs of fatty degeneration of the liver. It is postulated that the drug acts as a chelator of the minerals and enhances their absorption from the intestine. A Cu accumulation may occur during PHT treatment.

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“…Our patient did not show any manifestation of hypersensitivity such as skin rash, eosinophilia, lymphadenopathy, fever or exfoliative dermatitis. Immunoallergic mechanisms can thus be excluded [6,14,15]. We suggest that the liver damage was due to a toxic effect consequent to a constitutional inability to normally metabolize sulpiride with accumulation of the drug or formation of toxic metabolites.…”

Section: Discussionmentioning

confidence: 89%

Bile ductopenia following therapy with sulpiride

Villari

Rubino

Corica

et al. 1995

Vichows Archiv A Pathol Anat

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We report a case of ductopenia associated with cholestatic hepatitis in a 59-year-old woman treated for 41 years for temporal epilepsy. The patient developed jaundice, without any clinical or biochemical features of hypersensitivity, 10 months after the beginning of treatment with sulpiride. Liver biopsy showed ballooning and acidophilic degeneration of the hepatocytes, macrophages packed with lipofuscin, biliary pigment in Kupffer cells, some biliary plugs, confluent necrosis and absence of biliary ducts in all the portal tracts. These features and the presence of foci of cholangiolitis suggest a destructive cholangitis as the pathogenetic mechanism causing ductopenia. Other causes of ductopenia were excluded. Sulpiride is known to produce severe cholestatic jaundice, which we believe is due to ductopenia. The absence of hypersensitivity and the 10-month latency suggest that sulpiride may cause liver damage through a toxic mechanism in genetically susceptible subjects.

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Phenytoin hepatotoxicity

Cited by 68 publications

References 0 publications

Carbamazepine-Induced Hypersensitivity Syndrome in a Child with Epilepsy

Carbamazepine-Induced Hypersensitivity Syndrome in a Child with Epilepsy

The Effects of Phenytoin on Serum and Organ Concentrations of Zinc and Copper in Cat

Bile ductopenia following therapy with sulpiride

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