Phenytoin and hepatotoxicity

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  • 1987
  • Authors J M Egerton-Vernon, M J Fisk, A P Snell
  • Hepatic injury caused by
  • DILI has a worldwide estimated annual incidence between 14 to 19
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  • 1987
  • Drugs such as valproic acid, phenytoin, and felbamate, have a well-recognized association with liver toxicity

    The hepatic injury can be classified into hepatocellular, cholestatic and mixed, caused by increase in alanine aminotransferase and alkaline phosphatase than upper limit of normal

    The probability of an individual drug causing liver injury ranges from 1 in 10,000 to 100,000, with some drugs reported as having an incidence of 100 in 100,000 (chlorpromazine, isoniazid) [ 2,3 ]

    Presenting symptoms often include fever, rash, lymphadenopathy, hepatomegaly, anorexia, and myalgias or arthralgias

    According to Bauer and Blouin (1982) and Mendis et al

    The liver injury caused by phenytoin appears to be due to a hypersensitivity reaction and resembles cases of immunoallergic hepatotoxicity

    We examined individual Idiosyncratic hepatotoxicity is a rare adverse effect associated with antiepileptic drug (AED) therapy

    Phenytoin hepatotoxicity is a serious idiosyncratic reaction that occurs in less than one percent of patients

    2

    However, N-acetylcystein is an appropriate treatment in patients with clinically significant liver injury due to phenytoin and carbamazepine

    We examined individual susceptibility to toxicity from such metabolites by exposing Regarding hypersensitivity reactions, phenytoin is a classic, if not common, cause of hypersensitivity reactions

    8, 11

    The risk factors include idiosyncrasy, age, gender, alcohol consumption The hepatotoxicity of APAP rests predominantly with the highly toxic and reactive compound NAPQI,

    More importantly and not uncommonly, valproate can cause several forms of Mixed hepatitis is typical of many medications including phenytoin, sulfonamides, macrolide antibiotics and enalapril

    Prospective studies indicate that a sizeable proportion of patients taking carbamazepine have transient serum aminotransferase elevations (ranging from 1% to 22%)

    In human hepatocytes, we

    Treatment with the antiepileptics phenobarbital (PB) or phenytoin (PH) has been associated with increased incidence of acetaminophen (APAP) hepatotoxicity in patients

    3) Serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum total concentration is 10 to

    In clinical trials in diabetic neuropathy and epilepsy, therapy with gabapentin was not associated with an increased frequency of serum aminotransferase elevations or liver toxicity

    A 17-year-old woman with phenytoin-induced hepatotoxicity was compared with 23 other cases from the literature and pathologic findings indicate a mixed hepatocellular damage of cholestasis and necrosis

    Idiosyncratic hepatotoxicity is more likely a series of rare drug-related toxicities with different forms of pathogenesis than a single entity

    Acetaminophen-induced liver damage and hepatotoxicity are at increased risk when administered with which of the following? Select all that apply

    With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity

    There is no defined therapy, and the drug should be discontinued

    Drugs such as valproic acid, phenytoin, and felbamate, have a well-recognized association with liver toxicity

    Other common manifestations include jaundice, hepatomegaly, elevated serum transaminase levels, leukocytosis, and eosinophilia

    Drugs that cause dose-related toxicity may do so at lower doses in the presence of hepatic impairment than in individuals with normal liver function, and some drugs that produce reactions of the idiosyncratic kind do so more frequently in patients with Isoniazid (INH) is a potent bactericidal antibiotic used in the treatment of tuberculosis

    Levetiracetam has been linked to rare instances of serum aminotransferase and alkaline phosphatase elevations during treatment and to rare cases of clinically apparent drug induced liver disease

    Enzymes playing a major role in the corresponding pathway are denoted with a star

    64, 65 Minton et al reported on another phenytoin-treated patient who developed hepatotoxicity Fosphenytoin is a medication used to manage seizures (treatment of generalized tonic-clonic status epilepticus, focal [partial] onset seizures, or generalized onset seizures, and for the prevention and treatment of seizures occurring during neurosurgery)

    Dosing is 100 mg/kg (maximum of 6 g) IV loading dose over 30 minutes, followed by maintenance dosing of 50 mg/kg Hepatotoxicity: Cases of acute hepatotoxicity, including infrequent cases of acute hepatic failure, have been reported

    In these patients with acute hepatotoxicity, phenytoin should be immediately discontinued and not re-administered

    Phenytoin (PHT) was first synthesized as a barbiturate derivative and was approved in 1953 by the Food and Drug Administration

    The onset of symptoms occurs early in therapy, usually within the first six weeks

    29 ( 2) 175 Get Access Abstract A 17-year-old woman with phenytoin-induced hepatotoxicity was compared with 23 other cases from the

    This syndrome is more

    (2001) described the hepatotoxicity of phenytoin as antiepileptic hypersensitivity syndrome requiring immediate discontinuation of the

    10

    LiverTox ® provides up-to-date, unbiased and easily accessed information on the diagnosis, cause, frequency, clinical patterns and management of liver injury

    Other antiepileptic drugs, including phenobarbital, benzodiazepines, ethosuximide, and the newer generations of antiepileptic drugs, have only rarely been linked to hepatotoxicity

    The hepatic injury can be classified into hepatocellular, cholestatic and mixed, caused by increase in alanine aminotransferase and alkaline phosphatase than upper limit of normal

    More

    Presenting symptoms often include fever, rash, lymphadenopathy, hepatomegaly, anorexia, and myalgias or arthralgias

    4%], fatal or transplantation outcomes [10% vs 6%] as well as Lamotrigine is not an aromatic convulsant and is unrelated structurally to phenytoin and carbamazepine

    Fosphenytoin is a prodrug of phenytoin available in parenteral forms only

    (2 year old girl on carbamazepine and phenytoin developed coma and hypotension and marked ALT elevations [5220 and 4020 U/L] with minimal bilirubin

    (2

    [22], levetiracetam [14], phenytoin [14], valproate [9], clonazepam [8 Chronic alcohol abuse, concomitant treatment with phenytoin and isoniazid, and starvation worsen liver injury related to acetaminophen

    Hepatic injury caused by phenytoin is

    Likewise, liver disease can adversely affect the biotransformation of some of these drugs

    Idiosyncratic hepatotoxicity is more likely a series of rare drug-related toxicities with different forms of pathogenesis than a single entity

    Carbamazepine, phenytoin, phenobarbital (pheno-barbitone) and structurally related compounds may produce hepatic injury as part of a more widespread hypersensitivity reaction

    With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity

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