Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrofurantoin-induced hepatic injury has been established unequivocally as an entity by rechallenge experiences. We reviewed 12 previously reported cases in which rechallenge was described. The longest reported interval between initial injury and rechallenge-provoked injury was 4 yr. We report a 56-yr-old woman who experienced severe hepatocellular injury with brief low-dose administration of nitrofurantoin 17 yr after an initial hepatitis-like illness associated with ingestion of the drug. Despite a temporal relationship to nitrofurantoin administration and histologic features compatible with drug-induced hepatitis, the initial bout of hepatitis had been termed "infectious." Our case appears remarkable for the long interval between initial injury and rechallenge-induced injury. The severity of the hepatic injury seen on rechallenge underscores the concept that the inadvertent rechallenge can be dangerous. Failure to identify the first bout of hepatitis as nitrofurantoin-related, and failure to inform the patient about the possible relationship to nitrofurantoin, raises important risk-management concerns, because hepatic memory of nitrofurantoin hypersensitivity appears to be of long duration.
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PMID:Long-term hepatic memory for hypersensitivity to nitrofurantoin. 161 46

Nitrofurantoin is a widely utilized urinary antimicrobial drug which has been associated with pulmonary fibrosis, neuropathy, and hepatitis as well as hemolytic anemia in glucose-6-phosphate dehydrogenase-deficient individuals. Incubation of freshly isolated rat hepatocytes with nitrofurantoin caused oxygen activation as a result of futile redox cycling. Glutathione disulfide (GSSG) was formed and rapidly exported from the cell resulting in complete glutathione (GSH) depletion followed by cell death. However, fructose prevented the export of GSSG from the cell and GSH levels recovered rapidly without cytotoxicity occurring. Fructose did not affect nitrofurantoin metabolism but rapidly depleted cellular ATP levels by approximately 80% which remained depressed during the incubation period. Fructose, however, did not protect hepatocytes from nitrofurantoin-induced cytotoxicity if GSH was depleted beforehand. Protection by fructose only occurred at concentrations which caused ATP depletion. These results suggest that fructose prevents nitrofurantoin-induced toxicity by depleting ATP and thereby preventing the ATP-dependent GSSG efflux. GSSG is retained enabling NADPH and glutathione-reductase to reduce the GSSG back to GSH, thereby protecting the cell from nitrofurantoin-induced oxidative stress.
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PMID:Prevention of nitrofurantoin-induced cytotoxicity in isolated hepatocytes by fructose. 189 74

Nitrofurantoin has been described as a cause of both hepatocellular cholestatic hepatic injury. A case report of a patient in whom granulomatous hepatitis developed attributed to nitrofurantoin is given.
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PMID:Nitrofurantoin-induced granulomatous hepatitis. 726 24

This article presents a rare case of acute toxic hepatitis in thirty-one-year old primigravida. In the 36th week of gestation, the patient was introduced nitrofurantoin 100 mg a day due to symptoms of dysuria and enterococcus isolated from urine culture. After induced delivery at term because of hypertension, repeated laboratory findings showed increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and negative hepatitis C and B markers. The patient was subicteric at the time. Coagulation and complete blood count values were within the normal range. Nitrofurantoin therapy was discontinued. Abdominal ultrasound was normal with the exception of a slight hepatomegaly without any lesions, focal or diffuse. Given that discontinuation of nitrofurantoin and introduction of methylprednisolon therapy significantly lowered liver enzyme levels, restoring most of them to normal, we concluded that this was probably the case of toxic liver damage caused by nitrofurantoin.
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PMID:Nitrofurantoin-induced acute liver damage in pregnancy. 1978 66

Nitrofurantoin is a commonly prescribed antibiotic for the treatment of recurrent uncomplicated urinary tract infections. Its importance has been emphasized by the current international clinical practice guidelines for the management of uncomplicated cystitis. Since its introduction into clinical practice, nitrofurantoin has been associated with various adverse effects, including hepatotoxicity. We searched the English-language literature using PubMed and SCOPUS for the period 1961 through the end of February 2013. Key search terms included "nitrofurantoin AND hepatotoxicity" as well as "nitrofurantoin AND hepatitis." When studies or case reports were found, we assessed articles cited in those publications. A broad spectrum of liver toxicity associated with nitrofurantoin use has been reported, ranging from acute hepatitis, granulomatous reaction, cholestasis, or autoimmune-mediated hepatitis to chronic active hepatitis that could lead to cirrhosis or death. The mechanism of hepatotoxicity is poorly understood, but it is believed to be the result of an immunologic process or a direct cytotoxic reaction. It has been postulated that prolonged exposure to nitrofurantoin, female sex, advanced age, and reduced renal function increase the risk of developing hepatotoxicity. For the management of severe cases, corticosteroids have been used along with nitrofurantoin discontinuation. Because of mixed results, the utility of corticosteroids has not been proven and should be used judiciously. Given the severity and seriousness of the adverse effect of hepatotoxicity, clinicians should weigh the risks and benefits of nitrofurantoin before initiating therapy, especially in long-term prophylaxis in high-risk patients. Clinicians also should be well versed in recognizing and managing liver injury associated with nitrofurantoin.
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PMID:Nitrofurantoin-induced hepatotoxicity: a rare yet serious complication. 2492 77