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)

A 10-year-old girl with cervical tuberculosis was treated with Isoniazid, Rimfampicin and Ethambutol. After 2 weeks of treatment a hepatotoxic reaction developed. Withdrawal of therapy resulted in complete clinical improvement and in normalization of all laboratory measurements. Treatment was restarted with Rifampicin, Pyrazinamid and Ethambutol. Liver enzyme levels were monitored weekly. Seven weeks after this three-drug regiment was started, all therapy was discontinued because of elevated liver enzyme levels. However, the patient died 2 weeks later of progressive fulminant hepatitis.
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PMID:Fulminant hepatitis during treatment with rifampicin, pyrazinamid and ethambutol. 359 48

Isoniazid chemoprophylaxis recommendations include its use in persons who have positive tuberculin reactions, but neither recent conversion nor other activation risk factors, only if they are under age 35 years. Above this threshold, the isoniazid hepatitis risk is said to outweigh the benefit of preventing activation. Because this policy is controversial, we performed a decision analysis contrasting those who take with those who decline isoniazid therapy according to three outcome measures: life expectancy, likelihood of illness (isoniazid hepatitis and active tuberculosis), and likelihood of fatal illness. We found no threshold between ages 10 and 80 years by the measures of life expectancy and likelihood of fatal illness; isoniazid benefits outweigh risks for all, though the margin is small for the elderly. A threshold exists only in the likelihood of illness: isoniazid risks outweigh benefits for those aged 50 to 65 years. Only extreme variations of assumptions affect these findings. Chemoprophylaxis recommendations should include low-risk tuberculin reactors over age 35 years.
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PMID:The age threshold for isoniazid chemoprophylaxis. A decision analysis for low-risk tuberculin reactors. 377 78

The incidence and degree of liver injury was prospectively evaluated in 44 children, ages between 4 months and 14 years (mean age, 4.5 years) treated for tuberculosis with 15 to 20 mg isoniazid/kg/day and 15 mg rifampin/kg/day (INH-RIF). None of the patients had hepatic dysfunction before initiation of treatment. Elevation of the serum alanine aminotransferase (ALT) concentration (greater than 100 units) occurred in 36 patients (82%). One patient with an increase in the ALT value had coincidental infection with hepatitis B. The incidence of hepatotoxicity did not correlate with the patients' age or sex. Fifteen of the 36 patients developed clinical hepatitis with jaundice. In 7 patients liver enlargement and prolongation of the prothrombin time were also observed. In all but one patient liver dysfunction was recognized 6 to 30 days (mean, 14 days) after start of treatment. Biochemical signs of hepatic injury in the 35 surviving patients regressed completely without alteration of the INH-RIF regimen in 22 patients. These facts suggest the possibility that hepatocellular damage may be due to the effect of tubercle bacilli products liberated in the liver after their destruction by antituberculous drugs. However, the high rate of hepatotoxic reactions warns that the dose of 10 mg INH/kg/day should not be exceeded when that drug is combined with RIF.
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PMID:Hepatotoxic reactions in children with severe tuberculosis treated with isoniazid-rifampin. 400 Sep 89

The American Thoracic Society recommends that specific individuals who are classified as tuberculosis infected receive a year-long course of INH chemoprophylaxis. They further recommend that patients receiving medication be evaluated on a monthly basis to assess the individual for side effects related to the medication. The most prevalent side effects are hypersensitivity, GI distress, hepatitis and neurotoxicity. Subjective data relating to these side effects need to be elicited at every visit and a pertinent physical examination done. Careful monthly monitoring is required to evaluate the patient for the most prevalent and significant side effects of the medication. Nurses must be aware of the significance of this preventive measure, the adverse reactions which may occur with the drug therapy and the health teaching which contributes to patient compliance.
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PMID:Positive tuberculin skin tests and isoniazid chemoprophylaxis. 632 84

The activity of benzo (a) pyrene hydroxylase was estimated in liver biopsy material obtained by needle biopsy. The activity of the enzyme was lowest in patients with moderate to severe hepatitis or chronic active hepatitis, and highest in patients treated for tuberculosis with the tuberculostatic agents rifampicin, INH and ethambutol. A significant correlation was found between the activity of the benzo (a) pyrene hydroxylase in the biopsy specimens and the plasma clearance of the antidiabetic agent glymidine.
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PMID:Correlation between the activity of hepatic benzo (a) pyrene hydroxylase in human needle biopsies and the clearance of glymidine. 645 70

Recent experience suggests that the duration of chemotherapy of tuberculosis can be shortened to 6-9 months, without an increase in the relapse rate, if the treatment if started with 3 or 4 drugs including isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA). In a controlled study of culture-positive advanced pulmonary tuberculosis we have compared treatment regimens with PZA in a dosage of less than 2 g and with ethambutol (EMB). 113 patients were given, in random order for 2-3 months, either PZA (25 mg/kg body weight) or EMB (25 mg/kg) together with RMP (450 or 600 mg) and INH (5 mg/kg). The last two drugs were given for a total of 9 months. Patients treated with PZA showed a (not significantly) earlier conversion to negative cultures after an average of 7 weeks. After 18 months follow-up there have been no relapses on these regimens. 2 patients, both treated with EMB, did not respond to therapy. Drug-induced hepatitis was seen in 5 patients with PZA and in 2 patients with EMB. The hepatitis was always observed during the first month of therapy and was fully reversible. Three of the 4 patients with clinically apparent hepatitis were over 70 years of age. Three patients with elevated uric acid levels had arthralgia which led in one of them to termination of therapy. The preliminary results of our study show that the treatment regimen with PZA does not lead to a higher rate of side effects if used with particular moderation in older patients.
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PMID:[Pyrazinamide versus ethambutol in short-term therapy of lung tuberculosis. A randomized study]. 665 32

The effects of rifampicin (RMP) on isoniazid (INH) metabolism in rabbits were examined from the viewpoint of extensive hepatitis. After the RMP pretreatment, no remarkable changes were observed in the plasma levels of INH as well as its metabolites, acetylisoniazid (AcINH), acetylhydrazine (AcHz) and diacetylhydrazine (DAcHz) with the exception of hydrazine (Hz). After an oral administration of INH or Hz hydrate, the stochastic examination showed that the AUC0-8hr values of Hz plasma levels in RMP pretreated groups were significantly less than those in the control rabbits. RMP treatment was also shown to induce rabbit liver cytochrome P-450 activity. Histological studies demonstrated that Hz causes more remarkable hepatic necrosis in rabbits pretreated with RMP than in the control rabbits. These observations could suggest that Hz is a key intermediate of INH-hepatitis through the transformation of some hepatotoxic species by microsomal oxidation that is facilitated by RMP.
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PMID:Is isoniazid-hepatotoxicity induced by the metabolite, hydrazine? 667 29

Hepatitis developed in two patients treated with high doses (1000 mg/day) of isoniazid for severe tuberculous meningitis. Isoniazid was discontinued and later readministered in gradually increasing intrathecal and subsequently oral doses, up to the final dose of 400 mg/day. Transaminases remained normal, during 12 months on this dose, suggesting dose dependence of hepatotoxicity or a metabolic adaptation to the injury. Continued isoniazid treatment can be important in similar cases and it may become possible, if oral or intrathecal doses significantly lower than the initial hepatotoxic ones, are used.
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PMID:Hepatitis on high dose isoniazid: reintroduction of the drug in severe tuberculous meningitis. 685 18

In 95 patients with active tuberculosis, we investigated in a prospective study the influence of the acetylator phenotype on the hepatotoxic side effects of the antituberculous regimen isoniazid (INH) 10 mg/kg, rifampicin (RMP) 10 mg/kg, and ethambutol (EMB) 25 mg/kg. Besides a much higher incidence of isoniazid hepatitis (SGOT, SGPT greater than 200 U/l) in 12.6% of patients treated--as compared to the incidence reported in large chemoprophylaxis trials with isoniazid monotherapy in the range of 0.5%-1% (IUAT 1969, U.S.P.H.S. 1971)--we observed a significant, higher risk of isoniazid-induced hepatotoxicity in slow acetylators (p less than 0.01): in 26 of 56 slow acetylators (= 46.4%), but only in 4 of 30 rapid acetylators (=13.3%) were transaminases in the serum elevated greater than 50 U/l. The 12 patients with the most severe hepatotoxic side effects (SGOT, SGPT greater than 200 U/l) were all slow acetylators. Women developed severe hepatic injury more often than men (p less than 0.05). In cases with isoniazid hepatitis, triple therapy was either stopped or reduced to a combination RMP, EMB. In cases with less severe liver injury, triple therapy was continued. In all patients transaminases normalized within 2-4 weeks. On return to full triple therapy, none of the patients developed new elevation of transaminases. The constant occurrence of isoniazid hepatitis during the 2nd-4th week (19 +/- 7 days) as well as the normalization without any new hepatotoxic reaction suggest that there may be an interaction between RMP and isoniazid metabolism limited to the early phase of chemotherapy.
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PMID:[Incidence of hepatotoxic side effects during antituberculous therapy (INH, RMP, EMB) in relation to the acetylator phenotype (author's transl)]. 709 79

Enzyme induction during an antituberculous treatment with Rifampin, Isoniazid and Ethambutol was studied in 21 patients with tuberculosis. Two tests were used: increase in urinary excretion of D-saccharic acid and decrease of the half-life of antipyrineee. Induction is constant with D-saccharic acid. On the other hand there is a significant decrease in the half-life of antipyrin in only 10 patients. There is an increase in the 11 other patients: all of them are slow acetylators for isoniazid. We suggest that INH has an inhibitor effect on the hydroxylation of antipyrin. This study allows us to discuss the interactions of drugs with INH and Rifampin, as well the predominance of rapid acetylators among subjects suffering of isoniazid hepatitis, recently questioned.
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PMID:[Simultaneous study of the induction effect of rifampicin and the phenotype for acetylation of isoniazid in 21 patients with tuberculosis undergoing a combination treatment]. 718 65


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