Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to establish guidelines for prescribing drugs in patients treated with plasma exchange (PE), we studied the pharmacokinetics of paracetamol (5 patients), diclofenac (4 patients) and vidarabine (3 patients) during one or several PE. Results were compared with those obtained without PE. Diclofenac and paracetamol were chosen because they presented different volume distribution and protein binding characteristics. Vidarabine was studied because we use it for the treatment of patients with polyarteritis nodosa related to hepatitis B virus. Diclofenac (100 mg) and paracetamol (1000 mg) were given 1 hour before PE. Samples were obtained 60 and 30 min before PE, every 15 min during PE and hourly for 2 hours after the end of PE. Vidarabine was given in continuous infusion, 15 mg/kg/d during the first week of treatment and 7.5 mg/kg/d during subsequent weeks. Samples were obtained before PE, 3 times during PE and every 30 min for 4 hours after the end of PE. Paracetamol, diclofenac, vidarabine and hypoxanthine arabinoside were assayed by high performance liquid chromatography. During each PE 60 ml/kg were removed and replaced by albumin. We found that 17% of diclofenac, 4.3% of paracetamol and 4.9% of vidarabine were removed during each session. Plasmapheresis clearance was 51% of plasma clearance for diclofenac, 15% for paracetamol and 10% for vidarabine. Drugs which are mainly removed during PE are those which are bound to proteins with a small distribution volume. Those drugs, such as diclofenac, must be administered after the end of each PE session. Drugs which present a large distribution volume and low protein binding can be given before the session. Vidarabine can be administered during PE without loss of effectiveness due to drug removal.
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PMID:Pharmacokinetics of paracetamol, diclofenac and vidarabine during plasma exchange. 290 Feb 16

Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.
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PMID:Etiology and outcome for 295 patients with acute liver failure in the United States. 987 98

NCX-701 is a nitric oxide (NO)-releasing acetaminophen (APAP) derivative. In the present study we demonstrated that NCX-701 is as effective as APAP in controlling body temperature in a rat model of endotoxin-induced fever. Liver toxicity is a major complication of APAP overdosing. To investigate whether NCX-701 is hepatotoxic, BALB/C mice were injected with 100 - 500 mg kg(-1) APAP or NCX-701 alone or in combination (i.e. 500 mg kg(-1) of both compounds). Our results demonstrated that although APAP caused a dose-dependent liver injury, NCX-701 was completely devoid of liver toxicity. At the dose of 500 mg kg(-1) APAP caused an approximately 40 fold increase of AST plasma levels and extensive centrilobular necrosis. APAP and NCX-701 share the same metabolic pathway as demonstrated by the time-course of APAP-glucuronide concentrations in plasma and liver. NCX-701 was safe in mice with pre-existing chronic liver disease. Indeed, while C57BL6 transgenic mice expressing the hepatitis B virus (HBV) at the age of 8 months were significantly more susceptible to liver damage induced by APAP (500 mg kg(-1)) than their congenic littermates, treating HBV-transgenic mice with NCX-701, 500 mg kg(-1), caused no damage. Co-administration of NCX-701 at the dose 500 mg kg(-1) to mice treated with APAP, 500 mg kg(-1), completely protected against liver damage induced by APAP. APAP, but not NCX-701, upregulated liver Fas and Fas Ligand mRNA expression in vivo. Incubating mouse hepatocytes with APAP, but not with NCX-701, increased cell surface Fas expression and sensitized hepatocytes to death induced by challenge with a Fas-agonistic antibody. Collectively, these observations suggest that APAP toxicity is Fas mediated and that NCX-701 spares the liver by acting at several checkpoints in the Fas pathway.
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PMID:A NO-releasing derivative of acetaminophen spares the liver by acting at several checkpoints in the Fas pathway. 1933 75

Etiopathogenesis of acute hepatic failure (AHF) in Eastern and Western countries is distinct. In the East hepatitis viruses cause AHF in more than 95% of such cases, while causes of AHF in the West are quite heterogenous. Hepatitis E virus is the major etiological agent of AHF in countries like India where the virus is hyperendemic. Occult HBV infection may also be causing AHF in a sizable proportion of cases in areas where chronic HBV infection frequency is high. Paracetamol causes AHF in about 70% cases in the UK and about 20% cases in USA, whereas in France and Denmark, non-steroidal anti-inflammatory drugs are more frequently associated with AHF. Hepatitis B virus causes AHF in about one-third of cases in the latter two countries.
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PMID:Etiopathogenesis of acute hepatic failure: Eastern versus Western countries. 1247 48

A case is presented of a fatal drug interaction caused by ingestion of oxycodone (Oxycontin) and clonazepam (Klonapin). Oxycodone is an opium alkaloid used in long-term pain management therapy. Clonazepam is a benzodiazepine used for the treatment of seizures and panic disorders. The Drug Abuse Warning Network (DAWN) has reported an increase of 108% in the last two years of emergency department episodes related to Oxycontin. Six billion prescriptions were written for Oxycontin in the year 2000, an 18-fold increase from four years previous (1). Oxycontin has recently gained enormous notoriety at the local and national levels; however, there are very few previously documented cases of lethal drug interactions between oxycodone and clonazepam. Synergistic effects between these two drugs are postulated to arise from different agonistic mechanisms producing similar physiological changes. It is also theorized that clonazepam may inhibit the metabolism of oxycodone. A 38-year-old white female was found dead in Jefferson County, Tennessee in March of 2001. The deceased had physical evidence of previous drug abuse and positive serological findings of hepatitis B and C. Prescription pill bottles filled under the name of the deceased, as well as another name, were found with the body. Serum, urine and gastric contents from the deceased were screened for numerous drugs and metabolites using a combination of thin layer chromatography and immunoassay techniques (EMIT and FPIA). Analysis of biological specimens from the deceased revealed the presence of: benzodiazepines, opiates (oxycodone), and trazodone metabolites in the serum; cannabinoids, benzodiazepines, opiates (oxycodone), trazodone, trazodone metabolites, nicotine, and nicotine metabolite in the urine; and benzodiazepines, opiates (oxycodone), nicotine, and nicotine metabolite in the gastric contents. Quantitative analyses for clonazepam was performed by high performance liquid chromatography (HPLC) and revealed a plasma concentration of 1.41 microg/mL. Plasma oxycodone and urine 11-nor-carboxy-delta-9-tetrahydrocannabinol concentrations were determined by gas chromatography/mass spectrometry and revealed concentrations of 0.60 microg/mL and 27.9 ng/mL, respectively. The deceased had pathologies consistent with severe central nervous system (CNS) and respiratory depression produced by high concentrations of clonazepam and oxycodone including collapsed lungs, aspirated mucus, and heart failure. The pathologies were sufficient to cause death, which was officially attributed to a drug overdose; however, the manner of death was unknown.
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PMID:A fatal drug interaction between oxycodone and clonazepam. 1517 Nov 97

The cause of acute liver failure (ALF) is a major determinant of its outcome. Acetaminophen (paracetamol) overdose is a leading cause of ALF in some developed countries, whereas in others, such as Spain, it is extremely rare. To analyze the etiology, characteristics, and outcome of ALF in Spain, we performed a retrospective analysis of 267 patients whom we observed from 1992 to 2000. Seventeen tertiary-care hospitals with active liver transplantation (LT) programs contributed data. Causes of ALF were viral hepatitis in 98 (37%; hepatitis B virus in 75 patients), unknown in 86 (32%), drug or toxic reactions in 52 (19.5%; acetaminophen overdose in 6), and miscellaneous in 31 (11.6%). Overall survival was 58%. LT was performed in 150 patients, with a survival of 69%. Despite fulfilling criteria, 51 patients were not transplanted because of contraindications; their survival was only 7.8%. Forty-seven (85.5%) of 55 patients without transplant criteria survived. Hepatitis B virus is the most common cause of ALF in Spain, although the origin of 30% of cases remains undetermined. Acetaminophen overdose represents a very rare cause of ALF. LT was performed in >50% of cases. Patients without transplant criteria had a very good prognosis; those who fulfilled these criteria but who had contraindications for transplantation had a high mortality rate.
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PMID:Acute liver failure in Spain: analysis of 267 cases. 1790 41

The etiology of fulminant hepatitis varies in different countries and at different times. The main causes of fulminant hepatitis are viruses, paracetamol, drugs (other than paracetamol), poisons and 15-30% remained of undetermined origin. The prevalence of these etiologies varies according to the geographic region and has changed over the past 10 years. Paracetamol has now overtaken viruses (particularly hepatitis B virus) as the leading cause of fulminant hepatitis. Establishing the cause of fulminant hepatitis is an important step in the management of acute liver failure, so that specific therapy can be initiated and any contraindications to liver transplantation be eliminated.
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PMID:Epidemiology of liver failure. 2155 Mar 29