Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functional activity of the gamma-aminobutyric acid (GABAA) receptor-chloride ionophore complex was studied in rats with hepatic encephalopathy (HE) secondary to thioacetamide-induced fulminant hepatic failure (FHF). Muscimol stimulation and benzodiazepine potentiation of GABA receptor-mediated 36Cl- uptake into cerebral cortical synaptoneurosomes was compared in HE and control rats. [3H]Flumazenil binding assays were conducted to determine whether the levels of endogenous benzodiazepine-like ligands in extracts of cortex were increased with stages of encephalopathy in this animal model of HE. In both control and HE rats maximal uptake of 36Cl- via the GABAA receptor complex occurred at muscimol concentrations of 30 microM. Potentiation of muscimol-stimulated 36Cl- uptake into synaptoneurosomes by diazepam (5 microM) was equivalent in both groups. Aqueous extracts of proteolytically digested homogenates of cerebral cortices prepared from control and HE rats were effective in stimulating 36Cl- uptake into synaptoneurosomes. Alkaline organic extracts of proteolytically digested homogenates of cerebral cortices from HE rats were more effective than corresponding extracts from controls at inhibiting the binding of [3H]flumazenil. Inhibition of [3H] fumazenil binding by organic extracts derived from the cerebral cortices of HE rats did not increase with progression of encephalopathy. The results show that muscimol-stimulated 36Cl- uptake into synaptoneurosomes and, consequently, GABAA receptor-mediated chloride channel function are not significantly altered in the model of HE studied and are consistent with the hypothesis that HE results in an increased availability of one or more endogenous ligands which can augment GABA receptor-gated chloride conductance.
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PMID:Gamma-aminobutyric acid (GABAA) receptor-function in a rat model of hepatic encephalopathy. 196 8

We investigated the therapeutic effect of flumanezil on acute and chronic hepatic encephalopathy in a group of cirrhotics; its efficacy was evaluated using clinical data and neurophysiologic examination, e.g. brain mapping. Flumazenil was not found to induce significant changes in the clinical status or in maps of the cerebral activity of patients with chronic encephalopathy. In acute encephalopathy, flumazenil improved clinical status, as was confirmed neurophysiologically by improved cerebral activity on brain mapping.
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PMID:[Evaluation of the therapeutic effect of flumazenil in hepatic encephalopathy using cerebral cartography]. 249 14

If increased gamma-aminobutyric acid (GABA)-mediated neurotransmission contributes to the mediation of hepatic encephalopathy, it may be possible to induce ameliorations of the syndrome by pharmacologically antagonizing a component of the GABA/benzodiazepine receptor complex. To test this possibility we administered the benzodiazepine receptor antagonist flumazenil by intravenous injection to 14 patients with hepatic encephalopathy complicating cirrhosis. Flumazenil administration induced variable and transient, but distinct, improvements of the mental status in 71% of the patients. The degree of encephalopathy improved from stage IV to stage II in 4 patients and from stage IV to stage III in 2 patients. The mental status of all patients with less advanced encephalopathy (3 with stage III, 1 with stage II) also improved, but these responses were clinically less impressive. The arousal effect occurred within minutes after the injection and lasted for 1 to 2 h. Furthermore, it was associated with a significant increase of the mean electroencephalographic frequency from 4.2 to 5.2 cycle/s. Of the 8 patients who were ultimately discharged from the hospital, 7 had responded to flumazenil. No patient who died within 48 h of receiving flumazenil had shown any arousal effect. These findings strongly favor a prominent pathogenetic role of increased GABAergic tone in hepatic encephalopathy in humans and suggest that a positive response to flumazenil might be of prognostic value in predicting short-term survival in encephalopathic patients with liver disease.
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PMID:Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans. 254 50

We report on a 33-year-old female suffering from frequent complex-partial seizures who developed a non-convulsive status epilepticus after one week of antiepileptic therapy with valproate (VPA) which had been added to a basic medication with barbexaclone (BBC) in rapidly increasing dosage. The electroencephalogram (EEG) showed continuous rhythmic generalized sharp and slow wave activity with a frontal maximum. Intravenous administration of 3.0 mg of the benzodiazepine (BZ) receptor antagonist flumazenil under monitoring with video-EEG led to an immediate and marked electroclinical improvement, whereas 6.0 mg of the BZ receptor agonist midazolam was followed by a deterioration both clinically and in the EEG. We discuss the concept of VPA-encephalopathy and the possible mechanisms of the action of flumazenil on VPA-induced as well as on other toxic and metabolic encephalopathies. Flumazenil might antagonize increased benzodiazepine receptor activity with agonistic and even convulsive properties in these encephalopathic syndromes. Further investigations are needed concerning the relation of drug-induced or metabolic encephalopathies and central benzodiazepine receptor activity. We recommend a therapeutic trial with flumazenil, if stupor or decreased seizure control develop in patients treated with valproate.
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PMID:Temporary abolition of seizure activity by flumazenil in a case of valproate-induced non-convulsive status epilepticus. 789 43

1. Acute Encephalopathy in Cirrhosis A. GENERAL MEASURES. Tracheal intubation in patients with deep encephalopathy should be considered. A nasogastric tube is placed for patients in deep encephalopathy. Avoid sedatives whenever possible. Correction of the precipitating factor is the most important measure. B. SPECIFIC MEASURES i. Nutrition. In case of deep encephalopathy, oral intake is withheld for 24-48 h and i.v. glucose is provided until improvement. Enteral nutrition can be started if the patient appears unable to eat after this period. Protein intake begins at a dose of 0.5 g/kg/day, with progressive increase to 1-1.5 g/kg/day. ii. Lactulose is administered via enema or nasogastric tube in deep encephalopathy. The oral route is optimized by dosing every hour until stool evacuation appears. Lactulose can be replaced by oral neomycin. iii. Flumazenil may be used in selected cases of suspected benzodiazepine use. 2. Chronic Encephalopathy in Cirrhosis i. Avoidance and prevention of precipitating factors, including the institution of prophylactic measures. ii. Nutrition. Improve protein intake by feeding dairy products and vegetable-based diets. Oral branched-chain amino acids can be considered for individuals intolerant of all protein. iii. Lactulose. Dosing aims at two to three soft bowel movements per day. Antibiotics are reserved for patients who respond poorly to disaccharides or who do not exhibit diarrhea or acidification of the stool. Chronic antibiotic use (neomycin, metronidazole) requires careful renal, neurological, and/or otological monitoring. iv. Refer for liver transplantation in appropriate candidates. For problematic encephalopathy (nonresponsive to therapy), consider imaging of splanchnic vessels to identify large spontaneous portal-systemic shunts potentially amenable to radiological occlusion. In addition, consider the combination of lactulose and neomycin, addition of oral zinc, and invasive approaches, such as occlusion of TIPS or surgical shunts, if present. Minimal or Subclinical Encephalopathy Treatment can be instituted in selected cases. The most characteristic neuropsychological deficits in patients with cirrhosis are in motor and attentional skills (60). Although these may impact the ability to perform daily activities, many subjects can compensate for these defects. Recent studies suggest a small but significant impact of these abnormalities on patients' quality of life (61), including difficulties with sleep (62). In patients with significant deficits or complaints, a therapeutic program based on dietary manipulations and/or nonabsorbable disaccharides may be tried. Benzodiazepines should not be used for patients with sleep difficulties.
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PMID:Hepatic Encephalopathy. 1146 22