naloxone and Hepatic-Encephalopathy

This study aimed to assess the effectiveness and safety of naloxone in the management of hepatic encephalopathy (HE).. Cochrane collaboration methodology was used in a meta-analysis of randomized controlled trials of naloxone therapy for HE.. Seventeen randomized trials were identified with 15 studies involving 1054 patients meeting criteria for inclusion. Naloxone use was associated with a significant improvement in HE [relative risk (RR) 1.46; 95% confidence interval (CI) 1.27-1.67; P = 0.0005]. This comparison showed statistical heterogeneity (P < 0.10, and χ2 = 44.93). Subgroup analysis indicated naloxone administered parenterally by intermittent or continuous infusions to be effective (RR 1.34; 95% CI 1.17-1.53; P < 0.0001). A significant in trials by infusion route (RR 1.42; 95% CI 1.19-1.69; P < 0.0001) interaction was observed.. Naloxone may improve HE. However, published data are limited.

Topics: Hepatic Encephalopathy; Humans; Infusions, Intravenous; Naloxone; Narcotic Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Animals; Brain Edema; Cerebrovascular Circulation; Dipeptides; Hepatic Encephalopathy; Humans; Naloxone

To investigate the potential effects on cognitive function, prognosis, and neuropeptide levels of patients in response to combination therapy with ornithine aspartate plus naloxone for hepatic encephalopathy.. Eighty-four consecutive patients diagnosed with hepatic encephalopathy were randomly divided into two equal groups. The control group (n = 42) received traditional medical treatment, and the research group (n = 42) received the traditional medical treatment as well as the combination therapy with ornithine aspartate plus naloxone. The supplemental treatment was comprised of daily intravenous injection of 10-15 g ornithine aspartate in 250 ml of 5% glucose plus intravenous drip of 3 mg naloxone in 100 ml of 5% glucose, and was given in 7-day cycles for one or two cycles. The cognitive function of patients was assessed by Hasegawa Intelligence Scale (HDS) and Mini-Mental State Examination (MMSE) questionnaires. The effective rate and time duration from coma to consciousness were recorded. Changes in blood ammonia level, markers of liver function, and neuropeptide levels were measured by standard biochemical assays. Intergroup differences were assessed by the Chi-squared test.. The HDS and MMSE scores of the research group were significantly higher than those of the control group after therapy. The effective rate, time duration from coma to consciousness, blood ammonia, the liver function markers alanine aminotransferase, gamma-glutamyl-transpeptidase and total bilirubin, and the neuropeptides arginine vasopressin and beta-endorphin were remarkably improved after treatment in the research group, as compared with that in the control group.. Supplementing the traditional treatment for hepatic encephalopathy with ornithine aspartate plus naloxone combination therapy provides better therapeutic outcome than traditional treatment alone.

Topics: Adult; Dipeptides; Female; Hepatic Encephalopathy; Humans; Male; Middle Aged; Naloxone; Neuropeptides; Prognosis

Liver disease has been known for a long time to affect brain function. We now report the function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced by hepatic encephalopathy (HE) following bile duct ligation (BDL), a model of chronic liver disease. Assessment of spatial and object novelty detection memories was carried out in the non-associative task. It consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). Both spatial and object novelty detection memories were impaired by BDL after 4 weeks. In the BDL mice, pre-test intraperitoneal administration of naloxone (μ-opioidergic receptor antagonist) at dose of 0.9mg/kg restored while sulpiride (D2-like dopamine receptor antagonist) at dose of 40mg/kg potentiated object novelty detection memory deficit. However, SCH23390 (D1-like dopamine receptor antagonist) at dose of 0.04mg/kg or sulpiride (20mg/kg) restored spatial novelty detection memory deficit. Moreover, SCH23390 or sulpiride impaired while naloxone did not alter both memories in sham-operated mice. Furthermore, subthreshold dose co-administration of dopaminergic antagonists together or each one plus naloxone did not alter both memory impairments in BDL mice, while all of three co-administration groups impaired object novelty detection and co-administration of naloxone plus sulpiride impaired spatial detection memory in sham-operated mice. In conclusion, we suggest that opioidergic and dopaminergic systems through separate pathways may contribute in memory impairments induced by BDL in the non-associative task.

Topics: Animals; Benzazepines; Disease Models, Animal; Dopamine Antagonists; Exploratory Behavior; Hepatic Encephalopathy; Locomotion; Male; Memory; Mice; Naloxone; Narcotic Antagonists; Receptors, Dopamine; Receptors, Opioid; Space Perception; Sulpiride

Treatment of hepatic encephalopathy with drugs acting on the target organ of this syndrome, the brain, is unsatisfactory. Combination treatment with different neurotransmitter receptor antagonists may be a rational option to optimize treatment.. The effects of various doses of the benzodiazepine receptor antagonist Ro 15-3505 and the opioid receptor antagonist naloxone, alone or in combination, were tested on hepatic encephalopathy in rats with thioacetamide-induced hepatic failure in an open-field activity meter. Comparison of single and combination treatment was also done using a neurological test battery. In addition, we compared survival of treatment-responder rats with treatment non-responders.. Naloxone dose dependently increased ambulatory activity and improved neurological score. Ro 15-3505 also improved ambulatory activity and neurological score; however, the improvement was less evident at higher doses. Combination treatment was not superior to single treatment. Survival was increased in treatment-responder rats.. The failure of combination treatment with Ro 15-3505 and naloxone to further improve hepatic encephalopathy may suggest that the two neurotransmitter systems are interrelated or that hepatic encephalopathy may not be further improved by drugs acting on the brain.

Topics: Animals; Benzodiazepines; Benzodiazepinones; Drug Therapy, Combination; Hepatic Encephalopathy; Male; Motor Activity; Naloxone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Survival Analysis; Thioacetamide

The therapeutic role of naloxone was examined in a pilot study of 23 patients with hepatic (portal-systemic) encephalopathy. The results indicate that endogenous opioids (endorphins, enkephalins) are involved in the pathogenesis of hepatic encephalopathy. It is concluded that naloxone, a relatively pure opioid antagonist, may be an effective and well-tolerated drug for this particular pathology.

Topics: Drug Administration Schedule; Drug Evaluation; Female; Hepatic Encephalopathy; Humans; Infusions, Intravenous; Male; Middle Aged; Naloxone; Pilot Projects

Clinical observation has indicated a supersensitivity to morphine in patients with hepatic encephalopathy. With the aim of clarifying the issue, radioreceptor binding studies of opiate receptors were performed in frontal cortex and hypothalamus of 6 dogs with mild portal-systemic encephalopathy induced by chronic treatment with dimethylnitrosamine followed by porto-caval shunt end-to-side. beta-Endorphin assays were performed in the same areas with radioimmunoassay. Opiate receptors labeled with [3H]naloxone in both areas showed a significant increase in the receptor densities (Bmax) without changes in the dissociation constant (KD). In parallel beta-endorphin levels showed a decline during the development of encephalopathy in both areas. The increased densities of opiate receptors in the mild stage of encephalopathy may explain the supersensitivity to morphine in patients with liver diseases.

Topics: Animals; beta-Endorphin; Brain; Cerebral Cortex; Dogs; Endorphins; Female; gamma-Aminobutyric Acid; Hepatic Encephalopathy; Hypothalamus; In Vitro Techniques; Kinetics; Male; Naloxone; Receptors, Opioid

Topics: Adolescent; Child; Child, Preschool; Female; Hepatic Encephalopathy; Humans; Naloxone