naloxone and Hyperglycemia

Hyperglycemia after severe traumatic brain injury (TBI) occurs frequently and is associated with poor clinical outcome and increased mortality. In this review, we highlight the mechanisms that lead to hyperglycemia and discuss how they may contribute to poor outcomes in patients with severe TBI. Moreover, we systematically review the proper management of hyperglycemia after TBI, covering topics such as nutritional support, glucose control, moderated hypothermia, naloxone, and mannitol treatment. However, to date, an optimal and safe glycemic target range has not been determined, and may not be safe to implement among TBI patients. Therefore, there is a mandate to explore a reasonable glycemic target range that can facilitate recovery after severe TBI.

Topics: Blood Glucose; Brain; Brain Injuries, Traumatic; Diuretics, Osmotic; Glucose; Humans; Hyperglycemia; Hypoglycemic Agents; Hypothermia, Induced; Insulin; Intracranial Hypertension; Mannitol; Naloxone; Risk Factors

Tramadol is a synthetic opioid and poisoning is increasing around the world day by day. Various treatments are applied for tramadol poisoning. Due to the unknown effects of tramadol poisoning and some of its treatments on blood glucose levels, this study was conducted to investigate the overdose of tramadol and its common treatments (naloxone, diazepam), and their combination on blood glucose levels in male rats.. This study was conducted in 45 male Wistar rats. The animals were randomly divided into five groups of 9. They received a 75 mg/kg dose of tramadol alone with naloxone, diazepam, and a combination of both of these two drugs. On the last day, animals' tail vein blood glucose levels (BGL) were measured using a glucometer at different times, including before the tramadol injection (baseline) and 1 hour, 3 hours, and 6 hours after wards. The rats were anesthetized and sacrificed 24 h after the last injection. Blood samples were then taken, and the serum obtained was used to verify the fasting glucose concentration. Data were analyzed using SPSS software at a significance level of 0.05 using a one-way analysis of variance (ANOVA) and a generalized estimating equation (GEE).. According to the GEE model results, the diazepam-tramadol and naloxone-diazepam-tramadol groups showed blood glucose levels five units higher than the tramadol group (p < 0.05). The diazepam-tramadol group had significantly higher blood glucose levels than the naloxone-tramadol group (p < 0.05). The mean blood glucose levels before the intervention, 3 hours and 6 hours after the injection of tramadol did not differ between the groups, but the blood glucose levels 1 hour after the injection of tramadol in the group of naloxone-tramadol were significantly lower than in the control group (p < 0.05). Blood glucose levels did not differ between the groups 24 h after injection of tramadol.. The results of the present study showed tramadol overdose does not affect blood glucose levels. The diazepam-tramadol combination and the diazepam-naloxone-tramadol combination caused an increase in blood glucose levels.

Topics: Analgesics, Opioid; Animals; Blood Glucose; Diazepam; Drug Overdose; Hyperglycemia; Hypnotics and Sedatives; Male; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Tramadol

Topics: Adrenergic alpha-2 Receptor Agonists; Adult; Bradycardia; Clonidine; Drug Overdose; Emergency Service, Hospital; Female; Humans; Hyperglycemia; Naloxone

1. Naloxone, which is often regarded as a pure opioid antagonist, produces effects similar to those produced by morphine. 2. In conscious rabbits implanted with an intracerebroventricular (i.c.v.) cannula, naloxone, whether given intravenously (1 mg/kg) or i.c.v. (1-100 microg), produced a significant rise in blood glucose levels. 3. Hyperglycaemia in response to naloxone (1 mg/kg, i.v., or 100 microg, i.c.v.) was not influenced by the selective alpha1-adrenoceptor antagonist WB-4101 given either i.v. (50 microg) or i.c.v. (5 microg). 4. Hyperglycaemia in response to naloxone (1 mg/kg, i.v., or 100 microg, i.c.v.) was completely blocked by pretreatment with the alpha2-adrenoceptor antagonist yohimbine (1 mg/kg, i.v., or 100 microg, i.c.v.). However, hyperglycaemia to i.c.v. naloxone (100 microg) was not influenced by i.v. yohimbine (1 mg/kg). 5. Because naloxone behaves like morphine and produces hyperglycaemia in conscious rabbits, the drug may have an appreciable agonist activity and the hyperglycaemic response to naloxone is principally mediated via alpha2- but not alpha1-adrenoceptors.

Topics: Adrenergic alpha-Antagonists; Animals; Blood Glucose; Dioxanes; Hyperglycemia; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Rabbits; Receptors, Adrenergic, alpha-2; Yohimbine

The present study investigated the cause effect relationship between glycemic and algesic states. The hypo- and hyperglycemic conditions were induced physiologically through exercise (3 min swim at room temperature 28 degrees - 30 degrees C) and external dextrose (2 g/kg, ip) administration respectively in mice. Besides, flavone (50 mg/kg, sc) a known antinociceptive drug was chosen to study such a cause effect relationship. The anti-nociception was assessed by acetic acid assay, blood glucose measured using glucometer (Ames) and serum insulin by radioimmunoassay. The findings revealed that irrespective of the glycemic state whether hypo-, hyper, or euglycemic induced by swim stress, dextrose or flavone per se respectively, significant antinociceptive response was recorded. Pretreatment with flavone (50 mg/kg, sc) always exhibited a tendency to reverse the hyperglycemia, if any, but enhanced the antinociceptive response either after swim stress or after dextrose. These data support the contention that changes in the glycemic state in acute condition is not responsible for antinociceptive response and thereby suggesting dissociation between these two parameters. Extended studies estimating serum insulin level after the above mentioned maneuvers showed a significant rise whenever antinociceptive response was recorded irrespective of the glycemic state. It is suggested that serum insulin level, a hormonal parameter rather than the blood glucose level, which is a metabolic parameter, appears more reliable. It appears that the changes in serum insulin level produced by various treatments may have a relationship with the antinociceptive response. However, this study has the limitation that the results can apply only for acute conditions and extrapolation to clinical conditions is debatable.

Topics: Acetic Acid; Analgesics; Animals; Blood Glucose; Flavones; Flavonoids; Glucose; Hyperglycemia; Hypoglycemia; Insulin; Male; Mice; Naloxone; Narcotic Antagonists; Pain; Pain Threshold; Radioimmunoassay; Swimming

We investigated the effect of loperamide, a selective agonist of opioid mu-receptor, on the plasma glucose in diabetic rats induced by an intravenous injection of streptozotocin (STZ; 60 mg/kg). Intravenous injection of loperamide induced a dose-dependent decrease of plasma glucose in fasting STZ-diabetic rats at 30 min later, but did not modify the plasma glucose level in Wistar rats. Plasma glucose lowering effect of loperamide was abolished by the pretreatment with naloxone or naloxonazine at the dose sufficient to block opioid mu-receptor. In isolated skeletal muscle, loperamide enhanced the glucose uptake into soleus muscles in a concentration-dependent manner. Blockade of this action by naloxonazine indicated the mediation of opioid mu-receptor. These results suggest that an activation of opioid mu-receptor by loperamide can increase the utilization of glucose in peripheral tissue to lower the plasma glucose in STZ-diabetic rats.

Topics: Animals; Antidiarrheals; Blood Glucose; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Glucose; Hyperglycemia; Injections, Intravenous; Loperamide; Male; Muscle, Skeletal; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid, mu

The possibility that benzodiazepine-induced hyperglycaemia is mediated through the release of endogenous endorphins was tested. The results show that naloxone, the opiate antagonist, potentiated clonazepam-induced hyperglycaemia. Treatment with increasing doses of morphine for six days, which induced tolerance to endorphins, did not affect clonazepam-induced hyperglycaemia. The results indicate that endorphins do not mediate benzodiazepine-induced hyperglycaemia.

Topics: Animals; Blood Glucose; Clonazepam; Endorphins; Hyperglycemia; Injections, Subcutaneous; Male; Mice; Morphine; Naloxone

The tail pinch (t-p) method added to a basal restraint stress produced inhibition of the stress-induced hyperglycemia, an effect that was neutralized with intrathecal anesthesia but not with intracerebroventricular (i.c.v.) naloxone (50, 100, 1000 ng/100 g) or with intraperitoneal naloxone injections (0.1-0.3 mg/100 g). A similar negative result was obtained with i.c.v. administration of 500 and 1000 ng/100 g of beta-endorphin. In contrast, a single i.c.v. injection of 1000 ng/100 g of Met-enkephalin reproduced the t-p inhibitory effect. The latter was not elicited by i.c.v. FK 33824, an enkephalin analogue, a result that supports the specific participation of the delta-opioid receptors. The results obtained with central alpha-adrenoceptor antagonists and central noradrenergic chemical destruction, or central alpha-adrenoceptor agonists, support the production of a reinforcement of the alpha-adrenoceptor stress stimulation by the t-p procedure, probably through noradrenaline and enkephalin mediation.

Topics: Animals; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Enkephalin, Methionine; Hyperglycemia; Injections, Intraventricular; Insulin; Male; Naloxone; Pain; Rats; Rats, Inbred Strains; Restraint, Physical; Tail

Male Sprague-Dawley rats maintained under controlled lighting and temperature conditions were used in this experiment. Morphine dependency was induced by giving increasing doses of morphine by intraperitoneal injection (IP group) or by the ingestion of morphine through drinking water (PO group). Animals were injected with 10, 20, 30 and 50 mg/kg morphine sulfate at days 1, 2, 3 and 4, respectively. Another group of animals received increasing concentrations of morphine through drinking water from 0.1, 0.2, 0.3 to 0.4 mg/ml at 48 h intervals. Morphine dependent animals were given naloxone by the intraperitoneal route to precipitate withdrawal. Glucose (3 g/kg or 10 g/kg) was given 10 min prior to the administration of naloxone to the respective groups. Another two groups of animals were made diabetic by the administration of streptozotocin. In one group, animals received increasing concentrations of 10, 20, 30 and 50 mg/kg morphine sulfate by the IP route at days 1, 2, 3 and 4, while the other group was not treated with morphine but was assessed for withdrawal signs to serve as the control. Withdrawal signs were assessed by observing the presence of diarrhea, tremor, piloerection, hunchbacked posture, teeth chattering, salivation, erection, restless activity, territorial exploring, irritability to handling, vocalization and jumping. Results obtained indicate that glucose administration at 10 g/kg abolished most of the withdrawal signs, and we were unable to induce the same degree of morphine dependency in diabetic animals as compared to the non-diabetic groups. It was concluded from this study that hyperglycemia could suppress morphine withdrawal signs.

Topics: Animals; Behavior, Animal; Diabetes Mellitus, Experimental; Hyperglycemia; Male; Morphine Dependence; Naloxone; Rats; Rats, Inbred Strains; Substance Withdrawal Syndrome

The role of opioid receptors in diabetes and hyperglycemia-induced analgesia was studied in male Sprague-Dawley rats. Animals maintained under controlled environmental conditions were used in all studies. Pain latency was determined by the hot plate test (55 degrees C) and analgesy-meter force method. The results of these studies indicate that streptozotocin-induced diabetic animals have a significantly higher pain threshold (P less than 0.01) than the control groups. The pain threshold was found to be diurnally controlled with a peak at the beginning of the light phase (1000 hours) and a trough at the end of the dark phase (0800 hours). Diabetes-induced analgesia was found to be reversed by both acute or chronic insulin administration. In another study, glucose-induced hyperglycemic rats were found to have a significantly higher pain threshold (P less than 0.01) than control animals, with a peak occurring at the beginning of the dark phase (2000 hours), and a trough at the beginning of the light phase (0800 hours). The administration of the opioid antagonist naloxone (2 mg/kg) reversed the hyperglycemia and diabetic-induced analgesia. The results of these studies might indicate that analgesia found in diabetic or hyperglycemic animals may be related to the endogenous opioid system.

Topics: Analgesia; Animals; Circadian Rhythm; Diabetes Mellitus, Experimental; Hyperglycemia; Insulin; Male; Naloxone; Pain; Rats; Rats, Inbred Strains; Receptors, Opioid; Sensory Thresholds

The present study was designed to investigate the in vivo effects of beta-endorphin on plasma levels of glucagon, insulin and glucose in rabbits, and to elucidate some of the mechanisms involved. beta-Endorphin (50 micrograms) injected intravenously into fasted rabbits, decreased plasma levels of insulin (-4.5 +/- 1.3 microU/ml, P less than 0.05) and increased plasma levels of glucose (+2.7 +/- 0.4 mmol/l, P less than 0.05). Similar hypoinsulinemic and hyperglycemic effects were observed for 25 and 2.5 micrograms beta-endorphin in fasted and 50 and 0.5 micrograms beta-endorphin in fed rabbits. beta-Endorphin produced slight and transient increases in plasma levels of glucagon at the highest dose in fed rabbits, only (+80 +/- 9 pg/ml, P less than 0.05). The beta-endorphin-induced hypoinsulinemia was not inhibited by phentolamine, yohimbine, propranolol or atropine, which is in consistency with a direct inhibitory effect of beta-endorphin on the beta-cell in rabbits. The beta-endorphin-induced hyperglycemia was reduced by naloxone (+0.8 +/- 0.1 mmol/l) but not by N-methyl-naloxone (ORG 10908) a peripheral opiate receptor blocking drug (+2.2 +/- 0.2 mmol/l), suggesting a central nervous action on opiate receptors. This central action of beta-endorphin was probably not mediated by catecholamine release or other stimulation of adrenergic or muscarinic receptors, since the beta-endorphin-induced hyperglycemia was not inhibited by phentolamine, yohimbine, propranolol or atropine. These results suggest that the beta-endorphin-induced hyperglycemia was caused, at least in part, by a peripheral inhibition of insulin release and a central stimulation on glucoregulation.

Topics: Animals; Atropine; beta-Endorphin; Blood Glucose; Endorphins; Female; Glucagon; Hyperglycemia; Injections, Intravenous; Insulin; Naloxone; Phentolamine; Propranolol; Quaternary Ammonium Compounds; Rabbits; Yohimbine

Naloxone, an opiate antagonist, is reported to reverse hypotension and to improve survival in hemorrhaged and septic animals. We have found recently that naloxone also blunts the hyperglycemic response to hemorrhage. This could result from a naloxone-induced diminution of the hypotensive stimulus to hyperglycemia, from a naloxone-induced diminution of hormonal secretion or action, from a naloxone-mediated decrease in glucose production, or from a direct action of naloxone on glucose uptake in skeletal muscle and other peripheral tissues. In order to examine the direct effect of naloxone on glucose uptake in skeletal muscle, male Sprague-Dawley rats were perfused in a standardized isolated perfused hindlimb system with or without naloxone (0.5 microgram/ml of perfusate). No insulin was added to the perfusate. Glucose uptake in animals treated with naloxone was 30.2% greater than that of control animals (p less than 0.05). This increase was not dependent on insulin. Although no significant differences were noted in the individual products of glucose utilization, the total tissue glucose that could be accounted for by these intermediates was increased in naloxone-treated hindlimbs (p less than 0.05). Thus the increase in glucose uptake by skeletal muscle noted in these experiments may explain, in part, the blunted hyperglycemic response to hemorrhage that occurs after naloxone administration. These results also suggest the possibility that endogenous opiates may be important in regulating glucose metabolism after hemorrhage.

Topics: Animals; Glucose; Hemorrhage; Hindlimb; Hyperglycemia; Hypotension; Male; Naloxone; Perfusion; Rats; Rats, Inbred Strains

Intracerebroventricular (ICV) instillation of morphine and beta-endorphin causes centrally induced hyperglycemia. Locally active, endogenous opioids in the central nervous system may, therefore, also be involved in the elevation of blood sugar. This possibility was tested by examining the glucoregulatory response to central glucoprivation induced by ICV administration of 2-deoxy-D-glucose (2DG) in dogs. Administration of 2DG resulted in a rise in plasma glucose and immunoreactive glucagon (IRG) of 108 +/- 19 mg/dl and 70 +/- 20 pg/ml, respectively. These changes were attenuated by the simultaneous central infusion of the opiate antagonist naloxone: plasma glucose levels increased by 77 +/- 14 mg/dl and IRG by 43 +/- 3 pg/ml, both significantly different from the effect of 2DG alone (P less than 0.05-0.01). These findings suggest that opiate receptors participate in the counterregulatory response to central glucoprivation. They also provide a mechanism by which endogenous opioid peptides may play a role in the central regulation of glucose homeostasis.

Topics: Animals; Blood Glucose; Brain; Deoxyglucose; Dogs; Endorphins; Glucagon; Glucose; Homeostasis; Hyperglycemia; Naloxone; Radioimmunoassay

This study assessed the role of endogenous opiate systems in the hyperglycemic response to endotoxin challenge in mice. Blockade of opiate receptors by administration of the opiate antagonists naloxone (1.0 mg/kg) or naltrexone (1.0 or 5.0 mg/kg) significantly lessened to degree of hyperglycemia cause by endotoxin challenge (80 micrograms). Methyl naltrexone, a peripherally acting opiate antagonist, had no demonstrable effect on endotoxin-induced hyperglycemia. Finally, induction of tolerance to morphine prevented the hyperglycemic response to endotoxin challenge. These results suggest a causative role for central nervous system endorphinergic mechanisms in the hyperglycemic response to endotoxin administration. They support the view that centrally acting opiate antagonist, by blocking the brain opiate receptors, can influence metabolic adaptation to endotoxin shock.

Topics: Animals; Endorphins; Endotoxins; Hyperglycemia; Male; Mice; Mice, Inbred C3H; Morphine; Naloxone; Naltrexone; Quaternary Ammonium Compounds

The present study assessed the role of endogenous opiate systems in the hyperglycaemic response to challenge with endotoxin in mice. Blockade of opiate receptors by administration of the opiate antagonists naloxone (1.0 mg/kg) or naltrexone (1.0 or 5.0 mg/kg) significantly decreased the degree of hyperglycaemia caused by challenge with endotoxin (80 micrograms). Naltrexone methyl bromide, a peripherally acting opiate antagonist, had no demonstrable effect on the endotoxin-induced hyperglycaemia. Finally, induction of tolerance to morphine prevented the hyperglycaemic response to challenge with endotoxin. These results suggest a causative role for central endorphinergic mechanisms in the hyperglycaemic response to administration of endotoxin. They support the view that the centrally acting opiate antagonist, by blocking the brain opiate receptors, can influence metabolic adaptation to endotoxin-induced shock.

Topics: Animals; Blood Glucose; Drug Tolerance; Endorphins; Endotoxins; Hyperglycemia; Male; Mice; Mice, Inbred C3H; Morphine; Naloxone; Naltrexone

Synthetic human beta-endorphin increased plasma glucose concentration when administered intracisternally in chronically cannulated, conscious, unrestrained, adult male rats. This hyperglycemic effect of beta-endorphin was blocked by prior systemic administration of naloxone, supporting mediation of the effect at opioid receptors in brain. Adrenal denervation blocked the beta-endorphin-induced increase in plasma glucose, supporting a thesis that this effect is mediated at least in part by increased epinephrine secretion. The hyperglycemic response to intracerebral beta-endorphin was also blocked by either intracerebral hemicholinium-3 or somatostatin, supporting both a cholinergic link and a somatostatin neuron in the brain mechanism regulating endorphin-induced stimulation of sympathetic outflow.

Topics: Adrenal Medulla; Animals; Blood Glucose; Denervation; Endorphins; Female; Humans; Hyperglycemia; Male; Naloxone; Rats; Sympathetic Nervous System

Topics: Diazepam; Glucose; Hospitalization; Humans; Hyperglycemia; Methadone; Myelitis, Transverse; Myoglobinuria; Naloxone; Narcotics; New York City; Pneumonia, Aspiration; Propranolol; Pulmonary Edema; Respiration; Substance Withdrawal Syndrome; Substance-Related Disorders; Tetanus Toxoid