naloxone and Alcoholic-Intoxication

Hemodialysis therapy has been used in the treatment of acute alcohol intoxication for many years, especially acute severe alcohol intoxication.. This study aimed to evaluate whether the combination of conventional treatment and naloxone with hemodialysis has advantages over conventional treatment and naloxone alone in patients with acute severe alcohol intoxication.. After searching 12 databases and 2 clinical trial centers. According to the established inclusion and exclusion criteria, the qualified literatures were screened. The outcome indicators were length of hospital stay, coma time, time of symptom disappearance, the overall complication rate, the incidence of pancreatitis, the incidence of aspiration pneumonia, the incidence of hepatic and renal dysfunction. Analysis was performed using Revman 5.3.. This meta-analysis included 13 studies, including 932 subjects. In the treatment of acute severe alcohol intoxication, the use of hemodialysis on the basis of conventional treatment and naloxone could reduce the length of hospital stay (WMD = -15.16, 95% CI: -17.45 to -12.86, p < 0.001) in hours and (WMD = -4.89, 95% CI: -5.53 to -4.25, p < 0.001) in days; coma time (WMD = -5.43, 95% CI: -6.43 to -4.43, p < 0.001); time of symptom disappearance (WMD = -3.92, 95% CI: -5.37 to -2.47, p < 0.001); the overall complication rate (RR = 0.39, 95% CI: 0.28-0.55, p < 0.001); the incidence of pancreatitis (RR = 0.14, 95% CI: 0.05-0.43, p = 0.0006); the incidence of aspiration pneumonia (RR = 0.15, 95% CI: 0.04-0.66, p = 0.01), and the incidence of hepatic and renal dysfunction (RR = 0.21, 95% CI: 0.06-0.72, p = 0.01).. It can be concluded that compared with the use of conventional treatment and naloxone alone, the use of hemodialysis on the basis of conventional treatment and naloxone for acute severe alcohol intoxication can reduce the length of hospital stay, coma time, time of symptom disappearance, and the incidence of some complications rate. Large scale, multicenter, and well-designed RCTs are needed in the future to prove our conclusions.

Topics: Alcoholic Intoxication; Coma; Humans; Kidney Diseases; Multicenter Studies as Topic; Naloxone; Pancreatitis; Pneumonia, Aspiration; Renal Dialysis

To investigate the effectiveness and safety of Xingnaojing Injection (XNJ, ) compared with naloxone for the treatment of acute alcohol intoxication (AAI), and provide the latest evidence through evidence-based approach.. Seven electro-databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure Databases, Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Database (VIP) and Wanfang Database were searched from the inception to January 2018. Randomized controlled trials (RCTs) comparing XNJ with naloxone for patients with AAI and reporting at least one of the below outcomes were included: patients' conscious recovery time, stay length in emergency department, disappearance time of the ataxia symptom, the severity of the symptoms, the blood alcohol content as well as the adverse events. Methodological quality of included trials was assessed using the risk of bias tool which recommended by the Cochrane Collaboration. Meta-analysis was conducted by Review Manager 5.3 software.. Totally 141 trials with 13,901 patients were included in this review, all of them were assessed as unclear or high risk of bias. Results showed that on the basis of routine therapy, standard dose XNJ (10-20 mL) may have similar results with naloxone on the recovery time of consciousness (MD 12 min, 95% CI 7.2-17.4 min) and disappearance time of symptoms (MD 6 min, 95% CI-13.8-25.8 min) for patients with AAI. Larger dose of XNJ Injection (21-40 mL) may speed up the time (almost 1 h earlier). Combination of XNJ and naloxone seemed superior to the naloxone alone for all the relevant outcomes. The average difference of time in consciousness recovery was 2 h and the number of AAI patients whose consciousness recovery within 1 h was above 50% the combination group than in the control group (RR 1.42, 95% CI 1.29 to 1.56). No severe adverse events or adverse reactions of XNJ were reported in the included trials.. Low quality of evidence showed XNJ may have equal effect as naloxone and may achieve better effect as add-on intervention with naloxone for patients with AAI. We failed to evaluate the safety of XNJ Injection due to the insufficient evidence in this review. Registration number. in PROSPERO (No. CRD42018087804).

Topics: Alcoholic Intoxication; Blood Alcohol Content; Consciousness; Drug Therapy, Combination; Drugs, Chinese Herbal; Humans; Injections; Naloxone; Randomized Controlled Trials as Topic

Clinicians in the emergency department are often confronted with coma patients due to poisoning. A systematic general approach involving early consultation with a neurologist is of paramount importance. A high index of suspicion, a systematic first assessment already in the prehospital phase and early stabilisation of vital functions are the essential first steps. Specific antidotes like hypertonic glucose and thiamine are part of a "coma cocktail". The opiate antagonist naloxone should be used only when clinically indicated and in a titrated way. Flumazenil should only be used with caution and in restricted cases. Clinical neurological evaluation and technical investigations like CT-scan and laboratory tests should make part of a careful diagnostic plan. Toxicological tests deserve their place in the diagnostic work up of a coma patient with suspected poisoning. Knowledge of the possibilities of the toxicology lab and optimal communication with the clinical toxicologist is important for optimal patient care.

Topics: Accidental Falls; Alcohol-Induced Disorders, Nervous System; Alcoholic Intoxication; Antidotes; Brain Injuries; Coma; Diabetic Coma; Diagnosis, Differential; Diagnostic Tests, Routine; Drug Overdose; Emergencies; Ethanol; First Aid; Flumazenil; Glucagon; Glucose; Humans; Hypoglycemia; Hypoxia, Brain; Monitoring, Physiologic; Naloxone; Neurologic Examination; Stroke; Thiamine

Research of the alcohol action mechanism on the SNC in acute alcoholic intoxication (AAI) has been dealt in various ways. On one side the alcohol action--apparently most unspecific--on cellular membranes has been studied. Other authors, instead, have studied more specific alcohol effects on three types of neurotransmitters: opioid peptides, GABA and catecholamines. The effect of alcohol on cellular membranes seems to be beyond any doubt. Alcohol action on specific neurotransmitters is the object of controversy, especially in the case of endogenous opioids. There are data which strongly support the participation of the GABA receptors in the AAI. Modifications produced in the cellular membrane by alcohol action can modify the structure of the function of the membrane receptors. On the other hand, distinct receptors may be localized in the same neuron, while the existence of interactions between different neurotransmitters is well known. Therefore, the various hypotheses previously stated are not mutually exclusive.

Topics: Alcoholic Intoxication; Animals; Azides; Benzodiazepines; Brain; Cell Membrane; Ethanol; Humans; Naloxone; Neurons; Receptors, GABA-A; Receptors, Opioid

Topics: Alcoholic Intoxication; Humans; Naloxone

Substance abuse is a significant health problem in the adolescent population. Prevention is a formidable challenge, but attempts at discouraging experimentation in early adolescence and the promotion of healthy adult role models may be effective strategies. Questions that may elicit a history suggestive of abuse should be a routine part of the adolescent medical history. Pediatricians should be familiar with the important clinical findings resulting from intoxication with the various substances of abuse and should be able to recognize the "telltale" signs of abuse. Effective management is based on attention to the basics of life support, careful attention to the physical findings, and judicious use of specific therapeutic agents. Above all, a compassionate attitude should prevail if acute-phase recovery and long-term rehabilitation are to be successful.

Topics: Absorption; Adolescent; Adult; Alcoholic Intoxication; Amphetamines; Anti-Anxiety Agents; Benzodiazepines; Cocaine; Diagnosis, Differential; Female; Fever; Glucose; Hallucinogens; Humans; Hypotension; Illicit Drugs; Lysergic Acid Diethylamide; Marijuana Abuse; Mescaline; Methaqualone; Mushroom Poisoning; Naloxone; Narcotics; Nitrites; Poisoning; Solvents; Substance-Related Disorders

Topics: Alcoholic Intoxication; Animals; Central Nervous System Agents; Ethanol; Humans; Hyperbaric Oxygenation; Kinetics; Naloxone; Parasympathomimetics; Sympathomimetics; Thyrotropin-Releasing Hormone; Vasopressins; Vitamin B Complex

The first articles trying to link the effects of ethyl alcohol with those of opiates appeared in 1970. The first case of reversion from ethylic coma due to naloxone was described in 1978. Since then, many authors have reported different results related to the effectiveness of opiate antagonists in this clinical situation, without any of the studies showing a beneficial effect from its use. The purpose of the present study is to perform a double-blinded clinical trial with placebo to evaluate naloxone's clinical effectiveness in severe ethylic intoxication, using the Glasgow test (GT) to measure the level of consciousness. Treatment was randomly assigned to 38 patients of whom 18 received 2 mg of naloxone and 20 a placebo. Among the results, it was found that the best approximation of the level of alcoholemia responsible for ethylic coma, without the involvement of other toxic psychotropes, was made using the Glasgow test, especially in patients who are occasional drinkers. It was shown that naloxone indeed lacks effectiveness in ethylic coma, raising the level of consciousness only one or two points in the Glasgow test for the 15 to 45 minutes after its administration and primarily in the group of patients with the lowest levels of consciousness.

Topics: Adolescent; Adult; Alcoholic Intoxication; Double-Blind Method; Female; Humans; Male; Middle Aged; Naloxone

Naloxone administration to fasting normal male volunteers reverses the acute ethanol-induced increase in the blood [lactate]/[pyruvate] ratio, but fails to lower blood-ethanol concentration. The results are discussed in relation to factors affecting ethanol elimination and the mechanism of antagonism of acute alcohol intoxication by naloxone.

Topics: Adult; Alcoholic Intoxication; Ethanol; Humans; Lactates; Lactic Acid; Male; Metabolic Clearance Rate; Naloxone; Pyruvates; Pyruvic Acid

The reversal of acute alcohol intoxication by naloxone is controversial. Naloxone increases cortisol secretion but there are no reports of this effect during acute alcohol intoxication. This study examines the effect of 20 mg naloxone on alcohol-induced intoxication using a balanced placebo design to investigate the role of cortisol, participant expectancy of treatment, and possible pharmacokinetic interactions during intoxication. Our results show differences in the time course of subjective self-evaluation of drunkenness in the presence of naloxone. Also, changes are observed in naloxone pharmacokinetic parameters with the ingestion of alcohol, specifically a decrease in plasma clearance. Whereas the cortisol response induced by naloxone was greater in the subgroup of participants with positive expectancy, in the presence of alcohol the naloxone effect on cortisol response was not observed. These observations may help explain the observed reversal of alcohol-induced coma by naloxone in a subgroup of patients.

Topics: Adult; Alcoholic Intoxication; Ethanol; Humans; Hydrocortisone; Male; Naloxone

The effects of ethanol and subsequent administration of intravenous naloxone were studied in double-blind, placebo-controlled fashion with a group of six male chlorpropamide alcohol flushers (CPAF) and a group of 13 nonflushing males. The effect of ethanol intoxication on fine motor control was measured by a typing test. When sober, the two groups performed in comparable fashion. When intoxicated, the CPAF group displayed significantly greater impairment than the nonflushing group as measured by typing errors committed in 3 min (CPAF: 55.4 +/- 10.1 errors, n = 12; vs. nonflushing: 15.6 +/- 2.3, n = 32; p = 0.0000015 by Student's unpaired t test). Chlorpropamide alcohol flushers appeared to be more sensitive to ethanol. Naloxone reversed this effect for individuals in the CPAF group (saline treatment: 51.0 +/- 11.7 errors per minute; vs. naloxone treatment: 23.7 +/- 4.2; p = 0.034 by Student's paired t test, n = 6). Naloxone had no effect in the nonflushing group. Unlike the normal, nonflushing group, the CPAF group demonstrated an increased sensitivity to ethanol that was partially antagonized by naloxone.

Topics: Adult; Alcoholic Intoxication; Chlorpropamide; Double-Blind Method; Ethanol; Flushing; Humans; Male; Motor Skills; Naloxone

The effect of naloxone on ethanol-induced impairment of psychomotor performance was studied in a series of three placebo-controlled, double-blind trials. In all trials, two successive intravenous injections of naloxone (0.4 and 2.0 mg) were given at an interval of 0.5-1.5 hours. Cross-over trials with healthy volunteers (n = 17) were performed in laboratory. In these conditions, naloxone alone had no effect on performance. Ethanol alone (1.0 and 1.5 g/kg) dose-dependently induced nystagmus and impaired coordination, reactions, hand cooperation, body balance, flicker discrimination and extraocular muscle balance. When naloxone was given after ethanol, the first injection reduced slightly but significantly ethanol-induced (1.5 g/kg) nystagmus, while the second injection did not enhance this counteraction any more. Other alcohol effects were not significantly antagonized by naloxone. The clinical part of the study, consisting of parallel groups of either naloxone (n = 11) or saline (n = 7) -treated alcohol-intoxicated (mean blood alcohol concentration 2.9 mg/ml) out-patients, most of them alcoholics, showed that no counteraction of alcohol inebriation (measured by clinical inebriation tests) was associated with the treatment with naloxone in the clinical situation either. Our results suggest that naloxone has no clinical significance in antagonizing ethanol intoxication. The inebriating effects of ethanol are not importantly mediated via central opioid mechanisms.

Topics: Adult; Alcoholic Intoxication; Clinical Trials as Topic; Double-Blind Method; Ethanol; Humans; Male; Middle Aged; Naloxone; Nystagmus, Physiologic; Psychomotor Performance

Healthy human subjects performed a vigilance task involving decision making and motor responses under four drug conditions involving random assignment and double blind procedures. Naloxone (0.4 mg) or saline was injected intravenously before subjects consumed a drink of alcohol (0.56 gm ethanol per kg body weight) or a simulated alcoholic drink. Blood alcohol concentrations averaged 60 mg/dl. The impaired performance of the task by this blood alcohol concentration was ameliorated by prior administration of naloxone at one testing point in the study sequence (40 minutes after ingesting the alcohol). The effect was associated with a history of light drinking (mean intake 0.93 gm/kg of body weight/month). Further studies to characterize this phenomenon more fully are proposed.

Topics: Adult; Alcoholic Intoxication; Attention; Cognition; Ethanol; Humans; Male; Naloxone; Psychomotor Performance; Time Factors

Topics: Alcoholic Intoxication; Clinical Trials as Topic; Double-Blind Method; Ethanol; Humans; Naloxone; Random Allocation

Ethanol depresses the ventilatory responses to hypercapnia and hypoxia. We hypothesized that this ventilatory depression, like some other central nervous system effects of ethanol, might be mediated via endorphins. In a double-blind placebo-controlled study, we assessed the effect of the opiate antagonist naloxone on ventilatory responses during ethanol intoxication in 18 normal men. Standard rebreathing studies were done at baseline, after ethanol (1.5 ml/kg, p.o.), and after each of 2 intravenously administered injections. One of the injection sequences PP, NP, or PN (N = naloxone, 0.8 mg; P = placebo, 2 ml) was randomly assigned to each subject. The ventilatory responses were reduced after ethanol administration compared with those at baseline (p less than 0.05). In groups NP and PN, naloxone restored the hypercapnic response (p less than 0.05). Placebo injection did not significantly alter the response slopes. Hypoxic ventilatory responses showed the same trends but did not reach statistical significance. This study shows that naloxone reverses ethanol-induced depression of hypercapnic drive, suggesting that an opiate-mediated mechanism is responsible for this depression.

Topics: Adult; Alcoholic Intoxication; Clinical Trials as Topic; Double-Blind Method; Ethanol; Humans; Hypercapnia; Hypoxia; Male; Naloxone; Respiration

Topics: Adolescent; Adult; Alcohol Deterrents; Alcoholic Intoxication; Antidotes; Clinical Trials as Topic; Humans; Infusions, Parenteral; Injections, Intravenous; Middle Aged; Naloxone

Topics: Alcoholic Intoxication; Clinical Trials as Topic; Double-Blind Method; Humans; Naloxone

In a double-blind, cross-over study of twenty male volunteers intravenous injection of 0.4 mg naloxone prevented the impairment of psychomotor performance induced by low levels of blood alcohol. The possibility that alcohol produces intoxication by stimulating the release of endogenous opioid peptides should be investigated.

Topics: Adult; Alcoholic Intoxication; Blood Glucose; Clinical Trials as Topic; Ethanol; Humans; Male; Naloxone; Reaction Time

Topics: Adult; Aged; Alcoholic Intoxication; Biogenic Amines; Clinical Trials as Topic; Electroencephalography; Female; Humans; Male; Mental Disorders; Middle Aged; Naloxone; Schizophrenia

The differential diagnosis for the infant presenting with an apparent life-threatening event (ALTE) is broad. Toxic ingestions are a relatively uncommon cause of an ALTE, although several over-the-counter, prescription, and illicit drugs have been implicated. We present 2 cases of ethanol intoxication in infants as a previously unreported cause of an ALTE. Additionally, serial ethanol levels for these patients offer novel insight into the pharmacokinetics of ethanol metabolism in infants. Ethanol ingestion may be an underrecognized cause of an ALTE and should be considered if the history or physical examination is suggestive.

Topics: Alcoholic Intoxication; Brief, Resolved, Unexplained Event; Child Abuse; Diagnosis, Differential; Ethanol; Failure to Thrive; Foster Home Care; Humans; Infant; Male; Metabolic Clearance Rate; Naloxone; Narcotic Antagonists; Neurologic Examination; Substance Abuse Detection

It has been difficult to find conditioned preference for tactile cues paired with ethanol intoxication in rats. Toward understanding the ontogeny of ethanol reinforcement, we aimed at establishing a simple and reliable procedure for (1) assessing primary appetitive conditioning to ethanol in infant rats and (2) discerning the role the opioid system plays in ethanol-mediated conditioning at this age. Experiment 1 determined the parameters (i.e., dose, interval of conditioning) for assessing ethanol-mediated conditioning. Pups were then trained with differential Pavlovian conditioning (Experiments 2 and 3) in which ethanol intoxication (1.0-2.0 g/kg, intragastrically or intraperitoneally delivered) was paired with a tactile stimulus (sandpaper) while an alternative texture signaled the absence of ethanol's effects. Unpaired control conditions were also used. Tactile preferences were assessed after two conditioning sessions. Paired rats spent significantly more time on sandpaper than unpaired controls, an effect that was greater after intragastric administration of 1.0 than 2.0 g/kg ethanol. This effect was replicated in Experiments 4a and 4c and found to be inhibited by pretreatment with general (naloxone [NAL]) or specific (d-Pen-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 [CTOP] and naltrindole) opioid antagonists. Blood ethanol levels at conditioning were not altered by NAL (Experiment 4b). The study outlines a procedure that reveals appetitive conditioning to ethanol by infant rats. The results are discussed in terms of a potential ethanol-induced activation of the endogenous opioid system during the onset of the intoxication process.

Topics: Alcohol Drinking; Alcoholic Intoxication; Animals; Animals, Newborn; Conditioning, Classical; Ethanol; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Touch

We studied the actions of intoxicating doses of ethanol on excitatory inputs from the basolateral nucleus of the amygdala, a major afferent system projecting to the nucleus accumbens (NAcc). In view of the hypothesized role of opioid receptors on the effects of ethanol on NAcc physiology, we also explored whether naloxone modulates ethanol-induced suppression of NAcc excitability in halothane anesthetized and freely moving unanesthetized rats. Intraperitoneal administration of ethanol (1.2-1.4 g/kg) markedly suppressed a subgroup of amygdala-activated NAcc neurons. The ethanol-induced reduction in amygdala-activated NAcc neurons was not reversed by naloxone (5.0 mg/kg, intraperitoneally). Moreover, naloxone had no effect on the suppressive effects of ethanol on NAcc spontaneous activity in either halothane-anesthetized or unanesthetized freely moving preparations. These findings suggest that opiate mechanisms either are not participating or are not solely responsible for the inhibitory effects of acute intoxicating doses of ethanol on NAcc physiology.

Topics: Alcoholic Intoxication; Amygdala; Animals; Dose-Response Relationship, Drug; Electric Stimulation; Evoked Potentials; Male; Naloxone; Narcotic Antagonists; Neurons; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Synaptic Transmission

Experimental assays analyzing visual evoked potential (VEP) changes during an acute alcoholic intoxication were carried out in two groups of cats: One with continuous ethanol (0.06 g/kg.min) i.v. perfusion. Another one with a naloxone (400 micrograms/kg) i.v. injection 10 min before ethylic perfusion. Naloxone potentiates alcohol effects on VEP parameters, and on the appearance of isoelectric postpotential and flat VEP.

Topics: Acute Disease; Alcoholic Intoxication; Animals; Cats; Evoked Potentials, Visual; Male; Naloxone

Experimental assays analysing EEG changes during the recovery of an acute alcoholic intoxication were carried out in three groups of cats: 1) Recovery of acute alcoholic intoxication produced by continuous intravenous perfusion of ethanol, 0.06 g/kg/min, during 20 minutes. 2) Recovery of acute alcoholic intoxication by injecting naloxone (400 micrograms/kg), just after finishing alcohol perfusion. 3) Recovery of acute alcoholic intoxication by injecting naloxone (400 micrograms/kg), 15 min after finishing perfusion. Naloxone administered after an acute alcoholic intoxication worsens the recovery of EEG parameters; 1-2 (p less than 0.05), 1-3 (p less than 0.05).

Topics: Alcoholic Intoxication; Animals; Brain; Cats; Drug Synergism; Electroencephalography; Endorphins; Ethanol; Naloxone; Receptors, Opioid; Receptors, Opioid, mu

Groups of male CD-1 mice (n = 12/group) were injected intraperitoneally (IP) with 5 g ethanol/kg of body weight. After loss of righting reflex, they were given vehicle or one of 2-3 doses of reputed or potential antagonists of ethanol intravenously (IV). Sleep time was measured from loss to return of righting reflex. Mean sleep time (MST) was increased significantly (P less than 0.05) by a large dose of dl-amphetamine (24 mg/kg) and by 4-aminopyridine (1, 5 mg/kg). Significant (P less than 0.01) increases were also produced by small and large doses of aminophylline (25, 100 mg/kg) and by yohimbine (1, 5 mg/kg). MST was not altered significantly by small and medium doses of dl-amphetamine (6, 12 mg/kg), a medium dose of aminophylline (50 mg/kg), or by any doses of naloxone, thyrotropin-releasing hormone, propranolol, physostigmine, doxapram, or Ro 15-4513. When Ro 15-4513 was given IP 15 minutes before ethanol (n = 6/group), onset and duration of narcosis were not altered. None of the compounds tested was an effective IV antidote for deep ethanol narcosis because of drug side effects, toxicity, prolongation of MST, or insufficient shortening of MST.

Topics: 4-Aminopyridine; Alcoholic Intoxication; Aminophylline; Aminopyridines; Amphetamine; Animals; Azides; Benzodiazepines; Dextroamphetamine; Doxapram; Ethanol; Male; Mice; Naloxone; Physostigmine; Propranolol; Sleep; Thyrotropin-Releasing Hormone; Yohimbine

Beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) plasma concentrations were examined in ten chronic alcohol abusers, eight men and two women aged 25-56 years with histories of continuously elevated ethanol consumption dating from 5-30 years. Plasma levels of the two peptides were measured after acute alcohol consumption and then after 3, 6 and 9 days of forced abstinence, during chlordiazepoxide treatment. Beta-EP and beta-LPH concentrations were normal on all four occasions. A reduced sensitivity of opioid receptors to acute alcohol administration due to chronic alcohol consumption is suggested.

Topics: Adult; Alcohol Withdrawal Delirium; Alcoholic Intoxication; Alcoholism; beta-Endorphin; beta-Lipotropin; Female; Humans; Male; Middle Aged; Naloxone; Psychoses, Alcoholic; Receptors, Opioid

This paper describes experiments designed to evaluate whether the narcotic antagonist naloxone significantly interferes with seizures induced by tetrahydroisoquinolines (TIQs). In these experiments we found that naloxone significantly reduced seizure scores induced by intra-cranially infusing mice with 50 micrograms of the dopamine-derived tetrahydroisoquinoline (TIQ) alkaloid, 6,7-dihydroxy TIQ. These findings support an opioid involvement in the actions of TIQs and may lead to further understanding of opioid-mediated novel excitatory receptors.

Topics: Alcoholic Intoxication; Animals; Behavior, Animal; Convulsants; Ethanol; Isoquinolines; Naloxone; Receptors, Opioid; Seizures

Topics: Alcoholic Intoxication; Animals; Naloxone; Rats

Topics: Adult; Alcoholic Intoxication; Coma; Humans; Male; Naloxone; Narcotics; Substance-Related Disorders

The effects of naloxone hydrochloride (NAL) and other opiate antagonists on blood-ethanol concentration (BEC) in acutely-ethanol-intoxicated rats were examined. Using a 1 mg/kg body wt. dose of NAL, the maximum decrease in BEC was found to occur at 30 min. At 30 min after administration of various doses of NAL, it was found that BEC was decreased maximally by a 2 mg/kg dose, whereas the first significant decrease was caused by a 10 micrograms/kg dose. BEC was also decreased by naltrexone (1 mg/kg), but not by a 4 mg/kg dose of any of four Mr compounds (Mr 1452, Mr 1453, Mr 2266 and Mr 2267). It is suggested that pharmacokinetic antagonism of acute alcohol intoxication by naloxone and naltrexone is unrelated to the property of opiate antagonism, but may involve the ability of certain such antagonists to interact with hepatic NAD+-dependent oxidative metabolism.

Topics: Alcoholic Intoxication; Animals; Benzomorphans; Ethanol; Humans; Male; Morphinans; Naloxone; Naltrexone; Rats; Rats, Inbred Strains; Time Factors

Naloxone hydrochloride (2.0 mg/kg) has been found to reverse the significant decreases in the hepatic cytosolic and mitochondrial [NAD+]/[NADH] ratios observed after acute ethanol administration in rats. This correction of the ethanol-induced changes in the hepatocellular redox state by naloxone was, however, not associated with any lowering of serum ethanol concentrations or an observable reduction in the extent of intoxication. This lack of antagonism of alcohol intoxication by naloxone was not affected by the feeding status of the animals, the time point after naloxone administration at which serum ethanol concentration was determined or the method used for ethanol analysis. Thus this study has failed to confirm that naloxone antagonises acute alcohol intoxication, in spite of its potent ability to reverse the ethanol-induced changes in the hepatic redox state.

Topics: Alcoholic Intoxication; Animals; Ethanol; Liver; Male; Naloxone; Oxidation-Reduction; Rats; Rats, Inbred Strains

We have previously shown that proprietary naloxone hydrochloride (Narcan) reverses the disturbance of the redox states of the hepatic NAD(P) couples and causes a simultaneous lowering of blood-ethanol concentration in acutely-ethanol-intoxicated rats. We now confirm these findings by using pure naloxone hydrochloride and demonstrate the inability of the methyl-4-hydroxybenzoate preservative present in the Narcan ampoules to influence the above effects of ethanol.

Topics: Alcoholic Intoxication; Animals; Ethanol; Humans; Liver; Male; NAD; NADP; Naloxone; Oxidation-Reduction; Parabens; Rats; Rats, Inbred Strains

Topics: Alcoholic Intoxication; Coma; Double-Blind Method; Drug Evaluation; Humans; Naloxone; Random Allocation

Topics: Alcoholic Intoxication; Animals; Dogs; Humans; Naloxone

1 The effects of naloxone upon ethanol-induced coma have been investigated in dogs. In a double blind study, 15 mongrel dogs received ethanol i.v. (4 g/kg) followed by a single dose of naloxone (12 micrograms/kg). 2 Naloxone failed to affect either the duration of respiratory arrest or the time to recovery of motor coordination. In similar animals treated with the narcotic analgesic, fentanyl, naloxone induced a dramatic and complete reversal of the narcotic effects within 30 seconds. 3 It is concluded that, if naloxone has any effect in alcoholic coma, it is not comparable with its dramatic action in narcotic coma.

Topics: Alcoholic Intoxication; Animals; Blood Glucose; Dogs; Ethanol; Fentanyl; Humans; Naloxone; Postural Balance; Respiration

Topics: Alcoholic Intoxication; Ethanol; Humans; Kinetics; Naloxone

Topics: Adolescent; Adult; Alcoholic Intoxication; Coma; Electroencephalography; Electrolytes; Ethanol; Hemodynamics; Humans; Middle Aged; Naloxone; Respiration

1 An assessment of the current role of naloxone in clinical toxicology has been made in a series of three separate epidemiological studies. 2 Through the National Poisons Information Service we found that the role of naloxone in opioid poisoning is often not appreciated by the enquirer and that toxicological screening is often requested before the diagnostic use of naloxone. 3 The recommended dose of naloxone (0.4--1.2 mg i.v.) is not always adequate. In 51 cases where naloxone was effective, doses of up to 3.2 mg were necessary (mean 1.8 +/- 0.3 mg SEM i.v.). 4 In 31 cases of non-opioid poisoning, naloxone in doses of 0.4--1.2 mg i.v. caused no deterioration, whilst six patients in whom no opioids were detected showed clinical improvement. 5 In 300 cases of suspected ethanol-induced coma, 49 showed reversal of coma with naloxone, and in 38 cases ethanol was the sole cause of coma (mean plasma concentration 3.54 +/- 0.62 g/l SEM). 6 These results suggest that the role of naloxone in clinical toxicology is not fully appreciated. There is a need for further education as to its indications in opioid poisoning, together with additional studies to define more accurately the dose/response relationship. In addition, the role of naloxone in coma induced by ethanol and certain other non-opioids needs to be evaluated further.

Topics: Alcoholic Intoxication; Coma; Hemodynamics; Humans; Naloxone; Narcotics; Poisoning; Respiration; Suicide, Attempted

Topics: Alcoholic Intoxication; Emergencies; Female; Humans; Male; Naloxone

Topics: Alcoholic Intoxication; Arousal; Coma; Drug Interactions; Humans; Naloxone; Shock

Topics: Adult; Alcoholic Intoxication; Coma; Female; Humans; Male; Naloxone

Topics: Alcoholic Intoxication; Animals; Coma; Dogs; Humans; Naloxone

Topics: Alcoholic Intoxication; Coma; Humans; Naloxone

Naloxone has been said to be an antidote of acute ethanol intoxication in man. Experimental and clinical studies are however not convincing and contradictory. We have used naloxone to antagonize the effect of ethanol in mice. Results are compared to those obtained with morphine intoxication. Even at high doses (5 mg/kg) naloxone is not a good antagonist of ethanol intoxication in mice.

Topics: Alcoholic Intoxication; Animals; Humans; Male; Mice; Morphine; Naloxone

Topics: Alcoholic Intoxication; Humans; Naloxone

Naloxone lowers blood-ethanol concentration and causes a simultaneous reversal of the disturbances in the redox states of the hepatic nicotinamide-adenine dinucleotide (phosphate) couples in acutely-ethanol-intoxicated rats. It is suggested that these effects of naloxone form the basis of its antagonism of acute alcohol intoxication.

Topics: Acute Disease; Alcoholic Intoxication; Animals; Ethanol; Humans; Male; NAD; NADP; Naloxone; Rats; Rats, Inbred Strains

Topics: Adult; Alcoholic Intoxication; Ethanol; Humans; Male; Naloxone

Topics: Alcoholic Intoxication; Benzodiazepines; Coma; Drug Interactions; Ethanol; Humans; Naloxone

Topics: Adult; Alcoholic Intoxication; Blood Glucose; Endorphins; Ethanol; Female; Humans; Male; Middle Aged; Naloxone

Experimental and clinical results suggest a relationship between the action of ethanol and opiates. Therefore, we have tested whether the specific morphine antagonist naloxone (2 mg/kg intraperitoneally every six hours) affects signs of severe ethanol intoxication or modifies the withdrawal syndrome following chronic ethanol intoxication in rats. Using a double blind technique, we did not find any difference between saline treated and naloxone treated animals with respect to level of intoxication and severity of withdrawal symptoms. We must therefore conclude that naloxone does not modify signs of severe ethanol intoxication or change the ethanol withdrawal syndrome in the rat. These findings do not rule out that there might be a biochemical link between actions of ethanol and opiates, but this link is probably not localized at the level of specific drug receptor interaction.

Topics: Alcoholic Intoxication; Alcoholism; Animals; Double-Blind Method; Drug Evaluation, Preclinical; Humans; Injections, Intraperitoneal; Male; Naloxone; Rats; Substance Withdrawal Syndrome

Topics: Adult; Alcoholic Intoxication; Coma; Female; Humans; Male; Naloxone

Topics: Alcoholic Intoxication; Animals; Caffeine; Cats; Dextroamphetamine; Disease Models, Animal; Dogs; Ethanol; gamma-Aminobutyric Acid; Humans; Maleates; Naloxone; Pentylenetetrazole; Rabbits; Strychnine

Topics: Adult; Alcoholic Intoxication; Coma; Evaluation Studies as Topic; Humans; Injections, Intravenous; Male; Naloxone

Topics: Adult; Alcoholic Intoxication; Barbiturates; Child; Diazepam; Humans; Male; Naloxone

Topics: Adult; Alcoholic Intoxication; Antidotes; Coma; Ethanol; Humans; Injections, Intravenous; Male; Naloxone