Alcohol acute administration

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

Experimental studies have also suggested that alcohol may reduce N-methyl-D-aspartate (NMDA) receptor function following acute administration, and following withdrawal of alcohol the functioning of these receptors is enhanced. 

Gonzalez S, Fernandez-Ruiz J, Marzo VD, Hernandez M, Arevalo C, Nicanor C, Cascio MG, Ambrosio E, Ramos JA (2004) Behavioral and molecular changes elicited by acute administration of SR141716 to Delta9-tetrahydrocannabinol-tolerantrats an experimental model of cannabinoid abstinence. Drug Alcohol Depend 74 159-170... 

Chronic alcohol consumption has been implicated in osteoporosis (see Chapter 61). The reasons for this decreased bone mass remain unclear, although impaired osteoblastic activity has been implicated. Acute administration of ethanol produces an initial reduction in serum parathyroid... 

In general the opioid analgesics can enhance the CNS depressant effects of alcohol, which has been fatal in some cases this appears to be a particular problem with dextropropoxyphene. Alcohol has been associated with rapid release of hydromorphone and morphine from extended-release preparations, which could result in potentially fatal doses. Acute administration of alcohol and methadone appears to increase the blood levels of methadone. The bioavailability of dextropropoxyphene is increased by alcohol... 

Both opioids and alcohol are CNS depressants, and there may be enhanced suppression of the medullary respiratory control centre. " Acute administration of alcohol appears to increase methadone effects due to inhibition... 

TNF-a converting enzyme (TACE) is a newly discovered enzyme in the disintegrin and metalloproteinase (ADAM) family (78). This enzyme releases the 17-kD mature TNF-a fiom membrane-bound TNF-a by cleaving Ala 76 and Val 77 linkage. TACE has also been shown to be involved with other cell surface protein shedding events such as the p55 and p75 TNF-a receptors (79). Our laboratory has previously shown that acute administration of alcohol (EtOH)to rats suppresses TNF-a production posttranscriptionally in the lung and blood (20,80). Recently, we have further defined the mechanism of TNF-a inhibition by EtOH, which revealed... 

Wernicke s syndrome is a serious consequence of alcoholism and thiamine (vitamin Bx) deficiency. Certain characteristic signs of this disease, notably ophtalmoplegia, nystagmus, and ataxia, respond rapidly to the administration of thiamine but to no other-vitamin. Wernicke s syndrome may be accompanied by an acute global confusional state that may also respond to thiamine. Left untreated, Wernicke s syndrome frequently leads to a chronic disorder in which learning and memory are strongly impaired. This so-called Korsakoff s psychosis is characterized by confabulation, and is less likely to be reversible once established. 

Low K, Crestani F, Keist R, et al Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290 131-134, 2000 Luddens H, Pritchett DB, Kohler M, et al Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. Nature 346 648—651, 1990 LupoloverY, Safran AB, Desangles D, etal Evaluation ofvisual function in healthy subjects after administration of Ro 15-1788. Eur J Clin Pharmacol 27 505-507, 1984 Maher JF, Schreiner GE, Westervelt FB Jr Acute glutethimide intoxication 1. clinical experience (twenty-two patients) compared to acute barbiturate intoxication (sixty-three patients). Am J Med 33 70-82, 1962 Marks J The Benzodiazepines Use, Overuse, Misuse, Abuse. Baltimore, MD, University Park Press, 1978... 

McMillan DE, Snodgrass SH. (1991). Effects of acute and chronic administration of delta 9-tetrahydrocannabinol or cocaine on ethanol intake in a rat model. Drug Alcohol Dependence. 27(3) 263-74. 

The use of corticosteroids is often suggested for elderly patients with chronic tophaceous gout, since gout in the older individual often displays symptoms similar to those of rheumatoid arthritis. Patients can be given short-term administration of corticosteroids, especially for acute flare-ups. The concomitant use of alcohol, nonsteroidal antiinflammatory drugs, and most diuretics should be avoided. 

Alcohol withdrawal syndrome (acute) IV 100 mg per 25g of glucose concurrent administration with IV glucose. 

The spectrum of cognitive deficits associated with chronic alcohol use extends to the extreme of Wernicke s encephalopathy and Korsakoff s psychosis. Wernicke s encephalopathy is an acute neurologic syndrome caused by thiamine deficiency. Symptoms include mental confusion, ophthalmoplegia, and ataxia. Many of these symptoms reverse with administration of thiamine however about 50% of patients are left with some degree of ataxia. Left untreated, Wernicke s encephalopathy can progress to stupor, coma, and death. Approximately 80% to 90% of alcoholics treated for Wernicke s encephalopathy are left with Korsakoff s psychosis, a syndrome of impaired learning and recent memory produced by lesions of the medial dorsal nuclei of the thalamus. 

Johnson, K.M., and Balster, R.L. Acute and chronic phencyclidine administration Relationships between biodispositional-factors and behavioral effects. Subst. Alcohol Actions/Misuse 2 131-142, 1981. 

The increasingly accepted hypothesis that acetaldehyde may be the causative agent in initiating the multitude of acute pharmacological and chronic pathophysiological effects of alcohol prompted Nagasawa et al. to seek methods to reduce its blood levels. One possibility would be the administration of (S)-penicillamine (4), a compound related to cysteine. The condensation of this amino acid with acetaldehyde produced 2,5,5-trimethylthiazolidine-4-carboxylic acid 242). The chirality of this compound was deducted by NMR analysis to be 72% 2S, 4S and 28% 2R, 4S. Thus, this result is consistent with the configuration found previously for the thiazolidines formed from (R)-cysteine and aldehydes 241 ... 

Naltrexone is generally taken once a day in an oral dose of 50 mg for treatment of alcoholism. An extended-release formulation administered as an IM injection once every 4 weeks is also effective. The drug can cause dose-dependent hepatotoxicity and should be used with caution in patients with evidence of mild abnormalities in serum aminotransferase activity. The combination of naltrexone plus disulfiram should be avoided, since both drugs are potential hepatotoxins. Administration of naltrexone to patients who are physically dependent on opioids precipitates an acute withdrawal syndrome, so patients must be opioid-free before initiating naltrexone therapy. Naltrexone also blocks the therapeutic effects of usual doses of opioids. 

Toxicity. Sugar alcohols are classified as relatively harmless. Acute oral toxicity values in mice for mannitol and sorbitol (5) are given in Table 4. The acute oral LD5Q value for xyhtol in mice is 25.7 g/kg (205). Ingestion of 10 g/d of either mannitol or sorbitol by a normal human subject for one month resulted in no untoward effects (206). Xyhtol given to healthy humans for 21 d in increasing doses up to 75 g/d produced no adverse effects (207). The limiting dose of xyhtol for production of diarrhea in humans is 20—30 g (4), but tolerance usually develops on continued administration (207). 

Tiapride appears to be useful in alcohol withdrawal as an alternative to the benzodiazepines (2). It facilitates the management of ethanol withdrawal, but its use in patients at risk of severe reactions in acute withdrawal should be accompanied by adjunctive therapy for hallucinosis and seizures. Since it may prove difficult to identify such patients and since there is also a small risk of the neuroleptic malignant syndrome (particularly with parenteral administration), the usefulness of tiapride in this setting is likely to be limited. The potential risk of tardive dyskinesia at the dosage used in alcoholic patients following detoxification (300 mg/day) requires evaluation and necessitates medical supervision. It is unlikely to produce problems of dependence or abuse. 

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