Dependence alcohol

Prepared generally by ester interchange from polyvinylacelate (ethanoate) using methanol and base also formed by hydrolysis of the acetate by NaOH and water. The properties of the poly(vinyl alcohol) depend upon the structure of the original polyvinyl acetate. Forms copolymers. Used as a size in the textile industry, in aqueous adhesives, in the production of polyvinyl acetates (e.g. butynal) for safety glasses. U.S. production 1980... 

The reactions of thionyl chloride with organic compounds having hydroxyl groups are important. Alkyl chlorides, alkyl sulfites, or alkyl chlorosulfites form from its reaction with aUphatic alcohols, depending on reaction conditions, stoichiometry, and the alcohol stmcture ... 

Organic derivatives fall into 4 classes RP0(0H)2, HP0(0R)2, R P0(0R)2 and the phosphite esters R(OR)3 this latter class has no purely inorganic analogues, though it is, of course, closely related to PCI3. Some preparative routes have already been indicated. Reactions with alcohols depend on conditions ... 

Hydride addition to methylcyclohexanone leads either to cis or trans alcohols, depending on which face is attacked preferentially. 

Sanofi-Synthelabo researchers discovered pyrazole 53 and analogs to have potent Cannabinoid receptor-1 (CB-1) antagonist/inverse agonist activity and have progressed 53 into development for treatment of obesity and alcohol dependence. The synthesis of 53 was accomplished by heating the diketone sodium salt 51 with the aryl hydrazine hydrochloride in acetic acid to provide the intermediate 52, which was further derivatized... 

Heilig M, Koob GF (2007) A key role for corticotropinreleasing factor in alcohol dependence. Trends Neurosci 30 399-406... 

The 1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES), based on interviews with a national probability household sample of nearly 43,000 adults age 18 years and older, showed the 1-year prevalence of DSM-IV alcohol use disorder to be 7.4% (i.e., 3.0% with alcohol abuse and 4.4% with alcohol dependence) (Grant et al. 1994). Findings from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a community-based survey of nearly 43,000 individuals conducted in 2001—2002 (Grant... 

The pharmacodynamic effects of ethanol are complex, and any attempt to link its actions to specific neurotransmitters or isolated brain regions is simplistic. A complicated neural network involved in the actions of ethanol accounts for its reinforcing, intoxicating, and abstinence effects. At the present time, use of medications that target neurotransmitters and neuromodulators affected by ethanol represents a reasonable strategy for the development of pharmacotherapies that reduce the reinforcing effects of alcohol and the craving and withdrawal symptoms that commonly occur in the context of alcohol dependence. 

An important initial intervention for a minority of alcohol-dependent patients is the management of alcohol withdrawal through detoxification. The objectives in treating alcohol withdrawal are relief of discomfort, prevention or treatment of complications, and preparation for rehabilitation. Successful management of the alcohol withdrawal syndrome is generally necessary for subsequent efforts at rehabilitation to be successful treatment of withdrawal alone is usually not sufficient, because relapse occurs commonly. 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

As reviewed earlier in the section on the pharmacology of ethanol, several neurotransmitter systems appear to influence the reinforcing or discriminative stimulus effects of ethanol. Although these systems appear to function interactively in their influences on drinking behavior, the medications that have been employed to treat alcohol dependence affect neurotransmitter systems relatively selectively. Consequently, these systems will be discussed individually here. 

Opioidergic agents. Naltrexone and nalmefene, opioid antagonists with no intrinsic agonist properties, have been studied for the treatment of alcohol dependence. Naltrexone has been studied much more extensively than nalmefene for this indication. In 1984 naltrexone was approved by the FDA for the treatment of opioid dependence, and in 1994 it was approved for the treatment of alcohol dependence. Nalmefene is approved in the United States as a parenteral formulation for the acute reversal of opioid effects (e.g., after opioid overdose or analgesia). 

Using a primary-care model of treatment, O Malley et al. (2003) initially treated alcohol-dependent patients with open-label naltrexone for 10 weeks, in combination with either CBT or primary care management (PCM), a less intensive, supportive approach. They found no effect of psychosocial treatment on response to treatment, although CBT was associated with a lower risk of drinking. Treatment responders from this study were then randomly assigned to one of two placebo-controlled 24-week continuation studies in... 

Acamprosate. Acamprosate (calcium acetylhomotaurinate), an amino acid derivative, affects both GABA and excitatory amino acid (i.e., glutamate) neurotransmission (the latter effect most likely being the one that is important for its therapeutic effects in alcoholism). Initially evaluated in a singlecenter trial in France, acamprosate was shown to be twice as effective as placebo in reducing the rate at which alcoholic patients returned to drinking (Lhuin-tre et al. 1985). The safety and efficacy of the medication have been studied most widely in Europe, and three of these studies provided the basis for the recent approval of acamprosate by the FDA for clinical use in the United States. As with naltrexone, there exist a number of meta-analytic studies that provide consistent evidence of the efficacy of the medication in the treatment of alcohol dependence. 

Verheul et al. (2004) pooled data from seven European acamprosate studies in an effort to identify patient-related predictors of response to the medication. Although they examined a number of potential predictors, including patients level of physiological dependence before treatment, family history of alcoholism, age of onset of alcoholism, baseline anxiety symptom severity, baseline craving, and gender, none was shown to interact with acamprosate treatment. These findings led the authors to conclude that, although the effect size for acamprosate was moderate, the medication can be considered potentially effective for all patients with alcohol dependence. 

Anton RF, Pettinati H, Zweben A, et al A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence. J Clin Psychopharmacol 24 421 28, 2004 Aragon CM, Stotland LM, Amit Z Studies on ethanol-brain catalase interaction evidence for central ethanol oxidation. Alcohol Clin Exp Res 15 165-169, 1991 Arizzi MN, Correa M, Betz AJ, et al Behavioral effects of intraventricular injections of low doses of ethanol, acetaldehyde, and acetate in rats studies with low and high rate operant schedules. Behav Brain Res 147 203—210, 2003 Azrin NH, Sisson RW, Meyers R, et al Alcoholism treatment by disulfiram and community reinforcement therapy. J Behav Ther Exp Psychiatry 13 105—112, 1982 Babor TF, Kranzler HR, Lauerman RL Social drinking as a health and psychosocial risk factor Anstie s limit revisited, in Recent Developments in Alcoholism, Vol 5. Edited by Galanter M. New York, Plenum, 1987, pp 373 02... 

Behar KL, Rothman DL, Petersen KF, et al Preliminary evidence of low cortical GABA levels in localized 1FF-MR spectra of alcohol-dependent and hepatic encephalopathy patients. Am J Psychiatry 136 952-954, 1999... 

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