Ethanol detoxification

Modulation of GABA receptors is also beneficial in the treatment of several neuropsychiatric conditions, including anxiety disorders, insomnia, and agitation. The mechanisms are not well understood but may work through a general inhibition of neuronal activity. Benzodiazepines and ethanol use the same mechanism to influence GABA receptors. This property is the basis for ethanol detoxification with benzodiazepines (Grobin et ah, 1998). 

The detoxification of vinyl chloride provides an example of effective detoxification by a P450 isozyme (ethanol detoxification was previously discussed in Chapter 25). Vinyl chloride is used in the synthesis of plastics and can cause angiosarcoma in the liver of exposed workers. It is activated in a phase I reaction to a reactive epoxide by... 

Benzodiazepine prototype binds to BZ receptors of the GABA receptor-chloride ion channel complex facilitates the inhibitory actions of GABA by increasing the frequency of channel opening. Uses anxiety states, ethanol detoxification, muscle spasticity, status epilepticus. Tox dependence, additive effects with other CNS depressants. 

Cross-tolerance A condition where an individual who is tolerant to the pharmacological effects of one member of a drug family also shows tolerance to other members of that family. Cross-dependence allows drug substitution during detoxification (e.g., methadone for heroin or clomethiazole for ethanol), so reducing the severity and potential danger of withdrawal symptoms. 

Ethanol can increase the levels of many enzymes involved in metabolism of xenobiotics. Prolonged ethanol intake causes irreversible damage in the central nervous system and in the liver, resulting in marked decreased capacity for detoxification of xenobiotics and thereby increased sensitivity to a number of chemicals (KEMI 2003). 

The immediate concern in the treatment of alcoholics is detoxification and management of the ethanol withdrawal syndrome. Once the patient is detoxified, longterm treatment requires complete abstinence, psychiatric treatment, family involvement, and frequently support from lay organizations such as Alcoholics Anonymous. 

The use of recombinant microorganisms for cofermentation is one of the most promising approaches in the field of bioethanol production, though their use for large-scale industrial processes still requires fine-tuning of the reliability of the entire process (2). The technical hurdles of cofermentation increase when real biomass hydrolysates have to be fermented. In fact, whatever the biomass pretreatment, the formation of degradation byproducts that could inhibit the fermentation usually requires the addition of a further detoxification step. Therefore, the production of ethanol from hydrolysates should be considered in its entirety, from the optimal pretreatment to the choice of the proper fermentation process. 

Biogenic amines in wine and fermented foods are formed primarily via the microbial decarboxylation of amino acids. Examples, such as histamine, tyramine, and phenylethylamine are toxic, especially in alcoholic beverages. Ethanol can inhibit the monoamino oxidase responsible for amine detoxification (Maynard and Schenker, 1996). Histamine can induce allergenic reactions in humans, such as rashes, edema, headaches, hypotension. Tyramine and phenylethylamine can cause hypertension and other symptoms related to the release of noradrenaline. 

Sulfotransferases (SULTs) are cytosolic phase II detoxification enzymes involved in sulfonation of various xenobiotics and endobiotics. There are also membrane-bound SULTs that are not involved in phase II metabolism but are involved in the sulfonation of proteins and polysaccharides. Substrates of cytosolic SULTs include alcohols (ethanol, 2-butanol, cholesterol, bile acids), phenols (phenol, naphthol, acetaminophen), aromatic amines and hydroxyamines (2-naphthylamine, A-hydroxy 2-naphthylamine). SULTs transfer sulfonate (S03) to a hydroxy or amino group of a substrates from the cofactor 3 -phosphoadenosine-5 -phosphosulfate (PAPS), generating highly water-soluble metabolites for elimination through the kidney and liver. 

Studies have been conducted on the interaction of benzene with other chemicals, both in vivo and in the environment. Benzene metabolism is complex, and various xenobiotics can induce or inhibit specific routes of detoxification and/or activation in addition to altering the rate of benzene metabolism and clearance from the body. Toluene, Aroclor 1254, phenobarbital, acetone, and ethanol are known to alter the metabolism and toxicity of benzene. 

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. 

Esterification reactions involving alcohols are also favoured by yeast but the reason why this reaction occurs is not clear. It could involve detoxification or to produce attractant molecules to assist yeast dispersal by insects. Acetate esters, such as ethyl acetate are formed from ethanol and acetyl-CoA by alcohol acyltransferase (Fuji et al. 1994). An example of a grape derived compound is the esterification of 3-MH to the more aroma active 3-MHA (Swiegers et al. 2006). 

Dunn JD, Clarkson TW, Magos L. 1981a. Ethanol reveals novel mercury detoxification step in tissues. Science 213 1123-1125. 

Metabolism also plays a critical role in the pharmacology of cocaine. The rapid hydrolysis of cocaine via two different pathways leads to its rapid inactivation/detoxification. This rapid metabolism has been a major determinant in the methods and modes of cocaine abuse. Identification and characterization of these hydrolytic enzymes would be useful in that selective induction of these enzymes offers a potential treatment strategy for dealing with cocaine overdose. It is conceivable that long-term elevation of the enzyme or enzymatic activity could be used in conjunction with maintenance therapy for cocaine addicts. Hydrolases or esterases are also responsible for the transesterfication of cocaine. The pharmacological effect of cocaine is prolonged and enhanced when cocaine is used in conjunction with ethanol. A carboxylesterase catalyzes an ethyl transeterification of cocaine to cocaethylene, which is biologically active. 

We also demonstrated in this study that FAEE synthase activity could be induced nearly twofold in the WBC fraction of humans ingesting 2 oz of scotch whiskey for 6 d (Gorski. 1996). This supports the conclusion that FAEE synthase is regulated to some extent by the presence of ethanol. Ihe enzyme activity returned to baseline levels despite ingestion of 2 oz of scotch whiskey for an additional 3 d. In this report, it was also shown that alcoholic individuals have approximately half the WBC FAEE synthase activity detected in normal controls. The lower enzyme activity observed in the WBCs of alcoholics in a detoxification center may be the result of years of ethanol abuse, or it may be that alcoholics congenitally have low levels of FAEE synthase. If the latter is true, this finding may explain, in part, the genetic predisposition of many alcoholic individuals to ethanol abuse. 

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