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Dernière modification par netenn (03 mars 2020 à 11:47)
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The toxic effects of the cocaine-alcohol combination have been observed both in Emergency Department (ED) and in inpatient medical units. Ethanol alters the hepatic biotransformation of cocaine, resulting in a novel active metabolite, cocaethylene [9–11]. Oral cocaine was suggested to produce relatively larger concentrations of cocaethylene [12–15]. Drug abusers combine cocaine and alcohol to get intense high and less paranoia when coming off the high [16–18]. Both alcohol and cocaine cause liver toxicity, but cocaethylene appears to be more potent in its toxicity than cocaine [19–22].
The mechanisms by which cocaine causes liver cell injury appear to be similar to that of liver injury caused by the toxic metabolite of acetaminophen. It is related to production of highly reactive metabolites, with peroxidation, free radical formation, and covalent binding to hepatic proteins. Approximately 10% of cocaine undergoes N-demethylation in hepatocytes by the cytochrome P-450-mixed function oxidase system, forming norcocaine, a metabolite that elicits significant liver cell damage when injected intraperitoneally in mice [13–15]. This is due to further enzymatic breakdown to N-hydroxynorcocaine and norcocaine nitroxide [38]. Oxidation to the nitrosonium ion showed the latter to be highly reactive with glutathione, serving as catalyst for the conversion of alcohols, amines, and hydroxide ions to aldehydes, ketones, and hydrogen peroxide and causing lipid peroxidation of cell membranes [12, 39–41].
https://jamanetwork.com/journals/jama/a … act/200363
Dernière modification par prescripteur (03 mars 2020 à 12:42)
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