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Cocaine Pharmacology and Drug Interaction in the Fetal-Maternal Unit
Published in Richard J. Konkol, George D. Olsen, Prenatal Cocaine Exposure, 2020
George D. Olsen, Peter C. Schalock
Biotransformation of cocaine has been introduced and discussed briefly above. N-demethylation occurs in the cytochrome P-450 system of the liver. Hydrolysis takes place in many tissues including the plasma and the liver.32 There is an indication that an unidentified soluble metabolite of cocaine can inhibit cocaine N-demethylation, which may explain why in most species norcocaine is a minor metabolite of cocaine. Another explanation for the small amount of norcocaine detected in biologic fluids is the rapid hydrolysis of norcocaine to benzoylnorecgonine.32,36
The interpretation of hair analysis for drugs and drug metabolites
Published in Clinical Toxicology, 2018
Eva Cuypers, Robert J. Flanagan
A recent study [89] has highlighted the complexities of testing minor cocaine metabolites for definitive proof of deliberate cocaine consumption. Following analysis of 90 hair samples from cocaine users for cocaine, benzoylecgonine, norcocaine, cocaethylene, and tropococaine by GC-MS, cocaine usage was stratified as: light (0.5–3 ng/mg hair), moderate (3.1–10 ng/mg) and heavy (10.1–40 ng/mg). Cocaine concentrations ranged from 1.63–39.29 (mean 9.49) and benzoylecgonine ranged from 0.19–5.77 (mean 1.40). The benzoylecgonine:cocaine ratio was ≥5% (6.4–26.1%) in all samples. Norcocaine was present in 60% of samples (range: 0.22–3.14 ng/mg) and was strongly predictive only of heavy cocaine use (sensitivity 100% for cocaine concentrations >9.6 ng/mg). Cocaethylene was detected in 20 samples from moderate/heavy users (range 0.22–1.98, mean 0.73 ng/mg). However, both norcocaine and cocaethylene may occur in “street” cocaine if processing has involved the use of ethanol and potassium permanganate, hence hydroxycocaine and/or hydroxybenzoylecgonine are assumed to be more specific markers of cocaine exposure [90].
Acute toxic kidney injury
Published in Renal Failure, 2019
Nadezda Petejova, Arnost Martinek, Josef Zadrazil, Vladimir Teplan
Kidney biopsy confirmed acute tubular interstitial impairment with inflammatory infiltration and edema [97]. However, at the cellular and molecular level, the situation is more complex and apart from toxicity to other organs, cocaine and its metabolites, mainly norcocaine showed direct cytotoxic effects on human proximal tubular epithelial cells in one in vitro study [98]. Depending on cocaine and norcocaine concentration, intracellular glutathione and ATP levels decreased with following inhibition of mitochondrial activity and impaired glutathione redox cycle. Activation of apoptosis was the observed result of both pathophysiological processes [98].