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Sympathomimetics
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Cocaine is extensively metabolized, primarily by liver and plasma esterases, and only 1% of a dose is excreted in the urine unchanged. Approximately 70% of a dose can be recovered in the urine over a period of 3 days. About 25–40% of cocaine is metabolized to benzoylecgonine, the major metabolite found in the urine. About 18–22% is excreted as ecgonine methyl ester and 2–3% as ecgonine. Immunochemical techniques such as EMIT and RIA are designed to detect benzoylecgonine. Unchanged cocaine is sometimes discovered by chromatographic methods for up to 24 hours after a given dose, while benzoylecgonine can generally be spotted by immunoassays for 24–48 hours. The presence of cocaine and its metabolites in urine is confirmed by liquid chromatography/mass spectrometry (LC-MS), HPLC, and gas chromatography/mass spectrometry (GC-MS). Benzoylecgonine is generally detected in urine up to 2 days after cocaine use using gas-liquid chromatography (GLC) or LC-MS, the latter of which is the most specific of the chromatographic techniques.
Saliva Drug Analysis
Published in Steven H. Y. Wong, Iraving Sunshine, Handbook of Analytical Therapeutic Drug Monitoring and Toxicology, 2017
Edward J. Cone, Amanda J. Jenkins
The excretion of cocaine in saliva was first reported by Inaba et al.73 Radiolabeled cocaine was administered by the oral route, and radioactivity in saliva was measured. Peel et al.74 also reported the detection of cocaine in a single saliva sample in a survey of impaired drivers. Thompson et al.75 confirmed the presence of cocaine in saliva by GC/MS after single intravenous doses of cocaine hydrochloride to volunteer subjects. S/P (total) ratios for one subject across time averaged 1.26, with a range of 0.5 to 2.96. Ferko et al.76 reported similar parotid S/P ratios for cocaine in the rat after intravenous administration of various doses. In the latter study, they also reported detection of benzoylecgonine in amounts approximately equivalent to cocaine. Salivary cocaine was highly correlated with plasma concentrations in contrast to benzoylecgonine concentrations.
Toxicology
Published in John M. Wayne, Cynthia A. Schandl, S. Erin Presnell, Forensic Pathology Review, 2017
John M. Wayne, Cynthia A. Schandl, S. Erin Presnell
Answer B is correct. Benzoylecgonine is an inactive metabolite of cocaine. However, it does not readily cross the placenta while the parent compound, cocaine, does. Thus, the finding of benzoylecgonine in a fetal sample indicates that the fetus was alive and able to metabolize cocaine at the time the mother was exposed. It should be noted, however, that the placenta may also metabolize cocaine, so direct effects may be on the placenta or the fetus and such metabolism may serve to protect the fetus to some extent as well.
A French study of cocaine intoxication/exposure in children (2010–2020)
Published in Clinical Toxicology, 2023
Isabelle Claudet, Caroline Caula, Jean-Christophe Gallart, Gaelle Tourniaire, Marion Lerouge-Bailhache, Anne-Pascale Michard-Lenoir, Antoine Tran, Aline Maleterre, Frédéric Huet, Damien Dufour, Nicolas Billaud, Alexandra David, Marie Di Patrizio, Mathilde Granjon, Grégoire Benoist, Christine Laguille, Marie-Aline Guitteny, Martine Balençon, Bénédicte Vrignaud, Romain Basmaci, Marie Dampfhoffer, François Dubos, Hélène Chappuy, Philippe Minodier, Nicolas Médiamolle, Camille Bréhin
Because of the retrospective nature of the study, some data were insufficient (e.g., parental cocaine consumption, estimated time of exposure/intoxication). Some children could have been admitted to a non-pediatric emergency department setting but usually, because of the alarming clinical presentation, they were transferred to the nearest regional pediatric emergency department. Twenty-four pediatric emergency departments in the study admitted 38% of all national cases registered according to the French national ICD-10 diagnosis database while other cases were admitted to 630 emergency units spread across the French territory. The regional distribution of cases has to be cautiously interpreted: two regions seemed to have disproportionate intoxications/exposures (Ile-de-France and Occitanie) as they cumulated 50 of the 74 cases. All their university pediatric hospitals have participated while in other regions, none or part of them did. Benzoylecgonine has a half-life of 12 h, it can be detected in blood and/or urine for about 48 h after last use, screening for benzoylecgonine implies recent exposure but not necessarily acute toxicity. Co-intoxicants or adulterants were detected in 62% (n = 46) of the screened patients (n = 70), 16 children under 6 years old (47%), which means that clinical symptoms could also have been related to the toxicity of other substances.
Impact of multiple substance use on circulating ST2, a biomarker of adverse cardiac remodelling, in women
Published in Biomarkers, 2022
Elise D. Riley, Dhruv S. Kazi, Phillip O. Coffin, Eric Vittinghoff, Amanda N. Wade, Tommaso C. Bulfone, Kara L. Lynch, Zahra Atai, Alan H. B. Wu
In this community-recruited sample of unhoused and unstably housed women without known CVD at the time of enrolment, two-in-five participants had biomarker evidence of adverse cardiac remodelling (sST2 > 35 ng/mL). In adjusted analysis, cocaine use, alcohol use, and the interactive effect of heroin and fentanyl use were significantly associated with sST2 level, even after accounting for other CVD risk factors and a prior diagnosis of HF. These results are consistent with prior cross-sectional research showing significant correlation between serum concentrations of benzoylecgonine, a major cocaine metabolite, and sST2 in remnant hospital samples (Van Wijk et al. 2017). They extend prior findings through longitudinal analyses that adjust for the use of other substances and cardiovascular risk factors. Results are also consistent with prior research in this population showing that high-sensitivity cardiac troponin (hs-cTnI) is associated with cocaethylene, a metabolite of cocaine and alcohol co-use (Riley et al. 2020). Taken together, the existing evidence suggests that risk assessment strategies incorporating biomarkers, including sST2, will be influenced by multiple substances. More specifically, in an era where sST2 is emerging as a valuable prognostic factor, which significantly improves the accuracy of predicting heart failure (Lotierzo et al. 2020) and cardiovascular mortality (Zagidullin et al. 2020, Miftode et al. 2021) by using multiple biomarkers instead of a single biomarker, incorporating substance use alongside cardiac biomarkers may improve CVD risk assessment in vulnerable women.
The interpretation of hair analysis for drugs and drug metabolites
Published in Clinical Toxicology, 2018
Eva Cuypers, Robert J. Flanagan
As noted above, “cut-off” values have been proposed in an attempt to differentiate drug (self-) administration from incidental exposure. For cocaine, a cut-off value of 1 ng/mg (1 part cocaine per million parts of hair) has been suggested [65]. However, the use of “cut-off” values is unreliable because external contamination can occur at any concentration [43]. Another proposed method is the detection of metabolites of a drug. However, metabolites can occur through incidental ingestion of parent drug via contaminated surfaces, for example, as well as by deliberate (self-)administration. Some metabolites are also decomposition products of drugs, as exemplified by benzoylecgonine (from cocaine).