Laboratory Diagnosis of Cocaine: Intoxication and Withdrawal
Mark S. Gold, Marc Galanter, Barry Stimmel in Cocaine: Pharmacology, Addiction, and Therapy, 2014
Cocaine is rapidly and extensively metabolized. Studies with 3H labelled cocaine have demonstrated that the drug is biotransformed to ten metabolites in the rat. The concentration of unchanged cocaine in the urine is less than 10% of its major metabolite benzoylecgonine.6 Wallace et al.,7 demonstrated that benzoylecgonine is the principle cocaine metabolite in man with unchanged cocaine present at only substantially lower concentrations. Ambre et al.,8 recently identified ecgonine methyl ester as an additional major metabolite of cocaine. Other cocaine metabolites, such as ecgonine and norecgonine have also been found in humans, but their trace levels in urine makes analysis of these compounds useless in diagnosis of cocaine abuse.
Critical Review of Evidence for Neonatal Cocaine Intoxication and Withdrawal
Richard J. Konkol, George D. Olsen in Prenatal Cocaine Exposure, 2020
Emerging evidence indicates that BE may have significant pharmacologic properties. In the past, benzoylecgonine was believed to be pharmacologically inactive. The onset of seizures, strokes, and angina in some patients hours after the expected peak concentration of cocaine has raised the possibility of a long-lived, pharmacologically active metabolite of cocaine.31 Benzoylecgonine is associated with vasoconstriction in human coronary and cat cerebral arteries 31,32 It also has constrictive properties in both the pregnant ewe and fetus.33 Furthermore, intrathecally instilled benzoylecgonine causes agitation and seizures in rats in a dose-dependent manner.34,35 In the rat, the fetal maternal ratio for benzoylecgonine was less than 1, except for the brain where the fetal maternal ratio was 3, indicating that the fetal brain is exposed to high levels of benzoylecgonine relative to the adult.36 For a detailed discussion of the pharmacologic activity of benzoylecgonine, see Chapters 5 and 6. The data regarding the pharmacologic activity of benzoylecgonine supports the hypothesis that there may be a benzoylecgonine intoxication syndrome.
Saliva Drug Analysis
Steven H. Y. Wong, Iraving Sunshine in Handbook of Analytical Therapeutic Drug Monitoring and Toxicology, 2017
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.
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.
Underreporting of drug use among electronic dance music party attendees
Published in Clinical Toxicology, 2021
Joseph J. Palamar, Alberto Salomone, Katherine M. Keyes
Once ingested, drugs are incorporated into the hair, leading to a potential chronological trace of exposure. Farther periods correspond to hair segments more distant from the root. Hair is most ideal to detect repeated exposure over a long diagnostic window (e.g. over months), and the continuous improvement of analytical procedures and instrumental technologies now allows us to detect very small amounts of drugs (including single exposures), and for many months post-exposure [44,45]. We set the limits of detection as the minimum criterion to identify positive samples, although a further criterion to confirm cocaine exposure was the presence of benzoylecgonine (BZE), the main cocaine metabolite [46]. We used the minimum criterion because we aimed to detect any amount of exposure (e.g. via adulterants).
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.
Related Knowledge Centers
- Benzoic Acid
- Carboxylesterase
- Carboxylic Acid
- Cocaine
- Ecgonine
- Ester
- Hydrolysis
- Urine
- Liver
- Wastewater-Based Epidemiology