https://www.hopkinsmedicine.org/Press_releases/2008/Griffiths.pdf

Caffeinated energy drinks--a growing problem.

Neonatal abstinence syndrome (NAS) is a result of the sudden discontinuation of fetal exposure to substances that were used or abused by the mother during pregnancy. Withdrawal from licit or illicit substances is becoming more common among neonates in both developed and developing countries. NAS continues to be an important clinical entity throughout much of the world. NAS leads to a constellation of signs and symptoms involving multiple systems. The pathophysiology of NAS is not completely understood. Urine or meconium confirmation may assist the diagnosis and management of NAS. The Finnegan scoring system is commonly used to assess the severity of NAS; scoring can be helpful for initiating, monitoring, and terminating treatment in neonates. Nonpharmacological care is the initial treatment option, and pharmacological treatment is required if an improvement is not observed after nonpharmacological measures or if the infant develops severe withdrawal. Morphine is the most commonly used drug in the treatment of NAS secondary to opioids. An algorithmic approach to the management of infants with NAS is suggested. Breastfeeding is not contraindicated in NAS, unless the mother is taking street drugs, is involved in polydrug abuse, or is infected with HIV. Future studies are required to assess the long-term effects of NAS on children after prenatal exposure.

Neonatal Abstinence Syndrome

Congratulations to Dr. Baselt for the publication of his 10th edition and the expansion of his classic toxicology text to cover over 1,500 medications and chemicals. This enduring work provides a c...

Disposition of Toxic Drugs and Chemicals in Man

Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine's mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine's interaction with other substances or to the individuals' preexisting metabolism alterations or diseases.

/pdf/caffeine-cognitive-and-physical-performance-enhancer-or-g4hz4es15z.pdf

Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug?

http://physiology.elte.hu/gyakorlat/cikkek/Caffein%20use%20in%20children_what%20we%20know,%20what%20we%20have%20lft%20to%20learn%20and%20why%20we%20should%20worry.pdf

Caffeine use in children: what we know, what we have left to learn, and why we should worry.

Fatal caffeine overdose: Two case reports

Identification and quantification of synthetic cathinones in blood and urine using liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry.

Background: ELISAs are widely utilized in forensic drug analysis. A comparative assessment of microtiter plate assays for the detection of six common classes of drug in blood and urine is described.

Methods: ELISAs for opiates, methamphetamine, benzodiazepines, cocaine metabolite, phencyclidine (PCP), and tetrahydrocannabinol (THC) metabolite were evaluated in a side-by-side study. The analytical performance of 12 commercially available ELISAs was determined in terms of binding characteristics, dose–response curves, limits of detection, sensitivity, intra- and interassay imprecision, and lot-to-lot reproducibility. Assay performance was also compared using 855 forensic casework samples.

Results: Detection limits in whole blood for morphine, d-methamphetamine, nordiazepam, benzoylecgonine, nordiazepam, PCP, and l-11-nor-9-carboxy-Δ9-THC were 3, 2, <4, 5, 25, and 3 μg/L, respectively, for the STC ELISAs. Corresponding detection limits for Immunalysis ELISAs were <1, <2, <4, 5, <1, and 1 μg/L, respectively. Intraassay CVs (n = 8) at the immunoassay cutoff concentrations were 4.1–5.6% and 3.5–11% for STC and Immunalysis ELISAs, respectively. Corresponding interassay CVs were 3.1–10% and 6.5–20%. Of the 855 casework samples, there were a total of 92 discordant results (44 cannabinoid, 15 opiate, 15 methamphetamine, 11 benzodiazepine, and 7 cocaine metabolite). Gas chromatography–mass spectrometry analysis indicated a total of three unconfirmed positive results for Immunalysis assays and one unconfirmed positive for STC assays.

Conclusions: A comparative assessment of drugs-of-abuse assays from two manufacturers indicated some key differences in analytical performance. Overall, Immunalysis assays offered superior binding characteristics and detection limits, whereas STC assays offered improved overall precision and lot-to-lot reproducibility.

Comparison of ELISAs for Opiates, Methamphetamine, Cocaine Metabolite, Benzodiazepines, Phencyclidine, and Cannabinoids in Whole Blood and Urine

This report describes the outcomes of a process undertaken to review and update the National Safety Council's Alcohol, Drugs and Impairment Division's recommendations for the toxicological investigation of suspected alcohol and drug-impaired driving cases and motor vehicle fatalities. The updates to the recommendations are made based on a survey of practices in laboratories in the USA and Canada performing testing in these cases, consideration of existing epidemiological crash and arrest data, current drug use patterns, and practical considerations of widely available technology platforms in laboratories performing this work. The final recommendations updates are derived from a consensus meeting of experts recruited from survey respondents and the membership of the National Safety Council's Alcohol, Drug and Impairment Division. The principal changes in this round of recommendations include removal of butalbital, phenobarbital, and phencyclidine from Tier I (mandatory) to Tier II (optional) due to changes in prevalence. In addition, buprenorphine, fentanyl, tramadol, and their metabolites were moved from Tier II to Tier I due to increased prevalence and concerns about their potential for causing impairment. In addition, screening and confirmatory cutoffs for the oral fluid scope were further refined. Other additions were made to the list of Tier II compounds including fentanyl analogs (e.g., acetylfentanyl, butyrylfentanyl, furanylfentanyl, etc), mitragynine, novel opioids (e.g., MT-45, U-47700), atypical antipsychotics, and novel benzodiazepines (e.g., clonazolam, flubromazolam, etc).

/pdf/recommendations-for-toxicological-investigation-of-drug-1clm22gqp5.pdf

Recommendations for Toxicological Investigation of Drug-Impaired Driving and Motor Vehicle Fatalities-2017 Update.

The synthetic cathinones represent an important class of designer drugs. The widespread attention and publicity associated with these psychostimulants have resulted in numerous legislative actions at state and federal levels throughout the USA. These amphetamine-like compounds are characterized by a β-keto functional group. Although the synthetic cathinones share many properties of their phenethylamine counterparts, the presence of the ketone moiety is responsible for a number of unique and distinct differences in terms of their chemical characteristics and properties. Thermal degradation of methcathinone was first reported several decades ago but has received limited attention. In this study, we identified in situ thermal degradation products for 18 cathinones during gas chromatography-mass spectrometry (GC-MS) analysis. Oxidative degradation arises from the loss of two hydrogens, yielding a characteristic 2 Da mass shift. Degradation products were characterized by prominent iminium base peaks with mass-to-charge ratios 2 Da lower than the parent drug, and in the case of the pyrrolidine-containing cathinones, prominent molecular ions arising from the 2,3-enamine. Chromatographic and mass spectroscopic data are described for 4-ethylmethcathinone, 4-methylethcathinone, buphedrone, butylone, ethcathinone, ethylone, flephedrone, 3,4-methylenedioxy-α-pyrrolidinobutiophenone, 3,4-methylenedioxypyrovalerone, mephedrone, methcathinone, methedrone, methylone, 4-methyl-α-pyrrolidinobutiophenone, naphyrone, pentedrone, pentylone and pyrovalerone. Degradation was minimized by lowering injection temperatures, residence time in the inlet and eliminating active sites during chromatographic analysis. Chromatographic and mass spectral data for the cathinone degradation products are presented and discussed within the context of forensic toxicological analysis, selection of appropriate instrumental methods and implications for the interpretation of results.

Sarah Kerrigan

Papers

Fatal caffeine overdose: Two case reports

Identification and quantification of synthetic cathinones in blood and urine using liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry.

Comparison of ELISAs for Opiates, Methamphetamine, Cocaine Metabolite, Benzodiazepines, Phencyclidine, and Cannabinoids in Whole Blood and Urine

Recommendations for Toxicological Investigation of Drug-Impaired Driving and Motor Vehicle Fatalities-2017 Update.

Thermal Degradation of Synthetic Cathinones: Implications for Forensic Toxicology