-
Journal of Analytical Toxicology May 2024In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences...
In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences (e.g., metabolic capabilities, body size, etc.) between the pediatric and adult populations. In particular, the administration of over-the-counter (OTC) medications needs careful consideration, as dosages given to the pediatric population (0 days - 18 years), particularly those given to individuals less than five years of age, tend to be lower than those given to individuals closer to adulthood. Postmortem pediatric data from eleven years (2010-2020) was compiled. A total of 1413 positive cases contained one or more of the following common OTC medications: antihistamines (brompheniramine, chlorpheniramine, diphenhydramine, doxylamine, and pheniramine), pain relievers (acetaminophen, naproxen, ibuprofen, and salicylates), cold/flu medications (dextro/levomethorphan, guaifenesin, ephedrine, and pseudoephedrine), gastrointestinal (GI) aids (dicyclomine and loperamide), and/or sleep aids (melatonin). Antihistamines, cold/flu medications, and pain relievers are the most common classes of drugs encountered in the postmortem pediatric population. To evaluate trends, three main age groups were created: ≤5 years old (5U, birth-5 years old), middle childhood (MC, 6-11 years old), and early adolescence (EA, 12-18 years old). When considering the data, it must be noted that many of these drugs may be co-administered in single and/or multi-drug formulations. In addition, some drugs may have a variety of uses, e.g., antihistamines may also be used as sleep aids. Of note, the prevalence of cases involving those aged 6-11 years old was far less than their younger and older pediatric counterparts. With the widespread availability of OTC medications, unintentional overdoses, recreational misuse, and suicidal overdoses can occur in the vulnerable, pediatric population.
PubMed: 38771225
DOI: 10.1093/jat/bkae042 -
Journal of Analytical Toxicology Jan 2021Carbon nanotubes (CNTs) are useful for extracting chemical compounds due to their properties, such as surface area and the potential for chemical modification....
Carbon nanotubes (CNTs) are useful for extracting chemical compounds due to their properties, such as surface area and the potential for chemical modification. Especially the formation of CNTs with carboxylic acid functional group makes them disperse in water-based samples and have strong interaction forces with cationizable analytes. Based on these features, carboxylic acid functionalized multi-walled CNTs (COOH-MWCNTs) have been used as extraction sorbents. CNT can also be gathered using an external magnet by forming complex with iron oxide (Fe3O4) magnetic nanoparticles (MNPs). In this study, COOH-MWCNTs with MNPs were subjected to magnetic solid-phase extraction (mSPE) in order to extract the targeted substances such as diphenhydramine, doxylamine, tramadol, escitalopram, zolpidem, diphenamid, paclobutrazol, hexaconazole, cyproconazole and mepronil from human plasma samples. The following five factors were optimized: (i) the ratio of COOH-MWCNTs to MNPs as a sorbent from 1:1 to 1:4; (ii) sorbent amount starting from 12.5 to 75%; (iii) sample pH tested pH 2 to pH 10 with 1 N hydrochloride and 1 N sodium hydroxide; (iv) agitating time from 0 to 4 min and (v) elution solvent. Limit of detection of 10 targeted substances in human plasma were in the range of 0.1-0.4 mg/L. The recovery of targeted substances (except diphenamid) in human plasma was 73.06-110.28% for intra-day and 83.00-107.70% for inter-day and the precision (relative standard deviation, %) in human plasma was 0.3-13.3% for intra-day and 2.9-15.6% for inter-day. The method was applied to nine authentic biological samples from overdose patients in the emergency room of Chungnam National University Hospital. The performance of mSPE was compared with the liquid-liquid extraction method using ethyl acetate. The results showed that the newly developed method in this study can be used for screening analysis in forensic and clinical toxicology.
Topics: Chromatography, High Pressure Liquid; Humans; Limit of Detection; Magnetic Phenomena; Nanotubes, Carbon; Pesticides; Pharmaceutical Preparations; Plasma; Solid Phase Extraction
PubMed: 32369168
DOI: 10.1093/jat/bkaa029 -
Pediatrics Aug 2020A central tension in pediatric research ethics arises from our desire to protect children from harm while also allowing progress toward discoveries that could improve...
A central tension in pediatric research ethics arises from our desire to protect children from harm while also allowing progress toward discoveries that could improve child health. A prime example of this tension is research on a controversial yet increasingly common practice: the use of cannabis by women to treat nausea and vomiting of pregnancy. Studies of cannabis use in pregnancy face a combination of ethical hurdles because of the inclusion of pregnant women and involvement of a schedule I controlled substance. Given the growing need for research on the safety and efficacy of cannabis for nausea and vomiting of pregnancy, we reflect on the multiple historical contexts that have contributed to the challenge of studying cannabis use during pregnancy and make a case for the ethical rationale for such research.
Topics: Antiemetics; Dicyclomine; Doxylamine; Drug Approval; Drug Combinations; Ethics, Research; Female; Humans; Medical Marijuana; Morning Sickness; Ondansetron; Pediatrics; Pregnancy; Pregnant Women; Pyridoxine; Research Subjects; Teratogens; Thalidomide
PubMed: 32737240
DOI: 10.1542/peds.2020-0818R -
Complementary Therapies in Medicine Dec 2019This study seeks to understand whether people substitute between recreational cannabis and conventional over-the-counter (OTC) sleep medications. UPC-level grocery store...
This study seeks to understand whether people substitute between recreational cannabis and conventional over-the-counter (OTC) sleep medications. UPC-level grocery store scanner data in a multivariable panel regression design were used to compare the change in the monthly market share of sleep aids with varying dispensary-based recreational cannabis access (existence, sales, and count) in Colorado counties between 12/2013 and 12/2014. We measured annually-differenced market shares for sleep aids as a portion of the overall OTC medication market, thus accounting for store-level demand shifts in OTC medication markets and seasonality, and used the monthly changes in stores' sleep aid market share to control for short-term trends. Relative to the overall OTC medication market, sleep aid market shares were growing prior to recreational cannabis availability. The trend reverses (a 236% decrease) with dispensary entry (-0.33 percentage points, 95% CI -0.43 to -0.24, p < 0.01) from a mean market share growth of 0.14 ± 0.97. The magnitude of the market share decline increases as more dispensaries enter a county and with higher county-level cannabis sales. The negative associations are driven by diphenhydramine- and doxylamine-based sleep aids rather than herbal sleep aids and melatonin. These findings support survey evidence that many individuals use cannabis to treat insomnia, although sleep disturbances are not a specific qualifying condition under any U.S. state-level medical cannabis law. Investigations designed to measure the relative effectiveness and side effect profiles of conventional OTC sleep aids and cannabis-based products are urgently needed to improve treatment of sleep disturbances while minimizing potentially serious negative side effects.
Topics: Cannabis; Colorado; Humans; Illicit Drugs; Marijuana Use; Nonprescription Drugs; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders
PubMed: 31779999
DOI: 10.1016/j.ctim.2019.102207 -
BMJ (Clinical Research Ed.) Sep 2022
Topics: Acetaminophen; Animals; Chickens; Dextromethorphan; Doxylamine; Drug Combinations; Pseudoephedrine
PubMed: 36150731
DOI: 10.1136/bmj.o2298 -
Journal of Hazardous Materials Feb 2024Amine-based pharmaceuticals are a significant class of N-nitrosodimethylamine (NDMA) precursors. This study investigated the use of unactivated peroxymonosulfate (PMS)...
Amine-based pharmaceuticals are a significant class of N-nitrosodimethylamine (NDMA) precursors. This study investigated the use of unactivated peroxymonosulfate (PMS) to control amine-based pharmaceuticals and their NDMA formation potential. Kinetic analysis and product identification revealed that sumatriptan and doxylamine primarily underwent reactions at their tertiary amine group, while ranitidine and nizatidine had both tertiary amine and thioether group as reaction sites. The NDMA formation from sumatriptan and doxylamine during post-chloramination was significantly reduced with the abatement of the parent contaminants, while the formation of NDMA remained high even if full abatement of ranitidine and nizatidine was achieved. Product formation kinetics and reference standard tests revealed the great contribution of transformation products to NDMA formation. Ranitidine could be oxidized to sulfoxide-type product ranitidine-SO and N-oxide type product ranitidine-NO. Ranitidine-SO exhibited a high NDMA yield comparable to that of ranitidine (>90%), while ranitidine-NO showed a low NDMA yield (2%). With further oxidation of ranitidine-SO at the tertiary amine group, NDMA formation was reduced by more than 90%. The underlying mechanism for the importance of the tertiary amine group in NDMA formation was demonstrated by quantum chemical calculation. These findings underscore the potential of PMS pre-oxidation on NDMA control.
Topics: Amines; Ranitidine; Chloramines; Dimethylnitrosamine; Sumatriptan; Kinetics; Nizatidine; Doxylamine; Pharmaceutical Preparations; Water Purification; Water Pollutants, Chemical
PubMed: 37951171
DOI: 10.1016/j.jhazmat.2023.132961 -
Organic Letters Oct 2020We developed an approach for direct selective hydroxylation of heterobenzylic methylenes to secondary alcohols avoiding overoxidation to ketones by using a...
We developed an approach for direct selective hydroxylation of heterobenzylic methylenes to secondary alcohols avoiding overoxidation to ketones by using a KOBu-t/DMSO/air system. Most reactions could reach completion in several minutes to give hydroxylated products in 41-76% yields. Using DMSO-, this protocol resulted in difunctionalization of heterobenzylic methylenes to afford α-deuterated secondary alcohols (>93% incorporation). By employing this method, active pharmaceutical ingredients carbinoxamine and doxylamine were synthesized in two steps in moderate yields.
PubMed: 33026812
DOI: 10.1021/acs.orglett.0c03108 -
Biological Psychiatry Apr 2022Posttraumatic stress disorder (PTSD) develops consequent to complex gene-by-environment interactions beyond the precipitating trauma. To date, however, no known study...
BACKGROUND
Posttraumatic stress disorder (PTSD) develops consequent to complex gene-by-environment interactions beyond the precipitating trauma. To date, however, no known study has used a prospective design to examine how polygenic risk scores (PRSs) interact with social-environmental factors such as attachment style to predict PTSD development.
METHODS
PRSs were derived from a genome-wide association study of PTSD symptoms (N = 186,689; Million Veteran Program cohort). We evaluated combined effects of PRS and attachment style in predicting incident PTSD in a 7-year, nationally representative cohort of trauma-exposed, European-American U.S. military veterans without PTSD (N = 1083). We also conducted multivariate gene-by-environment interaction and drug repositioning analyses to identify loci that interact with multiple environmental factors and potential pharmacotherapies that may be repurposed for this disorder.
RESULTS
Veterans with higher PTSD PRS were more likely to have an incident-positive screen for PTSD over 7 years. A gene-by-environment interaction was also observed, such that higher PRS only predicted incident PTSD in veterans with an insecure attachment style and not those with a secure attachment style. At an individual locus level, the strongest gene-by-environment interaction was observed for the rs4702 variant of the FURIN gene with cumulative lifetime trauma burden. Drug repositioning revealed that genes implicated in PRS are perturbated by the drug doxylamine.
CONCLUSIONS
Attachment style moderates polygenic risk for the development of PTSD in European-American veterans. These findings may inform PTSD prevention and treatment for veterans with high polygenic risk for PTSD and suggest a potential pharmacotherapeutic target for risk genes moderated by social-environmental factors.
Topics: Genome-Wide Association Study; Humans; Military Personnel; Multifactorial Inheritance; Prospective Studies; Stress Disorders, Post-Traumatic; Veterans
PubMed: 34955171
DOI: 10.1016/j.biopsych.2021.09.025 -
The Australian & New Zealand Journal of... Aug 2021We conducted an online survey of 249 Australian women who currently or previously experienced severe nausea and vomiting of pregnancy (NVP) or hyperemesis gravidarum...
We conducted an online survey of 249 Australian women who currently or previously experienced severe nausea and vomiting of pregnancy (NVP) or hyperemesis gravidarum (HG) and examined their experiences in being denied medications during pregnancy. One in four women reported being denied medications for NVP/HG, which most commonly involved doxylamine and encounters with community pharmacists. Women's experiences reflected that lack of awareness of guidelines and unfavourable risk-benefit assessments appeared to be key barriers to facilitating medication access. Approaches towards identifying and effectively addressing barriers to the provision of effective treatments for severe NVP and HG are urgently needed.
Topics: Antiemetics; Australia; Female; Humans; Hyperemesis Gravidarum; Nausea; Pregnancy; Pregnant Women
PubMed: 33984156
DOI: 10.1111/ajo.13359 -
Gynecologie, Obstetrique, Fertilite &... Nov 2020In France there is no official recommendation for the drug management of nausea and vomiting during pregnancy. In the USA, Canada and Australia, vitamin B6 is officially...
In France there is no official recommendation for the drug management of nausea and vomiting during pregnancy. In the USA, Canada and Australia, vitamin B6 is officially recommended in the treatment of mild to moderate pregnancy sickness and vomiting. Indeed, some studies have shown some effectiveness of oral vitamin B6, most often in combination with doxylamine, in comparison with a placebo. In addition, the harmlessness of oral vitamin B6 during pregnancy has been established for doses up to 40-60mg/day, mainly in combination with doxylamine (40mg/40mg). Thus, in France, as in other countries, vitamin B6 could be integrated into the therapeutic arsenal of mild to moderate nausea and vomiting during pregnancy according to the following dosage schedule: oral intake of 10mg four times a day of a compounded preparation of vitamin B6, alone or in combination with doxylamine.
Topics: Female; Humans; Nausea; Pregnancy; Pregnancy Complications; Pyridoxine; Vitamin B 6; Vomiting
PubMed: 32961339
DOI: 10.1016/j.gofs.2020.09.005