-
Zhurnal Nevrologii I Psikhiatrii Imeni... 2023The article analyzes the current literature on the relationship of insomnia with affective disorders, in particular with depression and anxiety. Research shows that... (Meta-Analysis)
Meta-Analysis
The article analyzes the current literature on the relationship of insomnia with affective disorders, in particular with depression and anxiety. Research shows that there is a strong multi-channel relationship between insomnia, depression, and anxiety, with insomnia being considered a risk factor for mood disorders more often than vice versa. The so-called insomnia paradox of bipolar disorder is described, the essence of which is that in manic episodes the frequency of insomnia is higher than in depressive episodes. The data of a network meta-analysis, which found an evidence base for the use of a variety of drugs used for the pharmacological treatment of insomnia in adults, are presented. Efficiency and convenience in taking the drug Valocordin-Doxylamine are noted.
Topics: Adult; Humans; Sleep Initiation and Maintenance Disorders; Bipolar Disorder; Anxiety Disorders; Anxiety; Doxylamine
PubMed: 37275997
DOI: 10.17116/jnevro202312305243 -
Environmental Technology Feb 2024N-nitrosodimethylamine (NDMA) is a disinfection byproduct that forms at the presence of an organic nitrogen precursor. Doxylamine, an antihistaminic pharmaceutical, is a...
N-nitrosodimethylamine (NDMA) is a disinfection byproduct that forms at the presence of an organic nitrogen precursor. Doxylamine, an antihistaminic pharmaceutical, is a precursor of NDMA and has been shown to form NDMA in the presence of chloramine. In this study, the effect of Doxylamine as an NDMA precursor has been further studied during chloramination. The end product and byproducts during chloramination were investigated using a high-resolution mass spectrometer by taking samples at different time intervals. Results suggest that NDMA is not the only end product forming during chloramination of Doxylamine and several transformation products that do not end up as NDMA may form. A group of these transformation products have been selected based on their relative amounts during chloramination with time and notated as Focus Tentative Transformation Products (FTTP). The identification of these byproducts will make it easier to study the conditions during chloramination that may favour these known' transformation products with the use of less sophisticated analytical instruments. Then, it might lead to the establishment of chloramination protocols that will minimise the formation of NDMA from its precursors.
Topics: Dimethylnitrosamine; Doxylamine; Nitrogen; Disinfection; Water Purification; Water Pollutants, Chemical
PubMed: 36222397
DOI: 10.1080/09593330.2022.2135462 -
Journal of AOAC International Dec 2022The combination of pyridoxine hydrochloride (PYR) and doxylamine succinate (DOX) as an antiemetic binary mixture is used to treat nausea and vomiting during pregnancy.
Chemometric Quality Assessment of Doxylamine Succinate With Its Degradation Product: Implementation of Two Predictive Models on UV-Spectrophotometric Data of Anti-Emetic Binary Mixture.
BACKGROUND
The combination of pyridoxine hydrochloride (PYR) and doxylamine succinate (DOX) as an antiemetic binary mixture is used to treat nausea and vomiting during pregnancy.
OBJECTIVE
Two validated, accurate, and selective chemometric models were developed to assay binary mixture in the presence of DOX oxidative degradation product (DOX DEG) that could be characterized using LC-MS.
METHODS
Partial least squares (PLS) regression and principal component regression (PCR) were selected for the determination of our binary mixture in presence of degradation. To exhibit a training set of 25 mixtures that had various percentages of tested substances in five level 3 variables, an experimental design was chosen. A set of 18 synthetic mixtures in the concentration range 10.0-50.0 μg/mL, 12.00-20.0 μg/mL, and 6.0-30.0 μg/mL for PYR, DOX, and DOX DEG, respectively, were used in the construction of the calibration models. Then set of seven synthetic mixtures with different concentrations were used in the construction of the validation models.
RESULTS
In validation samples with low root mean square error of prediction (RMSEP), the suggested models successfully predicted the concentrations of our drugs. The models developed were evaluated by RMSEP calculation, and the values obtained were 0.341, 0.196, and 0.388 for PYR, DOX, and DOX DEG, respectively, using PLS. While using PCR, RMSEP calculation and the values obtained were 0.400, 0.256, and 0.375 for PYR, DOX, and DOX DEG, respectively. The developed models were validated according to ICH strategies.
CONCLUSIONS
The corresponding methods are suitable to determine PYR and DOX in pure form, pharmaceutical dosage form, and in the presence of DOX DEG product.
HIGHLIGHTS
The study of drug breakdown pathways is very important nowadays, so even in the presence of degradation and extreme spectral overlapping, the suggested PLS and PCR spectrophotometric approaches were able to identify PYR and DOX.
Topics: Antiemetics; Chemometrics; Spectrophotometry; Doxylamine; Least-Squares Analysis; Calibration; Spectrophotometry, Ultraviolet
PubMed: 35904581
DOI: 10.1093/jaoacint/qsac090 -
Journal of Hazardous Materials Aug 2024Ubiquitous distribution of pharmaceutical contaminants in environment has caused unexpected adverse effects on ecological organisms; however, how microorganisms recover...
Ubiquitous distribution of pharmaceutical contaminants in environment has caused unexpected adverse effects on ecological organisms; however, how microorganisms recover from their toxicities remains largely unknown. In this study, we comprehensively investigated the effect of a representative pollutant, doxylamine (DOX) on a freshwater microalgal species, Chlorella sp. by analyzing the growth patterns, biochemical changes (total chlorophyll, carotenoid, carbohydrate, protein, and antioxidant enzymes), and transcriptomics. We found toxicity of DOX on Chlorella sp. was mainly caused by disrupting synthesis of ribosomes in nucleolus, and r/t RNA binding and processing. Intriguingly, additional bicarbonate enhanced the toxicity of DOX with decreasing the half-maximum effective concentrations from 15.34 mg L to 4.63 mg L, which can be caused by inhibiting fatty acid oxidation and amino acid metabolism. Microalgal cells can recover from this stress via upregulating antioxidant enzymatic activities to neutralize oxidative stresses, and photosynthetic pathways and nitrogen metabolism to supply more energies and cellular signaling molecules. This study extended our understanding on how microalgae can recover from chemical toxicity, and also emphasized the effect of environmental factors on the toxicity of these contaminants on aquatic microorganisms.
Topics: Chlorella; Water Pollutants, Chemical; Transcriptome; Microalgae; Chlorophyll; Photosynthesis; Oxidative Stress; Carotenoids; Antioxidants
PubMed: 38815390
DOI: 10.1016/j.jhazmat.2024.134752 -
Therapeutic Drug Monitoring Apr 2022
Topics: Doxylamine; Heart Arrest; Humans; Pyridines
PubMed: 35026791
DOI: 10.1097/FTD.0000000000000960 -
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 -
Neurology. Clinical Practice Oct 2021
PubMed: 34840894
DOI: 10.1212/CPJ.0000000000000956 -
American Journal of Obstetrics and... Jul 2021Obstetrical healthcare providers frequently field questions about the safety of medications recommended or prescribed to their pregnant patients. Most women use as least... (Review)
Review
Obstetrical healthcare providers frequently field questions about the safety of medications recommended or prescribed to their pregnant patients. Most women use as least 1 medication during pregnancy; however, there is little information about the safety or appropriate dosing of many medications during this phase of life. In addition, the development of drugs for use in pregnant women trails behind the development of drugs intended for other sectors of the population. Our goal is to inform the obstetrics community about the US Food and Drug Administration authority and their role in approving drugs for marketing. We begin with the statutes that led to the creation of the Food and Drug Administration and its current organization. We then cover drug development and the Food and Drug Administration review process, including the role of the advisory committee. The different types of drug approvals are discussed, with some specific examples. Finally, we enumerate the drugs specifically approved for use in obstetrics and contrast them with drugs commonly used by pregnant women and drugs used "off-label" during pregnancy. The Food and Drug Administration is committed to protecting and advancing the public health of pregnant women by guiding the development and ensuring the availability of effective and safe therapeutics for obstetrical indications and for medical conditions during pregnancy. We hope this review will inspire more research addressing drug use during pregnancy.
Topics: Animals; Clinical Trials as Topic; Drug Approval; Female; Fetus; Humans; Lactation; Pregnancy; Pregnancy Complications; Prescription Drugs; Risk Assessment; Teratogens; United States; United States Food and Drug Administration
PubMed: 34215352
DOI: 10.1016/j.ajog.2021.02.032 -
Journal of Pharmaceutical Sciences Mar 2022The present work is concerned with tailoring and appraisal of a novel nano-cargo; bilosomes (BLS) dual laded with doxylamine succinate (DAS) and pyridoxine hydrochloride...
Harnessing of Doxylamine Succinate/Pyridoxine Hydrochloride-Dual Laden Bilosomes as a Novel Combinatorial Nanoparadigm for Intranasal Delivery: In Vitro Optimization and In Vivo Pharmacokinetic Appraisal.
The present work is concerned with tailoring and appraisal of a novel nano-cargo; bilosomes (BLS) dual laded with doxylamine succinate (DAS) and pyridoxine hydrochloride (PDH), the first treatment option against gestational nausea and vomiting, for intranasal delivery. This bifunctional horizon could surmount constraints of orally-commercialized platforms both in dosage regimen and pharmacokinetic profile. For accomplishing this purpose, DAS/PDH-BLS were elaborated integrating phospholipid, sodium cholate and cholesterol applying thin-film hydration method based on Box-Behnken design. Utilizing Design-Expert® software, the effect of formulation variables on BLS physicochemical features alongside the optimal formulation selection were investigated. Then, the optimum DAS/PDH-BLS formulation was incorporated into a thermally-triggered in situ gelling base. The in vivo pharmacokinetic studies were explored in rats for intranasal DAS/PDH-BLS in situ gel compared with analogous intranasal free in situ gel and oral solution. The optimized BLS disclosed vesicle size of 243.23 nm, ζ potential of -31.33 mV, entrapment efficiency of 59.18 and 41.63%, accumulative % release within 8 h of 63.30 and 85.52% and accumulative permeated amount over 24 h of 347.92 and 195.4 µg/cm for DAS/PDH, respectively. Following intranasal administration of the inspected BLS in situ gel, pharmacokinetic studies revealed a 1.64- and 2.3-fold increment in the relative bioavailability of DAS and a 1.7- and 3.73-fold increase for PDH compared to the intranasal free in situ gel and oral solution, respectively besides significantly extended mean residence times for both drugs. Thus, the intranasally exploited DAS/PDH-BLS could be deemed as a promising hybrid nanoplatform with fruitful pharmacokinetics and tolerability traits.
Topics: Administration, Intranasal; Animals; Biological Availability; Doxylamine; Drug Delivery Systems; Gels; Particle Size; Pyridoxine; Rats
PubMed: 34808217
DOI: 10.1016/j.xphs.2021.11.007 -
PloS One 2022To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014.
OBJECTIVE
To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014.
METHODS
We constructed population-based cohorts of pregnant women using administrative healthcare data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Saskatchewan), the Clinical Practice Research Datalink from the United Kingdom, and the IBM MarketScan Research Databases from the United States. We included pregnancies ending in live births, stillbirth, spontaneous abortion, or induced abortion. We determined maternal use of antiemetics from pharmacy claims in Canada and the United States and from prescriptions in the United Kingdom.
RESULTS
The most common outcome of 3 848 734 included pregnancies (started 2002-2014) was live birth (66.7% of all pregnancies) followed by spontaneous abortion (20.2%). Use of antiemetics during pregnancy increased over time in all three countries. Canada had the highest prevalence of use of prescription antiemetics during pregnancy (17.7% of pregnancies overall, 13.2% of pregnancies in 2002, and 18.9% in 2014), followed by the United States (14.0% overall, 8.9% in 2007, and 18.1% in 2014), and the United Kingdom (5.0% overall, 4.2% in 2002, and 6.5% in 2014). Besides use of antiemetic drugs being considerably lower in the United Kingdom, the increase in its use over time was more modest. The most commonly used antiemetic was combination doxylamine/pyridoxine in Canada (95.2% of pregnancies treated with antiemetics), ondansetron in the United States (72.2%), and prochlorperazine in the United Kingdom (63.5%).
CONCLUSIONS
In this large cohort study, we observed an overall increase in antiemetic use during pregnancy, and patterns of use varied across jurisdictions. Continued monitoring of antiemetic use and further research are warranted to better understand the reasons for differences in use of these medications and to assess their benefit-risk profile in this population.
Topics: Pregnancy; Female; Humans; Antiemetics; Abortion, Spontaneous; Cohort Studies; Retrospective Studies; Gastrointestinal Agents; Alberta
PubMed: 36454900
DOI: 10.1371/journal.pone.0277623