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Cureus Aug 2023A 52-year-old male with acute onset right-sided weakness, numbness, and buttock pain after consuming 30 tablets of doxylamine antihistamine the night prior. Laboratory...
A 52-year-old male with acute onset right-sided weakness, numbness, and buttock pain after consuming 30 tablets of doxylamine antihistamine the night prior. Laboratory tests showed elevated creatinine kinase, blood urea nitrogen, creatinine, troponins, liver transaminases, and phosphate. The patient was admitted to the medical intensive care unit for severe rhabdomyolysis, acute liver failure, and acute kidney injury secondary to doxylamine intoxication. Studies describe symptoms of severe doxylamine intoxication, such as impaired consciousness (coma), grand mal seizures, and cardiopulmonary arrest. Circulating myoglobin causes oxidative injury to the kidney through the formation of F2-isoprostanes leading to renal vasoconstriction. One study explained drug-induced rhabdomyolysis via two mechanisms: direct drug injury to the striated muscle and local muscle compression in seizure, coma, and metabolic abnormality. Treatment involves aggressive hydration with monitoring of serum electrolytes and renal function. Aggressive volume expansion via intravenous fluids remains critical in preventing rhabdomyolysis-associated nephrotoxicity and myoglobin-induced acute renal failure. Alkalinization of urine may prevent renal vasoconstriction resulting in enhanced excretion of the toxic metabolites of doxylamine and myoglobin via renal tubules, thereby reducing peak serum concentration time and preventing direct renal tissue damage.
PubMed: 37581198
DOI: 10.7759/cureus.43395 -
European Review For Medical and... Jun 2022Nausea and vomiting of pregnancy is a common disease that affects many women suffering from mild to severe symptoms. Amongst the different treatments, a fixed dose...
OBJECTIVE
Nausea and vomiting of pregnancy is a common disease that affects many women suffering from mild to severe symptoms. Amongst the different treatments, a fixed dose combination of doxylamine and pyridoxine has been proven safe and effective although the mechanism of action is not well established. There are different pharmaceutical dosage forms in the European market. The objective of this study was to compare the characteristics of a capsule formulation, Cariban® and a tablet formulation, Xonvea® to evaluate the potential impact of their release profiles on their onset of action.
MATERIALS AND METHODS
10 mg/10 mg of doxylamine succinate/pyridoxine hydrochloride capsules (Cariban®) and tablets (Xonvea®) were used as reference materials. Appearance, mass, composition, and in vitro dissolution profiles were compared. Bibliographic data from 4 pharmacokinetic studies of Xonvea® and 1 pharmacokinetic study of Cariban® was reviewed.
RESULTS
In vitro dissolution studies showed significant differences in dissolution profiles of tablets and capsules. The later exhibiting some release of both drug substances in acid conditions followed by a non-complete release after a total of 3 hours while the tablets demonstrated gastro-resistant properties and rapid API release in about 20-30 minutes after the acid stage. Comparison of PK data showed greater Cmax for pyridoxine.
CONCLUSIONS
At pH 6.8, complete and faster release of the fixed dose combination for Xonvea® gastro-resistant tablets compared to Cariban® capsules could possibly explain the greater Cmax observed in vivo for the tablet's formulation. This could translate into faster onset of action and relief of nausea for pregnant women taking the tablets vs. the capsules.
Topics: Antiemetics; Doxylamine; Female; Gastrointestinal Agents; Humans; Nausea; Pregnancy; Pyridoxine; Solubility; Tablets
PubMed: 35776043
DOI: 10.26355/eurrev_202206_29081 -
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 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2018Symptoms of sleep disruption are widely prevalent in general population, but they are not necessarily form the full clinical presentation of insomnia. Diagnostic process... (Review)
Review
Symptoms of sleep disruption are widely prevalent in general population, but they are not necessarily form the full clinical presentation of insomnia. Diagnostic process should consider somatic diseases usually accompanied by sleep disruption. This review presents the data on insomnia symptoms in gynecological diseases: menstrual cycle related disorders, endometriosis, peri- and postmenopausal symptoms.
Topics: Doxylamine; Endometriosis; Female; Histamine H1 Antagonists; Humans; Melatonin; Menopause; Menstrual Cycle; Prevalence; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 30059054
DOI: 10.17116/jnevro20181184267 -
Therapeutic Drug Monitoring Apr 2022
Topics: Doxylamine; Heart Arrest; Humans; Pyridines
PubMed: 35026791
DOI: 10.1097/FTD.0000000000000960 -
The Nurse Practitioner Dec 2018In 2018, the FDA approved several new drugs for use in primary care. This article highlights the following new drugs: bictegravir, emtricitabine, and tenofovir...
In 2018, the FDA approved several new drugs for use in primary care. This article highlights the following new drugs: bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy); doxylamine succinate and pyridoxine hydrochloride (Bonjesta); erenumab-aooe (Aimovig); lofexidine hydrochloride (Lucemyra); tezacaftor and ivacaftor (Symdeko); and tildrakizumab-asmn (Ilumya).
Topics: Adenine; Alanine; Amides; Aminophenols; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Benzodioxoles; Clonidine; Doxylamine; Drug Approval; Emtricitabine; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, 4 or More Rings; Humans; Indoles; Piperazines; Pyridones; Pyridoxine; Quinolones; Tenofovir; United States; United States Food and Drug Administration
PubMed: 30379711
DOI: 10.1097/01.NPR.0000547548.63764.6b -
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