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British Journal of Clinical Pharmacology Jun 2017Codeine containing analgesics are commonly taken in overdose, but the frequency of respiratory depression is unknown. We investigated whether paracetamol-codeine... (Observational Study)
Observational Study
AIMS
Codeine containing analgesics are commonly taken in overdose, but the frequency of respiratory depression is unknown. We investigated whether paracetamol-codeine combination overdoses caused respiratory depression more than paracetamol alone.
METHODS
We reviewed deliberate self-poisoning admissions with paracetamol (>2 g) and paracetamol-codeine combinations presenting to a tertiary toxicology unit (1987-2013). Demographic information, clinical effects, treatment (naloxone, length of stay [LOS], mechanical ventilation) were extracted from a prospective database. Primary outcome was naloxone requirement or ventilation for respiratory depression.
RESULTS
From 4488 presentations, 1376 admissions were included with paracetamol alone (929), paracetamol-codeine combinations (346) or paracetamol-codeine-doxylamine combinations (101) without co-ingestants. Median age was 23 years (12-89 years); 1002 (73%) were female. Median dose was 12 g (interquartile range [IQR]: 7.5-20 g). Median LOS was 16 h (IQR: 6.5-27 h) and 564 (41%) were given acetylcysteine. Significantly larger paracetamol doses were ingested and more acetylcysteine given in paracetamol alone versus paracetamol combination overdoses. Seven out of 1376 patients were intubated or received naloxone (0.5%; 95% CI: 0.2-1.1%), three intubated, three given naloxone and one both. Three out of 929 patients ingesting paracetamol alone (0.3%; 95% CI: 0.1-1%) required intubation or naloxone, compared to two out of 346 ingesting paracetamol-codeine combinations (0.6%; 95% CI: 0.1-2.3%; absolute difference, 0.26%; 95% CI: -0.7-1.2%; P = 0.62). Two out of 101 patients ingesting paracetamol-codeine-doxylamine combinations (2%; 95% CI: 0.3-8%) required intubation or naloxone. Four patients were intubated for reasons other than respiratory depression: hepatotoxicity (2), retrieval (1), no data (1). Two out of 929 (0.2%) paracetamol alone overdoses had a Glasgow coma score < 9 compared to three out of 346 (0.9%) in the paracetamol-codeine group.
CONCLUSIONS
Paracetamol-codeine combination overdoses are rarely associated with severe respiratory depression, with only two given naloxone and none intubated for respiratory depression.
Topics: Acetaminophen; Acetylcysteine; Adolescent; Adult; Aged; Aged, 80 and over; Antidotes; Child; Codeine; Critical Care; Drug Combinations; Drug Overdose; Female; Glasgow Coma Scale; Humans; Length of Stay; Male; Middle Aged; Naloxone; Narcotic Antagonists; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Suicide, Attempted; Treatment Outcome; Young Adult
PubMed: 28035699
DOI: 10.1111/bcp.13224 -
Drug Testing and Analysis May 2019Untargeted toxicological screening is an analytical challenge, given the high number of molecules and metabolites to be detected and the constant appearance of new...
Untargeted toxicological screening is an analytical challenge, given the high number of molecules and metabolites to be detected and the constant appearance of new psychoactive substances (NPS). The combination of liquid chromatography with high-resolution tandem mass spectrometry (HRMS/MS) in a data-dependent acquisition mode generates a large volume of high quality spectral data. Commercial software for processing MS data acquired during untargeted screening experiments usually compare measured features (mass, retention time, and fragmentation spectra) against a predefined list of analytes. However, there is a lack of tools for visualizing and organizing MS data of unknown compounds. Here, we applied molecular networking to untargeted toxicological screening. This bioinformatic tool allows the exploration and organization of MS/MS data without prior knowledge of the sample's chemical composition. The organization of spectral data is based on spectral similarity. Hence, important information can be obtained even before the annotation step. The link established between molecules enables the propagation of structural information. We applied this approach to three clinical and forensic cases with various matrices: (a) blood and a syringe content in a forensic case of death by self-injection, (b) hair segments in a case of drug-facilitated assault, and (c) urine and blood samples in a case of 3-methoxyphencyclidine intoxication. Data preprocessing with MZmine allows sample-to-sample comparison and generation of multisample molecular networks. Our present study shows that molecular networking can be a useful complement to conventional approaches for untargeted screening interpretation, for example for xenobiotics identification or NPS metabolism elucidation.
Topics: Adolescent; Antiemetics; Chlormequat; Designer Drugs; Doxylamine; Female; Forensic Toxicology; Humans; Male; Middle Aged; Phencyclidine; Tandem Mass Spectrometry; Young Adult
PubMed: 30468699
DOI: 10.1002/dta.2550 -
PloS One 2015There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine...
BACKGROUND
There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in '90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines.
AIM
To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries.
METHODS
We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases ≥3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance.
RESULTS
Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible.
CONCLUSIONS
Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by analytical studies is required, regulators and clinicians should consider risk-minimisation activities. Also antihistamines without signal but with peculiar use in a few Countries (e.g., levocetirizine) or with increasing consumption (e.g., rupatadine) deserve careful surveillance.
Topics: Administration, Oral; Adverse Drug Reaction Reporting Systems; Arrhythmias, Cardiac; Databases, Factual; Drug Utilization; Europe; Histamine H1 Antagonists; Humans; Pharmacovigilance
PubMed: 25785934
DOI: 10.1371/journal.pone.0119551 -
American Journal of Obstetrics and... Dec 2014Presently, 97.7% of prescriptions for the treatment of nausea and vomiting in pregnancy in the United States are with medications not labeled for use in pregnancy, not...
Presently, 97.7% of prescriptions for the treatment of nausea and vomiting in pregnancy in the United States are with medications not labeled for use in pregnancy, not indicated for nausea and vomiting in pregnancy, and not classified as safe in pregnancy by the Food and Drug Administration. The use of ondansetron for nausea and vomiting in pregnancy has increased from 50,000 monthly prescriptions in 2008 to 110,000 at the end of 2013, despite unresolved issues regarding fetal safety and Food and Drug Administration warnings about serious dysrhythmias. In April 2013, the Food and Drug Administration approved the combination of doxylamine and pyridoxine, specifically for nausea and vomiting in pregnancy symptoms. Now that a safe and effective drug is available in the United States, there is no reason for women to be exposed to a drug of unproven maternal and fetal safety.
Topics: Antiemetics; Dicyclomine; Doxylamine; Drug Approval; Drug Combinations; Female; Heart Defects, Congenital; Humans; Morning Sickness; Ondansetron; Practice Patterns, Physicians'; Pregnancy; Pyridoxine; Serotonin Syndrome; Torsades de Pointes; United States; United States Food and Drug Administration
PubMed: 25151184
DOI: 10.1016/j.ajog.2014.08.017 -
The Primary Care Companion For CNS... 2015To investigate the level of evidence supporting the use of common over-the-counter (OTC) agents (diphenhydramine, doxylamine, melatonin, and valerian) for occasional...
OBJECTIVE
To investigate the level of evidence supporting the use of common over-the-counter (OTC) agents (diphenhydramine, doxylamine, melatonin, and valerian) for occasional disturbed sleep or insomnia.
DATA SOURCES
A systematic review of the literature was conducted on July 31, 2014, using MEDLINE (PubMed) and the search terms (insomnia OR sleep) AND (over*the*counter OR OTC OR non*prescription OR antihistamine OR doxylamine OR diphenhydramine OR melatonin OR valerian) with the filters English, human, and clinical trials.
STUDY SELECTION
Identified publications (from 2003 to July 31, 2014, following previous published literature reviews) that met the inclusion criteria were selected. The criteria included randomized placebo-controlled clinical studies that utilized overnight objective (polysomnography) or next-day participant-reported sleep-related endpoints and that were conducted in healthy participants with or without occasional disturbed sleep or diagnosed insomnia.
RESULTS
Measures of efficacy and tolerability were summarized for each study individually and grouped according to OTC agent: H1 antagonists or antihistamines (3 studies, diphenhydramine), melatonin (8), and valerian or valerian/hops (7). Of the 3 sleep agents, studies conducted with melatonin, especially prolonged-release formulations in older individuals with diagnosed insomnia, demonstrated the most consistent beneficial effects (vs placebo) on sleep measures, specifically sleep onset and sleep quality, with favorable tolerability. In contrast, the clinical trial data for diphenhydramine, immediate-release melatonin, and valerian suggested limited beneficial effects.
CONCLUSIONS
A review of randomized controlled studies over the past 12 years suggests commonly used OTC sleep-aid agents, especially diphenhydamine and valerian, lack robust clinical evidence supporting efficacy and safety.
PubMed: 27057416
DOI: 10.4088/PCC.15r01798 -
The Gerontologist Apr 2017Getting a good night's sleep can be challenging for older adults with chronic medical conditions, which often interfere with sleep. As a result, many older adults turn...
Getting a good night's sleep can be challenging for older adults with chronic medical conditions, which often interfere with sleep. As a result, many older adults turn to over-the-counter (OTC) sleep aids, that is, products with diphenhydramine or doxylamine. However, these products are indicated only for occasional difficulty with sleep, not for chronic use; and their safety and efficacy has not been well established in general and in older adults specifically. To engage national stakeholders in a discussion of OTC sleep aids in older adults, the Gerontological Society of America (GSA) convened a multidisciplinary workgroup. The Workgroup examined differences between younger and older adults in sleep health and use of OTC sleep aids using data from the National Health and Wellness Survey; assessed the pharmacologic properties and medication effects of OTC sleep aids; and worked with stakeholders to promote strategies for safe and effective use. Older adults are more likely to take diphenhydramine or doxylamine products 15 or more days in a month, an indicator of inappropriate use. The Workgroup recommends research to investigate the ways older people use OTC sleep aids. The goal should be reduction in inappropriate use and associated risks, such as daytime sedation, compromised cognitive function, and falls. In addition, the Workgroup recommends a greater role for community pharmacists in counseling older adults on appropriate use of OTC sleep aids.
PubMed: 26511271
DOI: 10.1093/geront/gnv139 -
Iranian Journal of Allergy, Asthma, and... Apr 2020No Abstract.
No Abstract.
Topics: Allergens; Anaphylaxis; Basophil Degranulation Test; Basophils; Doxylamine; Drug Hypersensitivity; HLA-DR Antigens; Histamine H1 Antagonists; Humans; Immunophenotyping; Interleukin-3 Receptor alpha Subunit; Leukocyte Common Antigens; Male; Middle Aged
PubMed: 32372634
DOI: 10.18502/ijaai.v19i2.2774 -
Journal of Cancer 2020Our current study is to explore the prognostic value and molecular mechanisms underlying the role of lncRNA in non-homologous end joining pathway 1 (LINP1) in early...
Genome-wide RNA-sequencing dataset reveals the prognostic value and potential molecular mechanisms of lncRNA in non-homologous end joining pathway 1 in early stage Pancreatic Ductal Adenocarcinoma.
Our current study is to explore the prognostic value and molecular mechanisms underlying the role of lncRNA in non-homologous end joining pathway 1 (LINP1) in early stage pancreatic ductal adenocarcinoma (PDAC). Genome-wide RNA-seq datasets of 112 early stage PDAC patients were got from The Cancer Genome Atlas and analyzed using multiple online tools. Overall survival in high LINP1 expression patients was shorter than those with low expression (high-LINP1 vs. low-LINP1=481 vs. 592 days, log-rank P=0.0432). The multivariate Cox proportional hazard regression model suggested that high-LINP1 patients had a markedly higher risk of death than low-LINP1 patients (adjusted P=0.004, hazard ratio=2.214, 95% confidence interval=1.283-3.820). Analysis of genome-wide co-expressed genes, screening of differentially expressed genes, and gene set enrichment analysis indicated that LINP1 may be involved in the regulation of cell proliferation-, cell adhesion- and cell cycle-related biological processes in PDAC. Six small-molecule compounds including STOCK1N-35874, fenofibrate, exisulind, NU-1025, vinburnine, and doxylamine were identified as potential LINP1-targeted drugs for the treatment of PDAC. Our study indicated that LINP1 may serve as a prognostic biomarker of early stage PDAC. Analysis of genome-wide datasets led to the elucidation of the underlying mechanisms and identified six potential targeted drugs for the treatment of early PDAC.
PubMed: 32913451
DOI: 10.7150/jca.39888 -
PloS One 2019We aimed to describe medication use in pregnancies that resulted in births and abortions, as well as use after a pregnancy-related visit to characterize the receipt of...
We aimed to describe medication use in pregnancies that resulted in births and abortions, as well as use after a pregnancy-related visit to characterize the receipt of medication after knowledge of pregnancy. Abortions included both spontaneous and induced abortions. Rates of medication use among women with a pregnancy outcome (2001-2013) were described using the Manitoba Population Research Data Repository at the Manitoba Centre for Health Policy. Use was determined as ≥ 1 prescription filled during pregnancies that resulted in births (livebirth/stillbirth) and abortions. Rates were calculated at any time during pregnancy and after a pregnancy-related visit. Rates were additionally characterized by risk in pregnancy using Briggs classification (2017). Of 174,848 birth pregnancies, overall 64.9% filled ≥ 1 prescription during pregnancy (a significant increase from 62.3% to 68.8% from 2001-2013, p<0.0001); 55.4% filled ≥ 1 prescription after a pregnancy-related visit. Of 71,967 abortions, 44.7% filled ≥ 1 prescription (a significant increase from 42.6% to 46.8% from 2001-2013, p<0.0001). Only 3.7% of birth pregnancies had at least one prescription for a contraindicated medication (according to Briggs classification), whereas 10.8% of abortions filled a prescription for a contraindicated medication. The most common drugs used in pregnancy were amoxicillin, doxylamine, codeine combinations, nitrofurantoin, cephalexin, salbutamol and ranitidine. Fewer women filled prescriptions for undesirable medications according to Briggs classification during pregnancy after a pregnancy-related visit.
Topics: Abortion, Spontaneous; Adult; Canada; Female; Humans; Manitoba; Parturition; Pregnancy; Pregnancy Outcome; Prescription Drugs; Prescriptions; Retrospective Studies
PubMed: 30840711
DOI: 10.1371/journal.pone.0211319 -
Journal of Investigational Allergology... Dec 2018
Topics: Adult; Basophils; Doxylamine; Female; Humans; Hypersensitivity; Pregnancy
PubMed: 30530395
DOI: 10.18176/jiaci.0311