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BMJ (Clinical Research Ed.) Jun 1992
Topics: Adult; Chemistry, Pharmaceutical; Female; Humans; Injections, Intra-Arterial; Male; Rhabdomyolysis; Substance-Related Disorders; Temazepam
PubMed: 1628096
DOI: 10.1136/bmj.304.6842.1630 -
British Journal of Clinical Pharmacology 19791 Absorption, excretion and detoxification of temazepam were investigated in man, mouse, rat and dog. Considerable interspecies variation was apparent with respect to...
1 Absorption, excretion and detoxification of temazepam were investigated in man, mouse, rat and dog. Considerable interspecies variation was apparent with respect to excretion and metabolite patterns in blood and urine. Animal species were exposed to equal or greater concentrations of all the metabolites occurring in man. 2 Pharmacokinetics of temazepam in man were investigated in a single dose study at two dose levels, and in a multiple dose study. The results of both studies were analyzed and interpreted with the help of compartmental models. Values were obtained for excretion pattern (0-infinity), half lives (1.95, 0.5, 10.0 and 1.9 h), amounts in all compartments, and for steady-state conditions. 3 The bioavailability of the hard gelatin capsule dosage form was compared with that of a suspension serving as the ideal dosage form, and found to be acceptable.
Topics: Animals; Anti-Anxiety Agents; Biological Availability; Dogs; Female; Half-Life; Humans; Intestinal Absorption; Kinetics; Male; Mice; Pregnancy; Rabbits; Rats; Species Specificity; Temazepam
PubMed: 41539
DOI: 10.1111/j.1365-2125.1979.tb00451.x -
The Science of the Total Environment Jul 2018Reuse of treated wastewater for irrigation of crops is growing in arid and semi-arid regions, whilst increasing amounts of biosolids are being applied to fields to...
Reuse of treated wastewater for irrigation of crops is growing in arid and semi-arid regions, whilst increasing amounts of biosolids are being applied to fields to improve agricultural outputs. Due to incomplete removal in the wastewater treatment processes, pharmaceuticals present in treated wastewater and biosolids can contaminate soil systems. Benzodiazepines are a widely used class of pharmaceuticals that are released following wastewater treatment. Benzodiazepines are represented by a class of compounds with a range of physicochemical properties and this study was therefore designed to evaluate the influence of soil properties on the sorption behaviour and subsequent uptake of seven benzodiazepines (chlordiazepoxide, clonazepam, diazepam, flurazepam, oxazepam, temazepam and triazolam) in two plant species. The sorption and desorption behaviour of benzodiazepines was strongly influenced by soil type and hydrophobicity of the chemical. The partitioning behaviour of these chemicals in soil was a key controller of the uptake and accumulation of benzodiazepines by radish (Raphanus sativus) and silverbeet (Beta vulgaris). Benzodiazepines such as oxazepam that were neutral, had low sorption coefficients (K) or had pH-adjusted log octanol-water partition coefficients (log D, pH6.3) values close to 2 had the greatest extent of uptake. Conversely, benzodiazepines such as flurazepam that had an ionised functional groups and greater K values had comparatively limited accumulation in the selected plant species. Results also revealed active in-plant metabolism of benzodiazepines, potentially analogous to the known metabolic transformation pathway of benzodiazepines in humans. Along with this observed biological transformation of benzodiazepines in exposed plants, previously work has established the widespread presence of the plant signalling molecule γ-amino butyric acid (GABA), which is specifically modulated by benzodiazepines in humans. This highlights the need for further assessment of the potential for biological activity of benzodiazepines following their plant uptake.
Topics: Benzodiazepines; Crops, Agricultural; Humans; Soil; Soil Pollutants; Wastewater
PubMed: 29428856
DOI: 10.1016/j.scitotenv.2018.01.337 -
Journal of the American Geriatrics... May 2016To use primary care electronic health records (EHRs) to evaluate prescriptions and inappropriate prescribing in men and women at age 100.
OBJECTIVES
To use primary care electronic health records (EHRs) to evaluate prescriptions and inappropriate prescribing in men and women at age 100.
DESIGN
Population-based cohort study.
SETTING
Primary care database in the United Kingdom, 1990 to 2013.
PARTICIPANTS
Individuals reaching the age of 100 between 1990 and 2013 (N = 11,084; n = 8,982 women, n = 2,102 men).
MEASUREMENTS
Main drug classes prescribed and potentially inappropriate prescribing according to the 2012 American Geriatrics Society Beers Criteria.
RESULTS
At the age of 100, 73% of individuals (79% of women, 54% of men) had received one or more prescription drugs, with a median of 7 (interquartile range 0-12) prescription items. The most frequently prescribed drug classes were cardiovascular (53%), central nervous system (CNS) (53%), and gastrointestinal (47%). Overall, 32% of participants (28% of men, 32% of women) who received drug prescriptions may have received one or more potentially inappropriate prescriptions, with temazepam and amitriptyline being the most frequent. CNS prescriptions were potentially inappropriate in 23% of individuals, and anticholinergic prescriptions were potentially inappropriate in 18% of individuals.
CONCLUSION
The majority of centenarians are prescribed one or more drug therapies, and the prescription may be inappropriate for up to one-third of these individuals. Research using EHRs offers opportunities to understand prescribing trends and improve pharmacological care of the oldest adults.
Topics: Aged, 80 and over; Drug Utilization; Electronic Health Records; Female; Humans; Inappropriate Prescribing; Male; Polypharmacy; United Kingdom
PubMed: 27130965
DOI: 10.1111/jgs.14106 -
The Science of the Total Environment Jan 2023Z-drugs, benzodiazepines and ketamine are classes of psychotropic drugs prescribed for treating anxiety, sleep disorders and depression with known side effects including...
Z-drugs, benzodiazepines and ketamine are classes of psychotropic drugs prescribed for treating anxiety, sleep disorders and depression with known side effects including an elevated risk of addiction and substance misuse. These drugs have a strong potential for misuse, which has escalated over the years and was hypothesized here to have been exacerbated during the COVID-19 pandemic. Wastewater-based epidemiology (WBE) constitutes a fast, easy, and relatively inexpensive approach to epidemiological surveys for understanding the incidence and frequency of uses of these drugs. In this study, we analyzed wastewater (n = 376) from 50 cities across the United States and Mexico from July to October 2020 to estimate drug use rates during a pandemic event. Both time and flow proportional composite and grab samples of untreated municipal wastewater were analyzed using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry to determine loadings of alprazolam, clonazepam, diazepam, ketamine, lorazepam, nordiazepam, temazepam, zolpidem, and zaleplon in raw wastewater. Simultaneously, prescription data of the aforementioned drugs were extracted from the Medicaid database from 2019 to 2021. Results showed high detection frequencies of ketamine (90 %), lorazepam (87 %), clonazepam (76 %) and temazepam (73 %) across both Mexico and United States and comparatively lower detection frequencies for zaleplon (22 %), zolpidem (9 %), nordiazepam (<1 %), diazepam (<1 %), and alprazolam (<1 %) during the pandemic. Average mass consumption rates, estimated using WBE and reported in units of mg/day/1000 persons, ranged between 62 (temazepam) and 1100 (clonazepam) in the United States. Results obtained from the Medicaid database also showed a significant change (p < 0.05) in the prescription volume between the first quarter of 2019 (before the pandemic) and the first quarter of 2021 (pandemic event) for alprazolam, clonazepam and lorazepam. Study results include the first detections of zaleplon and zolpidem in wastewater from North America.
Topics: Humans; United States; Benzodiazepines; Alprazolam; Wastewater; Ketamine; Pandemics; Nordazepam; Zolpidem; Clonazepam; Lorazepam; Tandem Mass Spectrometry; COVID-19; Temazepam; Mexico; Diazepam
PubMed: 36243065
DOI: 10.1016/j.scitotenv.2022.159351 -
Basic & Clinical Pharmacology &... Mar 2019Long-term use of benzodiazepines or benzodiazepine receptor agonists is widespread, although guidelines recommend short-term use. Only few controlled studies have... (Randomized Controlled Trial)
Randomized Controlled Trial
Long-term use of benzodiazepines or benzodiazepine receptor agonists is widespread, although guidelines recommend short-term use. Only few controlled studies have characterized the effect of discontinuation of their chronic use on sleep and quality of life. We studied perceived sleep and quality of life in 92 older (age 55-91 years) outpatients with primary insomnia before and after withdrawal from long-term use of zopiclone, zolpidem or temazepam (BZDA). BZDA was withdrawn during 1 month, during which the participants received psychosocial support and blindly melatonin or placebo. A questionnaire was used to study perceived sleep and quality of life before withdrawal, and 1 month and 6 months later. 89 participants completed the 6-month follow-up. As melatonin did not improve withdrawal, all participants were pooled and then separated based solely on the withdrawal results at 6 months (34 Withdrawers. 55 Nonwithdrawers) for this secondary analysis. At 6 months, the Withdrawers had significantly (P < 0.05) shorter sleep-onset latency and less difficulty in initiating sleep than at baseline and when compared to Nonwithdrawers. Compared to baseline, both Withdrawers and Nonwithdrawers had at 6 months significantly (P < 0.05) less fatigue during the morning and daytime. Stress was alleviated more in Withdrawers than in Nonwithdrawers (P < 0.05). Satisfaction with life and expected health 1 year later improved (P < 0.05) in Withdrawers. In conclusion, sleep disturbances, daytime fatigue and impaired quality of life may resolve within 6 months of BZDA withdrawal. These results encourage withdrawal from chronic use of benzodiazepine-type hypnotics, particularly in older subjects.
Topics: Aged; Aged, 80 and over; Azabicyclo Compounds; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Male; Melatonin; Middle Aged; Piperazines; Quality of Life; Sleep; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome; Surveys and Questionnaires; Temazepam; Zolpidem
PubMed: 30295409
DOI: 10.1111/bcpt.13144 -
BMJ Open May 2019Hospitalised older patients frequently suffer from inadequate sleep, which can lead to patient distress and delayed recovery from acute illness or surgical procedure....
INTRODUCTION
Hospitalised older patients frequently suffer from inadequate sleep, which can lead to patient distress and delayed recovery from acute illness or surgical procedure. Currently, no evidence-based treatments exist for sleeping problems in hospitalised older patients. Benzodiazepines, such as temazepam, are regularly prescribed by physicians, although they have serious side effects; for older patients in particular. Melatonin is proposed as a safe alternative for sleeping problems in hospitalised older patients, but the efficacy of melatonin is unclear in this population. Therefore, the aim of this study is to investigate the effects of melatonin and temazepam compared with placebo on sleep quality among hospitalised older patients with sleeping problems.
METHODS AND ANALYSIS
This study is a multicentre, randomised, placebo-controlled trial. A total of 663 patients will be randomised in a 1:1:1 fashion to receive either melatonin (n=221), temazepam (n=221) or placebo (n=221). The study population consists of hospitalised patients aged 60 years and older, with new or aggravated sleeping problems for which an intervention is needed. The primary outcome is sleep quality measured with the Leeds Sleep Evaluation Questionnaire (LSEQ). Secondary outcomes include sleep parameters measured with actigraphy and medication-related adverse effects.
ETHICS AND DISSEMINATION
This study was approved by the Medical Ethics Committee of the Academic Medical Centre Amsterdam, (No 2015_302). Study findings will be disseminated through presentations at professional and scientific conferences and publications in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NTR6908; Pre-results.
Topics: Aged; Humans; Middle Aged; Arousal; Delayed-Action Preparations; Geriatrics; Hospitalization; Hypnotics and Sedatives; Melatonin; Placebos; Randomized Controlled Trials as Topic; Sleep; Sleep Wake Disorders; Temazepam; Treatment Outcome; Multicenter Studies as Topic
PubMed: 31122969
DOI: 10.1136/bmjopen-2018-025514 -
BMJ (Clinical Research Ed.) Nov 1988
Topics: Adult; Anti-Anxiety Agents; Dosage Forms; Female; Humans; Injections, Intravenous; Pregnancy; Substance-Related Disorders; Temazepam
PubMed: 2905899
DOI: 10.1136/bmj.297.6660.1402-a -
Medication use and the risk of motor vehicle collisions among licensed drivers: A systematic review.Accident; Analysis and Prevention Nov 2016Driving under the influence of prescription and over-the-counter medication is a growing public health concern. A systematic review of the literature was performed to... (Review)
Review
OBJECTIVES
Driving under the influence of prescription and over-the-counter medication is a growing public health concern. A systematic review of the literature was performed to investigate which specific medications were associated with increased risk of motor vehicle collision (MVC).
METHODS
The a priori inclusion criteria were: (1) studies published from English-language sources on or after January 1, 1960, (2) licensed drivers 15 years of age and older, (3) peer-reviewed publications, master's theses, doctoral dissertations, and conference papers, (4) studies limited to randomized control trials, cohort studies, case-control studies, or case-control type studies (5) outcome measure reported for at least one specific medication, (6) outcome measure reported as the odds or risk of a motor vehicle collision. Fourteen databases were examined along with hand-searching. Independent, dual selection of studies and data abstraction was performed.
RESULTS
Fifty-three medications were investigated by 27 studies included in the review. Fifteen (28.3%) were associated with an increased risk of MVC. These included Buprenorphine, Codeine, Dihydrocodeine, Methadone, Tramadol, Levocitirizine, Diazepam, Flunitrazepam, Flurazepam, Lorazepam, Temazepam, Triazolam, Carisoprodol, Zolpidem, and Zopiclone.
CONCLUSIONS
Several medications were associated with an increased risk of MVC and decreased driving ability. The associations between specific medication use and the increased risk of MVC and/or affected driving ability are complex. Future research opportunities are plentiful and worthy of such investigation.
Topics: Accidents, Traffic; Adult; Analgesics, Opioid; Antidepressive Agents; Automobile Driving; Cohort Studies; Dose-Response Relationship, Drug; Driving Under the Influence; Humans; Male; Middle Aged; Motor Vehicles; Risk Factors; Young Adult
PubMed: 27569655
DOI: 10.1016/j.aap.2016.08.001 -
The Journal of Physiology Feb 19991. As changes in core body temperature are generally associated with concomitant changes in sleep propensity, it is possible that the effects of hypnotic/soporific... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1. As changes in core body temperature are generally associated with concomitant changes in sleep propensity, it is possible that the effects of hypnotic/soporific agents may be related to changes in thermoregulation. Therefore, to increase our knowledge of the mechanisms by which these agents exert their soporific effects, we compared the thermoregulatory and soporific effects of temazepam (20 mg per os (p.o.)) with those of melatonin (5 mg p.o.) when administered at 14.00 h to 20 young healthy adults (13 male, 7 female; age, 23.5 +/- 0.4 years). 2. From 08.00 to 20.30 h, subjects lay in bed, and foot and rectal (Tc) temperatures were recorded. Sleep onset latency (SOL) was measured using 20 min multiple sleep latency tests, performed hourly from 11.00 to 20.00 h, during which time heart rate was recorded. 3. Compared with placebo, both melatonin and temazepam significantly reduced Tc (-0.17 +/- 0.02 and -0.15 +/- 0.03 C, respectively) and SOL (by 4.8 +/- 1.49 and 6.5 +/- 1.62 min, respectively). Although both treatments significantly increased heat loss, only melatonin demonstrated cardiac effects. Importantly, there was a temporal relationship between minimum SOL and the maximum rate of decline in Tc for both melatonin (r = 0.48) and temazepam (r = 0.44). 4. A possible role of thermoregulation in sleep initiation is suggested by the similar temporal relationship between Tc and SOL for two different classes of soporific agents.
Topics: Adolescent; Adult; Anti-Anxiety Agents; Body Temperature; Body Temperature Regulation; Double-Blind Method; Female; Humans; Male; Melatonin; Polysomnography; Sex Characteristics; Sleep; Temazepam
PubMed: 9882760
DOI: 10.1111/j.1469-7793.1999.905ad.x