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Biosensors Oct 2022Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable...
Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable sensing method. In this study, we developed a simple, highly sensitive electrochemical nanobiosensor to determine the desirable dose of alprazolam, averting the undesirable consequences of overdose. Gold nanourchins (AuNUs) and iron-nickel reduced graphene oxide (Fe-Ni@rGO) were immobilized on a glassy carbon electrode, which was treated beforehand. The electrode surface was characterized using cyclic voltammetry, Fourier transform infrared spectroscopy, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and differential pulse voltammetry. The fabricated sensor showed two linear ranges (4 to 500 µg L and 1 to 50 mg L), low limit of detection (1 µg L), high sensitivity, good repeatability, and good recovery. Increased -OH and carboxyl (-COOH) groups on the electrode surface, resulting in improved the adsorption of alprazolam and thus lower limit of detection. This nanobiosensor could detect alprazolam powder dissolved in diluted blood serum; we also studied other benzodiazepine drugs (clonazepam, oxazepam, and diazepam) with this nanobiosensor, and results were sensible, with a significant difference.
Topics: Alprazolam; Graphite; Nanocomposites; Gold; Electrodes; Electrochemical Techniques
PubMed: 36354454
DOI: 10.3390/bios12110945 -
Pharmaceutics Feb 2024Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and...
Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and are frequently used in conjunction with other illicit drugs including cannabis. Oxazepam is metabolized in an enantiomeric-specific manner by glucuronidation, with S-oxazepam metabolized primarily by UGT2B15 and R-oxazepam glucuronidation mediated by both UGT 1A9 and 2B7. The goal of the present study was to evaluate the potential inhibitory effects of major cannabinoids, Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD), and major THC metabolites, 11-hydroxy-Δ-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ-tetrahydrocannabinol (11-COOH-THC), on the UGT-mediated metabolism of R- and S-oxazepam. The cannabinoids and metabolites were screened as inhibitors of R- and S-oxazepam glucuronidation in microsomes isolated from HEK293 cells overexpressing individual UGT enzymes (rUGTs). The IC values were determined in human liver microsomes (HLM), human kidney microsomes (HKM), and rUGTs and utilized to estimate the nonspecific, binding-corrected K (K) values and predict the area under the concentration-time curve ratio (AUCR). The estimated K values observed in HLM for S- and R-oxazepam glucuronidation by CBD, 11-OH-THC, and THC were in the micromolar range (0.82 to 3.7 µM), with the K values observed for R-oxazepam glucuronidation approximately 2- to 5-fold lower as compared to those observed for S-oxazepam glucuronidation. The mechanistic static modeling predicted a potential clinically significant interaction between oral THC and CBD with oxazepam, with the AUCR values ranging from 1.25 to 3.45. These data suggest a pharmacokinetic drug-drug interaction when major cannabinoids like CBD or THC and oxazepam are concurrently administered.
PubMed: 38399297
DOI: 10.3390/pharmaceutics16020243 -
Journal of Hazardous Materials May 2022Concerns about environmental contamination by organic micropollutants (OMPs) are increasing, due to their potential bioaccumulative and toxic properties. This study...
Concerns about environmental contamination by organic micropollutants (OMPs) are increasing, due to their potential bioaccumulative and toxic properties. This study evaluated the risk posed by OMPs to aquatic ecosystems in Swedish freshwaters. The assessment was based on measured environmental concentrations (MEC) of OMPs in surface waters upstream and downstream of Swedish wastewater treatment plants (WWTPs). A novel optimised risk quotient (RQ) was used to identify potential high-risk substances in the aquatic environment. A secondary objective was to assess the impact of WWTP effluent on aquatic ecosystems using a novel impact factor (I) based on the risk quotient (RQ). Among the 126 substances investigated, four compounds (metformin, N,N-dimethyltetradecylamine, oxazepam, and venlafaxine) were identified as likely to pose a risk to aquatic ecosystems in Swedish surface waters (RQ>1), and five compounds (clindamycin, gemfibrozil, sertraline, o-desmethylvenlafaxine, and diclofenac) were identified as posing a moderate risk to aquatic ecosystems ( 0.1
Topics: Ecosystem; Environmental Monitoring; Fresh Water; Sweden; Wastewater; Water Pollutants, Chemical
PubMed: 35121296
DOI: 10.1016/j.jhazmat.2022.128302 -
BMC Geriatrics Apr 2021Benzodiazepines (BZDs) and Z-drugs have high potential for developing frequent adverse drug events in older adults (e.g., psychomotor sedation, drug-related dementia,...
The prevalence and prescribing patterns of benzodiazepines and Z-drugs in older nursing home residents in different European countries and Israel: retrospective results from the EU SHELTER study.
BACKGROUND
Benzodiazepines (BZDs) and Z-drugs have high potential for developing frequent adverse drug events in older adults (e.g., psychomotor sedation, drug-related dementia, deliria, drug dependence, etc.). Knowledge of the prevalence and patterns of the use of BZDs/Z-drugs in vulnerable older patients is important in order to prevent and reduce the burden caused by their drug-related complications. Our study focused on international comparisons of the prevalence, country-specific prescribing patterns and risk factors of regular BZD/Z-drug use in nursing home (NH) residents.
METHODS
This cross-sectional study retrospectively analysed data of 4156 NH residents, prospectively assessed in the Services and Health in the Elderly in Long TERm care (SHELTER) project conducted from 2009 to 2014. Residents aged 65+ in 57 NHs in 7 European countries and Israel were assessed by the InterRAI Long-Term Care Facilities instrument. Descriptive statistics and multiple logistic regression models were used to describe the country-specific prevalence, patterns and risk factors of BZD/Z-drug use.
RESULTS
The mean age of the participants was 83.4 ± 9.4 years, 73% were female and 27.7% used BZDs/Z-drugs. The prevalence of BZD/Z-drug use differed significantly across countries, ranging from 44.1% in Israel to 14.5% in Germany. The most frequently prescribed were zopiclone (17.8%), lorazepam (17.1%) and oxazepam (16.3%). Lorazepam, oxazepam and diazepam were used in most of the countries. Brotizolam, temazepam and zolpidem showed highest prevalence in Israel (99.4% of all regular users of this medication in the sample), the Netherlands (72.6%) and France (50.0%), respectively. Residing in Israel was the most significant factor associated with the use of BZDs/Z-drugs or BZDs only (odds ratio [OR] 6.7; 95% confidence interval [CI] 4.8-9.2 and OR 9.7, 95%CI 6.5-14.5, respectively). The use of Z-drugs only was most significantly associated with residing in France (OR 21.0, 95%CI 9.0-48.9).
CONCLUSIONS
Despite global recommendations and warnings, the preference for and extent of use of individual BZDs and Z-drugs in vulnerable NH residents differ significantly across countries. The strong association with country of residence compared to clinical and functional factors denotes that prescribing habits, social, cultural, behavioural, and regulatory factors still play an important role in the current diverse use of these medications.
Topics: Aged; Aged, 80 and over; Benzodiazepines; Cross-Sectional Studies; Europe; Female; France; Germany; Humans; Israel; Male; Netherlands; Nursing Homes; Pharmaceutical Preparations; Prevalence; Retrospective Studies
PubMed: 33902474
DOI: 10.1186/s12877-021-02213-x -
Environment International Oct 2021Pharmaceutically active compounds (PhACs) have been shown to accumulate in aquatic and riparian food-webs. Yet, our understanding of how temperature, a key environmental...
Pharmaceutically active compounds (PhACs) have been shown to accumulate in aquatic and riparian food-webs. Yet, our understanding of how temperature, a key environmental factor in nature, affects uptake, biotransformation, and the subsequent accumulation of PhACs in aquatic organisms is limited. In this study, we tested to what extent bioconcentration of an anxiolytic drugs (temazepam and oxazepam) is affected by two temperature regimes (10 and 20 °C) and how the temperature affects the temazepam biotransformation and subsequent accumulation of its metabolite (oxazepam) in aquatic organisms. We used European perch (Perca fluviatilis) and dragonfly larvae (Sympetrum sp.), which represent predator and prey species of high ecological relevance in food chains of boreal and temperate aquatic ecosystems. Experimental organisms were exposed to target pharmaceuticals at a range of concentrations (0.2-6 µg L) to study concentration dependent differences in bioconcentration and biotransformation. We found that the bioconcentration of temazepam in perch was significantly reduced at higher temperatures. Also, temperature had a strong effect on temazepam biotransformation in the fish, with the production and subsequent accumulation of its metabolite (oxazepam) being two-fold higher at 20 °C compared to 10 °C. In contrast, we found no temperature dependency for temazepam bioconcentration in dragonfly larvae and no detectable biotransformation of the parent compound that would result in measurable concentrations of oxazepam in this organism. Our results highlight that while organisms may share the same aquatic ecosystem, their exposure to PhACs may change differently across temperature gradients in the environment.
Topics: Animals; Aquatic Organisms; Biotransformation; Ecosystem; Odonata; Perches; Pharmaceutical Preparations; Temperature; Water; Water Pollutants, Chemical
PubMed: 34139590
DOI: 10.1016/j.envint.2021.106705 -
Pharmaceutics Aug 2021Uridine 5'-diphospho-glucuronosyltransferases (UGTs) are expressed in the small intestines, but prediction of first-pass extraction from the related metabolism is not... (Review)
Review
Uridine 5'-diphospho-glucuronosyltransferases (UGTs) are expressed in the small intestines, but prediction of first-pass extraction from the related metabolism is not well studied. This work assesses physiologically based pharmacokinetic (PBPK) modeling as a tool for predicting intestinal metabolism due to UGTs in the human gastrointestinal tract. Available data for intestinal UGT expression levels and in vitro approaches that can be used to predict intestinal metabolism of UGT substrates are reviewed. Human PBPK models for UGT substrates with varying extents of UGT-mediated intestinal metabolism (lorazepam, oxazepam, naloxone, zidovudine, cabotegravir, raltegravir, and dolutegravir) have demonstrated utility for predicting the extent of intestinal metabolism. Drug-drug interactions (DDIs) of UGT1A1 substrates dolutegravir and raltegravir with UGT1A1 inhibitor atazanavir have been simulated, and the role of intestinal metabolism in these clinical DDIs examined. Utility of an in silico tool for predicting substrate specificity for UGTs is discussed. Improved in vitro tools to study metabolism for UGT compounds, such as coculture models for low clearance compounds and better understanding of optimal conditions for in vitro studies, may provide an opportunity for improved in vitro-in vivo extrapolation (IVIVE) and prospective predictions. PBPK modeling shows promise as a useful tool for predicting intestinal metabolism for UGT substrates.
PubMed: 34575401
DOI: 10.3390/pharmaceutics13091325 -
Pakistan Journal of Medical Sciences 2022To explore the effect of grouping motivational interviewing on psychological craving of patients with alcohol dependence in the rehabilitation.
OBJECTIVE
To explore the effect of grouping motivational interviewing on psychological craving of patients with alcohol dependence in the rehabilitation.
METHODS
In this prospective study one hundred patients with convalescent alcohol dependence admitted to Hebei Province Veterans Hospital from October 2017 to June 2019 were randomly divided into two groups, the experimental group and the control group, 50 cases in each. The experimental group was administrated oxazepam as a replacement therapy and the motivational interviewing. The control group was administrated oxazepam as a replacement therapy and routine health education. Both groups continued treatment for three months. Curative effect was assessed before treatment, and two weeks, four weeks and three months after treatment by using Penn Alcohol Craving Scale (PACS), Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA).
RESULTS
PACS, HAMD and HAMA in the experimental group were significantly lower than those in the control group (P < 0.05).
CONCLUSION
Grouping motivational interviewing can effectively reduce the degree of psychological dependence on alcohol and improve the symptoms of anxiety and depression in patients with alcohol dependence during rehabilitation period.
PubMed: 36246683
DOI: 10.12669/pjms.38.7.4741 -
Evidence-based Complementary and... 2022To explore the efficacy of risperidone orally disintegrating tablets combined with oxazepam in the treatment of schizophrenia.
OBJECTIVE
To explore the efficacy of risperidone orally disintegrating tablets combined with oxazepam in the treatment of schizophrenia.
METHODS
From May 2019 to May 2021, 60 patients with schizophrenia treated in our hospital were recruited and assigned into an observation group (risperidone orally disintegrating tablets combined with oxazepam treatment) and a control group (alprazolam combined with chlorpromazine treatment) according to the random number table method. The positive and negative symptom score (PANSS), quality of life score (QOL-75), ability of daily living score (ADL), clinical efficacy, incidence of adverse reactions, and disease recurrence were compared between the two groups before and after treatment.
RESULTS
The PANSS scores were similar in the two groups before treatment ( > 0.05). The two groups presented a declining trend in PANSS score after treatment, whereas a remarkable lower score in the observation group was observed ( < 0.05). The QOL scores of the two groups of patients before treatment was not significantly different ( > 0.05). Both groups witnessed improvements one month and three months after treatment, with considerable improvements being obtained in the observation group (all < 0.05). The two groups did not differ in ADL scores before treatment ( > 0.05). At 1 month and 3 months after treatment, the ADL scores of the two groups were improved, with a higher score in the observation group ( < 0.05). The observation group had a markedly higher total effective rate as compared to the control group ( = 5.455, =0.020). Adverse reaction occurred in both groups, with milder results in the observation group. The recurrence rate of the two groups was not statistically different one month after treatment ( > 0.05), while two and three months after treatment, they were lower than those of the control group (all < 0.05).
CONCLUSION
Risperidone orally disintegrating tablets combined with oxazepam shows potential in the treatment of schizophrenia by relieving patients' mental symptoms, improving quality of life and activities of daily living, and minimizing the incidence of adverse reactions.
PubMed: 35990853
DOI: 10.1155/2022/2344946 -
Cells Nov 2020The constitutive androstane receptor (CAR) is the essential regulator of genes involved both in xenobiotic and endobiotic metabolism. Diazepam has been shown as a potent...
The constitutive androstane receptor (CAR) is the essential regulator of genes involved both in xenobiotic and endobiotic metabolism. Diazepam has been shown as a potent stimulator of CAR nuclear translocation and is assumed as an indirect CAR activator not interacting with the CAR cavity. In this study, we sought to determine if diazepam is a ligand directly interacting with the CAR ligand binding domain (LBD) and if it regulates its target genes in a therapeutically relevant concentration. We used different CAR constructs in translocation and luciferase reporter assays, recombinant CAR-LBD in a TR-FRET assay, and target genes induction studied in primary human hepatocytes (PHHs), HepaRG cells, and in CAR humanized mice. We also used in silico docking and CAR-LBD mutants to characterize the interaction of diazepam and its metabolites with the CAR cavity. Diazepam and its metabolites such as nordazepam, temazepam, and oxazepam are activators of CAR+Ala in translocation and two-hybrid assays and fit the CAR cavity in docking experiments. In gene reporter assays with CAR3 and in the TR-FRET assay, only diazepam significantly interacts with CAR-LBD. Diazepam also promotes up-regulation of CYP2B6 in PHHs and in HepaRG cells. However, in humanized CAR mice, diazepam significantly induces neither nor genes nor does it regulate critical genes involved in glucose and lipids metabolism and liver proliferation. Thus, we demonstrate that diazepam interacts with human CAR-LBD as a weak ligand, but it does not significantly affect expression of tested CAR target genes in CAR humanized mice.
Topics: Adult; Animals; Cell Line; Cell Proliferation; Constitutive Androstane Receptor; Diazepam; Female; Genes, Reporter; Hepatocytes; Humans; Ligands; Liver; Male; Mice; Middle Aged; Protein Domains; Protein Transport; Receptors, Cytoplasmic and Nuclear
PubMed: 33255185
DOI: 10.3390/cells9122532 -
Cureus Mar 2024Anesthesiologists often use benzodiazepines (BZDs) due to their remarkable amnestic and anxiolytic capabilities. Because of this, they are perfect for use during the... (Review)
Review
Anesthesiologists often use benzodiazepines (BZDs) due to their remarkable amnestic and anxiolytic capabilities. Because of this, they are perfect for use during the perioperative phase, when patients' anxiety levels are already high. Remimazolam has replaced certain commonly used intravenous (IV) anesthetics due to its excellent safety profile, rapid onset of action, and short half-life. The four classes of BZDs, 2-keto-benzodiazepines, 3-hydroxy-benzodiazepines, triazolobenzodiazepines, and 7-nitro-benzodiazepines based on chemical structure, provide various levels of drowsiness, forgetfulness, and anxiolysis. Based on their elimination half-life, short-acting BZDs typically have a half-life ranging from one to 12 hours, e.g., oxazepam; intermediate-acting BZDs have an average elimination half-life of 12 to 40 hours, e.g., alprazolam; and long-acting BZDs have an average elimination half-life of more than 40 hours, e.g., diazepam. The chloride ion channel is conformationally shifted by the benzodiazepine molecule resulting in central nervous system (CNS) inhibition and hyperpolarization. Each type of benzodiazepine has a favored use. For example, diazepam is used to treat anxiety. Midazolam is used for its anxiolytic and anterograde amnestic effects during the perioperative phase. Anxiety and epilepsy are two conditions that lorazepam effectively treats. There are now phase II and III clinical studies investigating remimazolam. It is not sensitive to alterations in its surroundings and has a brief half-life so that it may be removed rapidly, even after extensive infusion. Being a soft drug means the body easily breaks it down via metabolism, which explains many features. Remimazolam is hydrolyzed into methanol and its carboxylic acid metabolite CNS 7054 by esterase metabolism. Therefore, remimazolam has a shorter onset time and faster recovery than other BZDs. Remimazolam is metabolized independently of any particular organ. Patients with hepatic and renal problems will not see any changes in metabolism or excretion since the drug's ester moiety makes it a substrate for general tissue esterase enzymes. Like its predecessor, midazolam, it has a high potential for addiction. Some side effects that could occur during infusion include headaches and drowsiness. In clinical trials, hypotension, respiratory depression, and bradycardia were noted in participants. BZDs are helpful when used in conjunction with anesthesia. Remimazolam stands out, thanks to its unique pharmacokinetics, pharmacodynamics, safety profile, and potential medical applications. Its desirable properties make it a potential surgical premedication and sedative in the critical care unit. Anesthesiologists and other doctors could have access to more consistent and safer medication. However, additional comprehensive clinical trials are necessary to understand remimazolam's advantages and disadvantages.
PubMed: 38686236
DOI: 10.7759/cureus.57260