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BMC Public Health Jul 2023While the mandate to check patients' prescription history in Prescription Drug Monitoring Program (PDMP) database before prescribing/dispensing controlled drugs has been...
BACKGROUND
While the mandate to check patients' prescription history in Prescription Drug Monitoring Program (PDMP) database before prescribing/dispensing controlled drugs has been shown to be an important tool to curb opioid abuse, less is known about whether the mandate can reduce the misuse of other commonly abused prescription drugs. We examined whether PDMP use mandates were associated with changes in prescription stimulant and depressant quantities.
METHODS
Using data from Automated Reports and Consolidate Ordering System (ARCOS), we employed difference-in-differences design to estimate the association between PDMP use mandates and prescription stimulant and depressant quantities in 50 U.S. states and the District of Columbia from 2006 to 2020. Limited PDMP use mandate was specific only to opioids or benzodiazepines. Expansive PDMP use mandate was non-specific to opioid or benzodiazepine and required prescribers/dispensers to check PDMP when prescribing/dispensing targeted controlled substances in Schedule II-V. The main outcomes were population-adjusted prescription stimulant (amphetamine, methylphenidate, lisdexamfetamine) and depressant (amobarbital, butalbital, pentobarbital, secobarbital) quantities in grams.
RESULTS
There was no evidence that limited PDMP use mandate was associated with a reduction in the prescription stimulant and depressant quantities. However, expansive PDMP use mandate that was non-specific to opioid or benzodiazepine and required prescribers/dispensers to check PDMP when prescribing/dispensing targeted controlled substances in Schedule II-V was associated with 6.2% (95% CI: -10.06%, -2.08%) decline in prescription amphetamine quantity.
CONCLUSION
Expansive PDMP use mandate was associated with a decline in prescription amphetamine quantity. Limited PDMP use mandate did not appear to change prescription stimulant and depressant quantities.
Topics: Humans; Prescription Drug Monitoring Programs; Analgesics, Opioid; Controlled Substances; Prescriptions; Amphetamine; Benzodiazepines
PubMed: 37434122
DOI: 10.1186/s12889-023-16256-9 -
Journal of Animal Science Jan 2023The present study was conducted to investigate the effects of extrusion, fermentation, and enzymolysis of palm kernel cake on processing quality of pellet feed, nutrient...
The present study was conducted to investigate the effects of extrusion, fermentation, and enzymolysis of palm kernel cake on processing quality of pellet feed, nutrient digestibility, and intestinal microbiota of pigs. First, the pretreatment parameters of extrusion, enzymolysis, and fermentation of palm kernel cake were optimized. Then, PKC after three processing techniques were used to prepare pellet feed. A total of 160 crossbred piglets (Duroc × Landrace × Yorkshire) with an average body weight of 28 ± 0.5 kg were used in an 8-wk feeding experiment. Pigs were randomly assigned to five treatments with four replicates per treatment and eight pigs per replicates. The five experimental groups were as follows: basal diet group (whole corn-soybean meal), 10% PKC group (PKC), 10% extrusion PKC group (PPKC), 10% enzymolysis PKC group (EPKC), and 10% fermented PKC group (FPKC), respectively. At the end of the experiment, four pigs from each treatment (randomly collected one pig per pen) were sacrificed by administering a pentobarbital overdose, the gut and blood samples were collected for the quantification analysis of microbiota, hematological parameters, and apparent total tract nutrient digestibility. The results showed that all three processing techniques significantly decreased the contents of crude fiber of PKC (P < 0.01), pulverization rate (P < 0.01), powder content (P < 0.01), and increased the hardness and gelatinization starch of pellet feed (P < 0.05) compared to PKC group. In addition, PPKC significantly improved the dry matter, crude protein, and ether extract content, blood indices and average daily feed intake compared to PKC group (P < 0.01), while the parameters were similar among FPKC, EPKC, and control group (P > 0.01). Furthermore, all three processing techniques significantly increased the Lactobacillus and decreased the Escherichia levels in feces or gut compared to PKC. Collectively, extrusion, fermentation, and enzymolysis of PKC had positively enhanced the pellet quality, growth performance, nutrient digestibility, and gut microbiota, extrusion exhibited a superior feeding effect compared to fermentation and enzymolysis.
Topics: Swine; Animals; Gastrointestinal Microbiome; Digestion; Animal Feed; Diet; Nutrients
PubMed: 37357763
DOI: 10.1093/jas/skad217 -
Journal of Food and Drug Analysis Jun 2023Ashwagandha (Withania somnifera L. Dunal), an Indian medicinal plant that has been used for centuries to treat insomnia, exhibits a variety of biological activities,...
Ashwagandha (Withania somnifera L. Dunal), an Indian medicinal plant that has been used for centuries to treat insomnia, exhibits a variety of biological activities, such as improving cognitive function, immunity and anxiety. In this study, the effect of enzyme-treated Ashwagandha root extract (EA) and on sleep was evaluated using rodent models. Starch contained in the Ashwagandha root extract was removed by amylase treatment to prepare EA. To evaluate the sleep-promoting activity of EA, a pentobarbital-induced sleep test and electroencephalogram analysis were performed. In addition, the sleep-promoting mechanism of EA was elucidated by analyzing the expression of sleep-related receptors. In the pentobarbital-induced sleep test, EA dose-dependently increased sleep duration. Additionally, electroencephalogram analysis revealed that EA significantly increased δ-wave and non-rapid eye movement sleep times, which are involved in deep sleep, thereby improving sleep quality and quantity. EA also effectively relieved caffeine-induced insomnia symptoms. Furthermore, the γ-aminobutyric acid (GABA) content in the brain and mRNA and protein expression of GABA, GABA, and serotonin receptors were significantly increased by EA compared to the normal group. In particular, EA showed sleep-promoting activity by binding to various GABAA receptor sites. Collectively, EA exhibited sleep-promoting activity through the GABAergic system and may be used as a functional material to improve sleep deprivation.
Topics: Receptors, GABA; Withania; Sleep Initiation and Maintenance Disorders; Pentobarbital; Amylases; Plant Extracts; Sleep; gamma-Aminobutyric Acid
PubMed: 37335157
DOI: 10.38212/2224-6614.3456 -
Journal of Animal Science Jan 2023A sodium pentobarbital-induced sleep time study was conducted on 15 adult intact male Boer × Spanish goats selected for high (J+, n = 7) or low (J-, n = 8) juniper...
A sodium pentobarbital-induced sleep time study was conducted on 15 adult intact male Boer × Spanish goats selected for high (J+, n = 7) or low (J-, n = 8) juniper consumption (estimated breeding values of 13.1 ± 1.0 and -14.3 ± 0.8, respectively; mean ± standard deviation). Pentobarbital sleep time is an in vivo assay of Phase I hepatic metabolism that can be induced by exposure to barbiturates and monoterpenes. Monoterpenes and pentobarbital are initially oxidized by this pathway; thus, we hypothesized that J+ goats would have shorter sleep times than J- goats. Time to the righting reflex after pentobarbital-induced sleep was measured in all goats following a minimum period of 21 d on three different diets: 1) grazing juniper-infested rangeland (JIR), 2) forage diet with no monoterpenes (M0), and 3) forage diet with 8 g/kg added monoterpenes from camphor, sabinene, and α-pinene in a w/w ratio of 5:4:1 (M+). Fecal samples from the JIR diet were analyzed with near-infrared spectroscopy for the percentage of juniper in the diet. Fecal samples from the JIR and M+ diets were analyzed for camphor and sabinene concentrations. The percentage of juniper in the diet of J+ goats grazing rangelands was greater (P = 0.001) than J- goats (31.1% and 18.6%, respectively). Sleep time did not differ between selection lines (P = 0.36). However, the sleep time of the goats fed M+ diet was 26 min shorter (P < 0.001) than JIR or M0 diets, which were equal. The concentration of camphor and sabinene in the feces was higher (P < 0.001) for goats on the M+ diet than on the JIR diet. There were no differences between selection lines in the serum enzymes indicative of liver disease (aspartate aminotransferase, bilirubin, gamma-glutamyl transferase, and glutamate dehydrogenase; P > 0.12), and all treatment means were within the reference interval. Selecting goats for juniper consumption did not affect the Phase I detoxification system, and several alternative hypotheses for differences in juniper consumption between J+ and J- goats are discussed.
Topics: Animals; Male; Juniperus; Goats; Camphor; Metabolic Detoxication, Phase I; Pentobarbital; Plant Breeding; Diet; Monoterpenes; Liver
PubMed: 37328163
DOI: 10.1093/jas/skad180 -
International Journal of Molecular... May 2023Two groups of facts have been established in previous drug development studies of the non-benzodiazepine anxiolytic fabomotizole. First, fabomotizole prevents...
Pharmacological Analysis of GABA Receptor and Sigma1R Chaperone Interaction: Research Report I-Investigation of the Anxiolytic, Anticonvulsant and Hypnotic Effects of Allosteric GABA Receptors' Ligands.
Two groups of facts have been established in previous drug development studies of the non-benzodiazepine anxiolytic fabomotizole. First, fabomotizole prevents stress-induced decrease in binding ability of the GABA receptor's benzodiazepine site. Second, fabomotizole is a Sigma1R chaperone agonist, and exposure to Sigma1R antagonists blocks its anxiolytic effect. To prove our main hypothesis of Sigma1R involvement in GABA receptor-dependent pharmacological effects, we performed a series of experiments on BALB/c and ICR mice using Sigma1R ligands to study anxiolytic effects of benzodiazepine tranquilizers diazepam (1 mg/kg i.p.) and phenazepam (0.1 mg/kg i.p.) in the elevated plus maze test, the anticonvulsant effects of diazepam (1 mg/kg i.p.) in the pentylenetetrazole-induced seizure model, and the hypnotic effects of pentobarbital (50 mg/kg i.p.). Sigma1R antagonists BD-1047 (1, 10, and 20 mg/kg i.p.), NE-100 (1 and 3 mg/kg i.p.), and Sigma1R agonist PRE-084 (1, 5, and 20 mg/kg i.p.) were used in the experiments. Sigma1R antagonists have been found to attenuate while Sigma1R agonists can enhance GABARs-dependent pharmacological effects.
Topics: Animals; Mice; Anti-Anxiety Agents; Anticonvulsants; Benzodiazepines; Diazepam; Hypnotics and Sedatives; Ligands; Mice, Inbred ICR; Receptors, GABA-A; Research Report; Sigma-1 Receptor
PubMed: 37298532
DOI: 10.3390/ijms24119580 -
Frontiers in Pharmacology 2023A case of fatal poisoning involving multiple psychotropic drugs is presented. Quantitative toxicological analysis showed femoral blood concentrations of pentobarbital,...
A case of fatal poisoning involving multiple psychotropic drugs is presented. Quantitative toxicological analysis showed femoral blood concentrations of pentobarbital, phenobarbital, duloxetine, acetaminophen and tramadol were 10.39, 22.57, 0.22, 0.61 and 0.22 μg/ml, respectively. We concluded that the death was due to the additive effects of two barbiturates. As both pentobarbital and phenobarbital act on gamma-aminobutyric acid (GABA) receptors, central nervous system activity was suppressed, causing respiratory depression. Additive pharmacological effects should be considered in cases of massive ingestion of multiple drugs.
PubMed: 37292155
DOI: 10.3389/fphar.2023.1196565 -
Clinical Pharmacokinetics Jul 2023Pentobarbital pharmacokinetics (PK) remain elusive and the therapeutic windows narrow. Administration is frequent in critically ill children with refractory status...
BACKGROUND
Pentobarbital pharmacokinetics (PK) remain elusive and the therapeutic windows narrow. Administration is frequent in critically ill children with refractory status epilepticus (SE) and severe traumatic brain injury (sTBI).
OBJECTIVES
To investigate pentobarbital PK in SE and sTBI patients admitted to the paediatric intensive care unit (PICU) with population-based PK (PopPK) modelling and dosing simulations.
METHODS
Develop a PopPK model with non-linear mixed-effects modelling (NONMEM) with retrospective data (n = 36; median age 1.3 years; median weight 10 kg; 178 blood samples) treated with continuous intravenous pentobarbital. An independent dataset was used for external validation (n = 9). Dosing simulations with the validated model evaluated dosing regimens.
RESULTS
A one-compartment PK model with allometrically scaled weight on clearance (CL; 0.75) and volume of distribution (V; 1) captured data well. Typical CL and V values were 3.59 L/70 kg/h and 142 L/70 kg, respectively. Elevated creatinine and C-reactive protein (CRP) levels significantly correlated to decreased CL, explaining 84% of inter-patient variability, and were incorporated in the final model. External validation using stratified visual predictive checks showed good results. Simulations demonstrated patients with elevated serum creatinine and CRP failed to achieve steady state yet progressed to toxic levels with current dosing regimens.
CONCLUSIONS
The one-compartment PK model of intravenous pentobarbital described data well whereby serum creatinine and CRP significantly correlated with pentobarbital CL. Dosing simulations formulated adjusted dosing advice in patients with elevated creatinine and/or CRP. Prospective PK studies with pharmacodynamic endpoints, are imperative to optimise pentobarbital dosing in terms of safety and clinical efficacy in critically ill children.
Topics: Humans; Child; Infant; Anti-Bacterial Agents; Pentobarbital; Creatinine; Critical Illness; Retrospective Studies; Prospective Studies; Brain Injuries, Traumatic; Status Epilepticus
PubMed: 37247187
DOI: 10.1007/s40262-023-01249-z -
Molecular Neurobiology Sep 2023Epilepsy is a severe neurological condition affecting 50-65 million individuals worldwide that can lead to brain damage. Nevertheless, the etiology of epilepsy remains...
Identifying Novel Drug Targets for Epilepsy Through a Brain Transcriptome-Wide Association Study and Protein-Wide Association Study with Chemical-Gene-Interaction Analysis.
Epilepsy is a severe neurological condition affecting 50-65 million individuals worldwide that can lead to brain damage. Nevertheless, the etiology of epilepsy remains poorly understood. Meta-analyses of genome-wide association studies involving 15,212 epilepsy cases and 29,677 controls of the ILAE Consortium cohort were used to conduct transcriptome-wide association studies (TWAS) and protein-wide association studies (PWAS). Furthermore, a protein-protein interaction (PPI) network was generated using the STRING database, and significant epilepsy-susceptible genes were verified using chip data. Chemical-related gene set enrichment analysis (CGSEA) was performed to determine novel drug targets for epilepsy. TWAS analysis identified 21,170 genes, of which 58 were significant (TWAS < 0.05) in ten brain regions, and 16 differentially expressed genes were verified based on mRNA expression profiles. The PWAS identified 2249 genes, of which 2 were significant (PWAS < 0.05). Through chemical-gene set enrichment analysis, 287 environmental chemicals associated with epilepsy were identified. We identified five significant genes (WIPF1, IQSEC1, JAM2, ICAM3, and ZNF143) that had causal relationships with epilepsy. CGSEA identified 159 chemicals that were significantly correlated with epilepsy (P < 0.05), such as pentobarbital, ketone bodies, and polychlorinated biphenyl. In summary, we performed TWAS, PWAS (for genetic factors), and CGSEA (for environmental factors) analyses and identified several epilepsy-associated genes and chemicals. The results of this study will contribute to our understanding of genetic and environmental factors for epilepsy and may predict novel drug targets.
Topics: Humans; Transcriptome; Gene Expression Profiling; Genome-Wide Association Study; Brain; Epilepsy; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Cytoskeletal Proteins; Intracellular Signaling Peptides and Proteins; Trans-Activators
PubMed: 37246165
DOI: 10.1007/s12035-023-03382-z -
Clinical and Experimental Hypertension... Dec 2023Although great progress has been made in the diagnosis and treatment of acute myocardial infarction (AMI) in recent years, its morbidity and mortality are still...
Sestrin2 levels in patients with anxiety and depression myocardial infarction was up-regulated and suppressed inflammation and ferroptosis by LKB1-mediated AMPK activation.
Although great progress has been made in the diagnosis and treatment of acute myocardial infarction (AMI) in recent years, its morbidity and mortality are still relatively high. In this study, we explain that the function of Sestrin2 gene in Anxiety and Depression Myocardial infarction and its possible mechanism. 26 patients with Anxiety and Depression Myocardial infarction (ADMI) and 26 normal volunteers were collected from our hospital. All mice anaesthetized using 50 mg/kg of pentobarbital sodium and the left anterior descending arteries (LAD) were ligated to induce myocardial infarction. H9c2 cells were stimulated with 5% oxygen (O2) and 5% carbon dioxide (CO2) and 90% N2 for 24 h. The serum expression of Sestrin2 in patients with ADMI was up-regulated. Sestrin2 gene up-regulation reduced collagen I/II and KEAP1 mRNA expressions, and increased GPX4 and Nrf2 mRNA expressions in vitro model of AMI. Down-regulation of Sestrin2 increased collagen I/II and KEAP1 mRNA expressions, and decreased GPX4 and Nrf2 mRNA expressions in vitro model of AMI. These data confirmed that Sestrin2 reduced inflammation and ferroptosis in model of ADMI by LKB1-mediated AMPK activation. This infers that Sestrin2 is potential target to be used in the treatment of premature AMI.
Topics: Mice; Animals; AMP-Activated Protein Kinases; Kelch-Like ECH-Associated Protein 1; Ferroptosis; NF-E2-Related Factor 2; Depression; Myocardial Infarction; Anxiety; Inflammation; Collagen; RNA, Messenger
PubMed: 37183711
DOI: 10.1080/10641963.2023.2205049 -
Frontiers in Psychiatry 2023The utilization of Propofol, a widely used intravenous sedative or anesthetic, is characterized by its quick onset, predictable control, and fleeting half-life during...
BACKGROUND
The utilization of Propofol, a widely used intravenous sedative or anesthetic, is characterized by its quick onset, predictable control, and fleeting half-life during both general anesthesia and intensive care unit sedation. Recent evidence, however, has highlighted propofol's propensity to induce euphoria, particularly in patients undergoing painless procedures such as gastrointestinal or gastric endoscopy. Given its widespread use in patients undergoing such procedures, this study aims to investigate the clinical evidence and factors that may influence propofol-induced euphoria in these settings.
METHODS
The Addiction Research Center Inventory-Chinese Version (ARCI-CV) scale was administered to 360 patients undergoing gastric or gastrointestinal endoscopy using propofol as a sedative. Patient characteristics including past medical history, depression, anxiety, alcohol abuse, and sleep disturbance were recorded through history taking and assessment using various questionnaires prior to the examination. The euphoric and sedative statuses were assessed at 30 min and 1 week post-examination.
RESULTS
The experimental results of a survey of 360 patients who underwent gastric or gastrointestinal endoscopy using propofol showed that the mean Morphine-Benzedrine Group (MBG) score before the procedure and after 30 min of the procedure was 4.23 and 8.67, respectively. The mean Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) score before the procedure and after 30 min of the procedure was 3.24 and 6.22, respectively. These results showed that both MBG and PCAG scores increased significantly after the procedure. Certain factors, such as dreaming, propofol dose, duration of anesthesia, and etomidate dose, were all correlated with MBG both at 30 min and 1 week after the examination. In addition, etomidate had an effect of decreasing MBG scores and increasing PCAG scores both at 30 min and 1 week after the examination.
CONCLUSION
Taken together, propofol may elicit euphoria and potentially contribute to propofol addiction. There are several risk factors for the development of propofol addiction, including dreaming, propofol dose, duration of anesthesia, and etomidate dose. These findings suggest that propofol may have a euphoric effect and may have the potential for drug addiction and abuse.
PubMed: 37181900
DOI: 10.3389/fpsyt.2023.1001626