- StatPearls [BOOK]
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- Barbiturates are a class of sedative-hypnotic drugs. They are commonly used as antiepileptics (phenobarbital) and for the induction of general anesthesia (thiopental). Some states administer barbitur...
Barbiturates are a class of sedative-hypnotic drugs. They are commonly used as antiepileptics (phenobarbital) and for the induction of general anesthesia (thiopental). Some states administer barbiturates for physician-assisted suicide/euthanasia and use them for capital punishment by lethal injection. Their use in clinical practice has largely been replaced by benzodiazepines such as alprazolam, diazepam, and lorazepam due to the lower risk of overdose and available antidote to reverse toxicity. Barbiturates are used as a laboratory buffer and can be found in clinical and research laboratories. Barbiturates are controlled substances that pose a high risk for abuse given their psychoactive effects. Restrictions on access to barbiturates have caused the number of overdoses to decline. Common barbiturates include the following: Methohexital and thiopental are used as anesthetics. Phenobarbital and primidone are used in the treatment of seizures. Amobarbital is used as an investigative agent in the Wada test (neurological assessment of cerebral hemispheres) Butalbital, in combination with other medications, is used for headaches and muscle pain.
- A Systematic Review of Pharmacologic Treatments for School Refusal Behavior. [Journal Article]
- JCJ Child Adolesc Psychopharmacol 2018 May 09
- CONCLUSIONS: Data regarding pharmacological treatments for school refusal are sparse. Most trials in this area were conducted before development of newer antidepressants, were underpowered, and have significant methodological limitations that are characteristic of the time in which they were conducted. This systematic review highlights the need for more trials with newer pharmacologic agents, larger sample sizes, and improved systematic assessments of school refusal and comorbidities. School refusal represents an important functional outcome for many children, especially those with anxiety and depression. Future pharmacologic studies of anxiety and depression in children may benefit from incorporating specific school refusal measures as secondary outcomes.
- Contamination profiles, mass loadings, and sewage epidemiology of neuropsychiatric and illicit drugs in wastewater and river waters from a community in the Midwestern United States. [Journal Article]
- STSci Total Environ 2018 Aug 01; 631-632:1457-1464
- In this study, residues of the neuropsychiatric and illicit drugs including stimulants, opioids, hallucinogens, antischizophrenics, sedatives, and antidepressants were determined in influent and effl...
In this study, residues of the neuropsychiatric and illicit drugs including stimulants, opioids, hallucinogens, antischizophrenics, sedatives, and antidepressants were determined in influent and effluent samples from a small wastewater treatment plant, a receiving creek, and river waters in the Four Rivers region of the Midwestern United States. Nineteen neuropsychiatric drugs, eight illicit drugs, and three metabolites of illicit drugs were detected and quantitated in the water samples using HPLC-MS/MS. Residual concentrations of the drugs varied from below the detection limit to sub-μg/L levels. The source of residual cocaine and benzoylecgonine in wastewater is primarily from human consumption of cocaine rather than direct disposal. Wastewater based epidemiology is utilized to estimate the community usage of drugs based on the concentration of drug residues in wastewater, wastewater inflow, and the population served by the centralized wastewater treatment plant. The per-capita consumption rate of methamphetamine (1740 mg/d/1000 people) and amphetamine (970 mg/d/1000 people) found in this study were the highest reported per-capita consumption rates in the USA. Antidepressant venlafaxine found to have the highest environmental emission from the WWTP (333 ± 160 mg/d/1000 people) followed by citalopram (132 ± 60.2 mg/d/1000 people), methamphetamine (111 ± 43.6 mg/d/1000 people), and hydrocodone (108 ± 90.1 mg/d/1000 people). Bee Creek, an immediate receiving water body, is found to be a source of several neuropsychiatric and illicit drugs including methamphetamine, methadone, alprazolam, oxazepam, temazepam, carbamazepine, venlafaxine, citalopram, sertraline, oxycodone, and hydrocodone (p < 0.036) in the Clarks River.
- Trends in the long-term use of benzodiazepine anxiolytics and hypnotics: A national register study for 2006 to 2014. [Journal Article]
- PDPharmacoepidemiol Drug Saf 2018 May 04
- CONCLUSIONS: We found a declining trend in long-term BZD use, but the decline was not uniform between the substances-the long-term use of clonazepam and zolpidem even increased. Follow-up research is needed to assess whether the decline in BZD use is accompanied by an increased use of other types of anxiolytic or hypnotic drugs or other forms of treatment.
- Evidence that Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. [Journal Article]
- JPJ Pharmacol Exp Ther 2018 May 02
- Using non-human primates, we introduced a new set of behavioral categories for observable sedative effects based on pediatric anesthesiology classifications. We examined the effects of alprazolam and...
Using non-human primates, we introduced a new set of behavioral categories for observable sedative effects based on pediatric anesthesiology classifications. We examined the effects of alprazolam and diazepam (non-selective benzodiazepines), zolpidem (preferential binding to α1 subunit-containing GABAA receptors), HZ-166 (8-ethynyl-6-(2'-pyridine)-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester; functionally selective for α2 and α3 subunit-containing GABAA receptors), MRK-696 (7-cyclobutyl-6-(2-methyl-2H-1,2,4-triazol-2-ylmethoxy)-3-(2-flurophenyl)-1,2,4-triazolo(4,3-b)pyridazine; no selectivity but partial intrinsic activity), and TPA023B (6,2'-difluro-5'-(3-(1-hydroxy-1-methylethyl)imidazo(1,2-b((1,2,4)triazin-7-yl)(1,1'-biphenyl)-2-carbonitrile; selectivity for α2, α3, α5 subunit-containing GABAA receptors) using quantitative behavioral observation techniques in rhesus monkeys. We further examined the role of α1 subunit-containing GABAA receptors in benzodiazepine-induced sedative effects by pretreating animals with the α1 subunit-preferring antagonist β-carboline-3-carboxylate-t-butyl ester (βCCT). Increasing doses of alprazolam and diazepam resulted in the emergence of observable ataxia, rest/sleep posture, moderate and deep sedation. In contrast, zolpidem engendered dose-dependent observable ataxia and deep sedation but not rest/sleep posture or moderate sedation, while HZ-166 and TPA023 induced primarily rest/sleep posture. MRK-696 induced rest/sleep posture and observable ataxia. Zolpidem, but no other compounds, significantly increased tactile/oral exploration. The sedative effects engendered by alprazolam, diazepam, and zolpidem generally were attenuated by βCCT pretreatments, whereas rest/sleep posture and suppression of tactile/oral exploration were insensitive to βCCT administration. These data suggest that α2/3-containing GABAA receptor subtypes unexpectedly may mediate a mild form of sedation (rest/sleep posture), whereas α1-containing GABAA receptors may play a role in moderate/deep sedation.
- Removal of pharmaceutically active compounds from synthetic and real aqueous mixtures and simultaneous disinfection by supported TiO2/UV-A, H2O2/UV-A, and TiO2/H2O2/UV-A processes. [Journal Article]
- ESEnviron Sci Pollut Res Int 2018 May 01
- Pharmaceutically active compounds are carried into aquatic bodies along with domestic sewage, industrial and agricultural wastewater discharges. Psychotropic drugs, which can be toxic to the biota, h...
Pharmaceutically active compounds are carried into aquatic bodies along with domestic sewage, industrial and agricultural wastewater discharges. Psychotropic drugs, which can be toxic to the biota, have been detected in natural waters in different parts of the world. Conventional water treatments, such as activated sludge, do not properly remove these recalcitrant substances, so the development of processes able to eliminate these compounds becomes very important. Advanced oxidation processes are considered clean technologies, capable of achieving high rates of organic compounds degradation, and can be an efficient alternative to conventional treatments. In this study, the degradation of alprazolam, clonazepam, diazepam, lorazepam, and carbamazepine was evaluated through TiO2/UV-A, H2O2/UV-A, and TiO2/H2O2/UV-A, using sunlight and artificial irradiation. While using TiO2 in suspension, best results were found at [TiO2] = 0.1 g L-1. H2O2/UV-A displayed better results under acidic conditions, achieving from 60 to 80% of removal. When WWTP was used, degradation decreased around 50% for both processes, TiO2/UV-A and H2O2/UV-A, indicating a strong matrix effect. The combination of both processes was shown to be an adequate approach, since removal increased up to 90%. H2O2/UV-A was used for disinfecting the aqueous matrices, while mineralization was obtained by TiO2-photocatalysis.
- Recognizing drug-facilitated crimes: Detection and quantification of benzodiazepines in beverages using fast liquid-liquid extraction with low temperature partitioning and paper spray mass spectrometry. [Journal Article]
- DTDrug Test Anal 2018 Apr 16
- A novel methodology using liquid-liquid extraction with low temperature partitioning (LLE-LTP) and paper spray mass spectrometry (PS-MS) was developed to identify and quantify benzodiazepines in beve...
A novel methodology using liquid-liquid extraction with low temperature partitioning (LLE-LTP) and paper spray mass spectrometry (PS-MS) was developed to identify and quantify benzodiazepines in beverages. Four types of alcoholic beverages usually consumed in parties and bars were spiked with 5 distinct benzodiazepines (diazepam, alprazolam, bromazepam, clonazepam, and cloxazolam) simulating a drug-facilitated crime occurrence. The direct PS-MS analysis of the spiked beverages revealed a remarkable matrix effect with an unclear detection of protonated benzodiazepines. However, by the application of the LLE-LTP using liquid nitrogen, a prompt and doubtless detection of such compounds was achieved. The quantification potential of the LLE-LTP/PS-MS methodology was demonstrated by using beer as matrix, diazepam as target analyte and cloxazolam as an internal standard. Figures of merit (linearity, limit of detection, linear dynamic range, relative standard deviation, and recovery) were determined and adequate values were obtained. In conclusion, we demonstrated herein that the LLE-LTP/PS-MS methodology has potential to be applied directly at the crime scene through of a portable mass spectrometer and a thermal container for the transport of liquid nitrogen.
- Carfentanil in Impaired Driving Cases and the Importance of Drug Seizure Data. [Journal Article]
- JAJ Anal Toxicol 2018 Apr 12
- Drug seizures containing carfentanil continue to increase in Palm Beach County, FL, USA despite international efforts to control the distribution of the drug. The analysis of drug seizures from the c...
Drug seizures containing carfentanil continue to increase in Palm Beach County, FL, USA despite international efforts to control the distribution of the drug. The analysis of drug seizures from the county in 2016 and 2017 demonstrated that carfentanil was the most commonly identified fentanyl analog and was most often detected in combination with heroin, fentanyl, furanyl fentanyl and/or other fentanyl analogs. Carfentanil is an ultra-potent opioid requiring a method with adequate sensitivity for detection in blood specimens from impairment cases. Previous research indicated that carfentanil could not be identified in biological specimens by routine drug testing protocols and that detection requires targeted analysis with greater sensitivity. Due to the prevalence of carfentanil in drug seizures, a sensitive targeted qualitative method by liquid chromatography tandem mass spectrometry in antemortem blood samples was evaluated, validated and implemented. The method included identification of carfentanil, acetyl fentanyl, beta-hydroxythiofentanyl, butyryl fentanyl, fentanyl, furanyl fentanyl, kavain, mitragynine, MT-45 and U-47700. In 2017 carfentanil was the second most frequently detected drug, after ethanol, in driving under the influence blood cases. Of all blood cases in which drug testing was performed (n = 145), carfentanil was detected in 38% followed by alprazolam (29%), fentanyl (27%), delta-9-tetrahydrocannabinol (24%) and morphine (23%). In toxicology cases carfentanil was rarely identified alone (only four cases) and was most commonly identified with other opioids (73% of cases), benzodiazepines (43%) and stimulants (29%). The high incidence of carfentanil-positive cases detected by this method underscores the importance of continually monitoring regional drug seizure trends, and evaluating the adequacy of toxicology testing panels based on these trends.
- Decreasing Trend in the Use and Long-Term Use of Benzodiazepines Among Young Adults. [Journal Article]
- JCJ Child Adolesc Psychopharmacol 2018; 28(4):279-284
- Patterns of benzodiazepine (BZD) use and long-term use among young adults are not well known. Our aim was to study trends in BZD use and long-term use among 18-25-year-old young adults by gender and ...
Patterns of benzodiazepine (BZD) use and long-term use among young adults are not well known. Our aim was to study trends in BZD use and long-term use among 18-25-year-old young adults by gender and active substance in a nationwide retrospective longitudinal register-based setting.
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- Evaluating drugged driving: Effects of exemplar pain and anxiety medications. [Journal Article]
- TITraffic Inj Prev 2018 Feb 28; 19(sup1):S97-S103
- CONCLUSIONS: The findings suggest that impairing effects of this commonly prescribed combination of pharmacologic agents impact simulated driving performance. Negative changes in driving performance included measures of lateral and longitudinal control, although the deleterious effects on lateral control measures such as standard deviation of lane position (SDLP) were larger and more robust. Although the number of subjects was small, thus making it more difficult to draw conclusions on the narcotic effects, these results suggest that in this combination of central nervous system (CNS)-active drugs the benzodiazepine alprazolam accounted for the majority of impairing drug effects. The effect sizes associated with the hydrocodone preparation ranged from very small to medium. These results have potential implications for prescribing physicians and dispensing pharmacists, traffic safety experts, law enforcement officers, and patients themselves.