A Comparison of Moderate Oral Sedation Drug Regimens for Pediatric Dental Treatment: A Pilot Study

Purpose: Compare moderate oral sedation of pediatric patients using Hydroxyzine and Meperidine with either Diazepam or Midazolam in management of pediatric dental patients. Methods: Randomized, double-blind, crossover pilot study of patients 3 to 7 years of age requiring two sedation visits. Frankl and Houpt behavior scores recorded at injection time, initiation of treatment and 100% oxygen at end of treatment. Postoperative phone call surveys conducted within eight hours and within 24 hours of discharge. Wilcoxon Signed-Rank tests, Fisher’s Exact Chi-squared test and 0.10 significance level. Results: 25 subjects completed 35 sedations. Eight participants completed both treatments and demonstrated significantly higher total Houpt Scores with Diazepam at all treatment stages. Frankl scores favored Diazepam at injection time. More abnormal behavior was found with Midazolam, less memory of the visit with Diazepam, but longer sleep time with Diazepam. Conclusions: Sedation with the Hydroxyzine, Meperidine and Diazepam regimen may allow for a better overall sedation experience. Postoperative monitoring is essential. The results are promising and demonstrate the value of a larger study on sedation with Diazepam

Comparison of Triple Combination Oral Sedation Regimens for Pediatric Dental Treatment

Purpose: Compare the efficacy of two benzodiazepines (diazepam or midazolam) in combination with meperidine and hydroxyzine for pediatric dental sedation. Methods: A randomized, double blind observation study of behaviors and outcomes related to two sedation groups. Frankl and Houpt behavior scores were recorded at three time points: injection time, initiation of treatment and at the end of treatment. Postoperative phone call surveys were conducted within eight hours of discharge to assess sleep, activity, and behavior. Results: A total of 40 sedation subjects were included in the study, of which 20 were treated with diazepam triple Combination (Di+M+H) and 20 with midazolam triple regime (Mi+M+H). Treatment was successful for 45% of cases with midazolam and 70% with diazepam (P value=.20). Houpt sleep scores were significantly higher for diazepam than midazolam at injection (P-value=.0043) and during treatment (P-value=.0152). Although Frankl scores, Houpt move and Houpt cry scores tended to favor diazepam, none were statistically significantly different. More abnormal behavior was reported with midazolam, though not statistically significant (35% vs 6%, P-value=.0854). Postoperative sleep time was longer for midazolam, but not significantly different (median sleep time: 61 vs 45 minutes, P-value=.2071). Conclusion: The diazepam, meperidine, hydroxyzine triple combination sedation regimen shows promising results as a successful alternative to midazolam triple combination. Longer postoperative monitoring may be required with diazepam, but this study has shown postoperative sleep times to be less than previously reported. Larger sample size is needed to determine if the current trend will be maintained

Formation of biologically active benzodiazepine metabolites in Arabidopsis thaliana cell cultures and vegetable plants under hydroponic conditions.

The use of recycled water for agricultural irrigation comes with the concern of exposure to crops by contaminants of emerging concerns (CECs). The concentration of CECs in plant tissues will depend on uptake, translocation and metabolism in plants. However, relatively little is known about plant metabolism of CECs, particularly under chronic exposure conditions. In this study, metabolism of the pharmaceutical diazepam was investigated in Arabidopsis thaliana cells and cucumber (Cucumis sativus) and radish (Raphanus sativus) seedlings grown in hydroponic solution following acute (7 d)/high concentration (1 mg L-1), and chronic (28 d)/low concentration (1 μg L-1) exposures. Liquid chromatography paired with mass spectrometry, 14C tracing, and enzyme extractions, were used to characterize the metabolic phases. The three major metabolites of diazepam - nordiazepam, temazepam and oxazepam - were detected as Phase I metabolites, with the longevity corresponding to that of human metabolism. Nordiazepam was the most prevalent metabolite at the end of the 5 d incubation in A. thaliana cells and 7 d, 28 d seedling cultivations. At the end of 7 d cultivation, non-extractable residues (Phase III) in radish and cucumber seedlings accounted for 14% and 33% of the added 14C-diazepam, respectively. By the end of 28 d incubation, the non-extractable radioactivity fraction further increased to 47% and 61%, indicating Phase III metabolism as an important destination for diazepam. Significant changes to glycosyltransferase activity were detected in both cucumber and radish seedlings exposed to diazepam. Findings of this study highlight the need to consider the formation of bioactive transformation intermediates and different phases of metabolism to achieve a comprehensive understanding of risks of CECs in agroecosystems

Diazepam, alcohol use and violence among male young offenders: 'the devil's mixture’

Citation for published version (APA): Forsyth, A., Khan, F., & McKinlay, W. (2011). Diazepam, alcohol use and violence among male young offenders: 'the devil's mixture’. Drugs: Education, Prevention and Policy, 18(6), 468-476. 10.3109/09687637.2011.563762 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the ResearchOnline@GCU portal Take down polic

Trends in long-term prescribing of dependence forming medicines

Using patient-level primary care data to estimate the extent to which antidepressant medicines are prescribed to people continuously for long periods of time. Aim This descriptive research used patient-level primary care data to estimate the extent to which antidepressant medicines are prescribed to people continuously for long periods of time. The study also drew on survey data and data on the number of prescriptions dispensed. Findings - The number of antidepressant prescriptions dispensed each year in England doubled between 2008 and 2018 - Survey data show that the proportion of adults reporting use of antidepressants in the past year increased in the 1990s, and again between 2007 and 2014 - The average length of time that antidepressants are continuously prescribed to people for has increased over time. - Some types of antidepressants (for example, tricyclics and other antidepressants) tend to be prescribed for longer periods than other types (such as SSRIs). - In 2014, one in twelve prescribing periods for tricyclics and other antidepressants lasted for three years or more Methods The analyses in this report are descriptive and show the overall prevalence of long-term prescribing in each year. We used a sample of around 50,000 patients prescribed at least one antidepressant medicine between 2000 and 2017. This was drawn from the Clinical Practice Research Datalink (CPRD). The CPRD contains data about prescriptions issued by GPs (including the length and size of prescription) and characteristics of the patients prescribed to (such as their age, sex, and area where they live). Medicines were grouped for analysis into: tricyclics, selective serotonin reuptake inhibitors (SSRIs), and other ADMs. The length of individual prescriptions and continuous prescribing periods were derived using information on consultation dates, the quantity of tablets prescribed, and the numeric daily dose

Tetramethylenedisulfotetramine alters Ca²⁺ dynamics in cultured hippocampal neurons: mitigation by NMDA receptor blockade and GABA(A) receptor-positive modulation.

Tetramethylenedisulfotetramine (TETS) is a potent convulsant that is considered a chemical threat agent. We characterized TETS as an activator of spontaneous Ca²⁺ oscillations and electrical burst discharges in mouse hippocampal neuronal cultures at 13-17 days in vitro using FLIPR Fluo-4 fluorescence measurements and extracellular microelectrode array recording. Acute exposure to TETS (≥ 2 µM) reversibly altered the pattern of spontaneous neuronal discharges, producing clustered burst firing and an overall increase in discharge frequency. TETS also dramatically affected Ca²⁺ dynamics causing an immediate but transient elevation of neuronal intracellular Ca²⁺ followed by decreased frequency of Ca²⁺ oscillations but greater peak amplitude. The effect on Ca²⁺ dynamics was similar to that elicited by picrotoxin and bicuculline, supporting the view that TETS acts by inhibiting type A gamma-aminobutyric acid (GABA(A)) receptor function. The effect of TETS on Ca²⁺ dynamics requires activation of N-methyl-D-aspartic acid (NMDA) receptors, because the changes induced by TETS were prevented by MK-801 block of NMDA receptors, but not nifedipine block of L-type Ca²⁺ channels. Pretreatment with the GABA(A) receptor-positive modulators diazepam and allopregnanolone partially mitigated TETS-induced changes in Ca²⁺ dynamics. Moreover, low, minimally effective concentrations of diazepam (0.1 µM) and allopregnanolone (0.1 µM), when administered together, were highly effective in suppressing TETS-induced alterations in Ca²⁺ dynamics, suggesting that the combination of positive modulators of synaptic and extrasynaptic GABA(A) receptors may have therapeutic potential. These rapid throughput in vitro assays may assist in the identification of single agents or combinations that have utility in the treatment of TETS intoxication

Manual control analysis of drug effects on driving performance

The effects of secobarbital, diazepam, alcohol, and marihuana on car-driver transfer functions obtained using a driving simulator were studied. The first three substances, all CNS depressants, reduced gain, crossover frequency, and coherence which resulted in poorer tracking performance. Marihuana also impaired tracking performance but the only effect on the transfer function parameters was to reduce coherence

Examining the patient and caregiver experience with diazepam nasal spray for seizure clusters: Results from an exit survey of a phase 3, open-label, repeat-dose safety study

BACKGROUND: Ideal rescue treatments for acute treatment of seizure clusters should be easy to administer, so it is important to assess user perceptions of these treatments. Diazepam nasal spray is designed to have a rapid, noninvasive, and socially acceptable route of administration. Patient and caregiver (including care partner) responses to surveys from a phase 3 safety study of diazepam nasal spray are reported. METHODS: The study enrolled patients aged 6-65 years with seizure clusters. Surveys distributed to patients and caregivers at study end, completion, or discontinuation collected data on comfort using diazepam nasal spray outside the home, timing of administration and return to their usual selves, and comfort of use compared with rectal diazepam. Safety was assessed. RESULTS: Of 175 patients enrolled at the October 31, 2019, interim cutoff, 158 received diazepam nasal spray. Sixty-seven (42.4%) patients and 84 (53.2%) caregivers responded to the surveys (including 35 matched pairs). Most patients (78.8%, 52/66) responded that they were very comfortable doing activities outside the home with diazepam nasal spray available; 59.4% of patients returned to their usual selves within an hour of administration. Twenty-seven (40.3%) of these patients reported self-administration, 48% doing so at the first sign of a seizure. Administration of diazepam nasal spray was rated extremely or very easy by 93.8% of caregivers. Safety profile was consistent with diazepam rectal gel; no patient discontinued owing to treatment-emergent adverse events. Nasal discomfort was typically mild and transient. Among patients who had used diazepam rectal gel, most were not at all comfortable using it outside the home (86.7%) or at home (64.5%) compared with diazepam nasal spray, whereas caregivers reported that diazepam rectal gel was not at all easy to use compared with diazepam nasal spray. CONCLUSIONS: This survey from the phase 3 safety study of diazepam nasal spray shows that patients and caregivers were satisfied with, and more comfortable using, diazepam nasal spray than rectal diazepam in public. NCT02721069