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The Canadian Veterinary Journal = La... Jan 2022The objective of this study was to compare effects of butorphanol (BUT) or buprenorphine (BUP), in combination with detomidine and diazepam, on the sedation quality,...
The objective of this study was to compare effects of butorphanol (BUT) or buprenorphine (BUP), in combination with detomidine and diazepam, on the sedation quality, surgical conditions, and postoperative pain control after cheek tooth extraction in horses, randomly allocated to 2 treatment groups (BUT: = 20; BUP: = 20). A bolus of detomidine (15 μg/kg, IV) was followed by either BUP (7.5 μg/kg, IV) or BUT (0.05 mg/kg, IV). After 20 min, diazepam (0.01 mg/kg, IV) was administered and sedation was maintained with a detomidine IV infusion (20 μg/kg/h), with rate adjusted based on scores to 5 variables. All horses received a nerve block (maxillary or mandibular), and gingival infiltration with mepivacaine. Sedation quality was assessed by the surgeon from 1 (excellent) to 10 (surgery not feasible). A pain scoring system (EQUUS-FAP) was used to assess postoperative pain. Serum cortisol concentrations and locomotor activity (pedometers) were measured. Horses in BUP and BUT required a median detomidine infusion rate of 30.2 μg/kg/h (20 to 74.4 μg/kg/h) and 32.2 μg/kg/h (20 to 48.1 μg/kg/h), respectively ( = 0.22). Horses in the BUP group had better sedation quality ( < 0.05) during surgery and higher step counts ( < 0.001) postoperatively. Buprenorphine combined with detomidine provided a more reliable sedation than butorphanol. However, the EQUUS-FAP pain scale became unreliable because of BUP-induced excitement behavior.
Topics: Animals; Buprenorphine; Butorphanol; Cheek; Diazepam; Horse Diseases; Horses; Hypnotics and Sedatives; Imidazoles; Pain, Postoperative; Tooth Extraction
PubMed: 34975166
DOI: No ID Found -
British Medical Journal Feb 1969
Topics: Diazepam; Epilepsy, Tonic-Clonic; Humans; Injections, Intravenous
PubMed: 4974299
DOI: 10.1136/bmj.1.5641.440-a -
Protein & Cell Feb 2017
Topics: Analgesics, Opioid; Animals; Cattle; Diazepam; Diazepam Binding Inhibitor; Dose-Response Relationship, Drug; Mice; Morphine; Receptors, GABA-A; Swine
PubMed: 28032250
DOI: 10.1007/s13238-016-0355-5 -
The Cochrane Database of Systematic... May 2022Developments in ultrasound assessment of pregnancy has resulted in the increasing diagnosis of antenatal fetal issues. Many structural fetal conditions as well as... (Review)
Review
BACKGROUND
Developments in ultrasound assessment of pregnancy has resulted in the increasing diagnosis of antenatal fetal issues. Many structural fetal conditions as well as complications associated with multiple pregnancies have the potential for in-utero treatment to improve both pregnancy and neonatal outcomes. Procedures such as laser ablation for twin-twin syndrome or cord occlusion for selective fetal termination require fetal immobilisation. Immobilisation of the fetus can occur through administration of medication to the mother or directly to the fetus. This improves procedural success and reduces the ongoing risk to the pregnancy. Evidence regarding the best medication and mode of delivery helps to ensure the optimal decision is made for both the mother and the fetus.
OBJECTIVES
To assess the effects of perioperative pharmacological interventions for fetal immobilisation during fetal surgery and invasive procedures on fetal, neonatal, and maternal outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 May 2021), and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) which compared different classes of medication administered to the mother or fetus to allow in-utero procedures to be performed. We also included cluster-randomised trials but excluded cross-over trials.
DATA COLLECTION AND ANALYSIS
We used the standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy.
MAIN RESULTS
One study with three trial reports met the inclusion criteria. This involved 54 women with a multiple pregnancy. The study was conducted in a tertiary European hospital maternal-fetal medicine unit and compared remifentanil to diazepam for fetal immobilisation and maternal sedation during fetoscopic surgery. Low-certainty evidence suggested that remifentanil may reduce fetal movement more than diazepam for two outcomes of fetal movement, one of fetal immobilisation at 40 minutes using a visual analogue score (VAS) (where 0 = immobile and 100 = baseline mobility), and one of gross body and limb movements (score was absolute number of movements), both assessed by a sonographer evaluating a taped ultrasound sequence (mean difference (MD) -65.00, 95% confidence interval (CI) -69.38 to -60.62 and MD -10.00, 95% CI -11.62 to -8.38; 1 study, 50 women). Surgeons may also report being more satisfied with the procedure when using remifentanil rather than diazepam (risk ratio (RR) 2.88, 95% CI 1.60 to 5.15; 1 study, 50 women; low-certainty evidence). However, maternal respiratory rate may decrease more during the surgical procedure with remifentanil compared with diazepam (MD -6.00, 95% CI -8.29 to -3.71; 1 study, 50 women; low-certainty evidence). Maternal sedation may also be worse with remifentanil compared with diazepam (RR 0.09, 95% CI 0.01 to 0.65; 1 study, 50 women; low-certainty evidence) measured using an observer assessment of alertness/sedation (where a score of < 4 equates to profound sedation and > 4 equates to insufficient sedation). Perinatal mortality and time taken to perform the procedure were not reported in the trial. We prespecified 20 outcomes and planned to use GRADE for 6 of them, all other outcomes were not able to be reported against for the purpose of meta-analysis due to data not being provided or unable to be interpreted. We assessed the included study at low risk of selection bias (appropriate random sequence generation and allocation concealment), performance bias (blinding of participants and personnel), detection bias (outcome assessors were blinded), attrition bias (incomplete outcome data minimal), and reporting bias. Our GRADE assessment for certainty of the evidence indicates that there is low certainty of the evidence.
AUTHORS' CONCLUSIONS
We were only able to include one study with a small number of women, from a single centre, a European tertiary hospital. This study was published in 2005 with an abstract of this trial published in 2004. This study evaluated two intravenous medications administered to the mother - remifentanil and diazepam. This study reported our prespecified primary outcome but only evaluated several of our secondary outcomes, which limited further assessment. Low-certainty evidence suggested that remifentanil may be better at reducing fetal movements and surgeons were more satisfied with the procedure. However, maternal sedation and depression of breathing may be worse with remifentanil. Further high-quality RCTs assessing both fetal and maternal medications are required to evaluate their efficacy for fetal immobilisation as well as safety for both mother and fetus.
Topics: Diazepam; Female; Fetus; Humans; Infant, Newborn; Perinatal Mortality; Pregnancy; Prenatal Care; Remifentanil
PubMed: 35553414
DOI: 10.1002/14651858.CD011068.pub2 -
Journal of the Association For Research... Oct 2021Management of vestibular dysfunction may include treatment with medications that are thought to act to suppress vestibular function and reduce or eliminate abnormal...
Management of vestibular dysfunction may include treatment with medications that are thought to act to suppress vestibular function and reduce or eliminate abnormal sensitivity to head motions. The extent to which vestibular medications act centrally or peripherally is still debated. In this study, two commonly prescribed medications, meclizine and diazepam, and a candidate for future clinical use, JNJ7777120, were evaluated for their effects on short latency compound action potentials generated by the peripheral vestibular system and corresponding central neural relays (i.e., vestibular sensory-evoked potentials, VsEPs). The effects of the selected drugs developed slowly over the course of two hours in the mouse. Findings indicate that meclizine (600 mg/kg) and diazepam (> 60 mg/kg) can act on peripheral elements of the vestibular maculae whereas diazepam also acts most effectively on central gravity receptor circuits to exert its suppressive effects. The novel pharmacological agent JNJ7777120 (160 mg/kg) acts in the vestibular periphery to enhance macular responses to transient stimuli (VsEPs) while, hypothetically, suppressing macular responses to sustained or slowly changing stimuli.
Topics: Animals; Diazepam; Indoles; Meclizine; Mice; Piperazines; Vestibular System; Vestibule, Labyrinth
PubMed: 34009490
DOI: 10.1007/s10162-021-00803-5 -
Anesthesiology Dec 1980The purpose of this study was to examine the respiratory depression produced by diazepam and by midazolam. Ventilatory and mouth occlusion pressure responses to CO2 were...
The purpose of this study was to examine the respiratory depression produced by diazepam and by midazolam. Ventilatory and mouth occlusion pressure responses to CO2 were measured in eight healthy volunteers before and after the intravenous administration of 0.3 mg/kg of diazepam and 0.15 mg/kg of midazolam. The mean ventilatory response to CO2 (mean +/- SEM) decreased after administration of diazepam or midazolam from 2.0 +/- 0.2 to 1.3 +/- 0.1 1.min-1/torr or from 2.1 +/- 0.2 to 1.4 +/- 0.1 1.min-1/torr, respectively. In the same volunteers, the mouth occlusion pressure responses decreased from 0.54 +/- 0.05 to 0.30 +/- 0.04 cm H2O/torr after midazolam and from 0.67 +/- 0.12 to 0.28 +/- 0.07 cm H2O/torr after diazepam. When compared with the control slopes of the ventilatory and mouth occlusion pressure responses, the drug slopes were significantly different. Respiration was similarly depressed after diazepam and after midazolam. That both the ventilatory and mouth occlusion pressure responses to CO2 are equally depressed by intravenous injections of midazolam and of diazepam at equipotent doses suggests a direct depression of the central respiratory drive by these drugs.
Topics: Adult; Airway Obstruction; Benzodiazepines; Diazepam; Female; Humans; Male; Midazolam; Phlebitis; Respiration
PubMed: 7457966
DOI: 10.1097/00000542-198012000-00010 -
British Journal of Clinical Pharmacology Nov 2001To evaluate the electroencephalographic (EEG) effects, blood concentrations, vehicle irritation and dose-effect relationships for diazepam administered nasally. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
AIMS
To evaluate the electroencephalographic (EEG) effects, blood concentrations, vehicle irritation and dose-effect relationships for diazepam administered nasally.
METHODS
The study had a cross-over design with eight healthy volunteers (one drop out). It consisted of four legs with four different administrations: intranasal (i.n.) placebo, 4 mg diazepam i.n., 7 mg diazepam i.n. and 5 mg intravenous (i.v.) diazepam. Polyethylene glycol 300 (PEG300) was used as a vehicle in the nasal formulations to solubilize a clinically relevant dose of diazepam. Changes in N100, P200 and P300 brain event-related potentials (ERP) elicited by auditory stimulation and electroencephalographic beta-activity were used to assess effects on neurological activity.
RESULTS
The mean [95% confidence intervals] differences between before and after drug administration values of P300-N100 amplitude differences were -0.9 [-6.5, 4.7], -6.4 [-10.1, -2,7], -8.6 [-11.4, -5.8] and -9.6 [-12.1, -7.1] for placebo, 4 mg i.n., 7 mg i.n. and 5 mg i.v. diazepam, respectively, indicating statistically significant drug induced effects. The bioavailabilities of 4 and 7 mg i.n. formulations, were found to be similar, 45% [32, 58] and 42% [22, 62], respectively.
CONCLUSION
The present study indicates that it is possible to deliver a clinically effective nasal dose of diazepam for the acute treatment of epilepsy, using PEG300 as a solubilizer.
Topics: Administration, Intranasal; Adult; Anticonvulsants; Area Under Curve; Biological Availability; Cross-Over Studies; Diazepam; Double-Blind Method; Electroencephalography; Female; Humans; Injections, Intravenous; Male; Polyethylene Glycols
PubMed: 11736860
DOI: 10.1046/j.0306-5251.2001.01486.x -
Molecules (Basel, Switzerland) Apr 2015In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid... (Comparative Study)
Comparative Study
Simultaneous Quantification of Diazepam and Dexamethasone in Plasma by High-Performance Liquid Chromatography with Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Comparison between Normoxic and Hypoxic Rats.
In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of diazepam and dexamethasone in rat plasma was developed and validated. The chromatographic separation of analytes was successfully achieved on an XTerra® MS C18 column using a gradient elution of methanol and water containing 0.1% formic acid at a flow rate of 0.5 mL/min. This method demonstrated good linearity and no endogenous material interferences. The linear ranges were 1.0-100 ng/mL for diazepam and 2.0-200 ng/mL for dexamethasone. The intra- and inter-day precision for the two compounds in plasma were lower than 10.0%, and the accuracy was between -7.9% and 11.5%. Our method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of diazepam and dexamethasone between normoxic and hypoxic rats. The results provide the important and valuable information for discovering and developing novel anti-hypoxia drug combinations, as well as a better understanding of the safety and efficacy of these drugs.
Topics: Animals; Chromatography, High Pressure Liquid; Dexamethasone; Diazepam; Drug Therapy, Combination; Hypoxia; Male; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry
PubMed: 25913929
DOI: 10.3390/molecules20046901 -
Epilepsia Open Apr 2024Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It...
Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]). Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Data from a phase 3 safety study were used to determine the proportion of second doses used within 24 h (ie, a proxy for effectiveness) and SEIVAL. Adverse events were recorded. Of 163 treated patients, 89 were female, and 74 were male. Approximately 16% of both sexes self-administered the study drug. A slightly higher proportion of seizure clusters was treated with a second dose in female (14.7%) than male (9.4%) patients. SEIVAL increased significantly and substantially over a year for all patients. The safety profile was generally similar between the sexes. These results suggest that potential sex differences in benzodiazepine pharmacokinetics do not meaningfully influence outcomes associated with diazepam nasal spray. PLAIN LANGUAGE SUMMARY: Some drugs may have differences in absorption and metabolism between genders that could translate into differences in safety and effectiveness. This safety study looked at diazepam nasal spray for treating seizure clusters in patients at least 6 years old. It found that safety was about the same for females and males. For both groups, most clusters stopped after only 1 dose of the drug, and the time between treated clusters got longer over a year.
Topics: Humans; Female; Male; Child; Nasal Sprays; Anticonvulsants; Diazepam; Benzodiazepines; Seizures
PubMed: 38340025
DOI: 10.1002/epi4.12907 -
Epilepsia Oct 2014To determine the feasibility of administering a diazepam nasal spray formulation (diazepam-NS) to adults with epilepsy during a generalized tonic-clonic seizure or in... (Clinical Trial)
Clinical Trial
OBJECTIVE
To determine the feasibility of administering a diazepam nasal spray formulation (diazepam-NS) to adults with epilepsy during a generalized tonic-clonic seizure or in the postictal period following a tonic-clonic or other seizure type, to assess pharmacokinetics and to assess tolerability.
METHODS
An open-label study was conducted in patients admitted to the epilepsy monitoring unit. Eligible patients received a single dose of diazepam-NS approximating 0.2 mg/kg. Plasma diazepam concentrations were measured serially up to 12 h postdose, and maximum observed plasma concentration (Cmax ); time to maximum concentration (Tmax ); and the area under the plasma concentration-time curve for time zero to last sampling time (AUC0-12 ) were estimated and dose-normalized. Pharmacodynamic assessments included Kaplan-Meier analysis to determine the time-to-next seizure. Safety and tolerability were assessed.
RESULTS
Of the 78 patients who consented, 30 had treatment and pharmacokinetic data. Ten patients were treated during a convulsive tonic-clonic seizure, seven within 5 min following the last clonic jerk, and 13 in the postictal period ≥ 5 min after a tonic-clonic or following other seizure-types. Diazepam median Tmax was 45 min. Dose-normalized mean Cmax and AUC0-12 values of diazepam were comparable among patients regardless of the timing of diazepam-NS administration in relation to seizure. Of those treated, 65% were seizure-free during the 12-h observation period and 35% had post-dose seizures. Treatment was well tolerated, with no unexpected safety findings: 74% had mild and 25% had moderate adverse events. Nasopharyngeal signs were resolved by 12 h postdose.
SIGNIFICANCE
Diazepam can be delivered in effective therapeutic concentrations by a nasal spray device during the convulsive phase of tonic-clonic seizures or in the postictal periods following tonic-clonic or other seizure types.
Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anticonvulsants; Diazepam; Epilepsy, Tonic-Clonic; Feasibility Studies; Female; Humans; Male; Middle Aged; Treatment Outcome; Young Adult
PubMed: 25154625
DOI: 10.1111/epi.12755