Administration Of Diazepam Research Articles

The Haematotoxicity and Nephrotoxicity Effects of Diazepam Administration in Male Albino Rats

Objectives: This study aimed to assess the haematological and nephrotoxic effects of diazepam at varying doses in male albino rats. Materials and Methods: Rats were administered therapeutic (0.062 mg/kg/day), high (0.33 mg/kg/day), and extremely high (0.661 mg/kg/day) doses of diazepam orally for 14 and 28 days. Blood and kidney samples were collected for haematological and biochemical analysis.Results: Diazepam administration significantly reduced red blood cell count (RBC), packed cell volume (PCV), and platelet count (PLT), while other haematological indices were not notably affected. Plasma creatinine and urea levels increased, and total protein decreased across all doses. The treatment also elevated renal thiobarbituric acid reactive substances (TBARS) levels, while reducing antioxidant enzyme activity superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Conclusions: Diazepam poses significant risks of oxidative stress, haematotoxicity, and nephrotoxicity. While effective in managing anxiety, caution is necessary due to its potentially harmful effects on blood and renal function.

Stimulation of central histaminergic transmission attenuates diazepam-induced motor disturbance on rota-rod and beam walking tests in mice.

Diazepam administration has been shown to influence the release of histamine in various brain areas involved in motor behavior. Therefore, the present study explored the plausible regulatory role of the central histaminergic system in diazepam-induced deficits in motor performance in mice using the rota-rod and beam walking tests. In this study, several doses of diazepam (0.5, 1, 2, and 3 mg/kg, i.p.) were assessed in mice for changes in motor performance on the rota-rod and beam walking test. In addition, the brain histamine levels were determined after diazepam administration, and the diazepam-induced motor deficits were assessed in mice, pretreated centrally (intracerebroventricular) with histaminergic agents such as histamine (0.1, 10 µg), histamine precursor (L-histidine: 0.1, 2.5 µg), histamine neuronal releaser/H 3 receptor antagonist (thioperamide: 0.5, 10 µg), H 1 and H 2 receptor agonist [2-(3-trifluoromethylphenyl) histamine (FMPH: 0.1, 6.5 µg; amthamine: 0.1, 5 µg)/antagonist (H 1 : cetirizine 0.1 µg) and (H 2 : ranitidine: 50 µg)]. Results indicate that mice treated with diazepam at doses 1, 2 mg/kg, i.p. significantly increased the brain histamine levels. Moreover, in mice pretreated with histaminergic transmission-enhancing agents, the diazepam (2 mg/kg, i.p.)-induced motor incoordination was significantly reversed. Contrastingly, diazepam (1 mg/kg, i.p.) in its subeffective dose produced significant motor deficits in mice preintracerebroventricular injected with histamine H 1 and H 2 receptor antagonists on both the employed tests. Therefore, it is postulated that endogenous histamine operates via H 1 and H 2 receptor activation to alleviate the motor-impairing effects of diazepam.

The efficacy of diazepam administration during embryo transfer: a retrospective multicenter cohort study on reproductive outcomes.

This retrospective multicenter cohort study aimed to investigate the impact of diazepam administration during embryo transfer on reproductive outcomes, focusing primarily on the live birth rate. Secondary outcomes included the positive beta-hCG rate, clinical pregnancy rate, miscarriage rate, ectopic pregnancy rate, and preterm birth rate. Data from 5607 embryo transfers, encompassing 465 cases with diazepam administration, were retrospectively analyzed. The study included single blastocyst transfers from 12 clinics in Portugal and Spain between January 2015 and December 2022. Comparison of reproductive outcomes between patients receiving diazepam and those who did not showed no statistically significant differences. Positive beta-hCG rates (60.8% non-diazepam vs. 60.4% diazepam, p = 0.92, adjusted p = 0.32) and clinical pregnancy rates (45.6% non-diazepam vs. 46.2% diazepam, p = 0.81, adjusted p = 0.11) were comparable. Miscarriage rates (11.0% diazepam vs. 9.3% non-diazepam, p = 0.25, adjusted p = 0.26) and ectopic pregnancy rates (0.9% diazepam vs. 0.1% non-diazepam, p = 0.1, adjusted p = 0.20) were similar. Live birth rates (36.3% non-diazepam vs. 35.3% diazepam, p = 0.69, adjusted p = 0.82) and prematurity rates (0.3% non-diazepam vs. 0% diazepam, p > 0.99, adjusted p = 0.99) also exhibited no statistically significant differences. Based on the results, diazepam administration during embryo transfer did not show a discernible impact on reproductive outcomes, including live birth rates, suggesting its limited effectiveness in enhancing success.

Unveiling the Dark Side of Datura in Pediatric Poisoning With Insights From Jordanian Experience : A Retrospective Clinical Study.

Datura stramonium , jimsonweed, is a toxic plant with hallucinogenic properties. Although there are many studies on Datura poisoning, none reported cases in Jordan. This study offers a comprehensive review on D. stramonium ingestion, covering its epidemiology, clinical presentation, and treatment. We aimed to provide better understanding of the factors for Datura ingestion, identify prevention and management strategies, and address research challenges. This study adopted a retrospective review design to evaluate the cases of Datura poisoning in Al Karak, province of Jordan during the spring of 2022. Data collected from medical records, toxicology databases, and consultation records were analyzed using descriptive statistics. The common symptoms of Datura poisoning included agitation, mydriasis, and tachycardia. The management approaches comprised supportive care, administration of Diazepam for agitation, and, in some cases, neostigmine to counteract anticholinergic effects. Understanding the risks associated with D. stramonium poisoning and implementing effective prevention and management strategies are crucial. This study highlights the importance of recognizing Datura poisoning as a potential diagnosis in children presenting with unexplained anticholinergic symptoms or agitation to the emergency room.

Effects of diazepam on hippocampal blood flow in people at clinical high risk for psychosis

Elevated hippocampal perfusion has been observed in people at clinical high risk for psychosis (CHR-P). Preclinical evidence suggests that hippocampal hyperactivity is central to the pathophysiology of psychosis, and that peripubertal treatment with diazepam can prevent the development of psychosis-relevant phenotypes. The present experimental medicine study examined whether diazepam can normalize hippocampal perfusion in CHR-P individuals. Using a randomized, double-blind, placebo-controlled, crossover design, 24 CHR-P individuals were assessed with magnetic resonance imaging (MRI) on two occasions, once following a single oral dose of diazepam (5 mg) and once following placebo. Regional cerebral blood flow (rCBF) was measured using 3D pseudo-continuous arterial spin labeling and sampled in native space using participant-specific hippocampus and subfield masks (CA1, subiculum, CA4/dentate gyrus). Twenty-two healthy controls (HC) were scanned using the same MRI acquisition sequence, but without administration of diazepam or placebo. Mixed-design ANCOVAs and linear mixed-effects models were used to examine the effects of group (CHR-P placebo/diazepam vs. HC) and condition (CHR-P diazepam vs. placebo) on rCBF in the hippocampus as a whole and by subfield. Under the placebo condition, CHR-P individuals (mean [±SD] age: 24.1 [±4.8] years, 15 F) showed significantly elevated rCBF compared to HC (mean [±SD] age: 26.5 [±5.1] years, 11 F) in the hippocampus (F(1,41) = 24.7, pFDR < 0.001) and across its subfields (all pFDR < 0.001). Following diazepam, rCBF in the hippocampus (and subfields, all pFDR < 0.001) was significantly reduced (t(69) = −5.1, pFDR < 0.001) and normalized to HC levels (F(1,41) = 0.4, pFDR = 0.204). In conclusion, diazepam normalized hippocampal hyperperfusion in CHR-P individuals, consistent with evidence implicating medial temporal GABAergic dysfunction in increased vulnerability for psychosis.

Value and Limitations of Urethrotech Catheterisation Device to Manage Difficult Urethral Catheterisation in Male Spinal Cord Injury Patients.

We used a Urethrotech catheterisation device in 57 male patients with spinal cord injury, in whom urethral catheterisation was unsuccessful or previous catheterisation was difficult. Urethrotech catheter could be inserted in 51 patients. No patient developed urinary tract infection. In one patient, the guidewire could not be introduced into the bladder, and a coude Foley catheter was inserted. In two patients, the guidewire was inserted into the bladder, but a 16 CH catheter could not be advanced over the guidewire. Emergency suprapubic cystostomy was performed in one case; in the other, urethral stricture was dilated; a size 12 CH catheter was inserted. In three patients, the guidewire curled back into the urethra because of severe spasm of the urethral sphincter. Catheterisation with a Tiemann catheter was successful after administration of diazepam and/or stretching of the anal sphincter by another health professional, which caused reflex relaxation of the urethral sphincter. Complications of Urethrotech catheterisation included urethral bleeding, haematuria, pain, doubling back of the guidewire due to spasm of the urethral sphincter or from an empty bladder.We adopted variations in technique, eg filling the bladder with saline prior to catheterisation when feasible, insertion of the guidewire by the side of the old catheter, use of Tiemann tip catheters, administration of antibiotics, diazepam to control spasms, nifedipine to control autonomic dysreflexia, analgesics, stretching of the anal sphincter to induce reflex relaxation of the urethral sphincter, urgent imaging studies to confirm correct positioning of the catheter, omitting anticoagulants and monitoring patients, who developed bleeding. Use of Urethrotech in spinal injury patients warranted adaptations to the technique, which required expertise, experience, and backup facilities. To ensure patient safety, Urethrotech catheter should be used in a hospital setting, and by medical personnel with experience in the management of spinal cord injury patients.

Rapid Rescue Treatment with Diazepam Nasal Spray Leads to Faster Seizure Cluster Termination in Epilepsy: An Exploratory Post Hoc Cohort Analysis.

Although prompt treatment of status epilepticus is standard of care, the effect of timing of rescue therapy administration for seizure clusters in epilepsy remains unknown. Seizure clusters are a rare but clinically important condition, and benzodiazepines are the cornerstone rescue therapy for seizure clusters in epilepsy. We characterized temporal patterns from a large dataset of treated seizure clusters in the safety study of diazepam nasal spray. This post hoc analysis used timing data of treated seizure clusters recorded by care partners and patients in seizure diaries during a 1-year safety study. Data analysis used time from seizure start to administration of diazepam. From 4466 observations, 3225 had data meeting criteria for analysis. Overall, median times from seizure start to dose administration, dose administration to seizure termination, and total seizure duration were 2, 3, and 7min, respectively. In seizure clusters treated in < 5min (median 1.0min), median time from dose to seizure termination was 2.0min, and median total seizure duration was 4.0min. Among seizure clusters treated in ≥ 5min (median 10.0min), median time to seizure termination was 10.0min, and median total seizure duration was 23.0min. Previously published safety results reported that over a mean participation of 1.5years, 82.2% of patients had ≥ 1 treatment-emergent adverse events (TEAEs) irrespective of relationship to treatment, including 30.7% with serious TEAEs; 18.4% had TEAEs deemed at least possibly related to the study drug, none of which were serious. There were no events of cardiorespiratory depression. Echoing the importance of early use of benzodiazepines in status epilepticus, the findings from this exploratory analysis of patients with refractory epilepsy and frequent seizure clusters identify a potential benefit of early diazepam nasal spray treatment leading to faster seizure resolution within the seizure cluster. Trial Registration Information: ClinicalTrials.gov identifier NCT02721069 ( https://clinicaltrials.gov/ct2/show/NCT02721069 ).

Brain PET imaging using 11C-flumazenil and 11C-buprenorphine does not support the hypothesis of a mutual interaction between buprenorphine and benzodiazepines at the neuroreceptor level

Among opioids, buprenorphine presents a favorable safety profile with a limited risk of respiratory depression. However, fatalities have been reported when buprenorphine is combined to a benzodiazepine. Potentiation of buprenorphine interaction with opioid receptors (ORs) with benzodiazepines, and/or vice versa, is hypothesized to explain this drug-drug interaction (DDI). The mutual DDI between buprenorphine and benzodiazepines was investigated at the neuroreceptor level in nonhuman primates (n = 4 individuals) using brain PET imaging and kinetic modelling. The binding potential (BPND) of benzodiazepine receptor (BzR) was assessed using 11C-flumazenil PET imaging before and after administration of buprenorphine (0.2 mg, i.v.). Moreover, the brain kinetics and receptor binding of buprenorphine were investigated in the same individuals using 11C-buprenorphine PET imaging before and after administration of diazepam (10 mg, i.v.). Outcome parameters were compared using a two-way ANOVA. Buprenorphine did not impact the plasma nor brain kinetics of 11C-flumazenil. 11C-flumazenil BPND was unchanged following buprenorphine exposure, in any brain region (p > 0.05). Similarly, diazepam did not impact the plasma or brain kinetics of 11C-buprenorphine. 11C-buprenorphine volume of distribution (VT) was unchanged following diazepam exposure, in any brain region (p > 0.05). To conclude, our PET imaging findings do not support a neuropharmacokinetic or neuroreceptor-related mechanism of the buprenorphine/benzodiazepine interaction.

Protracted respiratory failure in a case of global spinal syringomyelia and Chiari malformation following administration of diazepam: illustrative case.

Syringomyelia is defined as dilation of the spinal cord's central canal and is often precipitated by skull base herniation disorders. Although respiratory failure (RF) can be associated with skull base abnormalities due to brainstem compression, most cases occur in pediatric patients and quickly resolve. The authors report the case of an adult patient with global spinal syringomyelia and Chiari malformation who developed refractory RF after routine administration of diazepam. A 31-year-old female presented with malnutrition, a 1-month history of right-sided weakness, and normal respiratory dynamics. After administration of diazepam prior to magnetic resonance imaging (MRI), she suddenly developed hypercapnic RF followed MRI and required intubation. MRI disclosed a Chiari malformation type I and syrinx extending from C1 to the conus medullaris. After decompressive surgery, her respiratory function progressively returned to baseline status, although 22 months after initial benzodiazepine administration, the patient continues to require nocturnal ventilation. Administration of central nervous system depressants should be closely monitored in patients with extensive syrinx formation given the potential to exacerbate diminished central respiratory drive. Early identification of syrinx in the context of Chiari malformation and hemiplegia should prompt clinical suspicion of underlying respiratory compromise and early involvement of intensive care consultants.

Effects of N-acetylcysteine and acetyl-L-carnitine on acute PTZ-induced seizures in larval and adult zebrafish.

Epilepsy is a prevalent neurological disease, affecting approximately 1-2% of the global population. The hallmark of epilepsy is the occurrence of epileptic seizures, which are characterized by predictable behavioral changes reflecting the underlying neural mechanisms of the disease. Unfortunately, around 30% of patients do not respond to current pharmacological treatments. Consequently, exploring alternative therapeutic options for managing this condition is crucial. Two potential candidates for attenuating seizures are N-acetylcysteine (NAC) and Acetyl-L-carnitine (ALC), as they have shown promising neuroprotective effects through the modulation of glutamatergic neurotransmission. This study aimed to assess the effects of varying concentrations (0.1, 1.0, and 10mg/L) of NAC and ALC on acute PTZ-induced seizures in zebrafish in both adult and larval stages. The evaluation of behavioral parameters such as seizure intensity and latency to the crisis can provide insights into the efficacy of these substances. Our results indicate that both drugs at any of the tested concentrations were not able to reduce PTZ-induced epileptic seizures. On the other hand, the administration of diazepam demonstrated a notable reduction in seizure intensity and increased latencies to higher scores of epileptic seizures. Consequently, we conclude that, under the conditions employed in this study, NAC and ALC do not exhibit any significant effects on acute seizures in zebrafish.

Out-of-hospital rescue medication in dogs with emergency seizure disorders: an owner perspective.

Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively more resistant to treatment. Early administration of rescue medication in canine epileptic patients, in particular benzodiazepines, at seizure onset by the owners can be life-saving and brain protecting. Clinical studies in dogs evaluating the use of rescue medication in hospital environment exist, however, the owner perspective has not been assessed to date. To evaluate the use of rescue medication in dogs with seizure emergencies by the owner at home. Observational study based on online surveys of owners of dogs with emergency seizure disorders. The questionnaire was answered by 1,563 dog owners, of which 761 provided complete and accurate answers suitable for analysis. Of these, 71% administered diazepam, 19% midazolam, 6% levetiracetam, 3% lorazepam, and 4% more than one rescue or other medication. Overall, the success rates based on owners' perspective for intranasal midazolam and rectal diazepam were 97 and 63%, respectively. Owners reported a compliance level of 95 and 66% for intranasal midazolam and rectal diazepam administration, respectively. Even though rectal diazepam was the most used rescue medication in this survey population, intranasal midazolam was perceived by the owners as a better option regarding effectiveness, time to seizure cessation and owner compliance.

The Anxiolytic Effect of Polysaccharides from Stellariae Radix through Monoamine Neurotransmitters, HPA Axis, and ECS/ERK/CREB/BDNF Signaling Pathway in Stress-induced Male Rats

BackgroundStellaria dichotoma L. var. lanceolata Bge. is renowned for its efficacy in "clearing deficiency heat" and represents a significant traditional Chinese medicine (TCM) resource. Modern pharmacology has demonstrated the anti-anxiety effects of Stellaria dichotoma L. var. lanceolata Bge. polysaccharides (SDPs). SDPs are one of the active constituents of Stellaria dichotoma L. var. lanceolata Bge. This study presents the first extraction of SDPs and investigates their potential molecular mechanisms and anxiolytic effects that are not previously reported. MethodsFirst, SDPs were obtained by water extraction and alcohol precipitation and analyzed for their monosaccharide composition by high performance liquid chromatography (HPLC). Male SD rats were subjected to a two-week indeterminate empty bottle stress procedure and a three-day acute restraint stress procedure, during which diazepam (DZP) (1 mg/kg) and SDPs (50, 100 and 200 mg/kg, intragastrically) were administered. A number of behavioral tests, including the elevated plus maze test (EPM), the open field test (OFT) and the light/dark box test (LDB), were used to assess the anti-anxiety potential of SDPs. Serum levels of Corticosterone (CORT) and Adrenocorticotropic hormone (ACTH), as well as the levels of Dopamine (DA) and serotonin (5-HT) found in the hippocampus and frontal cortex, were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits. In addition, protein levels of key proteins cAMP-response element binding protein (CREB), phospho-CREB (p-CREB), brain-derived neurotrophic factor (BDNF), ERK½, p-ERK½, and GAPDH expression in rat hippocampus were measured by Western blot analysis, and modulation of the endocannabinoid system was assessed by immunohistochemistry. ResultsFollowing administration of SDPs (50, 100, 200 mg/kg) and diazepam 1 mg/kg, anxiolytic activity was exhibited through an increase in the percentage of arm opening times and arm opening time of rats in the elevated plus maze. Additionally, there was an increase in the number of times and time spent in the open field center, percentage of time spent in the open box, and shuttle times in the LDB. Furthermore, tissue levels of DA and 5-HT were increased in the hippocampus and frontal cortex of rats after treatment with SDPs. In addition, SDPs significantly decreased serum levels of CORT and ACTH in rats. SDPs also effectively regulated the phosphorylation of the extracellular regulated protein kinases (ERK) and CREB-BDNF pathway in the hippocampus. Moreover, the expression levels of CB1 and CB2 proteins were heightened due to SDPs treatment in rats. ConclusionsThe study verified that SDPs alleviate anxiety in the EBS and ARS. The neuroregulatory behavior is accomplished by regulating the Monoamine neurotransmitter, HPA axis, and ECB-ERK-CREB-BDNF signaling pathway.

Age-related changes in glutamic acid decarboxylase 1 gene expression in the medial prefrontal cortex and ventral hippocampus of fear-potentiated rats subjected to isolation stress

Gamma-aminobutyric acid (GABA) plays a crucial role as a neurotransmitter in anxiety circuits, prominently in the hippocampus, amygdala, and prefrontal cortex. The synthesis of GABA in the central nervous system is primarily governed by glutamic acid decarboxylase 67 (GAD67). Aging is associated with emotional alterations, and isolation stress has been linked to increased anxiety. This study aimed to investigate the impact of aging on the gene expression of GAD67 (Gad1) in the medial prefrontal cortex (m PC) and ventral hippocampus (v Hip) of fear-potentiated rats subjected to isolation stress. To conduct the study, Wistar rats of different age groups 21-day-old (immature), 42-day-old (peri-adolescent), and 365-day-old (mature adult) were utilized. Each age level was categorized into four groups: 1) Control group - no pre-stressor, no maze, no drug, 2) Innate fear group (M) - no pre-stressor, maze, no drug, 3) Fear-potentiated group (IM) - isolation pre-stressor for 120 min, maze, no drug, and 4) Diazepam-treated group (IMD) - isolation pre-stressor for 120 min, maze, and diazepam administration. Following the tests, the (m PC) and (v Hip) regions were dissected, and Gad1 gene expression changes were assessed using Real-time PCR technique. The results revealed that, across all age groups, Gad1 expression in both the (m PC) and (v Hip) was significantly higher in the fear-potentiated groups (IM) compared to the control and innate fear (M) groups. Notably, in aged 365-day-old rats from the innate fear group (M), the expression of Gad1 in (v Hip) was also higher than that in the control group. Additionally, aged fear-potentiated rats exhibited elevated Gad1 gene expression in both structures compared to other age groups. These findings suggest that isolation stress before exposure to the elevated plus maze (EPM) can elevate Gad1 gene expression in both the (v Hip) and (m PC), and age may play a role in modulating its expression.

The effects of continuous administration of diazepam on the recovery of lesion-induced nystagmus in unilaterally labyrinthectomised rats

Background Diazepam, a gamma-aminobutyric acid type A receptor agonist, is classified as a vestibular suppressant and is effective in treating acute vertigo. However, its effects on vestibular compensation (VC) remain unclear. Objectives We examined the effects of continuous administration of diazepam on the frequency of spontaneous nystagmus (SN) after unilateral labyrinthectomy (UL) as an index of the initial process of VC in rats. Materials and methods Diazepam was continuously administered at doses of 3.5 and 7.0 mg/kg/day, intraperitoneally, via an osmotic minipump. The frequency of SN beating against the lesion side after UL was measured. Potassium chloride (KCl) solution (1 M) was injected intratympanically to induce SN beating to the injection side. Results Continuous administration of diazepam significantly and dose-dependently decreased the frequency of SN after UL, and also reduced the x intercept of the nonlinear regression curve of the decline in UL-induced SN with time in rats. However, the continuous administration of diazepam did not affect the frequency of intratympanic KCl-induced SN in the rats. Conclusion These findings suggested that continuous administration of diazepam accelerates the initial process of VC; however, it does not suppress the nystagmus-driving mechanisms in rats.

Behavioral and electrophysiological (ECoG) effects of haplophyllum robustum and TRPA1 antagonist in adult male wistar rats

This article aimed to investigate the effects of Haplophyllum robustum hydroalcoholic extract on animals’ behavioral and electrocorticographic changes. This plant is mainly found in Turkey, Iran, and Central Asia, and is reported to have convulsive effects.In this article, we worked on the effects of its hydroalcoholic extract on electrocorticography (ECoG), along with changes induced by intracerebroventricular administration of GABAA antagonists. Furthermore, the effects of low doses of this extract on behavioral depression were examined.Four animal sets were used to compare ECoG in Wistar rats. A group of negative control, a group of positive control (PTZ), and two groups received an injection of plant extract (500 mg/kg, ip), with or without administration of Diazepam (5 mg/kg).Also, three sets were applied to compare receiving and not receiving intracerebroventricular (icv) injection of Transient receptor potential ankyrin 1 antagonist (HC-030031) (2 μg/kg) on plant-induced seizure delay and animal death. Two groups of control and a group with plant extract together with TRPA1 antagonist were administrated.Furthermore, in the present study, the forced swimming test (FST) was used as a model of depression. The behaviors of animals in three groups of negative control and positive control (Fluoxetine) and plant extract (200 mg/kg, ip) were compared.According to the ECoG, high doses of extract of plants led to seizures similar to PTZ, which were then reduced by diazepam injection. At this dose, injection of TRPA1 antagonist did not significantly delay the onset of seizures or the death of the animals. Further, a subconvulsive dose of hydroalcoholic plant extracts was equally effective in treating depression as Fluoxetine injections.

Sublingual lorazepam as rescue therapy for seizure emergencies in adults

ObjectiveLimited acute home treatments are available for patients with prolonged (>5 minutes) or repetitive (≥2 in 24 hours) seizures. While this early seizure treatment may reduce the need for emergency care, intermittent intranasal benzodiazepine formulations are expensive and rectal diazepam administration is often socially unacceptable. We determined whether caregivers could use sublingual lorazepam oral concentrate solution effectively as acute treatment for adults with prolonged and repetitive seizures. MethodsPatients prescribed sublingual lorazepam solution at the Johns Hopkins Epilepsy Center for acute seizure treatment during a 5-year period (2012–2017) were screened. We determined clinical history of seizure patterns and number of antiseizure medications (ASMs) through patient and caregiver surveys, and we verified this history in patients’ medical records and charts. During a 2-year span (2017–2018), patients and caregivers were surveyed on responses to their most recent use of sublingual lorazepam solution, including seizure cessation (prolonged seizure stopping <5 minutes or ≤1 repetitive seizure), presence of sedation and adverse events within 24 hours of administration, and whether refrigeration limited use. ResultsIn total, 52 patients used sublingual lorazepam for treatment of acute seizures during the study period (median dose 1 mg, range 0.5 to 2 mg). Of them, 48 patients participated in treatment survey interviews. Family caregivers usually administered lorazepam (88%); 3 self-administered. Patients were surveyed on responses to their most recent use of sublingual lorazepam treatment: 66% (23/35) of patients with repetitive seizures reported no further seizure activity after administering treatment; 70% (7/10) with prolonged seizures reported seizure activity ceased within 5 minutes of treatment. Three patients treated auras and had no seizures. There were no serious adverse events during most recent use: 31% of patients developed moderate/severe sedation. Of note, 98% refrigerated lorazepam, often with coolers; 44%, however, said this limited treatment access. There was high treatment satisfaction; 79% reported that having the emergency treatment available made them feel safer. SignificanceThis patient survey and retrospective chart review demonstrates that home treatment with sublingual lorazepam solution may be effective for interrupting prolonged and repetitive seizures. No patients had sedation complications with home doses of 0.5 to 2 mg, and patients report high satisfaction with the treatment.

Prophylactic use of a lidocaine constant rate infusion versus saline in dogs undergoing balloon valvuloplasty for management of pulmonic stenosis: A randomized control trial

ObjectiveTo evaluate the effect of a prophylactic lidocaine constant rate infusion (CRI) on the incidence and malignancy of catheter-induced ventricular ectopic complexes (VECs) during balloon valvuloplasty for management of pulmonic stenosis in dogs. Study designSingle-centre, prospective, randomized study. AnimalsClient-owned dogs (n = 70) with pulmonic stenosis. MethodsDogs were randomly assigned to one of two anaesthetic protocols: administration of lidocaine 2 mg kg–1 bolus followed by a CRI (50 μg kg–1 minute–1; group LD) or a saline placebo (group SL) during balloon valvuloplasty. All dogs were premedicated with methadone (0.3 mg kg–1) intramuscularly and a digital three-lead Holter monitor was applied. Anaesthetic co-induction was performed with administration of alfaxalone (2 mg kg–1) and diazepam (0.4 mg kg–1), and anaesthesia was maintained with isoflurane vaporised in 100% oxygen. CRIs were started on positioning of the dog in theatre and discontinued as the last vascular catheter was removed from the heart. All dogs recovered well and were discharged 24 hours postoperatively. Blinded Holter analysis was performed by an external veterinary cardiologist using commercially available dedicated analysis software; p < 0.05. ResultsOf the 70 dogs enrolled in the study, 61 were included in the final analysis: 31 in group LD and 30 in group SL.There was no significant difference between sinus beats (p = 0.227) or VECs (p = 0.519) between groups. In group LD, 19/31 (61.3%) dogs had a maximum ventricular rate ≥250 units and 20/30 (66.7%) dogs in group SL (p = 0.791). Conclusion and clinical relevanceIn this study, the use of a prophylactic lidocaine bolus followed by CRI in dogs undergoing balloon valvuloplasty for management of pulmonic stenosis did not significantly decrease the incidence nor the malignancy of VECs during right heart catheterization compared with a saline CRI.

Acute Toxicity and Anxiolytic Activity Screening of Hydroalcoholic Leaf Extracts of Bryophyllum pinnatum, Terminalia catappa and Tapinanthus dodoneifolius Growing on Terminalia catappa Tree in MIce

Aims: Hydroalcoholic T. dodoneifolius, B.pinnatum and T. catappa leaf extracts were investigated for their acute toxicity and anxiolytic activities. Study Design: Acute toxicity (LD50) was determined using the limit dose acute and Anxiolytic activities were assessed by open-field field behavioural testing in mice. Place and Duration of Study: The study took place in the Neurobehavioural room of Department of Pharmacology &amp; Therapeutics, Faculty of Pharmacy, Ahmadu Bello University, Zaria in late December 2022. Methodology: Groups of mice (n=6; equal sexes) were each exposed to the open-field paradigm (OFT) following 1 hour of single oral administration of distilled water, extracts (125, 250, and 500 mg/kg) and diazepam (0. 5 mg/kg) using the behavioural indices of mean centre zone time (M%CZT), centre zone re-entry (MCZR) and defeaction/urination frequency (MD/UF). Results: Acute toxicity testing shows that the three extracts are safe with LD50 of 5g/kg. Behavioural results indicate, compared to the distilled water treatment (M%CZT, 6.39±1.53; MCZR, 4.67±1.15, &amp; MU/UF, 4.83±0.75), single acute T. dodoneifolius (M%CZT, 7.50±1.73, 13.72±2.43, &amp; 20.94±3.91*; MCZR, 7.33±0.88, 9.50±0.76, &amp; 11.50±1.6*; MD/UF, 4.17±0.48, 3.17±0.54, &amp; 1.83±0.60*), and B.pinnatum (M%CZT, 9.72±1.91, 9.78±1.32, &amp; 19.67±2.01*; MCZR, 6.00±1.15, 10.50±0.76, &amp; 12.50±1.72*; MD/UF, 3.17±0.79, 2.33±0.42, &amp; 1.33±0.49*) extract treatments demonstrated consistent dose-dependency in their anxiolytic activity across the three parameters with T. catappa extract (M%CZT, 6.95±1.27, 12.17±2.01, &amp; 16.84±1.49*; MCZR, 8.17±1.60, 10.17±1.67, &amp; 10.83±1.96; MD/UF, 2.83±0.60, 2.00±0.73, &amp; 3.67±0.42) exhibiting dose-pendent anxiolytic effect only on the M%CZT. However, at the highest dose level of 500 mg/kg, all plant extract treatments caused anxiolytic effects that are comparable with those of 0.5 mg/kg diazepam treatments (M%CZT, 22.61±1.31*; MCZR, 12.17±1.66*; &amp; MD/UF, 2.62±0.21*). Conclusion: These findings justify the traditional use of these medicinal plant extracts in the remediation of nervous and related disorders.

Creation of a Novel Child Simulator and Curriculum to Optimize Administration of Seizure Rescue Medication.

Although most cases of pediatric convulsive status epilepticus start in the prehospital setting, many patients do not receive treatment. The use of prehospital seizure rescue medications by caregivers is crucial, but studies suggest a lack of proper training on medication use. We created a novel proof of principle mannequin and simulation for training proper administration of rectal diazepam, with a scoring paradigm to standardize and assess the educational process. Twenty-three health care providers (nurses and nurse practitioners, residents/fellows, and attending physicians) and 5 patient guardians/parents were included in the study. The rectal diazepam simulator displayed a high degree of physical and emotional realism (mean ≥ 4/5 on Likert scale survey) that effectively decreased time to treatment (-12.3 seconds; SD, 16.3) and improved the accuracy of medication delivery in a simulation setting (-4.2 points; SD, 3.1). The scoring technique had appropriate interrater reliability (≥86% on all but 2 prompts) and was a feasible instrument to assess the effectiveness of the educational intervention. A unique procedure-focused child simulator and rescue medication score offer an innovative and effective means to train caregivers on the use of lifesaving seizure rescue medications.

Formulation and Evaluation of Diazepam as a Rectal Preparation

Diazepam has become a commonly used drug for treatment of acute repetitive epileptic seizures and febrile convulsions in children. Considering the advantages of rectal administration of diazepam, the objective of this study was to formulate and evaluate rectal hydrogels containing diazepam as a drug substance in combination with suitable co - solvents and preservatives.Prepared HPMC (hydroxypropyl methylcellulose) hydrogels containing different concentrations of diazepam (2, 4 and 6 mg I ml) manifested good quality in respect to physicochemical parameters (pH value, drug content, ingredients content and viscosity), antimicrobial efficiency and microbiological quality. Under the proposed HPLC conditions, satisfactory separation of diazepam and the preservatives used was achieved. In vitro release studies have shown that the total amount ofdiazepam was released in a period of 3 hours. Prepared formulations were stable for four months at 26 C (ambient temperature characteristic of the second climate zone