Prescribing Pattern of Benzodiazepine Receptor Agonists (BZRA) and Factors Associated With Duration of BZRA Use in a Malaysian Psychiatry Outpatient Clinic

@#Introduction: Benzodiazepine receptor agonist (BZRA) are among the most frequently used psychotropic medications worldwide. We aim to understand the pattern of prescription of BZRA in the government healthcare facilities and identify factors affecting the likelihood of BZRA prescription and duration of use. Method: This is a retrospective study. Data was obtained from record of outpatient clinical notes. Medications studied were midazolam, alprazolam, lorazepam, bromazepam, clonazepam, diazepam and zolpidem. Mean duration per prescription, mean dosage per prescription and duration per patient per year were calculated for each sedative hypnotic. The likelihood of factors affecting duration of prescription were also analysed. Results: The prevalence of sedative hypnotic use in psychiatry outpatient clinic was 12.16%. Clonazepam was found to have the longest duration per patient per year (306.5 days). Insomnia and anxiety are the two most common reasons for sedative hypnotic prescription. Factors found to affect duration of prescription were unemployment, borderline personality disorder, alcohol and substance use disorders. Conclusion: Implementation of effective monitoring system on sedative hypnotic prescribing and increase use of non-pharmacological interventions for insomnia and anxiety are necessary to curb prolonged use of sedative hypnotic.

Abuse of Pharmaceutical Drugs and Its Prevention / 法医学杂志

Abuse of pharmaceutical drugs is a major public health and social problem worldwide. Mostly abused drugs mainly include opioids such as morphine, tramadol, methadone and fentanyl, sedative-hypnotics such as benzodiazepines and non-benzodiazepines, and central stimulants such as Ritalin (methylphenidate), Adderall (amphetamine and dextroamphetamine) and modafinil. Abuse of pharmaceutical drugs not only causes direct damage to multiple systems of the body, but also significantly increases risks of mental and physical diseases, imposing a heavy burden on individuals, families and society. Therefore, the prevention and control of pharmaceutical drug abuse are of vital importance. The Chinese government has taken strict administration measures for pharmaceutical drugs with abuse risk. However, confronting endless new drugs and changing abuse trends, it is necessary to further strengthen management and prevention of pharmaceutical drugs, monitor the trend of abuse, establish rapid response mechanisms, popularize relevant knowledge, and develop specific therapeutic drugs and intervention means, in order to promote prevention and treatment of pharmaceutical drug abuse.

Epidemiological Characteristics of Sedative-Hypnotics and Opioid Painkillers at High-Frequency Exposure / 法医学杂志

Drug poisoning has a high incidence and serious consequences in medical institutions; its epidemiological characteristics also directly affect the changes in national laws and policies and the implementation of local management policies. Chinese statistics on drug-related abnormal death cases generally come from judicial appraisal centers and medical units. However, due to differences in work content and professional restrictions, there are differences in information management forms, which makes it difficult for appraisers to conduct a professional and systematic analysis of drug-related cases. This article focuses on the analysis of epidemiological characteristics of sedative-hypnotics and opioid painkillers and their exposure patterns in cases of poisoning death by analyzing the annual report of the American Association of Poison Control Center, combined with the characteristics of drug exposure in China.

Appraising the Neurobehavioural Toxicity Potential of Aqueous Methanol Leaf Extract of Tapinanthus globiferus Growing on Azadirachta indica

The high prevalence and disease burden of anxiety disorders against the paucity and liabilities of existing anxiolytics indicates a need for the discovery of additional/new anti-anxiety agents. However, it is necessary to further screen these new/putative anxiolytic compounds/extracts to rule out the unwanted neurobehavioural toxicities inherent in the existing anti-anxiety drugs. Aqueous methanol leaf extract of Tapinanthus globiferusgrowing on Azadirachta indicahost tree has previouslydemonstrated significant (p<0.05) anxiolytic effects in mice. This study, therefore, set out to counter-screen this extract for locomotion-suppressant, acute amnesic, sedative (myorelaxant) and hypnotic effects using standard mouse behavioural and biochemical paradigms. The leaf extract (150, 500 and 1500 mg/kg) did not cause significant (p>0.05) alterations in spontaneous locomotor activity, motor coordination/balance, sleep onset or duration,but dose-dependent and significant (p<0.05) increases (63.28±5.63, 65.63±4.12 and 69.18±3.69) in novel object recognition indices of extract-treated compared to 51.54±4.03 and 61.06±2.91 scores in diazepam-and aqua-treated mice, respectively.These findings indicate the aqueous methanol leaf extract is mostly devoid of the evaluated neurobehavioural toxicities and may possess short-term memory enhancement property in mice. These findings may justifythe traditional use of Tapinanthus globiferusextracts for memory enhancement

Rapid Determination of 13 Sedative Substances and Their Metabolites in Blood by LC-MS/MS / 法医学杂志

Objective To establish an analysis method for simultaneous determination of 13 sedative substances and their metabolites in blood by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry （LC-MS/MS） technology and to apply the method to actual cases. Methods The samples were extracted with ethyl acetate after an internal standard was added. The extract was condensed until it was nearly dry and then its residues were dissolved with methanol, filtered through 0.22 μm filter and finally determined. The 13 sedative substances and their metabolites were separated through the C18 chromatographic column, then gradient elution was performed on them with methanol and 20 mmol/L ammonium formate （containing 0.1% formic acid） solution. After that, they were determined in the electrospray positive ion mode and quantified by internal standard method. Results The 13 sedative substances and their metabolites in blood showed good linearity in the range of 5-200 μg/L with correlation coefficients ranging from 0.990 3 to 0.999 8. The detection limits were 0.1-1.0 μg/L. Recovery rates of sedative substances were in the range of 71.2%-93.4% when solutions with concentrations of 10, 50 and 200 μg/L were added. The deviations of intra-day and inter-day relative standard deviations （RSD） were not more than 8.6%. Accuracies （bias） were within ±9.8%. Conclusion This method is rapid, simple, effective and sensitive, and can be applied to analysis of 13 sedative substances and their metabolites in blood in forensic toxicology.

Citrus limon (L.) Burm f. Essential Oil Has Anxiolytic and Sedative Properties by Modulating GABAA-Receptors

Abstract The high prevalence of anxiety disorders associated with pharmacotherapy side effects have motivated the search for new pharmacological agents. Species from Citrus genus, such as Citrus limon (sicilian lemon), have been used in folk medicine as a potential therapy to minimize emotional disorders. In order to searching for new effective treatments with fewer side effects, the present study evaluated the anxiolytic mechanism of action and the hypnotic-sedative activity from the Citrus limon fruit's peels essential oil (CLEO). Adults male Swiss mice were submitted to barbiturate-induced sleep test; elevated plus-maze (EPM) and light-dark box (LDB) (evaluation of the mechanism of action); rotarod; and catalepsy tests. CLEO oral treatment decreased latency and increased the sleep total time; moreover it induced in animals an increased the number of entries and percentage of time spent into open arms of the EPM; an increased the number of transitions and the percentage of time into light compartment in the LDB; which were only antagonized by flumazenil pretreatment, with no injury at motor function. Thus, results suggest that CLEO treatment induced an anxiolytic behavior suggestively modulated by the benzodiazepine binding site of the GABAA receptor or by an increase of GABAergic neurotransmission, without cause impairment in the motor coordination.

Strategies against sleep deprivation in military personnel: Recent progress / 第二军医大学学报

Modern military actions and non-military operations characterized by high-intensity, sudden emergencies and long continuous working inevitably lead to sleep deprivation of military personnel. High-intensity actions require military personnel to maintain excellent action abilities all the times; sudden emergencies need them to maintain alert; and the continuous work need them to maintain a healthy mental state. Therefore, how to effectively combat sleep deprivation, keep alert and have high stress ability have become the focus of modern military medical research. This article reviews the research progress of central nervous system stimulants, preventive sleep medications, sleep induction and rapid recovery drugs, and non-drug measures to combat sleep deprivation.

Evolving concepts in guidelines for analgesic and sedative treatment / 中国小儿急救医学

In 2018, the Society of Critical Care Medicine(SCCM) and the Chinese Society of Critical Care Medicine(CSCCM) drawn up guidelines for analgesic and sedative treatment in adult patients in the intensive care unit successively.In 2019, the emergency group of Chinese Pediatric Society, Chinese Medical Association published "the experts′ consensus on sedation and analgesia for children in pediatric intensive care unit of China" . The new guidelines have been revised and updated on the basis of the previous ones.Especially, some new concepts have been gradually implemented.This paper seeked to summarize these new concepts and aid clinicians in clinical decision-making in intensive care unit.

Sedative and Hypnotic Effects and Transcriptome Analysis of Polygala tenuifolia in Aged Insomnia Rats / 中国结合医学杂志

OBJECTIVE@#To study the sedative and hypnotic effects and underlying mechanisms of Polygala tenuifolia (PT) on treating aged insomnia rats.@*METHODS@#Sixty Sprague-Dawley male rats were divided into 6 groups by a random number table, including control group, model group, diazepam group (0.92 mg/kg), as well as PT low-, medium- and high-dose groups (0.0875, 0.175, 0.35 g/kg, respectively), 10 rats in each group. Aged insomnia rat model was established with subcutaneous injection of D-galactose for 42 days and then intraperitoneal injection of para-chlorophenylalanine for 3 days. PT and diazepam were respectively given to aged insomnia rats by intragastric administration for 7 days after model establishment. Then the rats were investigated by body weight, Morris water maze test, pentobarbital test, enzyme-linked immunosorbent assay, and transcriptome sequencing.@*RESULTS@#Compared with the model group, PT increased the body weight, improved memory ability, and prolonged pentobarbital-induced sleep time of aged insomnia rats (P<0.01 or P<0.05). The medium dose of PT also increased the neurotransmitter levels of 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA), and decreased the level of Glu in the hippocampus of aged insomnia rats (P<0.05 or P<0.01). Twenty-four differentially expressed genes (DEGs) were overlapped among model group, medium-dose PT group, and diazepam group in transcriptome analysis. Fuom and Pcp2 were down-regulated by the treatment of medium-dose PT (P<0.01 or P<0.05). The metabolic pathways of PT were relatively less than diazepam (91 vs. 104).@*CONCLUSIONS@#The sedative and hypnotic effects of PT in aged insomnia rats might be related to neuro, metabolism pathways, especially through GABAergic signaling pathway. It provided more effective herb choice for the treatment of senile insomnia.

Safety on Chloral Hydrate Oral Solution for Sedative and Hypnotic in Children ：A Systematic Review / 中国药房

OBJECTIVE：To systematically evaluate the safety of Chloral hydr ate（CH）oral solution for sedative and hypnotic in children，and to provide evidence-based reference for clinical use. METHODS ：Retrieved from 9 electronic databases （PubMed， Cochrane Library ，Embase，CINAHL，International Pharmaceuticals ，CNKI，CBM，Wanfang Database ，VIP），3 clinical trial registry platforms （Clinical Trials ，Cochrane Clinical Trial Database ，WHO Clinical Trial Database ）and 18 adverse drug reaction （ADR）monitoring systems （ADR monitoring websites of WHO ，USA，Switzerland，China and other countries/areas/international organizations），during the date of database establishment to March 2019，the reports of randomized controlled trials ，cohort studies，case-control studies ，case series studies ，case reports ， cross-sectional studies and adverse reactions monitoring network of chloral hydrate versus other interventions （blank 85503205。E-mail：chenzhehx@163.com control，placebo or other sedative hypnotics ）for children ’s sedative and hypnotic safety were collected. After data extraction of included literatures met inclusion criteria ，quality mail：zhanglingli@scu.edu.cn evaluation of included s tudies with Cochrane bias risk evaluation manual （RCT），Newcastle-Ottawa scale evaluation tool （Cohort study and case control study ），Australian JBI quality assessment tool （case series study and case report study ），Meta-analysis was performed by Rev Man 5.3 software，or descriptive analysis was conducted. RESULTS ：A total of 54 studies were included ，among which there were 13 RCTs，9 cohort studies ，17 case series studies ，13 case reports ，and 2 reports from ADR monitoring network. Based on the results of RCT and cohort studies ， the incidence of Chloral hydrate oral solution adverse events was 7.25％. There was no statistical significance in the incidence of digestive system [RR ＝0.87，95％ CI（0.14，5.42），P＝0.88]，nervous system [RR ＝0.13，95％ CI（0.01，2.41），P＝0.17]， cardiovascular system [RR ＝2.12，95％ CI（0.08，56.57），P＝0.65] adverse event between Chloral hydrate oral solution and midazolam. The incidence of respiratory system adverse events induced by Chloral hydrate oral solution was higher than that of midazolam [RR ＝3.07，95％CI（1.94，4.86），P＜0.01]. There was no statistical significance in the incidence of digestive system adverse events between Chloral hydrate oral solution and diazepam [RR ＝0.71，95％CI（0.47，1.10），P＝0.13]. There was no statistical significance in the incidence of digestive system ，nervous system and cardiovascular system adverse events between Chloral hydrate oral solution and barbiturates （P＞0.05）. CONCLUSIONS ：Chloral hydrate oral solution is similar to midazolam ， diazepam and barbiturates in terms of digestive ，nervous and cardiovascular systems adverse events ，but the incidence of respiratory system adverse events is higher than midazolam.

Sedative and electrocardiographic effects of low dose dexmedetomidine in healthy cats / Efeitos sedativos e eletrocardiográficos da baixa dose de dexmedetomidina em gatos saudáveis

In feline veterinary practice sedation is often needed to perform diagnostic or minimally invasive procedures, minimize stress, and facilitate handling. The mortality rate of cats undergoing sedation is significantly higher than dogs, so it is fundamental that the sedatives provide good cardiovascular stability. Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist utilized in cats to provide sedation and analgesia, although studies have been utilized high doses, and markedly hemodynamic impairments were reported. The aim of this study was to prospectively investigate how the sedative and electrocardiographic effects of a low dose of DEX performing in cats. Eleven healthy cats were recruited; baseline sedative score, systolic arterial pressure, electrocardiography, and vasovagal tonus index (VVTI) were assessed, and repeated after ten minutes of DEX 5μg/kg intramuscularly (IM). A smooth sedation was noticed, and emesis and sialorrhea were common adverse effects, observed on average seven minutes after IM injection. Furthermore, electrocardiographic effects of a low dose of DEX mainly include decreases on heart rate, and increases on T-wave amplitude. The augmentation on VVTI and appearance of respiratory sinus arrhythmia, as well as sinus bradycardia in some cats, suggesting that DEX enhances parasympathetic tonus in healthy cats, and therefore will be best avoid in patients at risk for bradycardia.(AU)

Na rotina clínica da medicina veterinária felina a sedação é frequentemente requerida para realização de procedimentos diagnósticos ou minimamente invasivos, para minimizar o estresse e facilitar o manuseio dos pacientes. A taxa de mortalidade de gatos submetidos à sedação é mais elevada do que em cães, por esse motivo, é fundamental que os sedativos confiram estabilidade hemodinâmica. A dexmedetomidina (DEX) é um α2-agonista utilizado em felinos para promover sedação e analgesia, porém os estudos têm utilizado doses elevadas, e com isso prejuízos hemodinâmicos importantes foram relatados. O objetivo desta investigação foi avaliar os efeitos sedativos e eletrocardiográficos da baixa dose de DEX em gatos. Para tal, onze felinos saudáveis foram recrutados, foram obtidos valores basais para escore de sedação, pressão arterial sistólica e eletrocardiografia, além do índice de tônus vaso vagal (ITVV). Após dez minutos da aplicação intramuscular (IM) de DEX 5μg/kg todos os exames foram repetidos. Após a DEX, sedação suave foi detectada, e a êmese e sialorreia foram efeitos adversos comuns, observados em média 7 minutos após a injeção IM. Ademais, os principais efeitos eletrocardiográficos foram redução na frequência cardíaca e aumento na amplitude da onda T. O ITVV mais elevado e surgimento de arritmia sinusal respiratória, bem como bradicardia sinusal em alguns gatos, sugerem que a DEX eleva o tônus parassimpático, e por esse motivo deve ser utilizada com cautela em pacientes com predisposição à bradicardia.(AU)

Research status and prospect of herbal volatile oil in prevention and treatment of emotional diseases / 中草药

Volatile oil is the representative effective component of aromatic Chinese materia medica (CMM), which has pharmacological activities such as anti-anxiety, antidepressant, sedative and neuroprotective effects. They can regulate people’s mood through olfactory, skin and other ways of administration, play a role in regulating consciousness, and have unique advantages in the prevention and treatment of emotional diseases such as depression, anxiety, insomnia and so on. As a unique health service resource, it can also play an auxiliary role in the prevention, treatment and rehabilitation of other physical and mental diseases. However, at present, there are some problems, such as weak basic research, lack of effective and high-quality preparations and products. In this paper, the relevant research literature is summarized, the administration route, efficacy and action mechanism are systematically combed, the existing problems are analyzed and the countermeasures are put forward, so as to provide reference for its in-depth research, further development and utilization.

Analgesic and sedative effects of Mongolian medicine Syringa pinnatifolia / 中国中药杂志

The peeled root,stem or twig of Syringa pinnatifolia is a representative Mongolian folk medicine with the effects of antidepression and pain relief. It has been used for the treatments of heart tingling,heart palpitations,upset,insomnia and other symptoms. Inspired by Mongolian medical theory and clinical practices,this study evaluated the analgesic effect of S. pinnatifolia ethanol extract( T) through three analgesic models including acetic acid writhing test,formalin test,and hot plate test,and the sedative effect of T was evaluated by locomotor activity and synergistic sleeping experiments,and furthermore the effects of T on the GABAergic nervous system were investigated by ELISA,immunohistochemistry,Western blot,and PCR methods. The results showed that T can significantly reduce the number of writhing,the time of paw licking and extend the thermal threshold of mice,suggesting the analgesic effect of T.T also can indicate its sedative effect by reducing the number of activities,decreasing latency of sleeping and extending sleeping time of mice. ELISA results showed that T can increase the content of GABA/Glu in rat cortex,hippocampus,and hypothalamus,and the most significant increase in hypothalamus. The immunohistochemistry and Western blot results showed that T can up-regulate the expression of GAD67 protein in hypothalamus,and the PCR results showed that T can up-regulate the expression of GABAA Rα1,α2,α3,α5,β1-3,γ1-3 genes,suggesting a sedative effect through the GABAergic nervous system. In conclusion,this study shed insight into the theoretical basis and clinical application of S. pinnatifolia,and also provides inspiration for subsequent development and application.

Optimization of flavonoid extraction from Passiflora quadrangularis leaves with sedative activity and evaluation of its stability under stress conditions

Abstract Passiflora species have been widely used in folk medicine as tranquilizers, and previous pharmacological studies have reported sedative activity for P. quadrangularis L., Passifloraceae, leaf extracts. The aim of this work was to contribute to the standardization of P. quadrangularis leaf extract with sedative activity. For this purpose, the extraction of total flavonoids was optimized, evaluating variables such as drug-solvent ratio, extraction solvents and extraction time, using Response Surface Methodology. The stability of total and individual flavonoids on the optimized extract of P. quadrangularis leaves under stress conditions was also evaluated. Sedative activity was verified by the ethyl ether-induced hypnosis test in Swiss ICR mice. Based on the results, the highest concentration of total flavonoids was obtained at a drug-solvent ratio of 1:15 (w:v), extraction solvent EtOH:H2O (1:1, v/v) and percolation time of 48 h. Regarding stability under stress conditions, it was found that the flavonoids from the optimized extract are photostable, and practically stable under neutral hydrolysis and oxidation, but labile by acid and basic hydrolysis, with the main degradation products being identified. Finally, it was demonstrated that the optimized extract improves the sedative effect when compared to previously evaluated extract in the ethyl ether-induced hypnosis test.

Effect of agomelatine on psychomotor function tests in healthy human volunteers

Background: Agomelatine is a melatonergic agonist that acts specifically on MT1/MT2 melatonergic receptors and 5-HT2C antagonism. The present study was taken up to evaluate the effect of Agomelatine 25mg on psychomotor function in healthy human volunteers.Methods: The effect of Agomelatine was studied in 12 healthy volunteers of either gender. The study was a randomised, cross over, placebo controlled study, done after obtaining permission from NIMS Institutional Ethics Committee and informed consent taken from all the subjects, after briefly explaining the study procedure and training them adequately. Psychomotor function was assessed using Choice reaction time (CRT), Critical Flicker fusion test (CFFT), Digit letter substitution test (DLST), Six letter cancellation test (SLCT), Card sorting test (CST) and Visual analog scale (VAS). Psychomotor function tests were performed, 90 minutes after administering Agomelatine 25 mg or placebo. Washout period of seven days was allowed between the cross over. Statistical analysis was done by comparing groups using unpaired t test.Results: There was significant decrease in the mean percentage of time (p<0.01) in CRT in Agomelatine group (20.09±9.47%) when compared to placebo (10.48±3.68%). Improved mean percentage of performance was seen in CFFT with Agomelatine (6.2±2.1%) compared to placebo (9.11±2.99%). No significant difference was noted in the performance of DLST, SLCT and CST. Drug was subjectively rated as sedative on VAS.Conclusions: There is no significant effect of Agomelatine on psychomotor performance. CNS processing of information also improved. Agomelatine can thus be safely administered to depressed patients.

Analysis of the effect of oral midazolam and triazolam premedication before general anesthesia in patients with disabilities with difficulty in cooperation

BACKGROUND: When performing dental treatment under general anesthesia in adult patients who have difficulty cooperating due to intellectual disabilities, anesthesia induction may be difficult as well. In particular, patients who refuse to come into the dental office or sit in the dental chair may have to be forced to do so. However, for adult patients with a large physique, physical restraint may be difficult, while oral sedatives as premedication may be helpful. Here, a retrospective analysis was performed to investigate the effect of oral sedatives. METHODS: A hospital-based medical information database was searched for patients who were prescribed oral midazolam or triazolam between January 2009 and December 2017. Pre-anesthesia evaluation, anesthesia, and anesthesia recovery records of all patients were analyzed, and information on disability type, reason for prescribing oral sedatives, prescribed medication and dose, cooperation level during anesthesia induction, anesthesia duration, length of recovery room stay, and complications was retrieved. RESULTS: A total of 97 patients were identified, of whom 50 and 47 received midazolam and triazolam, respectively. The major types of disability were intellectual disabilities, autism, Down syndrome, blindness, cerebral palsy, and epilepsy. Analyses of changes in cooperation levels after drug administration showed that anesthesia induction without physical restraint was possible in 56.0% of patients in the midazolam group and in 46.8% of patients in the triazolam group (P = 0.312). CONCLUSIONS: With administration of oral midazolam or triazolam, general anesthesia induction without any physical restraint was possible in approximately 50% of patients, with no difference between the drugs.

Research process on pharmacological effect and substance basis of Perilla frutescens / 中草药

Perilla frutescens is one of traditional Chinese diaphoretics, and is produced in many areas of China. The chemical composition is rich in P. frutescens, including volatile oil, aliphatic acids, flavonoids, phenolic acids, coloring matter and so on. Because of the function of relieving superficial pathogenic factors to dissipate cold and promoting qi flowing to regulate the stomach, P. frutescens can be used to treat the diseases of wind-cold, stagnation of gastrosplenic qi, vomiting and poisoning by eating fish and crab. The study showed that P. frutescens exhibited the effects which related with the traditional uses of relieving cough, bacteriostasis, relieving fever, analgesia, etc., and besides, it showed a few new founded effects, such as sedative effects, antioxidative effects, effects of reducing blood pressure, and regulating glucose/lipid metabolism. This paper summarized the research progess on the chemical composition and main pharmacological activities of P. frutescens, and discussed its therapeutic material basis based on the summarise, which could provide a reference for the development of P. frutescens.

Effectiveness of sedative and analgesic bundle on delirium and clinical prognosis in mechanically ventilated patients / 中国实用护理杂志

Objective To research the intervention effect of the ABCDE Bundle in mechanically ventilated patients. Methods A prospective randomized controlled trail (RCT) was selected 84 mechanically ventilated patients aged 22-45 years in the ICU of respiratory and severe medical center of the affiliated hospital of Logistics University of PAP from January to December in 2016. The research samples were randomly divided into intervention group (n=42) and control group (n=42). Samples were chosen to compare the difference of basic situation, ICU length of stay, 28-day hospital survival rate and the incidence of delirium between the patients of intervention group and control group. Results The average ICU hospitalization time in the intervention group was (11.76± 5.15) days, while that in the control group was (17.64 ± 8.04) days, and the difference between the 2 groups was statistically significant (t=3.99, P<0.01). The 4-week survival rate and delirium incidence rate in intervention group were 90.48％ (38/42) and 66.67％ (28/42) respectively, while those in control group were 71.43％ (30/42) and 40.48％ (17/42) respectively, and the difference between 2 groups was statistically significant (χ2=4.94, 5.79, P<0.05). Conclusion The application of bundles of care strategy could reduce the incidence of delirium and improve the clinical outcome of mechanically ventilated patients.

Sedative and muscle relaxant activities of diterpenoids from Phlomidoschema parviflorum

Abstract Phlomidoschema parviflorum (Benth.) Vved. (Basionym: Stachys parviflora Benth.) Lamiaceae, have significance medicinal importance as it is used in number of health disorders including diarrhea, fever, sore mouth and throat, internal bleeding, weaknesses of the liver and heart genital tumors, sclerosis of the spleen, inflammatory tumors and cancerous ulcers. The present contribution deals with the sedative and muscle relaxant like effects of diterpenoids trivially named stachysrosane and stachysrosane, isolated from the ethyl acetate soluble fraction of P. parviflorum. Both compounds (at 5, 10 and 15 mg/kg, i.p) were assessed for their in vivo sedative and muscle relaxant activity in open field and inclined plane test, respectively. The geometries of both compounds were optimized with density functional theory. The molecular docking of both compounds were performed with receptor gamma aminobutyric acid. Both compounds showed marked activity in a dose dependent manner. The docking studies showed that both compounds interact strongly with important residues in receptor gamma aminobutyric acid. The reported data demonstrate that both compounds exhibited significant sedative and muscle relaxant-like effects in animal models, which opens a door for novel therapeutic applications.

Evaluation of antipyretic, sedative and hypnotic activities of methanol extract of Tabebuia hypoleuca (C. Wright ex Sauvalle) Urb. stems / [Evaluación de la actividad antipirética, sedante e hipnótica del extracto metanólico de los tallos de Tabebuia hypoleuca (C. Wright ex Sauvalle) Urb

Species of the genus Tabebuia are used in traditional medicine and are reported in the literature for their properties against various diseases. The objective of this study was to evaluate the antipyretic, sedative and hypnotic activities of methanol extract of Tabebuia hypoleuca stems (THME) using the Brewer's yeast induced pyrexia, Open field and Sodium thiopental-induced sleeping time tests, respectively. In the Brewer's yeast induced pyrexia test, THME at 500 mg/kg produced a significant (p<0.001) decrease of the fever as from the first hour after administration and was sustained for 4 h. In the Open-field test, THME did not cause any significant change in the number of crossings, rearing, preening and defecation, and either in the time of immobility. Moreover, THME did not produce changes in neither the sleeping latency nor the sleeping time induced by sodium thiopental. These results showed that THME administered orally at 500 mg/kg exerts antipyretic activity, probably mediated by the inhibition of the enzyme cyclooxygenase-2. This study also showed that THME does not exert sedative and hypnotic effects at the doses tested.

Especies del género Tabebuia se utilizan en la medicina tradicional y se reportan en la literatura por sus propiedades contra diversas enfermedades. El objetivo de este estudio fue evaluar la actividad antipirética, sedante e hipnótica del extracto metanólico de los tallos de Tabebuia hypoleuca (THME) utilizando las pruebas de pirexia inducida por levadura de cerveza, campo abierto y tiempo de sueño inducido por tiopental sódico respectivamente. En el ensayo de pirexia inducida por levadura de cerveza, THME a 500 mg/kg produjo una reducción significativa (p<0.001) de la fiebre a partir de la primera hora después de la administración y se mantuvo durante cuatro horas. En el ensayo de campo abierto, THME no causó ningún cambio significativo en el número de cruces, levantamientos, acicalamientos y defecación, ni en el tiempo de inmovilidad. Además, THME no produjo cambios ni en la latencia de sueño, ni en el tiempo de sueño inducido por tiopental sódico. Estos resultados mostraron que THME administrado oralmente en dosis de 500 mg/kg posee actividad antipirética, mediado probablemente a la inhibición de la enzima ciclooxigenasa-2. Este estudio también demostró que THME no posee actividad sedante e hipnótica en las dosis ensayadas.