Home About us Contact
|
Home About us Contact | ||
|
|
||
Sedative
Terms modified by Sedative Selected AbstractsSedative and anticonvulsant activities of goodyerin, a flavonol glycoside from Goodyera schlechtendalianaPHYTOTHERAPY RESEARCH, Issue 3 2002Xiao-Ming Du Abstract Goodyerin is a flavonol glycoside isolated from the whole plants of Goodyera schlechtendaliana which has been used as a substitute for the crude drug, Anoectochilus formosanus. The pharmacological properties of goodyerin were assayed for effects on spontaneous locomotor activity, on pentobarbital-induced hypnosis, and on anticonvulsant activity against picrotoxin-induced seizures in rodents. Goodyerin exhibited a significant and dose-dependent sedative and anticonvulsant effect. Copyright © 2002 John Wiley & Sons, Ltd. [source] Synthesis and Structure Investigations of Potential Sedative and Anticonvulsant Hydroxy- and Acetoxy-N-(3-oxobutyl)-pyrido[2,3-d]pyridazinones.CHEMINFORM, Issue 1 2003Edith Goessnitzer Abstract For Abstract see ChemInform Abstract in Full Text. [source] A placebo-controlled trial of mirtazapine for the management of methamphetamine withdrawalDRUG AND ALCOHOL REVIEW, Issue 3 2008CHRISTOPHER C. CRUICKSHANK Abstract Introduction and Aims. As an antidepressant with sedative and anxiolytic properties, mirtazapine may be an appropriate pharmacotherapy for methamphetamine withdrawal. This study sought to examine whether mirtazapine improves retention and alleviates methamphetamine withdrawal symptoms in an out-patient setting. Design and Methods. An out-patient double-blind, randomised placebo-controlled trial of mirtazapine for the treatment of methamphetamine withdrawal was conducted (15 mg nocte for 2 days, 30 mg nocte for 12 days). Both groups were offered narrative therapy counselling. Measures recorded on days 0, 3, 7, 14 and 35 included: treatment retention, Amphetamine Cessation Symptoms Assessment, the Athens Insomnia Scale, the Brief Symptom Inventory, the Depression,Anxiety,Stress Scale (DASS), Severity of Dependence scale and the Opiate Treatment Index Drug Use subscale. Results. Thirty-one participants were recruited (18 placebo, 13 mirtazapine) and 52% completed the 2-week medication phase. No significant differences between the mirtazapine and placebo groups in retention, or any symptom measure were observed, except greater DASS,anxiety and longer sleep duration were measured at baseline among the mirtazapine group. Discussion and Conclusions. Results suggest that mirtazapine does not facilitate retention or recruitment in out-patient methamphetamine withdrawal treatment, although recruitment may have been insufficient to identify a significant treatment effect. The potential role of narrative therapy for methamphetamine dependent patients deserves further exploration. [source] Preclinical abuse potential assessment of the anticonvulsant zonisamideDRUG DEVELOPMENT RESEARCH, Issue 2 2001Jenny L. Wiley Abstract Zonisamide (Zonegran®) is a broad-spectrum antiepileptic agent that shares some pharmacological properties with other anticonvulsants, including phenytoin, carbamazepine, and valproic acid, but is differentiated from these agents by the ability to significantly block T-type calcium channels. Zonisamide interacts with the ,-amino-butyric acid (GABA) receptor in an allosteric manner, and thus does not modulate GABA receptor effects. However, given the potential of drugs within the latter class for drug abuse in humans, an evaluation of zonisamide for abuse potential is an important component of its potential side-effect profile. In the present study, zonisamide was tested in animal models of the subjective and reinforcing effects of central nervous system (CNS) depressant drugs, e.g., diazepam discrimination in rats and intravenous self-administration in rhesus monkeys, respectively. In addition, zonisamide was evaluated for physical dependence liability in a chronic infusion model using rats. Zonisamide did not substitute for diazepam in rats trained to discriminate 2.5-mg/kg diazepam from vehicle nor was it self-administered by rhesus monkeys experienced in methohexital-reinforced responding. Continuous infusion of zonisamide (400 or 600 mg/kg/day) did not prevent the loss of body weight associated with discontinued pentobarbital infusion. These doses of zonisamide did produce some incomplete attenuation of observable signs of pentobarbital withdrawal, likely due to direct sedative or depressant effects of these high doses. These results suggest that zonisamide would not produce diazepam-like intoxication in humans nor would it likely be subject to abuse when made more widely available. Further, when administered chronically, zonisamide would not be expected to produce physical dependence of the CNS depressant type. Taken together, these results support the prediction that zonisamide would have low abuse liability. Drug Dev. Res. 54:66,74, 2001. © 2001 Wiley-Liss, Inc. [source] REVIEW: The alcohol-preferring P rat and animal models of excessive alcohol drinkingADDICTION BIOLOGY, Issue 3-4 2006Richard L. Bell ABSTRACT The alcohol-preferring, P, rat was developed by selective breeding to study ethanol drinking behavior and its consequences. Characterization of this line indicates the P rat meets all of the criteria put forth for a valid animal model of alcoholism, and displays, relative to their alcohol-non-preferring, NP, counterparts, a number of phenotypic traits associated with alcohol abuse and alcoholism. Behaviorally, compared with NP rats, P rats are less sensitive to the sedative and aversive effects of ethanol and more sensitive to the stimulatory effects of ethanol. Neurochemically, research with the P line indicates the endogenous dopaminergic, serotonergic, GABAergic, opiodergic, and peptidergic systems may be involved in a predisposition for alcohol abuse and alcoholism. Paralleling the clinical literature, genetically selected P rats display levels of ethanol intake during adolescence comparable to that seen during adulthood. Binge drinking has been associated with an increased risk for health and other problems associated with ethanol abuse. A model of binge-like drinking during the dark cycle indicates that P rats will consume 6 g/kg/day of ethanol in as little as three 1-hour access periods/day, which approximates the 24-hour intake of P rats with free-choice access to a single concentration of ethanol. The alcohol deprivation effect (ADE) is a transient increase in ethanol intake above baseline values upon re-exposure to ethanol access after an extended period of deprivation. The ADE has been proposed to be an animal model of relapse behavior, with the adult P rat displaying a robust ADE after prolonged abstinence. Overall, these findings indicate that the P rat can be effectively used in models assessing alcohol-preference, a genetic predisposition for alcohol abuse and/or alcoholism, and excessive drinking using protocols of binge-like or relapse-like drinking. [source] Etomidate for Pediatric Sedation Prior to Fracture ReductionACADEMIC EMERGENCY MEDICINE, Issue 1 2001Richard Dickinson MD Abstract. Objective: While etomidate is reported as a procedural sedative in adults, its use in children has not been extensively reported. The authors describe their experience with etomidate for procedural sedation in children with extremity fractures and major joint dislocations. Methods: This was a retrospective descriptive chart review. The setting was a university-based emergency department (ED) that follows national guidelines for procedural sedation. Subjects were children less than 18 years old who received etomidate prior to fracture reduction or major joint dislocations. Standardized data were abstracted from the medical records, including patient demographics, diagnosis, weight, types and doses of sedative and analgesic agents used, number of boluses of etomidate, attempts at reduction, complications encountered, vitals signs before, during, and after the reduction, disposition, and the time from procedure to discharge. Descriptive statistics calculated included means and proportions with 95% confidence intervals. Results: Fifty-three children received etomidate for fracture reduction. Their mean age was 9.7; 41.5% were females. Indications for reduction included forearm fractures (38), ankle fractures (12), upper arm fractures (2), and hip dislocations (1). In most cases (83%) reduction was successful after one attempt only. The mean initial and total doses of etomidate were 0.20 mg/kg (range, 0.1 to 0.4) and 0.24 mg/kg (range, 0.13 to 0.52), respectively. Thirteen patients required a second bolus of etomidate or midazolam. Thirty-four patients (64%) were discharged from the ED after a mean observation of 94 minutes (range, 35 to 255). There were no major adverse events (95% CI = 0% to 5.7%). One patient reported nausea and one required a fluid bolus for hypotension. One patient receiving multiple sedatives and opioid analgesics was admitted for observation due to prolonged sedation. No patient required assisted ventilation or intubation. Conclusions: These results suggest that etomidate is a safe and effective agent for procedural sedation in children requiring fracture and major joint reductions. [source] Interrater reliability of the Psychiatric Research Interview for Substance and Mental Disorders in an HIV-infected cohort: experience of the National NeuroAIDS Tissue ConsortiumINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2006S. Morgello Abstract The interrater reliability of the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) was assessed in a multicentre study. Four sites of the National NeuroAIDS Tissue Consortium performed blinded reratings of audiotaped PRISM interviews of 63 HIV-infected patients. Diagnostic modules for substance-use disorders and major depression were evaluated. Seventy-six per cent of the patient sample displayed one or more substance-use disorder diagnoses and 54% had major depression. Kappa coefficients for lifetime histories of substance abuse or dependence (cocaine, opiates, alcohol, cannabis, sedative, stimulant, hallucinogen) and major depression ranged from 0.66 to 1.00. Overall the PRISM was reliable in assessing both past and current disorders except for current cannabis disorders when patients had concomitant cannabinoid prescriptions for medical therapy. The reliability of substance-induced depression was poor to fair although there was a low prevalence of this diagnosis in our group. We conclude that the PRISM yields reliable diagnoses in a multicentre study of substance-experienced, HIV-infected individuals. Copyright © 2006 John Wiley & Sons, Ltd. [source] Concurrent Detection of Heroin, Fentanyl, and Xylazine in Seven Drug-related Deaths Reported from the Philadelphia Medical Examiner's OfficeJOURNAL OF FORENSIC SCIENCES, Issue 2 2008Stella C. Wong D.O. Abstract:, Recreational drugs, such as cocaine and heroin, are often adulterated with other pharmacological agents to either enhance or diminish the drug effects. Between April 21, 2006 and August 8, 2006, the Philadelphia Medical Examiner's Office detected xylazine (a veterinary sedative) and fentanyl (a synthetic opioid) in specimens taken from seven cases. Initial immunoassay screening was performed on urine and blood for fentanyl, opiate, cocaine, phencyclidine (PCP), and benzodiazepines. All tests reported positive were confirmed by gas chromatography-mass spectrometry. All seven xylazine positive cases tested positive for fentanyl and six cases tested positive for 6-acetylmorphine (a metabolite and definitive marker for heroin). The seventh case was positive for morphine and had a history of heroin abuse. Xylazine was present in urine in all seven cases and blood levels were detected in three cases. The blood concentrations ranged from trace to 130 ng/mL. Fentanyl was present in the blood and urine in each case and blood concentrations ranged from 4.7 to 47 ng/mL. Adulteration of illicit drugs has become an epidemic health concern for drug users. Healthcare professionals need to be aware of this issue, so the patients can be treated in an effective, timely manner. [source] Subjective Response to Alcohol: A Critical Review of the LiteratureALCOHOLISM, Issue 3 2010Meghan E. Morean Background:, Subjective response to alcohol (SR), which reflects individual differences in sensitivity to the pharmacological effects of alcohol, may be an important endophenotype in understanding genetic influences on drinking behavior and alcohol use disorders (AUDs). SR predicts alcohol use and problems and has been found to differ by a range of established risk factors for the development of AUDs (e.g., family history of alcoholism). The exact pattern of SR associated with increased risk for alcohol problems, however, remains unclear. The Low Level of Response Model (LLR) suggests that high-risk individuals experience decreased sensitivity to the full range of alcohol effects, while the Differentiator Model (DM) asserts that high risks status is associated with increased sensitivity to alcohol's positive effects but decreased sensitivity to negative effects. Aims:, The current paper (1) reviews two prominent models of subjective response, (2) reviews extant laboratory-based research on subjective response, (3) highlights remaining gaps in our understanding and assessment of subjective response, and (4) encourages collaborative efforts to address these methodological and conceptual concerns. Methods:, This paper reviews studies which employed placebo-controlled and non-placebo-controlled alcohol challenge paradigms to assess a range of alcohol effects including impairment, stimulation, and sedation. Results:, The research literature provides at least partial support for both the LLR and DM models. High-risk individuals have been shown to have a reduced response to alcohol with respect to sedative or impairing effects, particularly on the descending limb of the blood alcohol curve (BAC). There is also evidence that ascending limb stimulant effects are more pronounced or operate differently for high-risk individuals. Discussion:, Despite commendable advances in SR research, important questions remain unanswered. Inconsistent results across studies may be attributable to a combination of an inadequate understanding of the underlying construct and methodological differences across studies (e.g., number and timing of assessments across the BAC, inclusion of a placebo condition). With respect to the underlying construct, existing measures fail to adequately distinguish between cognitive/behavioral impairment and sedation, aspects of which may be perceived positively (e.g., anxiolysis) due to their ability to act as negative reinforcers. Conclusions:, Addressing the concerns raised by the current review will be integral to making meaningful scientific progress in the field of subjective response. [source] Thr105Ile, a Functional Polymorphism of Histamine N-Methyltransferase, Is Associated with Alcoholism in Two Independent PopulationsALCOHOLISM, Issue 3 2005Gabor Oroszi Background: Histamine is expressed in cortical and limbic areas that are involved in emotion and cognition and modulates these behaviors. H1 receptor antagonists are sedative. Histamine N-methyltransferase (HNMT) catalyzes the N, methylation of histamine, the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain. A common and functionally significant polymorphism, a C314T transition in exon 4 of the HNMT gene results in a Thr105Ile substitution of the protein encoded. The Thr105 allele is associated with ,2-fold higher enzyme activity, leading to the prediction that it might be associated with diminished histamine levels, resulting in differences in anxiety, cognition, and sedation that play important roles in alcoholism. In two ethnically distinct populations, we tested whether the Thr105Ile polymorphism was associated with alcoholism and with harm avoidance, a dimensional measure of anxious personality. Methods: A 5, exonuclease assay (TaqMan) was used to genotype Thr105Ile in psychiatrically interviewed Finnish Caucasian (n= 218) and Plains American Indian (n= 186) alcoholics, along with ethnically matched, psychiatrically interviewed, controls (Finns: n= 313, Plains Indian: n= 140). Results: Ile105 allele frequencies were significantly lower in alcoholics compared with nonalcoholics in both populations (Finns: 0.12 vs. 0.17, ,2= 6, p= 0.015; Plains Indians: 0.03 vs. 0.08, ,2= 5, p= 0.023). Genotype distributions also differed significantly. In Finns, Ile105 showed borderline significance for an association with lower harm avoidance (p= 0.070) after correcting for alcoholism diagnosis. Conclusions: Decreased levels of brain histamine consequent to the Thr105 allele may result in higher levels of anxiety and, as a consequence, vulnerability to alcoholism. [source] Parental presence during induction enhances the effect of oral midazolam on emergence behavior of children undergoing general anesthesiaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2007Y.-C. P. Arai Background:, Pre-anesthetic anxiety and emergence agitation are major challenges for anesthesiologists in pediatric anesthesia. Thus, sedative premedication and parental presence during induction of anesthesia (PPIA) are used to treat pre-anesthetic anxiety in children. The aim of the present study was to test if a combination of mother presence and midazolam premedication is effective for improving emergence condition in children undergoing general anesthesia. Methods:, Sixty children were allocated to one of three groups: a sedative group (0.5 mg/kg oral midazolam), a PPIA group or a sedative and PPIA group. When anesthesia was induced with 7% sevoflurane in 100% oxygen, qualities of mask induction were rated. Anesthesia was maintained with sevoflurane (1.5,2.5%) in 60% oxygen and intravenous fentanyl 4 ,g/kg. During emergence from anesthesia, the score of the child's emergence behavior was rated. Results:, The children in the midazolam group showed a better quality of mask induction compared with those in the PPIA group, the addition of parental presence to oral midazolam did not provide additional improvement of mask induction. In contrast, the children in the midazolam + PPIA group were less agitated than those in the other groups at emergence from anesthesia. Conclusion:, Parental presence during induction of anesthesia enhanced the effect of oral midazolam on emergence behavior of children undergoing general anesthesia. [source] Genetic Control of Acute Ethanol-Induced Behaviors in DrosophilaALCOHOLISM, Issue 8 2000Carol M. Singh Background: In most organisms in which acute ethanol exposure has been studied, it leads to similar changes in behavior. Generally, low ethanol doses activate the central nervous system, whereas high doses are sedative. Sensitivity to the acute intoxicating effects of ethanol is in part under genetic control in rodents and humans, and reduced sensitivity in humans predicts the development of alcoholism (Crabbe et al., 1994; Schuckit, 1994). We have established Drosophila melanogaster as a model organism to study the mechanisms that regulate acute sensitivity to ethanol. Methods: We measured the effects of ethanol vapor on Drosophila locomotor behaviors by using three different assays. Horizontal locomotion was quantified in a locomotor chamber, turning behavior was assayed in narrow tubes, and ethanol-induced loss of postural control was measured in an inebriometer. Mutants with altered sensitivity to the acute effects of ethanol were generated by treatment with ethyl methane sulfonate and isolated by selection in the inebriometer. We ascertained the effects of these mutations on ethanol pharmacokinetics by measuring ethanol levels in extracts of flies at various times during and after ethanol exposure. Results: Among nearly 30,000 potentially mutant flies tested, we isolated 19 mutant strains with reduced and 4 strains with increased sensitivity to the acute effects of ethanol as measured in the inebriometer. Of these mutants, four showed changes in ethanol absorption. Two mutants, named barfly and tipsy to reflect their reduced and increased ethanol sensitivity in the inebriometer, respectively, were analyzed for locomotor behaviors. Both mutants exhibited ethanol-induced hyperactivity that was indistinguishable from wild type. However, barfly and tipsy displayed reduced and increased sensitivity to the sedative effects of ethanol, respectively. Finally, both mutants showed an increased rate of ethanol-induced turning behavior. Conclusions: The effects of acute ethanol exposure on Drosophila locomotor behaviors are remarkably similar to those described for mammals. The analysis of mutants with altered sensitivity to ethanol revealed that the genetic pathways which regulate these responses are complex and that single genes can affect hyperactivity, turning, and sedation independently. [source] Correlation between serum concentrations following continuous intravenous infusion of dexmedetomidine or medetomidine in cats and their sedative and analgesic effectsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2000Ansah Dexmedetomidine (DEX) may have some therapeutic advantages over the racemate medetomidine (MED). Here we have examined how serum concentrations of DEX correlate with some of its anaesthetic effects. Cats (n = 6) were administered with a continuous stepwise intravenous (i.v.) infusion of DEX or MED on different occasions in a cross-over design. Maintenance infusion rates (mg/kg/min) used were: DEX = 0.25 (MED = 0.50); DEX = 1 (MED = 2) and DEX = 4 (MED = 8) for infusion steps 1, 2 and 3, respectively. Each maintenance infusion lasted at least 50 min and was preceded with a loading dose. There was no significant difference between serum DEX and 0.5 serum MED concentrations at any dose level nor was there a significant difference between serum DEX and the (entire) serum MED concentrations. There was no significant difference between DEX and MED for sedation, analgesia, muscular relaxation and heart and respiratory rates. For both DEX and MED, serum drug concentration and analgesia were dose-dependent and sedation increased until the end of infusion step 2 (dose level 2) and decreased at the end of step 3 (dose level 3). Muscular relaxation was not dose-dependent. We conclude that increasing the blood concentration of DEX or MED beyond a certain level decreases the level of sedation instead of increasing it even though analgesia increases. The rate at which DEX and MED are metabolized in cats may not be the same. [source] Clinical trial: a dose,response study of fospropofol disodium for moderate sedation during colonoscopyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2008L. B. COHEN Summary Background, An effective agent is needed that provides rapid onset of sedation and quick recovery for patients undergoing colonoscopy. Aim, To assess the efficacy and safety of fospropofol disodium in providing sedation in patients undergoing colonoscopy. Methods, A randomized, double-blind, multicentre trial evaluated 127 adult patients who received fospropofol (2, 5, 6.5 or 8 mg/kg) or midazolam 0.02 mg/kg following pre-treatment with fentanyl. Supplemental doses of study medication were allowed to reach a Modified Observer's Assessment of Alertness/Sedation scale score ,4. Efficacy end points included sedation success, measures of clinical benefit, sedation, and recovery as well as patient- and doctor-rated satisfaction. Results, Fospropofol produced a significant dose-dependent increase in sedation success from 24% (2 mg/kg), 35% (5 mg/kg) and 69% (6.5 mg/kg) to 96% (8 mg/kg; P < 0.001). There were also dose-dependent trends for time to sedation, requirements for alternative sedative medication, supplemental doses of sedative and fentanyl, time to ready for discharge and doctor-rated satisfaction scores. Fospropofol was well tolerated, with most adverse events mild-to-moderate in severity. Conclusion, The 6.5 mg/kg dose of fospropofol provides the ideal balance of efficacy and safety for patients undergoing colonoscopy and has been selected for phase 3 clinical development. [source] Single-dose dexmedetomidine attenuates airway and circulatory reflexes during extubationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2005G. Guler Background:, The alpha agonist dexmedetomidine, a sedative and analgesic, reduces heart rate and blood pressure dose-dependently. We investigated whether it also has the ability to attenuate airway and circulatory reflexes during emergence from anaesthesia. Methods:, Sixty ASA I,III patients received a standard anaesthetic. Five minutes before the end of surgery, they were randomly allocated to receive either dexmedetomidine 0.5 µg/kg (Group D) (n = 30) or saline placebo (Group P) (n = 30) intravenously (i.v.) over 60 s in a double-blind design. The blinded anaesthetist awoke all the patients, and the number of coughs per patient was continuously monitored for 15 min after extubation; coughing was evaluated on a 4-point scale. Any laryngospasm, bronchospasm or desaturation was recorded. Heart rate (HR) and systolic and diastolic blood pressure (SAP, DAP) were measured before, during and after tracheal extubation. The time from tracheal extubation and emergence from anaesthesia were recorded. Results:, Median coughing scores were 1 (1,3) in Group D and 2 (1,4) in Group P (P < 0.05), but there were no differences between the groups in the incidence of breath holding or desaturation. HR, SAP and DAP increased at extubation in both groups (P < 0.05), but the increase was less significant with dexmedetomidine. The time from tracheal extubation and emergence from anaesthesia were similar in both groups. Conclusion:, These findings suggest that a single-dose bolus injection of dexmedetomidine before tracheal extubation attenuates airway-circulatory reflexes during extubation. [source] Experiences of intensive care nurses assessing sedation/agitation in critically ill patientsNURSING IN CRITICAL CARE, Issue 4 2008Stephanie Weir Abstract Background:, Patients admitted to the intensive care unit (ICU) will more often than not require sedative and analgesic drugs to enable them to tolerate the invasive procedures and therapies caused as a result of their underlying condition and/or necessary medical interventions. Aim:, This article reports a study exploring the perceptions and experiences of intensive care nurses using a sedation/agitation scoring (SAS) tool to assess and manage sedation and agitation amongst critically ill patients. The principle aims and objectives of this study were as follows: ,,to explore nurse's everyday experiences using a sedation scoring tool; ,,to explore and understand nurse's attitudes and beliefs of the various components of assessing and managing sedation among critically ill patients. Method:, Using a descriptive qualitative approach, semistructured interviews were carried out with a purposive sample of eight ICU nurses within a district general hospital ICU. The interviews focused on nurse's own experiences and perceptions of using a sedation scoring tool in clinical practice. Burnard's 14-stage thematic content analysis framework was employed to assist in the data analysis process. Results:, Three key themes emerged that may have implications not only for clinical practice but for further research into the use of the SAS tool. ,,Benefits to patient care as a direct result of using a sedation scoring tool. ,,The concerns of nursing staff. ,,The implications of using such a tool in clinical practice. Conclusion:, This paper reinforces the potential benefits to patients as a direct result of implementing the SAS scoring tool and clinical guidelines. Furthermore, it highlights the reluctance of a number of staff to adhere to such guidelines and discusses the concerns regarding less experienced nurses administering sedative agents. Attention was also drawn to the educational requirements of nursing and medical staff when using the SAS scoring tool. [source] Midazolam as a sole sedative for computed tomography imaging in pediatric patientsPEDIATRIC ANESTHESIA, Issue 9 2009RANJU SINGH MD Summary Objective:, To evaluate the efficacy and adverse effects of i.v. midazolam as a sole agent for sedation in children for computed tomography (CT) imaging. Materials and Methods:, Prospective clinical trial in which 516 children under ASA classification II,IV (273 boys and 243 girls) in the age group of 6 months to 6 years for elective CT scan were enrolled over a 17-month period. Patients were administered i.v. midazolam 0.2 mg·kg,1 and further boluses of 0.1 mg·kg,1 (total 0.5 mg·kg,1) if required. Measurements included induction time, efficacy, side effects, complications, and degree of sedation. Sedation was graded on the basis of Ramsay sedation score (RSS) as over sedated (RSS 5,6), adequately sedated (AS, RSS 3,4), under sedated (RSS 1,2), or failed if the procedure could not be completed or another agent had to be administered. Results:, Of the 516 procedures, 483 brains, 16 chests, and 17 abdomens were scanned with a mean duration of 4.75 ± 1.75 min with a mean dose of 0.212 mg·kg,1 of i.v. midazolam. Four hundred and sixty-five (90.12%) patients were AS in 5.9 ± 0.7 min while 40 (7.75%) patients required additional boluses. Of these 40 patients, 24 (4.65%) required a single bolus, 12 (2.32%) required two boluses, whereas the remaining four (0.78%) required three boluses. In 11 (2.13%; P < 0.0001) patients, the scan could not be completed satisfactorily. Side effects were seen in 46 (9.11%) patients in the form of desaturation, hiccups (seven patients, 1.38%), and agitation (four patients, 0.79%). Desaturation (SpO2 90,95%) was seen in 35 (6.93%) patients, which was corrected by topical application of oxygen. None of the patients exhibited any complications such as pulmonary aspiration or need to maintain airway. The patients were kept under observation for 1 h after the procedure. Conclusion:, The level of sedation achieved in children with midazolam 0.2 mg·kg,1 is adequate for imaging with minimal side effects, no airway complications, and fast recovery. It can be recommended as the sole agent for sedation in pediatric patients for CT imaging. [source] Use of premedication for intubation in tertiary neonatal units in the United KingdomPEDIATRIC ANESTHESIA, Issue 7 2009RAJIV CHAUDHARY MBBS MRCPCH Summary Background:, Endotracheal intubation and laryngoscopy are frequently performed procedures in neonatal intensive care. These procedures represent profoundly painful stimuli and have been associated with laryngospasm, bronchospasm, hemodynamic changes, raised intracranial pressure and an increased risk of intracranial hemorrhage. These adverse changes can cause significant neonatal morbidity but may be attenuated by the use of suitable premedication. Aims:, To evaluate current practices for premedication use prior to elective intubation in UK tertiary neonatal units. Methods:, Telephone questionnaire survey of all 50 tertiary neonatal units in the UK. Results:, Ninety percent of units report the routine use of sedation prior to intubation and 82% of units routinely use a muscle relaxant. Morphine was the most commonly used sedative and suxamethonium was the most commonly used muscle relaxant. Approximately half of the units also used atropine during intubation. Seventy seven percent of units had a written policy for premedication. Ten percent of the units did not routinely use any sedatives or muscle relaxants for elective intubation. Conclusions:, In comparison with data from a 1998 survey, our study demonstrated an increase in the number of units that have adopted a written policy for premedication use, and in the number routinely using premedication drugs for elective intubation. There remains little consensus as to which drugs should be used and in what dose. [source] Current United Kingdom sedation practice in pediatric intensive carePEDIATRIC ANESTHESIA, Issue 7 2007IAN A. JENKINS FRCPE FRCA Summary Background:, The aim of this study was to investigate the current practice of sedation, analgesia, and neuromuscular blockade in critically ill children on pediatric intensive care units (PICUs) in the UK and identify areas that merit further study. Methods:, Data were gathered in a prospective observational study of 338 critically ill children in 20 UK PICUs. Results:, There is considerable variation in clinical practice. A total of 24 different sedative and analgesic agents were used during the study. The most commonly used sedative and analgesic agents were midazolam and morphine. Four different neuromuscular blockers (NMBs) were used, most commonly vecuronium. There were differences in treatment between cardiac and noncardiac children, but there were a greater number of infants and neonates in the cardiac group. NMBs were used in 30% of mechanically ventilated patients. Withdrawal symptoms were reported in 13% of ventilated patients, relatively early in their stay; weaning sedative agents (,tapering') was apparently of no benefit. The use of clonidine in this setting was noted. Physical restraints were used in 7.4%. Propofol was used but in only 2.6% of patients, all over the age of 4 years, and not exceeding 2 mg·kg,1·h,1. No side effects attributable to ,propofol syndrome' were noted. Conclusions:, There is considerable heterogeneity of sedation techniques. NMBs are used in a large portion of this population. Withdrawal symptoms were associated with higher doses of sedation and greater lengths of stay and were not ameliorated by withdrawing sedation gradually (,tapering'). [source] Increased risk of hip fracture in the elderly associated with prochlorperazine: is a prescribing cascade contributing?,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 9 2010Gillian E. Caughey Abstract Purpose To examine the prescribing of prochlorperazine secondary to the prescribing of a medicine which could lead to symptoms for which prochlorperazine is indicated and commonly used. Given the range of potential hypotensive, sedative, dystonic and other extra-pyramidal side effects associated with prochlorperazine, its association with hip fracture was also examined. Methods Prescription/event sequence symmetry analyses were undertaken from 1st January 2003 to 31st December 2006, using administrative claims data from the Department of Veterans' Affairs, Australia. This method assesses asymmetry in the distribution of an incident event (either prescription of another medicine or hospitalization) before and after the initiation of prochlorperazine. Crude and adjusted sequence ratios (ASR) with 95% confidence intervals (CI) were calculated. Results A total of 34,235 persons with incident use of prochlorperazine were identified during the study period. Statistically significant positive associations were found for a number of commonly used medicines, including cardiovascular medicines, NSAIDs, opioids and sedatives and the subsequent initiation of prochlorperazine that ranged from 1.07 (95%CI 1.01,1.14) for diuretics to 1.50 (95%CI 1.40,1.61) for statins. Prescription event analysis showed a 49% (95%CI 1.19,1.86) increased risk of hospitalisation for hip fracture following dispensing of prochlorperazine. Conclusions Prescribers should consider the possible contributing role of newly initiated medicines with the potential to cause of dizziness, and where possible address this through dose reduction or cessation of the medicine, rather than prescribing prochlorperazine. Copyright © 2010 John Wiley & Sons, Ltd. [source] Evaluation of anxiolytic activity of spray dried powders of two South Brazilian Passiflora speciesPHYTOTHERAPY RESEARCH, Issue 5 2006Flįvio H. Reginatto Abstract The Passiflora extracts have been used in folk medicine because of its reputed sedative and anxiolytic properties. The present study aimed to compare the potential anxiolytic activity of two Passiflora spray-dried powders obtained from P. alata and P. edulis, known in Brazil as ,maracujį'. Male adult Swiss rats were treated with 200, 400 and 800 mg/kg of spray-dried powders p.o. and anxiolytic activity was evaluated using the elevated plus-maze test. The spray-dried powders showed anxiolytic activity in doses of 400 and 800 mg/kg. Our results support the potential anxiolytic effect of Passiflora spray-dried powders (P. alata and P. edulis). Copyright © 2006 John Wiley & Sons, Ltd. [source] Free radical scavenging capacity and protective effect of Bacopa monniera L. on DNA damagePHYTOTHERAPY RESEARCH, Issue 8 2003Alessandra Russo Abstract Bacopa monniera L. (family Scrophulariaceae) (BM) is an Ayurvedic medicine, clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative. In this work, the free radical scavenging capacity of a methanol extract of BM and the effect on DNA cleavage induced by H2O2 UV-photolysis was investigated. In addition, we examined whether this plant extract is capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized ,broblasts. It showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage. These results were con,rmed by a signi,cant protective effect on H2O2 , induced cytoxicity and DNA damage in human non-immortalized ,broblasts. The antioxidant capacity of BM may explain, at least in part, the reported antistress, immunomodulatory, cognition-facilitating, antiin,ammatory and antiaging effects produced by it in experimental animals and in clinical situations and may justify further investigation of its other bene,cial properties. Moreover, this experimental evidence suggests that because of its antioxidant activity, this Ayurvedic drug may be useful in the treatment of human pathologies in which free radical production plays a key role. Copyright © 2003 John Wiley & Sons, Ltd. [source] Sedative and anticonvulsant activities of goodyerin, a flavonol glycoside from Goodyera schlechtendalianaPHYTOTHERAPY RESEARCH, Issue 3 2002Xiao-Ming Du Abstract Goodyerin is a flavonol glycoside isolated from the whole plants of Goodyera schlechtendaliana which has been used as a substitute for the crude drug, Anoectochilus formosanus. The pharmacological properties of goodyerin were assayed for effects on spontaneous locomotor activity, on pentobarbital-induced hypnosis, and on anticonvulsant activity against picrotoxin-induced seizures in rodents. Goodyerin exhibited a significant and dose-dependent sedative and anticonvulsant effect. Copyright © 2002 John Wiley & Sons, Ltd. [source] Use of remifentanil as a sedative agent in critically ill adult patients: a meta-analysisANAESTHESIA, Issue 12 2009J. A. Tan Summary This meta-analysis examined the benefits of using remifentanil as a sedative agent in critically ill patients. A total of 11 randomised controlled trials, comparing remifentanil with another opioid or hypnotic agent in 1067 critically ill adult patients, were identified from the Cochrane controlled trials register and EMBASE and MEDLINE databases, and subjected to meta-analysis. Remifentanil was associated with a reduction in the time to tracheal extubation after cessation of sedation (weighted-mean-difference ,2.04 h (95% CI ,0.39 to ,3.69 h); p = 0.02). Remifentanil was, however, not associated with a significant reduction in mortality (relative risk 1.01 (95% CI 0.67,1.52); p = 0.96), duration of mechanical ventilation, length of intensive care unit stay, and risk of agitation (relative risk 1.08 (95% CI 0.64,1.82); p = 0.77) when compared to an alternative sedative or analgesic agent. The current evidence does not support the routine use of remifentanil as a sedative agent in critically ill adult patients. [source] Bilateral ankle blocks: A prospective auditANZ JOURNAL OF SURGERY, Issue 1-2 2005Glenda E Rudkin Background: There are significant advantages to the practice of bilateral ankle block. However, clinicians are reluctant to employ this technique due to concerns over reliability, local anaesthetic longevity and toxicity, surgical efficiency, and patient comfort. Methods: Sixty-six patients undergoing bilateral ankle blocks during mid- and forefoot surgery were audited to determine success rate, local anaesthetic safety and efficacy, and patient acceptance. Intravenous sedation was administered both during insertion of ankle blocks and intraoperatively, as requested by the patient and as deemed necessary by the anaesthetist. The choice of local anaesthesia was either a 50/50 mixture of lignocaine 1.5% plain and ropivacaine 7.5 mg/mL, ropivacaine 7.5 mg/mL alone or ropivacaine 7.5 mg/mL and clonidine 1 µg/kg. Results: A total of 89% of patients had a successful bilateral ankle block. Ropivacaine and clonidine combination, ropivacaine, and ropivacaine and lignocaine combination provided a mean length of action of 17 h, 14 h and 8 h, respectively. No adverse local anaesthetic events were reported. Sixty-one per cent of patients remembered intraoperative events; only one patient would choose not to have the procedure performed again under ankle blocks. Conclusions: The present audit demonstrates that bilateral ankle blocks are a safe and efficient technique. With appropriate doses of sedative drugs both during insertion of the ankle block and surgery, patients remain comfortable. [source] Potential benefit of clove oil sedation on animal welfare during salmon smolt, Salmo salar L. transport and transfer to seaAQUACULTURE RESEARCH, Issue 2 2009Martin Iversen Abstract The purpose of this study was to determine the effect of clove oil (4.0 mg L,1) sedation, compared with non-sedation, on the primary (plasma cortisol), secondary (osmoregulation) and tertiary (mortality) stress responses in Atlantic salmon smolts during transport and transfer to sea. Clove oil sedation during on- and off-loading sufficiently reduced the primary stress response to lower mortality (2.1%) during transfer to sea compared with unsedated fish, which experienced a mortality rate above 12.2%. The unsedated fish experienced an acute mortality that stabilized only 6 days after the transport. None of the secondary stress responses measured in this experiment could contribute towards explaining this phenomenon, with the possible exception of plasma magnesium (Mg2+). Plasma Mg2+ differed between the groups; while plasma Mg2+ in the clove oil sedated group returned to pre-stress levels 72 h after transport, the unsedated group showed no such recovery even 1 week after transport, which may indicate a disturbance in the hydromineral balance, and provides a plausible explanation for the delayed mortality in this group. Eugenol-based anaesthetics appear to be promising as a stress-reducing sedative for Atlantic salmon smolts, and, if used properly, this chemical could improve animal welfare and survivability during and after common aquaculture-related incidents. [source] An audit of the prevalence of recorded nicotine dependence treatment in an Australian psychiatric hospitalAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 3 2010Paula Wye Abstract Objectives: To investigate the prevalence of recorded smoking status, nicotine dependence assessment, and nicotine dependence treatment provision; and to examine the patient characteristics associated with the recording of smoking status. Method: A retrospective systematic medical record audit was conducted of all psychiatric inpatient discharges over a six-month period (1 September 2005 to 28 February 2006), at a large Australian psychiatric hospital, with approximately 2,000 patient discharges per year. A one-page audit tool identifying patient characteristics and prevalence of recorded nicotine dependence treatment, and requiring ICD-10-AM diagnoses coding was used. Results: From 1,012 identified discharges, 1,000 medical records were available for audit (99%). Documentation of smoking status most frequently occurred on the admission form (28.8%) and diagnoses summary (41.6%). Documentation of nicotine dependence was not found in any record, and recording of any nicotine dependence treatment was negligible (0-0.5%). The rate of recorded smoking status on discharge summaries was 6%. Patients with a diagnosis of alcohol, cannabis, sedative use disorders or asthma were twice as likely to have their smoking status recorded compared to those who did not have these diagnoses. Conclusions: Mental health services, by failing to diagnose and document treatment for nicotine dependence, do not conform to current clinical practice guidelines, despite nicotine dependence being the most commonly diagnosed psychiatric disorder. Implications: Considerable system change and staff support is required to provide an environment where a primary prevention approach such as smoking care can be sustained. [source] Effects of the Non-Competitive NMDA Receptor Antagonist Memantine on the Volitional Consumption of Ethanol by Alcohol-Preferring RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2010Gloria E. Malpass This study examined the effects of memantine, a low-affinity, open channel NMDA antagonist, on volitional consumption of ethanol by alcohol-preferring rats and potential locomotor, sedative and hypothermic effects. Volitional consumption of ethanol in a 24-hr two-choice paradigm was determined for male Myers' high-ethanol-preferring (mHEP) rats. Effects of memantine (0.3, 1.0, 3.0 and 10.0 mg/kg, i.p., b.i.d. [twice daily] for 3 days) or vehicle on volitional consumption of ethanol, proportion of ethanol to total fluids consumed, total fluid intake and consumption of food were observed. Potential sedating and locomotor effects of memantine (10.0 mg/kg, i.p., b.i.d.) were determined using an elevated plus maze and an Auto-Track Opto-Varimex activity monitoring system. Rectal temperature was measured to determine if memantine (10.0 mg/kg, i.p.) produces a hypothermic effect. The results indicate that memantine dose-dependently decreased the amount of ethanol and proportion of ethanol to total fluids consumed daily, reaching 48% and 24%, respectively, at the highest dose. These effects did not appear to be anti-caloric. Memantine (10.0 mg/kg) partially reversed both the sedation and the reductions in locomotor activity induced by ethanol. This dose did, however, produce a small, partially reversible hypothermic effect. In conclusion, memantine may decrease ethanol consumption with fewer side effects than other NMDA receptor antagonists, such as phencyclidine (PCP), MK 801 and ketamine. [source] A nitric oxide (NO)-releasing derivative of gabapentin, NCX 8001, alleviates neuropathic pain-like behavior after spinal cord and peripheral nerve injuryBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2004Wei-Ping Wu Nitric oxide (NO) participates, at least in part, to the establishment and maintenance of pain after nerve injury. Therefore, drugs that target the NO/cGMP signaling pathway are of interest for the treatment of human neuropathic pain. Various compounds endowed with NO-releasing properties modulate the expression and function of inducible nitric oxide synthase (iNOS), the key enzyme responsible for sustained NO production under pathological conditions including neuropathic pain. With this background, we synthesized a new chemical entity, [1-(aminomethyl)cyclohexane acetic acid 3-(nitroxymethyl)phenyl ester] NCX8001, which has a NO-releasing moiety bound to gabapentin, a drug currently used for the clinical management of neuropathic pain. We examined the pharmacological profile of this drug with respect to its NO-releasing properties in vitro as well as to its efficacy in treating neuropathic pain conditions (allodynia) consequent to experimental sciatic nerve or spinal cord injuries. NCX8001 (1,30 ,M) released physiologically relevant concentrations of NO as it induced a concentration-dependent activation of soluble guanylyl cyclase (EC50=5.6 ,M) and produced consistent vasorelaxant effects in noradrenaline-precontracted rabbit aortic rings (IC50=1.4 ,M). NCX8001, but not gabapentin, counteracted in a concentration-dependent fashion lipopolysaccharide-induced overexpression and function of iNOS in RAW264.7 macrophages cell line. Furthermore, NCX8001 also inhibited the release of tumor necrosis factor alpha (TNF,) from stimulated RAW264.7 cells. NCX8001 (28,280 ,mol kg,1, i.p.) reduced the allodynic responses of spinal cord injured rats in a dose-dependent fashion while lacking sedative or motor effects. In contrast, gabapentin (170,580 ,mol kg,1, i.p.) resulted less effective and elicited marked side effects. NCX8001 alleviated the allodynia-like responses of rats to innocuous mechanical or cold stimulation following lesion of the sciatic nerve. This effect was not shared by equimolar doses of gabapentin. Potentially due to the slow releasing kinetics of NO, NCX8001 alleviated pain-like behaviors in two rat models of neuropathic pain in a fashion that is superior to its parent counterpart gabapentin. This new gabapentin derivative, whose mechanism deserves to be explored further, offers new hopes to the treatment of human neuropathic pain. British Journal of Pharmacology (2004) 141, 65,74. doi:10.1038/sj.bjp.0705596 [source] Stereoselective modulatory actions of oleamide on GABAA receptors and voltage-gated Na+ channels in vitro: a putative endogenous ligand for depressant drug sites in CNSBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2000Bernard Verdon cis -9,10-octadecenoamide (,oleamide') accumulates in CSF on sleep deprivation. It induces sleep in animals (the trans form is inactive) but its cellular actions are poorly characterized. We have used electrophysiology in cultures from embryonic rat cortex and biochemical studies in mouse nerve preparations to address these issues. Twenty ,Mcis -oleamide (but not trans) reversibly enhanced GABAA currents and depressed the frequency of spontaneous excitatory and inhibitory synaptic activity in cultured networks. cis -oleamide stereoselectively blocked veratridine-induced (but not K+ -induced) depolarisation of mouse synaptoneurosomes (IC50, 13.9 ,M). The cis isomer stereoselectively blocked veratridine-induced (but not K+ -induced) [3H]-GABA release from mouse synaptosomes (IC50, 4.6 ,M). At 20 ,Mcis -oleamide, but not trans, produced a marked inhibition of Na+ channel-dependent rises in intrasynaptosomal Ca2+. The physiological significance of these observations was examined by isolating Na+ spikes in cultured pyramidal neurones. Sixty-four ,Mcis -oleamide did not significantly alter the amplitude, rate of rise or duration of unitary action potentials (1 Hz). cis -Oleamide stereoselectively suppressed sustained repetitive firing (SRF) in these cells with an EC50 of 4.1 ,M suggesting a frequency- or state-dependent block of voltage-gated Na+ channels. Oleamide is a stereoselective modulator of both postsynaptic GABAA receptors and presynaptic or somatic voltage-gated Na+ channels which are crucial for synaptic inhibition and conduction. The modulatory actions are strikingly similar to those displayed by sedative or anticonvulsant barbiturates and a variety of general anaesthetics. Oleamide may represent an endogenous modulator for drug receptors and an important regulator of arousal. British Journal of Pharmacology (2000) 129, 283,290; doi:10.1038/sj.bjp.0703051 [source] | ||||||||||||||||||||||||||||||||||