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Benzodiazepines
Terms modified by Benzodiazepines Selected AbstractsRELUCTANCE OF OLDER PEOPLE TO DISCONTINUE LONG-TERM BENZODIAZEPINES AND RELATED HYPNOTICSJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2010BSc (Hons) Pharmacy, Sinead Jennings MB Bch BAO No abstract is available for this article. [source] Benzodiazepine misuse by illicit drug misusersADDICTION, Issue 2 2001Nicholas Seivewright First page of article [source] Benzodiazepine prescribing in elderly Australian general practice patientsAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 4 2007Alice Windle Abstract Objective: The use of benzodiazepines by elderly people is of limited therapeutic benefit and increases the risk of adverse events. This study aimed to examine the extent to which benzodiazepines are prescribed for elderly Australians. Methods: Data for 3,970 individuals aged 65 years or more were extracted from a general practice database. Benzodiazepine prescriptions for 2002 were reviewed. Results: Overall, 16% (95% CI 11,21%) of elderly patients had at least one benzodiazepine prescription. Females were almost twice as likely as males to be prescribed a benzodiazepine and prescription prevalence increased with age. Conclusions: Despite risks, benzodiazepines are widely prescribed for the elderly. Limited availability and cost of alternative therapies and pressures on the primary care system in Australia may contribute to their continued overuse. Implications: The prescribing of benzodiazepines for elderly Australians needs to be reduced by better managing sleep and anxiety problems. [source] Structure Activity Studies of a Novel Cytotoxic Benzodiazepine.CHEMINFORM, Issue 1 2004Anthony Boitano Abstract For Abstract see ChemInform Abstract in Full Text. [source] A New Series of Potent Benzodiazepine ,-Secretase Inhibitors.CHEMINFORM, Issue 18 2003Ian Churcher Abstract For Abstract see ChemInform Abstract in Full Text. [source] Methadone and impairment in apprehended driversADDICTION, Issue 3 2009Jean-Paul Bernard ABSTRACT Aims According to Norwegian guidelines, patients who are in opioid-assisted rehabilitation programmes are permitted to drive a motor vehicle provided that certain requirements are met. The purpose of this study was to investigate apprehended drivers who had methadone in their blood at the time of apprehension and, further, the relationship between blood methadone concentration and impairment as measured by the clinical test of impairment (CTI). Methods The division of Forensic Toxicology and Drug Abuse (DFTDA) at the Norwegian Institute of Public Heath analyses blood samples from all drivers suspected of driving under the influence of drugs nation-wide. Cases with positive results for methadone in blood were collected over the period 2001,2006. Results A total of 635 drivers with methadone found in their blood samples were identified. The majority of drivers were men (>80%), aged between 30 and 40 years. Methadone was the only psychoactive drug detected in blood in only 10 cases. Benzodiazepines were a frequent finding (in approximately 90% of cases). A significant difference in blood methadone concentration was found between cases where only methadone was detected [median 0.46 mg/l (range 0.19,0.65)] and cases where methadone was detected in combination with other psychoactive drugs [median 0.28 mg/l (range 0.06,1.24)]. A CTI had been carried out, in conjunction with blood sampling, in 577 of the cases. A concentration,impairment relationship was not seen for methadone in these cases. Conclusions Cases of driving impairment involving methadone alone were very rare, with combination use most frequent. No correlation between methadone concentration and impairment as judged by the CTI was seen either for these cases or for the material as a whole. [source] EFNS guideline on the diagnosis and management of alcohol-related seizures: report of an EFNS task forceEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2005G. Bråthen Despite being a considerable problem in neurological practice and responsible for one-third of seizure-related admissions, there is little consensus as to the optimal investigation and management of alcohol-related seizures. The final literature search was undertaken in September 2004. Consensus recommendations are given graded according to the EFNS guidance regulations. To support the history taking, use of a structured questionnaire is recommended. When the drinking history is inconclusive, elevated values of carbohydrate-deficient transferrin and/or gammaglutamyl transferase can support a clinical suspicion. A first epileptic seizure should prompt neuroimaging (CT or MRI). Before starting any carbohydrate containing fluids or food, patients presenting with suspected alcohol overuse should be given prophylactic thiamine parenterally. After an alcohol withdrawal seizure (AWS), the patient should be observed in hospital for at least 24 h and the severity of withdrawal symptoms needs to be followed. For patients with no history of withdrawal seizures and mild to moderate withdrawal symptoms, routine seizure preventive treatment is not necessary. Generally, benzodiazepines are efficacious and safe for primary and secondary seizure prevention; diazepam or, if available, lorazepam, is recommended. The efficacy of other drugs is insufficiently documented. Concerning long-term recommendations for non-alcohol dependant patients with partial epilepsy and controlled seizures, small amounts of alcohol may be safe. Alcohol-related seizures require particular attention both in the diagnostic work-up and treatment. Benzodiazepines should be chosen for the treatment and prevention of recurrent AWS. [source] Synthesis of Pyridodiazepinediones by Using the Ugi Multicomponent ReactionEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 28 2010An M. Van den Bogaert Abstract Benzodiazepines show a broad spectrum of biological activities. In an ongoing effort to extend molecular diversity in this type of systems, we developed a strategy for synthesizing3,4-dihydro-1H -pyrido[2,3- e][1,4]diazepine-2,5-dione compounds starting from 2-hydroxynicotinic acid and by using an Ugi reaction as a key step in the synthesis. We opted to use 2-isocyanophenyl benzoate instead of Armstrong's convertible isocyanide in this multicomponent reaction. [source] Benzodiazepines prescription in Dakar: a study about prescribing habits and knowledge in general practitioners, neurologists and psychiatristsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2006Amadou Moctar Dièye Abstract Benzodiazepines are relatively well-tolerated medicines but can induce serious problems of addiction and that is why their use is regulated. However, in developing countries like Senegal, these products are used without clear indications on their prescription, their dispensation or their use. This work focuses on the prescription of these medicines with a view to make recommendations for their rational use. Benzodiazepine prescription was studied with psychiatrists or neurologists and generalists in 2003. Specialist doctors work in two Dakar university hospitals and generalists in the 11 health centres in Dakar. We did a survey by direct interview with 29 of 35 specialists and 23 of 25 generalists. All doctors were interviewed in their office. The questionnaire focused on benzodiazepine indications, their pharmacological properties, benzodiazepines prescribed in first intention against a given disease and the level of training in benzodiazepines by doctors. Comparisons between specialists and generalists were made by chi-square test. Benzodiazepines were essentially used for anxiety, insomnia and epilepsy. With these diseases, the most benzodiazepines prescribed are prazepam against anxiety and insomnia and diazepam against epilepsy. About 10% of doctors do not know that there is a limitation for the period of benzodiazepine use. The principal reasons of drugs choice are knowledge of the drugs, habit and low side effects of drugs. All generalists (100%) said that their training on benzodiazepines is poor vs. 62.1% of specialists, and doctors suggest seminars, journals adhesions and conferences to complete their training in this field. There are not many differences between specialists and generalists except the fact that specialists prefer prazepam in first intention in the insomnia treatment where generalists choose bromazepam. In addition, our survey showed that specialists' training in benzodiazepines is better than that of generalists. Overall, benzodiazepine prescription poses problems particularly in training, and national authorities must take urgent measures for rational use of these drugs. [source] Self-report of memory and affective dysfunction in association with medication use in a sample of individuals with chronic sleep disturbanceHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2000Mary Pat McAndrews Abstract Benzodiazepines produce memory disturbance after acute administration. It is not clear whether chronic use of benzodiazepines is hazardous to memory processes. Epidemiological data indicate that a large proportion (10,30 per cent) of individuals with sleep dysfunction take hypnotic aids for a year or longer. The purpose of the present study was to evaluate self-reported memory dysfunction in a sample of individuals who considered their sleep disturbance sufficiently severe to seek investigation in sleep clinics. It was hypothesized that individuals taking benzodiazepines for sleep would report greater perceived everyday memory failures than individuals taking other sleep aids or no medication. Questionnaires were given to 368 individuals referred into the study by investigators in six sleep disorders clinics. All respondents completed a lengthy (700-item) questionnaire, which included scales assessing memory difficulties, affective status and sleep disturbance. Respondents also reported any medication use for sleep problems and duration of use of the current drug. Information on medication use was reported by 289 participants. Fifty-six per cent of respondents reported using some form of psychoactive medication (antidepressants, benzodiazepines, Zopiclone). Twenty-two per cent reported using no medication. Analysis of covariance showed that these medications had no detectable effect on subjective memory difficulties during chronic use, F(4,226)=1·34, p=0·25. Copyright © 2000 John Wiley & Sons, Ltd. [source] Cognitive toxicity of pharmacotherapeutic agents used in social anxiety disorderINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2009I. Hindmarch Summary Objective:, To compare cognitive impairment of medications used in social anxiety disorder (SAD). Methods:, Data from peer-reviewed publications (1975,2007) of controlled, crossover design, pharmacodynamic studies on SAD medications in healthy volunteers were analysed. The number of objective psychometrics for each drug/dose level at all time points after dosing, and of instances of statistically significant impairment of cognitive function, enabled calculation of drug-induced cognitive impairment. The magnitude of impairment between drugs was compared using proportional impairment ratios (PIRs). Results:, Olanzapine, oxazepam, lorazepam and mianserin had twice the average cognitive toxicity of other treatments. Selective serotonin reuptake inhibitors (SSRIs) impaired cognition to a lesser extent than other pharmacological groupings. There was extensive intra-class variation: fluvoxamine (PIR = 0.08) possessed little detrimental cognitive activity, whereas sertraline (PIR = 5.33) caused impairment over five times the SSRI group average. Benzodiazepines caused noticeable cognitive impairment. Conclusions:, Substantial differences exist, both between and within therapeutic classes, in the behavioural toxicity of medications used for SAD. [source] Trends in suicide from drug overdose in the elderly in England and Wales, 1993,1999INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2002Rajen Shah Abstract Background Drug overdose is a common method of suicide in the elderly. Hence, an understanding of current trends in epidemiology of these deaths is important when considering measures to decrease suicide rates. Methods Analysis of the Office for National Statistics (ONS) database of deaths from overdose and poisoning. Suicide and undetermined deaths from drug overdose between 1993,1999 in the over 65 year olds were studied. Socio-demographic data from the four drug groups most commonly used in overdose were extracted, and age and sex specific mortality rates calculated. Enumeration districts were ranked into five quintiles based on their Carstairs scores, and death rates in each quintile for men and women calculated. Results There were 1864 deaths from drug overdose during the study period. Suicide and undetermined death rates from drug overdose remained stable between 1993,1999. Drugs most commonly used in overdose were (in order) paracetamol (and related compounds), benzodiazepines, antidepressants, and opiates. Women comprised 62% of deaths. Death rates increased with age, with highest rates in men over 75 (37.7 deaths per million). Benzodiazepines showed the most marked increase with age. Co-proxamol comprised 32% of deaths from paracetamol compounds, and 95% of antidepressant deaths were due to tricyclic antidepressants. There was no association in women between Carstairs area deprivation and suicide rates; in men rates were highest in the most deprived areas. Conclusion Suicides in the over 65 year olds may be decreased by changes in prescription practice. Paracetamol, co-proxamol, tricyclic antidepressants and benzodiazepines should be prescribed with caution to the elderly with depression or at high risk of depression. Copyright © 2002 John Wiley & Sons, Ltd. [source] A Novel Strategy for the Construction of Functionalized 1,5- Benzodiazepines via a Tandem Conjugated Addition/Cyclization ProcessADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 2-3 2010Jian Li Abstract A novel approach for the synthesis of functionalized 1,5-benzodiazepine is described. The protocol is triggered by a tandem conjugated addition/cyclization process from the readily available starting materials 1,2-phenylenediamine and ethyl propiolate. The products have secondary amino and ester groups, and a ,-enamino ester, which can serve in further functionalizations to produce molecular diversity. [source] Premedication with clonidine is superior to benzodiazepines.ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010A meta analysis of published studies Background: Premedication is considered important in pediatric anesthesia. Benzodiazepines are the most commonly used premedication agents. Clonidine, an ,2 adrenoceptor agonist, is gaining popularity among anesthesiologists. The goal of the present study was to perform a meta-analysis of studies comparing premedication with clonidine to Benzodiazepines. Methods: A comprehensive literature search was conducted to identify clinical trials focusing on the comparison of clonidine and Benzodiazepines for premedication in children. Six reviewers independently assessed each study to meet the inclusion criteria and extracted data. Original data from each trial were combined to calculate the pooled odds ratio (OR) or the mean differences (MD), 95% confidence intervals [95% CI] and statistical heterogeneity were accessed. Results: Ten publications fulfilling the inclusion criteria were found. Premedication with clonidine, in comparison with midazolam, exhibited a superior effect on sedation at induction (OR=0.49 [0.27, 0.89]), decreased the incidence of emergence agitation (OR=0.25 [0.11, 0.58]) and produced a more effective early post-operative analgesia (OR=0.33 [0.21, 0.58]). Compared with diazepam, clonidine was superior in preventing post-operative nausea and vomiting (PONV). Discussion: Premedication with clonidine is superior to midazolam in producing sedation, decreasing post-operative pain and emergence agitation. However, the superiority of clonidine for PONV prevention remains unclear while other factors such as nausea prevention might interfere with this result. [source] The Role of Benzodiazepines in the Treatment of InsomniaJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2001Meta-Analysis of Benzodiazepine Use in the Treatment of Insomnia PURPOSE: To obtain a precise estimate of the efficacy and common adverse effects of benzodiazepines for the treatment of insomnia compared with those of placebo and other treatments. BACKGROUND: Insomnia, also referred to as disorder of initiating or maintaining sleep, is a common problem and its prevalence among older people is estimated to be 23% to 34%.1 The total direct cost in the United States for insomnia in 1995 was estimated to be $13.9 billion.2 The complaint of insomnia in older people is associated with chronic medical conditions; psychiatric problems, mainly depression, chronic pain, and poor perceived general condition;1,3,4 and use of sleep medications.5 Thus in most cases, insomnia is due to some other underlying problem and is not just a consequence of aging.6 Accordingly, the management of insomnia should focus on addressing the primary problem and not just short-term treatment of the insomnia. Benzodiazepines belong to the drug class of choice for the symptomatic treatment of primary insomnia.7 This abstract will appraise a meta-analysis that compared the effect of benzodiazepines for short-term treatment of primary insomnia with placebo or other treatment. DATA SOURCES: Data sources included articles listed in Medline from 1966 to December 1998 and the Cochrane Controlled Trials Registry. The medical subject heading (MeSH) search terms used were "benzodiazepine" (exploded) or "benzodiazepine tranquillizers" (exploded) or "clonazepam,""drug therapy,""randomized controlled trial" or "random allocation" or "all random,""human," and "English language." In addition, bibliographies of retrieved articles were scanned for additional articles and manufacturers of brand-name benzodiazepines were asked for reports of early trials not published in the literature. STUDY SELECTION CRITERIA: Reports of randomized controlled trials of benzodiazepine therapy for primary insomnia were considered for the meta-analysis if they compared a benzodiazepine with a placebo or an alternative active drug. DATA EXTRACTION: Data were abstracted from 45 randomized controlled trials representing 2,672 patients, 47% of whom were women. Fifteen studies included patients age 65 and older and four studies involved exclusively older patients. Twenty-five studies were based in the community and nine involved inpatients. The duration of the studies ranged from 1 day to 6 weeks, with a mean of 12.2 days and median of 7.5 days. The primary outcome measures analyzed were sleep latency and total sleep duration after a sleep study, subjects' estimates of sleep latency and sleep duration, and subjects' report of adverse effects. Interrater reliability was checked through duplicate, independent abstraction of the first 21 articles. Overall agreement was between 95% and 98% (kappa value of 0.90 and 0.95 accordingly) for classification of the studies and validity of therapy, and 76% (kappa value of 0.51) for study of harmful effects. A scale of 0 to 5 was used to rate the individual reports, taking into account the quality of randomization, blinding, follow-up, and control for baseline differences between groups. Tests for homogeneity were applied across the individual studies and, when studies were found to be heterogeneous, subgroup analysis according to a predefined group was performed. MAIN RESULTS: The drugs used in the meta-analysis included triazolam in 16 studies; flurazepam in 14 studies; temazepam in 13 studies; midazolam in five studies; nitrazepam in four studies; and estazolam, lorazepam, and diazepam in two studies each. Alternative drug therapies included zopiclone in 13 studies and diphenhydramine, glutethimide, and promethazine in one study each. Only one article reported on a nonpharmacological treatment (behavioral therapy). The mean age of patients was reported in 33 of the 45 studies and ranged between 29 and 82. SLEEP LATENCY: In four studies involving 159 subjects, there was sleep-record latency (time to fall asleep) data for analysis. The pooled difference indicated that the latency to sleep for patients receiving a benzodiazepine was 4.2 minutes (95% CI = (,0.7) (,9.2)) shorter than for those receiving placebo. Patient's estimates of sleep latency examined in eight studies showed a difference of 14.3 minutes (95% CI = 10.6,18.0) in favor of benzodiazepines over placebo. TOTAL SLEEP DURATION: Analysis of two studies involving 35 patients in which total sleep duration using sleep-record results was compared indicated that patients in the benzodiazepine groups slept for an average of 61.8 minutes (95% CI = 37.4,86.2) longer than those in the placebo groups. Patient's estimates of sleep duration from eight studies (566 points) showed total sleep duration to be 48.4 minutes (95% CI = 39.6,57.1) longer for patients taking benzodiazepines than for those on placebo. ADVERSE EFFECTS: Analysis of eight studies (889 subjects) showed that those in the benzodiazepine groups were more likely than those in the placebo groups to complain of daytime drowsiness (odds ratio (OR) 2.4, 95% confidence interval (CI) = 1.8,3.4). Analysis of four studies (326 subjects) also showed that subjects in the benzodiazepine groups were more likely to complain of dizziness or lightheadedness than the placebo groups. (OR 2.6, 95% CI = 0.7,10.3). Despite the increased reported side effects in the benzodiazepine groups, drop-out rates were similar in the benzodiazepine and placebo groups. For patient reported outcome, there was no strong correlation found for sleep latency data, (r = 0.4, 95% CI = (,0.3) (,0.9)) or for sleep duration (r = 0.2, 95% CI = ,0.8,0.4) between benzodiazepine dose and outcome. COMPARISON WITH OTHER DRUGS AND TREATMENTS: In three trials with 96 subjects, meta-analysis of the results comparing benzodiazepines with zopiclone, did not show significant difference in sleep latency in the benzodiazepine and placebo groups, but the benzodiazepine groups had increased total sleep duration (23.1 min. 95% CI = 5.6,40.6). In four trials with 252 subjects, the side effect profile did not show a statistically significant difference (OR 1.5, CI 0.8,2.9). There was only one study comparing the effect of behavioral therapy with triazolam. The result showed that triazolam was more effective than behavioral therapy in decreasing sleep latency, but its efficacy declined by the second week of treatment. Behavioral therapy remained effective throughout the 9-week follow-up period. There were four small trials that involved older patients exclusively, with three of the studies having less than 2 weeks of follow-up. The results were mixed regarding benefits and adverse effects were poorly reported. CONCLUSION: The result of the meta-analysis shows that the use of benzodiazepines results in a decrease in sleep latency and a significant increase in total sleep time as compared with placebo. There was also a report of significantly increased side effects, but this did not result in increased discontinuation rate. There was no dose-response relationship for beneficial effect seen with the use of benzodiazepines, although the data are scant. Zopiclone was the only alternative pharmacological therapy that could be studied with any precision. There was no significant difference in the outcome when benzodiazepines were compared with zopiclone. There was only one study that compared the effect of benzodiazepines with nonpharmacological therapy; thus available data are insufficient to comment. [source] Use of night-time benzodiazepines in an elderly inpatient populationJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2002M. Ramesh MPharm PGDCP FICP Aim:,To examine benzodiazepine prescribing for sleep induction in an elderly medical inpatient population to determine if hospital prescribing may have encouraged benzodiazepine use following discharge. Secondary objectives included assessment of quality of sleep in hospital compared with home and monitoring for possible benzodiazepine side-effects. Method:,Inpatient and discharge prescribing of benzodiazepines used for sleep induction were recorded in two medical wards over a 3-month period. A questionnaire was used to obtain information on patients' sleep patterns at home and in hospital. A follow-up telephone survey at 2,3 weeks post-discharge was made for those patients who were prescribed benzodiazepine at discharge. Results:,Benzodiazepines were prescribed for 20% of patients with 94% of prescriptions being for temazepam. Of the 54 patients prescribed benzodiazepines during admission, 57% were not taking a benzodiazepine at home prior to their hospital admission. At discharge, 14 patients were prescribed benzodiazepines for home use, eight of whom had not used them at home previously. On follow-up none of these eight patients expressed a desire to continue benzodiazepine use for sleep induction. There was a significant (P < 0·05) reduction in sleep onset latency and number of nocturnal awakenings in hospital when compared with home. There was no change in sleep duration and overall quality of sleep. There was an association between early morning insomnia and benzodiazepine use. Conclusion:,Discharge prescribing of benzodiazepines was appropriately limited to temazepam and did not encourage home use in previous non-users. Benzodiazepines (primarily temazepam) were effective in the short term for inducing sleep in the hospital setting, with little evidence of side-effects. [source] Diazepam Promotes ATP Recovery and Prevents Cytochrome c Release in Hippocampal Slices After In Vitro IschemiaJOURNAL OF NEUROCHEMISTRY, Issue 3 2000Francesca Galeffi Abstract: Benzodiazepines protect hippocampal neurons when administered within the first few hours after transient cerebral ischemia. Here, we examined the ability of diazepam to prevent early signals of cell injury (before cell death) after in vitro ischemia. Ischemia in vitro or in vivo causes a rapid depletion of ATP and the generation of cell death signals, such as the release of cytochrome c from mitochondria. Hippocampal slices from adult rats were subjected to 7 min of oxygen-glucose deprivation (OGD) and assessed histologically 3 h after reoxygenation. At this time, area CA1 neurons appeared viable, although slight abnormalities in structure were evident. Immediately following OGD, ATP levels in hippocampus were decreased by 70%, and they recovered partially over the next 3 h of reoxygenation. When diazepam was included in the reoxygenation buffer, ATP levels recovered completely by 3 h after OGD. The effects of diazepam were blocked by picrotoxin, indicating that the protection was mediated by an influx of Cl - through the GABAA receptor. It is interesting that the benzodiazepine antagonist flumazenil did not prevent the action of diazepam, as has been shown in other studies using the hippocampus. Two hours after OGD, the partial recovery of ATP levels occurred simultaneously with an increase of cytochrome c (,400%) in the cytosol. When diazepam was included in the reoxygenation buffer, it completely prevented the increase in cytosolic cytochrome c. Thus, complete recovery of ATP and prevention of cytochrome c release from mitochondria can be achieved when diazepam is given after the loss of ATP induced by OGD. [source] Antiglutamatergic Strategies for Ethanol Detoxification: Comparison With Placebo and DiazepamALCOHOLISM, Issue 4 2007Evgeny M. Krupitsky Background: Benzodiazepines are the standard pharmacotherapies for ethanol detoxification, but concerns about their abuse potential and negative effects upon the transition to alcohol abstinence drive the search for new treatments. Glutamatergic activation and glutamate receptor up-regulation contribute to ethanol dependence and withdrawal. This study compared 3 antiglutamatergic strategies for ethanol detoxification with placebo and to the benzodiazepine, diazepam: the glutamate release inhibitor, lamotrigine; the N -methyl- d -aspartate glutamate receptor antagonist, memantine; and the AMPA/kainite receptor inhibitor, topiramate. Methods: This placebo-controlled randomized single-blinded psychopharmacology trial studied male alcohol-dependent inpatients (n=127) with clinically significant alcohol withdrawal symptoms. Subjects were assigned to 1 of 5 treatments for 7 days: placebo, diazepam 10 mg TID, lamotrigine 25 mg QID, memantine 10 mg TID, or topiramate 25 mg QID. Additional diazepam was administered when the assigned medication failed to suppress withdrawal symptoms adequately. Results: All active medications significantly reduced observer-rated and self-rated withdrawal severity, dysphoric mood, and supplementary diazepam administration compared with placebo. The active medications did not differ from diazepam. Conclusions: This study provides the first systematic clinical evidence supporting the efficacy of a number of antiglutamatergic approaches for treating alcohol withdrawal symptoms. These data support the hypothesis that glutamatergic activation contributes to human alcohol withdrawal. Definitive studies of each of these medications are now needed to further evaluate their effectiveness in treating alcohol withdrawal. [source] Clonidine in paediatric anaesthesia: review of the literature and comparison with benzodiazepines for premedicationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2006H. Bergendahl Background:, Children undergoing anaesthesia and surgery can experience significant anxiety and distress during the peri-operative period, but whether routine premedication is necessary is currently debated. Benzodiazepines are the most frequently used drugs as premedication in paediatric anaesthesia. In the US, 50% of young children undergoing surgery receive premedication and midazolam is the most frequently used drug in this context (1). Nishina and coworkers (2) concluded in a review article in 1999 that clonidine, administered via an oral, rectal, or caudal route, is a promising adjunct to anaesthetics and analgesics to enhance quality of peri-operative management in infants and children. Later publications also support the use of clonidine for premedication (3,6). The aim of this communication is to review the use of clonidine in paediatric anaesthesia and to propose clonidine as a promising alternative to midazolam. Clonidine is associated with a number of beneficial effects in the context ofanaesthesia both in adults and children. Why clonidine is not routinely use in clinical practice despite the massive publication list is to a large extent due to the lack of marketing efforts from the pharmaceutical industry since multiplegeneric preparations are now readily available on most markets. Midazolam is also associated with a number of beneficial effects, but is far from an ideal premedicant in children, especially with regards to the amnesia, confusion and long term behavioural disturbances. Clonidine has contrary to midazolam no effect on respiration. We believe that clonidine is a good alternative to midazolam as premedication in infants and children. [source] Effects of midazolam on small bowel motility in humansALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2000Castedal Background: Benzodiazepines are used as sedatives for some intestinal procedures and as hypnotics, and this is the reason for studying their effects on duodenojejunal motility. Methods: Antroduodenojejunal manometry was performed in 13 healthy volunteers on two different occasions, when placebo or midazolam were given intravenously (randomized, double-blind). A bolus dose of midazolam 0.03 mg/kg was followed by 0.015 mg/kg after 1.5, 3 and 4.5 h. After 5 h observation of interdigestive motility, the volunteers were given a test meal and recording continued for another hour. Twenty-eight motility variables were compared. Results: With midazolam the median motility index of phase III in the proximal duodenum was increased by 37% (P < 0.05), which was a consequence of both a longer duration (P < 0.01) and higher pressure amplitudes (P < 0.05), compared with placebo. A longer duration (9%) of phase III was also seen in the distal duodenum (P < 0.05). With midazolam the duration of the migrating motor complex was shortened by 27% (P < 0.05). No statistically significant difference was found for the number of episodes of phase III registered (P=0.09), or for the other 22 motility variables compared including the duodenal retroperistalsis in late phase III. Conclusion: Midazolam does affect some aspects of duodenal motility, especially in the proximal part, but phase III-related retroperistalsis is not affected. [source] Considering the Risks of Benzodiazepines and Opioids TogetherPAIN MEDICINE, Issue 6 2010Lynn R. Webster MD No abstract is available for this article. [source] Benzodiazepines and injury: a risk adjusted model,,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2005Dustin D. French MA Abstract Background Benzodiazepines (BZD) are one class of medications that are generally acknowledged to be a risk factor for injuries. Objective Our objective was to link outpatient prescription data with clinical data in order to develop a risk adjusted binary model that associates BZD usage with the risk for a healthcare encounter for an injury. Methods In total, 3 years of outpatient BZD prescription data, totaling 133,872 outpatient BZD prescriptions for 13,745 patients for a VA medical center, were combined with data from inpatient and outpatient administrative databases. The model incorporated Elixhauser comorbidity measures with 1-year look back period, along with hospital discharges, marital status, age, mean arterial pressure and body mass index. The model also included the dose of the drug, converted to valium equivalents and its duration. The model was analyzed using generalized estimation equations (GEE). Results Dose, duration, discharges and various comorbidities were associated with an increased risk for injury, while being married reduced the risk. Increased body mass was associated with increased injury risk. Increased mean arterial pressure was associated with decreased risk. Conclusions These findings offer guidance on how specific combinations of risk factors and potential protective effects may impact accidental injury risk. Clinicians prescribing or adjusting BZDs can use these results to more accurately tailor medication regimens for a patient. Our findings suggest that clinicians should also consider the nature of the social support system available to the patient in assessing total injury risk. Copyright © 2004 John Wiley & Sons, Ltd. [source] Longitudinal patterns of new Benzodiazepine use in the elderly,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2004Gillian Bartlett PhD Abstract Purpose To characterize longitudinal patterns of Benzodiazepine use in the elderly. Methods Prospective cohort of 78,367 community-dwelling Quebec residents aged 66 years or more who were new Benzodiazepine users, was followed for 5 years, 1989,1994. Data acquired from four population-based, provincial administrative databases were used to create time-dependent measures of change in dosage, switching or adding Benzodiazepines for 11 drugs listed in the provincial formulary. Subject-specific Spearman's rank correlation coefficients between dose and time were used to measure the tendency of increasing dose with consecutive periods of use. Multiple logistic regression and generalized estimating equations (GEE) models evaluated subject characteristics associated with increasing dose. Results The mean duration of uninterrupted Benzodiazepine use was 75.5 days. The mean daily dose was about half the recommended adult daily dose but 8.6% of subjects exceeded the recommended adult dose. Some of them (28.8%) switched medications at least once and 8.2% filled two or more prescriptions concurrently. For women, older age at date of first prescription was associated with increasing dose over time (odds ratio (OR) for 10 year age increase,=,1.23, p,<,0.001). Conclusion Long periods of Benzodiazepine use are frequent among Quebec elderly. The evidence of increasing dose, particularly for older women, and long-duration of use has important implications for clinicians. Copyright © 2003 John Wiley & Sons, Ltd. [source] Benzodiazepines in catatonia associated with systemic lupus erythematosusPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 6 2006HUNG-YU WANG md Abstract, Neuropsychiatric disturbances are found in 50,70% of systemic lupus erythematosus (SLE) patients. However, there are rare cases of catatonia being described in SLE. Some studies have shown the effectiveness of high-dose steroid, plasma exchange and electroconvulsive therapy (ECT) in lupus catatonia. Herein are described two SLE patients with catatonia who had good response to i.v. diazepam (i.e. relief of catatonia symptoms). Patient 1, with mild cortical atrophy, had great improvement in catatonia symptoms on i.v. diazepam 150 mg during a period of 5 days. Patient 2, without cortical atrophy, had quick response to i.v. diazepam 10,20 mg. Both patients had no recurrence during 6-month follow up. In conclusion, benzodiazepines may play an important role in the treatment of catatonia associated with SLE if patients refuse ECT treatment. [source] Catatonia in childhood and adolescencePSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2003Ken Takaoka Abstract Child and adolescent catatonia has been poorly investigated. A literature review was undertaken to clarify phenomenology, diagnosis, etiology, and treatment as well as ethical problems of catatonia in childhood and adolescence. Although there are no accepted standardized criteria for catatonia in childhood and adolescence, catatonic features described by child psychiatrists are similar to Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria for catatonia. With respect to etiology, the motor and behavioral symptoms that are part of catatonia bear some similarities with those seen in autism. Several case reports suggest an association between catatonia and general medical conditions. Certain drugs abused by youngsters as well as prescribed medicine can induce catatonia. Regarding catatonic cases originally diagnosed as schizophrenia, it is unclear whether all of these cases should be identified as schizophrenia or whether some of them are pervasive developmental disorders that develop psychic features in adolescence. Environmental changes preceding the onset of catatonia in patients with mood disorder play a possibly important role. Examples that suggest stress-induced catatonia, although rare, also exist. A few patients exhibit features of malignant catatonia, some without taking neuroleptics and others having taken them. Benzodiazepines and electroconvulsive therapy are considered to be effective treatments for catatonic youngsters. [source] Intraarticular Lidocaine versus Intravenous Procedural Sedation with Narcotics and Benzodiazepines for Reduction of the Dislocated Shoulder: A Systematic ReviewACADEMIC EMERGENCY MEDICINE, Issue 8 2008Robert Warne Fitch MD Abstract Background:, Anterior shoulder dislocations commonly present to the emergency department (ED). The time associated with procedural sedation for the reduction of anterior shoulder dislocations can be lengthy and may require use of additional personnel. Complications associated with intravenous (IV) medications for procedural sedation are well documented. Objectives:, The aim was to determine if intraarticular lidocaine (IAL) injection is as effective as IV procedural sedation with narcotics and benzodiazepines for reduction of anterior shoulder dislocations. Methods:, This was a systematic review of randomized controlled trials (RCTs). The authors performed a PubMed, EMBASE, and Cochrane database search using key words: "shoulder dislocation" and "reduction" and retrieved every RCT published that compared the use of IV sedation to IAL as medication for reduction. Each manuscript was reviewed and the results of each was compared regarding medications used, success of reduction, complications, pain perceived, ease of reduction, and time spent in the ED. Results:, Six Level 1 RCTs were identified. No studies showed a statistically significant difference in success rate between IAL versus IV sedation. The complication rate was significantly higher in the IV sedation groups (p < 0.001), and the total time spent in the ED was longer for the IV sedation group. Conclusions:, The use of IAL for reduction of anterior shoulder dislocations should be strongly considered as a first line therapy because it is effective and safe and may potentially reduce time spent in the ED. [source] Benzodiazepines in epilepsy: pharmacology and pharmacokineticsACTA NEUROLOGICA SCANDINAVICA, Issue 2 2008J. Riss Benzodiazepines (BZDs) remain important agents in the management of epilepsy. They are drugs of first choice for status epilepticus and seizures associated with post-anoxic insult and are also frequently used in the treatment of febrile, acute repetitive and alcohol withdrawal seizures. Clinical advantages of these drugs include rapid onset of action, high efficacy rates and minimal toxicity. Benzodiazepines are used in a variety of clinical situations because they have a broad spectrum of clinical activity and can be administered via several routes. Potential shortcomings of BZDs include tolerance, withdrawal symptoms, adverse events, such as cognitive impairment and sedation, and drug interactions. Benzodiazepines differ in their pharmacologic effects and pharmacokinetic profiles, which dictate how the drugs are used. Among the approximately 35 BZDs available, a select few are used for the management of seizures and epilepsy: clobazam, clonazepam, clorazepate, diazepam, lorazepam and midazolam. Among these BZDs, clorazepate has a unique profile that includes a long half-life of its active metabolite and slow onset of tolerance. Additionally, the pharmacokinetic characteristics of clorazepate (particularly the sustained-release formulation) could theoretically help minimize adverse events. However, larger, controlled studies of clorazepate are needed to further examine its role in the treatment of patients with epilepsy. [source] ,Using the "benzodiazepine switch" in difficult childhood epilepsy'DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 8 2008Rajesh Chatha No abstract is available for this article. [source] Pharmacodynamic Analysis of the Interaction between Tiagabine and Midazolam with an Allosteric Model That Incorporates Signal TransductionEPILEPSIA, Issue 3 2003Daniël M. Jonker Summary: ,Purpose: The objective of this study was to characterize quantitatively the pharmacodynamic interaction between midazolam (MDL), an allosteric modulator of the ,-aminobutyric acid subtype A (GABAA) receptor, and tiagabine (TGB), an inhibitor of synaptic GABA uptake. Methods: The in vivo concentration,response relation of TGB was determined through pharmacokinetic/pharmacodynamic (PK/PD) modeling. Rats received a single intravenous dose of 10 mg/kg TGB in the absence and the presence of a steady-state plasma concentration of MDL. The EEG response in the 11.5- to 30-Hz frequency band was used as the pharmacodynamic end point. Results: Infusion of MDL resulted in a mean steady-state plasma concentration of 66 ± 3 ng/ml. A significant pharmacokinetic interaction with TGB was observed. MDL inhibited TGB clearance by 20 ± 7 ml/min/kg from the original value of 89 ± 6 ml/min/kg. However, no changes in plasma protein binding of both drugs were observed. The concentration,EEG relation of TGB was described by the sigmoid- Emax model. The pharmacodynamic parameter estimates of TGB were: Emax = 327 ± 10 ,V, EC50 = 392 ± 20 ng/ml, and nH = 3.1 ± 0.3. These values were not significantly different in the presence of MDL. Factors that may explain the lack of synergism were identified by a mechanism-based interaction model that separates the receptor activation from the signal-transduction process. High efficiency of signal transduction and the presence of a baseline response were shown to diminish the degree of synergism. Conclusions: We conclude that the in vivo pharmacodynamic interaction between MDL and TGB is additive rather than synergistic. This strongly suggests that allosteric modulation of the antiseizure activity of a GAT-1 inhibitor by a benzodiazepine does not offer a therapeutic advantage. [source] PRECLINICAL STUDY: Mice lacking Gad2 show altered behavioral effects of ethanol, flurazepam and gabaxadolADDICTION BIOLOGY, Issue 1 2010Yuri A. Blednov ABSTRACT ,-Aminobutyric acid (GABA) is synthesized in brain by two isoforms of glutamic acid decarboxylase (Gad), Gad1 and Gad2. Gad1 provides most of the GABA in brain, but Gad2 can be rapidly activated in times of high GABA demand. Mice lacking Gad2 are viable whereas deletion of Gad1 is lethal. We produced null mutant mice for Gad2 on three different genetic backgrounds: predominantly C57BL/6J and one or two generations of backcrossing to 129S1/SvimJ (129N1, 129N2). We used these mice to determine if actions of alcohol are regulated by synthesis of GABA from this isoform. We also studied behavioral responses to a benzodiazepine (flurazepam) and a GABAA receptor agonist (gabaxadol). Deletion of Gad2 increased ethanol palatability and intake and slightly reduced the severity of ethanol-induced withdrawal, but these effects depended strongly on genetic background. Mutant mice on the 129N2 background showed the above three ethanol behavioral phenotypes, but the C57BL/6J inbred background did not show any of these phenotypes. Effects on ethanol consumption also depended on the test as the mutation did not alter consumption in limited access models. Deletion of Gad2 reduced the effect of flurazepam on motor incoordination and increased the effect of extrasynaptic GABAA receptor agonist gabaxadol without changing the duration of loss of righting reflex produced by these drugs. These results are consistent with earlier proposals that deletion of Gad2 (on 129N2 background) reduces synaptic GABA but also suggest changes in extrasynaptic receptor function. [source] | ||||||||||||||||||||||||||||||||||||||||