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Benzodiazepines in complex biological matrices: Recent updates on pretreatment and detection methods
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作者 Yi-Xin Zhang Yuan Zhang +5 位作者 Yu Bian Ya-jie Liu Ai Ren Yu Zhou Du Shi Xue-Song Feng 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2023年第5期442-462,共21页
Benzodiazepines(BDZs)are used in clinics for anxiolysis,anticonvulsants,sedative hypnosis,and muscle relaxation.They have high consumptions worldwide because of their easy availability and potential addiction.They are... Benzodiazepines(BDZs)are used in clinics for anxiolysis,anticonvulsants,sedative hypnosis,and muscle relaxation.They have high consumptions worldwide because of their easy availability and potential addiction.They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault.The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging.Efficient pretreatment methods followed by accurate and sensitive detections are necessary.Herein,pretreatment methods for the extraction,enrichment,and preconcentration of BDZs as well as the strategies for their screening,identification,and quantitation developed in the past five years have been reviewed.Moreover,recent advances in various methods are summarized.Characteristics and advantages of each method are encompassed.Future directions of the pretreatment and detection methods for BDZs are also reviewed. 展开更多
关键词 benzodiazepinE Biological matrices Detectionmethods Samplepreparation
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The FDA Mandate to Reassess Benzodiazepines: Alprazolam Induces a Positive Conditioned Place-Preference in Male Rats 被引量:1
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作者 Cheyenne Moffett Katherine J. Kost +6 位作者 Austen Thompson Michael H. Ossipov Joseph V. Pergolizzi Junior Sumiyo Umeda-Raffa Robert B. Raffa Tally M. Largent-Milnes Todd Vanderah 《Journal of Biosciences and Medicines》 2021年第3期1-8,共8页
On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated ... On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines”. With this announcement, the FDA proclaimed that much more needs to be known about the initiation, continuation, and discontinuation of these widely-used drugs. Unfortunately, relevant information is lacking, since for many years, there has been a notable sparsity in the funding and conduct of basic and clinical research on these drugs. In order to begin to fill the void, it is valuable to (re)examine animal models. We here describe a model of conditioned place-preference (CPP) for rats and for the first time, to our knowledge, show that the representative benzodiazepine alprazolam induces positive place-preference in male rats. 展开更多
关键词 benzodiazepines Conditioned Place-Preference ALPRAZOLAM REINFORCEMENT Affective State
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Novel,efficient,and green procedure for the synthesis of 1,5-benzodiazepines catalyzed by MgBr_2 in aqueous media 被引量:1
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作者 Shivaji S.Pawar Murlidhar S.Shingare Shivaji N.Thore 《Chinese Chemical Letters》 SCIE CAS CSCD 2009年第1期32-36,共5页
MgBr2 performs as a novel catalyst for the synthesis of various 1,5-benzodiazepine derivatives from wide range of substituted o- phenylenediamines and various ketones in good to excellent isolated yields (93-98%) us... MgBr2 performs as a novel catalyst for the synthesis of various 1,5-benzodiazepine derivatives from wide range of substituted o- phenylenediamines and various ketones in good to excellent isolated yields (93-98%) using water as solvent at ambient temperature. Several solvents were examined for this reaction; however, in terms of reaction yield and time, water was found to be the optimum solvent. The remarkable advantages offered by this method are easily and inexpensive available catalyst, simple procedure, mild conditions, much faster (40-60 man) reactions and good to excellent yields of products. 展开更多
关键词 MgBr2 O-PHENYLENEDIAMINES KETONES Aqueous media 1 5-benzodiazepine
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Fast Determination of Benzodiazepines in Human Urine via Liquid-Liquid Extraction with Low Temperature Partitioning and LC-HRMS 被引量:3
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作者 Elisangela Jaqueline Magalhaes Clesia Cristina Nascentes +3 位作者 Rodinei Augusti Maria Eliana Lopes Ribeiro de Queiroz Julio Cesar Cardoso da Silva Robson Jose de Cassia Franco Afonso 《American Journal of Analytical Chemistry》 2012年第2期118-124,共7页
A simple and high-throughput method to simultaneously determine selected benzodiazepines (i.e., diazepam, lorazepam, clonazepam, and bromazepam) in urine was developed and validated. The entire methodology consisted o... A simple and high-throughput method to simultaneously determine selected benzodiazepines (i.e., diazepam, lorazepam, clonazepam, and bromazepam) in urine was developed and validated. The entire methodology consisted of the application of an innovative extraction/cleanup procedure, namely liquid-liquid extraction with low-temperature partitioning (LLE-LTP), and analysis by liquid chromatography combined with high-resolution mass spectrometry (LC-HRMS). The LLE-LTP procedure was optimized via factorial design and by evaluating crucial variables, specifically the freezing mode (either slow or fast), the urine/acetonitrile volume ratio, and the sample ionic strength. The benzodiazepines were quantified using matrix-matched calibration curves where the following parameters were assessed by validation protocol: in general, linearity range of 17 - 200 μg?L–1 (r > 0.9957);limits of detection lower than 5 μg?L–1;relative standard deviations (RSD) lower than 12.5%;and accuracy ranging from 72.3 to 117%. To test this procedure’s performance, the method was applied to determine the content of diazepam in actual urine samples. The validation results obtained for the method demonstrated that the present methodology could be potentially applied in proficient laboratories as a routine approach for determining benzodiazepines compounds content in urine. 展开更多
关键词 benzodiazepines URINE LC-HRMS Extraction Procedure Low-Temperature Partitioning
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Intranasal Delivery of Two Benzodiazepines, Midazolam and Diazepam, by a Microemulsion System
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作者 Shafir Botner Amnon C. Sintov 《Pharmacology & Pharmacy》 2011年第3期180-188,共9页
Nasal application of benzodiazepines might be an alternative to intravenous administration in acute clinical situations such as seizures emergencies. However, irritation and pain as well as symptoms like teary eyes, d... Nasal application of benzodiazepines might be an alternative to intravenous administration in acute clinical situations such as seizures emergencies. However, irritation and pain as well as symptoms like teary eyes, dizziness, discomfort, nasal drainage and bad taste usually accompany subject received midazolam and diazepam via the nasal route. The purpose of this study was to evaluate the use of a new alcohol-free microemulsion system as a carrier for diazepam or midazolam given intranasally. Midazolam (base) or diazepam was solubilized in the microemulsion to obtain a high drug concentration of 25 mg/g (2.5% by weight), to provide 2.5 mg drug in 100 μl spray (d ≈ 1.00 g/ml). The nasal absorption of both drugs from the same microemulsion formulation (containing 20% aqueous phase) was found to be fairly rapid after administration of 0.4 mg/kg to rabbits. The absolute bioavailability of diazepam after intranasal administration using this formulation was 33.45% ± 12.36% and the tmax was 18.33 ± 23.09 min, which was twice longer than the tmax obtained after midazolam administration, 9.25 ± 6.75 min. The pharmacokinetic parameters of midazolam in W/O (20% water) microemulsion and their comparison with midazolam in O/W (50% water) microemulsion have shown that both formulations resulted in a relatively short time to reach the peak plasma level (tmax), that is, 9.25 ± 6.75 min and 6.75 ± 5.67 min, respectively. However, the peak plasma levels (Cmax) and the absolute bioavailability (FA) of midazolam were significantly higher after administration of the W/O formulation than those obtained after application of O/W formulation, i.e., 46.62 ± 17.38 μg/ml vs. 15.44 ± 4.00 μg/ml, and 35.19% ± 11.83% vs. 19.83% ± 16.32%, respectively. Our results suggest that the new microemulsion system may be useful for getting rapid-onset of midazolam and diazepam following intranasal administration, resulting in reasonable peak plasma levels and bioavailability, but most importantly, providing a high measure of tolerability and comfort. 展开更多
关键词 MICROEMULSION INTRANASAL Drug Delivery benzodiazepines NASAL Spray DIAZEPAM MIDAZOLAM
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Original and Simple Protocol for Withdrawal of Benzodiazepines to Achieve Sustained Remission
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作者 Granato Philippe Shreekumar Vinekar +3 位作者 Fontaine Audrey Paradis Philippe Danel Thierry Cottencin Olivier 《Open Journal of Psychiatry》 2016年第2期195-202,共8页
Benzodiazepines are psychotropic medications for effective management of anxiety. However, after over 50 years of unrestrained prescription use, prescribers realize the severity of side effects in select patients. The... Benzodiazepines are psychotropic medications for effective management of anxiety. However, after over 50 years of unrestrained prescription use, prescribers realize the severity of side effects in select patients. The most challenging of these side effects is the emergence of a physiological dependence that explains virtual impossibility of successful withdrawal that can ensure sustained abstinence. We propose a method for successful withdrawal using substitution and innovative downward tapering of diazepam oral solution for all benzodiazepines to attain sustained remission. Our protocol reported here allowed not only successful withdrawal for all of 20 patients included in this pilot study but also helped in totally weaning them off of benzodiazepines demonstrating absence of relapse even 2 years after the total discontinuance. 展开更多
关键词 benzodiazepinE WITHDRAWAL Success
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Research progress on benzodiazepines to treat alcohol withdrawal syndrome
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作者 Tiankai Jiang Yuhang Liang +3 位作者 Lan Jiang Yinhang Li Tiantian Jiang Ye Ruan 《Journal of Translational Neuroscience》 2022年第4期12-16,共5页
Alcohol withdrawal syndrome(AWS)refers to a series of symptoms and signs that chronic al-coholics experience when they suddenly stop drinking or reduce their drinking,usually 12 to 24 h later.These in-clude tremors,fa... Alcohol withdrawal syndrome(AWS)refers to a series of symptoms and signs that chronic al-coholics experience when they suddenly stop drinking or reduce their drinking,usually 12 to 24 h later.These in-clude tremors,fatigue,sweating,hyperreflexia,and gas-trointestinal symptoms.This article will analyze the drug treatment of this disease and make a brief review. 展开更多
关键词 alcohol withdrawal syndrome(AWS) benzodiazepine(bdz) symptom-triggered regimens
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Psychoactive Chemical Constituents of Carissa edulis (Forssk.) Vahl Roots and Its Safety Limits in Folk Treatment: Benzodiazepines Analogous
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作者 Intisar Salih Ahmed Damra Elhaj Mustafa 《Journal of Chemistry and Chemical Engineering》 2020年第4期113-118,共6页
Carissa edulis Vahl is well known in Sudanese herbal medicine,commonly used for treatment of epilepsy,headache,chest pains,rheumatism,skin lesions,mania and other psychoactive diseases.The investigations of the safety... Carissa edulis Vahl is well known in Sudanese herbal medicine,commonly used for treatment of epilepsy,headache,chest pains,rheumatism,skin lesions,mania and other psychoactive diseases.The investigations of the safety use for psychoactive purposes in Sudanese healing traditions and identifying secondary metabolites of the plant extracts are the key steps towards determination of appropriate medicinal doses.Therefore,one of the chemical constituents was isolated and structurally identified by 1H-NMR and LC-MS.With the aim of evaluating Carissa edulis folk random uses,the isolated compound was compared with reference artificial drugs Lormetazepam,a potentially toxic compound.Structure investigations confirm that the isolated product was benzodiazepines analogous 7-chloro 1,4-benzodiazepine-2-ones.It is important to know the potential toxicity of certain plant in order to assess the therapeutic effect of it,as these are slight distinctions between the medicinal and toxic doses.In general the results obtained justify the use of the roots of Carissa edulis in traditional medicine for the treatment of some psychiatric diseases. 展开更多
关键词 Carissa edulis psychoactive purposes Lormetazepam benzodiazepines potential toxicity
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A New Approach to 2,3-Dihydro-1H-1,5-Benzodiazepines from the Reaction of o-Nitrophenylazide with α,β-Unsaturated Ketones Promoted by Samarium Diiodide
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作者 Xiao Yuan CHEN Wei Hui ZHONG Yong Min ZHANG 《Chinese Chemical Letters》 SCIE CAS CSCD 2001年第1期5-6,共2页
o-Nitrophenylazide was reduced by SmI2 in anhydrous THF at room temperature to produce active intermediate 2 (samarium amide), "living" double-anion in situ which reacted smoothly with α,β-unsaturated ket... o-Nitrophenylazide was reduced by SmI2 in anhydrous THF at room temperature to produce active intermediate 2 (samarium amide), "living" double-anion in situ which reacted smoothly with α,β-unsaturated ketones to afford 2,3-dihydro-1H-1,5-benzodiazepines in good yields under mild and neutral conditions. 展开更多
关键词 Samarium diiodide reduction nitro group azide 2 3-dihydro-1H-1 5-benzodiazepine.
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Pilot Studies on the Novel Hypothesis that TSPO (Peripheral Benzodiazepine Receptor) Is Involved in Benzodiazepine/“Z-Drug” Physical Dependence and/or Withdrawal
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作者 Cheyenne Moffett Katherine J. Kost +4 位作者 Austen Thompson Joseph V. Pergolizzi Jr. Tally M. Largent-Milnes Robert B. Raffa Todd Vanderah 《Pharmacology & Pharmacy》 CAS 2023年第3期72-83,共12页
Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite t... Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite their popularity, benzodiazepine prescribing often exceeds recommendations and the consequences can be severe. On September 23, 2020, the United States FDA announced a new requirement for a Boxed Warning for benzodiazepines prescribing. Along with this announcement, the FDA stated that relevant information regarding the initiation, continuation, and discontinuation of benzodiazepines is lacking. Here, we describe initial pilot studies intended to investigate the questions 1) can animal models be developed that demonstrate benzodiazepine physical dependence and/or withdrawal symptoms, and 2) determine whether translocator protein (TSPO) plays a role in benzodiazepine dependence and/or withdrawal processes. The former was demonstrated, methodological limitations prevented the latter. 展开更多
关键词 benzodiazepinE TSPO Rats In Vivo Tests Western-Blot Analysis
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艾司西酞普兰联合运动方案对苯二氮[艹卓]类药物依赖焦虑症患者睡眠质量的影响
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作者 王惠强 王哲伟 《世界睡眠医学杂志》 2024年第2期454-457,共4页
目的:探讨艾司西酞普兰联合运动方案对苯二氮[艹卓]类(BDZ)药物依赖焦虑症患者睡眠质量的影响。方法:选取2021年9月至2023年2月泉州市第三医院收治的BDZ类药物依赖焦虑症患者120例作为研究对象,按照抛掷法随机分为对照组(n=58)和观察组(... 目的:探讨艾司西酞普兰联合运动方案对苯二氮[艹卓]类(BDZ)药物依赖焦虑症患者睡眠质量的影响。方法:选取2021年9月至2023年2月泉州市第三医院收治的BDZ类药物依赖焦虑症患者120例作为研究对象,按照抛掷法随机分为对照组(n=58)和观察组(n=62)。对照组仅予以艾司西酞普兰治疗,观察组予以艾司西酞普兰联合运动方案治疗。比较2组睡眠质量、失眠程度、负性情绪以及生命质量。结果:治疗后,观察组匹兹堡睡眠质量指数(PSQI)中主观睡眠质量、入睡时间、睡眠效率、睡眠障碍、日间功能5个维度评分及总分均低于对照组,差异均有统计学意义(均P<0.05),失眠严重程度指数(ISI)评分低于对照组,差异有统计学意义(P<0.05);观察组汉密尔顿焦虑抑郁量表(HADS)评分均较对照组低,差异有统计学意义(P<0.05),健康调查简表(SF-36)评分较对照组高,差异有统计学意义(P<0.05)。结论:艾司西酞普兰联合运动方案能明显提高BDZ类药物依赖焦虑症患者的睡眠质量,改善失眠症状,缓解负性情绪,提高生命质量。 展开更多
关键词 艾司西酞普兰 运动方案 苯二氮[艹卓]类 药物依赖 睡眠质量
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基于FAERS数据库对酒精使用障碍治疗药品不良事件信号的挖掘与评价
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作者 王占璋 陈芸 尚德为 《广东药科大学学报》 CAS 2024年第5期104-112,共9页
目的基于美国FDA不良事件(adverse drug event,ADE)报告数据库(FDA adverse event reporting system,FAERS)对临床常用的酒精使用障碍治疗药品的ADE信号进行挖掘和分析,为临床合理用药提供参考。方法采用报告比值比法、比例报告比法和... 目的基于美国FDA不良事件(adverse drug event,ADE)报告数据库(FDA adverse event reporting system,FAERS)对临床常用的酒精使用障碍治疗药品的ADE信号进行挖掘和分析,为临床合理用药提供参考。方法采用报告比值比法、比例报告比法和贝叶斯可信区间递进神经网络法,对11种临床常用治疗药品(苯二氮䓬类药物:阿普唑仑、地西泮、劳拉西泮、奥沙西泮;非苯二氮䓬类药物:阿坎酸、巴氯芬、戒酒硫、加巴喷丁、纳曲酮、普瑞巴林、托吡酯)的ADE信号进行挖掘分析,利用《监管活动医学词典》术语集进行系统器官归类。结果共收集到11种药品治疗酒精使用障碍的ADE报告14945份,发现阳性信号737个、说明书未记载的高频信号68个,其中阳性信号涉及24个系统器官归类,主要集中在精神病类疾病、神经系统疾病、全身性疾病及给药部位反应和各类损伤、中毒及操作并发症。结论常用酒精使用障碍治疗药品的ADE信号具有差异性,临床使用时,应根据患者情况实现个体化给药,提高用药安全性。 展开更多
关键词 酒精使用障碍 苯二氮䓬类药物 药品不良事件 FAERS 药物警戒 信号挖掘
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干血斑中34种苯二氮卓类物质的实时直接分析-串联质谱快速筛查研究 被引量:1
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作者 刘富邦 张瑛 +2 位作者 王继芬 周沛龙 侯晓龙 《分析测试学报》 CAS CSCD 北大核心 2024年第2期309-314,共6页
该文通过优化仪器条件和前处理方法建立了实时直接分析-串联质谱快速筛查干血斑(DBS)中34种苯二氮卓类物质(BZDs)的方法。首先将50μL血液沉积在采血卡上形成DBS,DBS经溶剂充分提取后取上层溶液,使用DART 12Dip-It^(TM)模块进样5μL,在... 该文通过优化仪器条件和前处理方法建立了实时直接分析-串联质谱快速筛查干血斑(DBS)中34种苯二氮卓类物质(BZDs)的方法。首先将50μL血液沉积在采血卡上形成DBS,DBS经溶剂充分提取后取上层溶液,使用DART 12Dip-It^(TM)模块进样5μL,在多反应监测模式下检测。结果表明:选用400℃作为载气加热器温度,以乙酸乙酯-水(体积比3∶1)混合溶剂提取DBS样品,所得响应强度较高且建立的筛查方法选择性良好,无延迟效应影响,除阿地唑仑、奥沙西泮和α-羟基三唑仑外,其他物质的检出限均在5~50 ng/mL。所建方法可在90.3%的阳性检材中成功筛选出BZDs物质,方法快速、简便、有效,适用于服药自杀等类案件中DBS检材的快速筛查检验。 展开更多
关键词 实时直接分析 干血斑 苯二氮卓类物质 快速筛查
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基于“增效减毒”策略探究酸枣仁缓解苯二氮类药物依赖性的作用机制
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作者 史鑫波 刘长乐 +6 位作者 宋忠兴 唐志书 许洪波 李国龙 孙琛 刘红波 陈佳昕 《西安交通大学学报(医学版)》 CAS CSCD 北大核心 2024年第5期828-836,共9页
目的基于“增效减毒”的中药和化学药物联用思路,采用网络药理学方法与分子动力学模拟技术,探讨酸枣仁缓解苯二氮类药物(benzodiazepine,BDZ)依赖性的活性成分及分子机制。方法首先通过文献检索酸枣仁的主要成分,其次基于网络药理学和... 目的基于“增效减毒”的中药和化学药物联用思路,采用网络药理学方法与分子动力学模拟技术,探讨酸枣仁缓解苯二氮类药物(benzodiazepine,BDZ)依赖性的活性成分及分子机制。方法首先通过文献检索酸枣仁的主要成分,其次基于网络药理学和分子对接探讨酸枣仁缓解BDZ依赖性的主要有效成分及作用靶点。最后通过分子动力学模拟技术进一步验证关键蛋白和核心成分之间的关系。结果酸枣仁共检索出24个化学成分,共作用于731个靶点。通过构建“成分-靶点-通路”网络,拓扑分析得到亚油酸、棕榈酸、油酸、豆蔻酸、斯皮诺素、齐墩果酸、酸枣仁皂苷A等9个核心成分和AR、PTGS2、PPARG、RXRA和CYP19A15个关键靶点。KEGG富集分析得到钙离子信号通路、cAMP信号通路、IL-17信号通路和TNF信号通路等关键通路。分子对接结果表明酸枣仁核心成分和关键靶点之间有着良好的结合能力且结合主要以氢键为主。分子动力学模拟实验进一步表明Jujuboside-A和RXRA、Oleanolic-acid和RXRA、Spinosin和PPARGC结合稳定,三种活性成分对改善BDZ依赖性有重要作用。结论酸枣仁中的活性成分可能通过免疫调节、抗焦虑、抗失眠等过程,发挥多靶点、多通路干预BDZ依赖性的作用。 展开更多
关键词 网络药理学 酸枣仁 苯二氮依赖性 分子对接 分子动力学模拟
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氟溴唑仑的奖赏效应及其神经环路机制研究
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作者 黄为国 江炜楷 +3 位作者 邵雨微 陈志刚 唐苏苏 洪浩 《中国药科大学学报》 CAS CSCD 北大核心 2024年第3期390-396,共7页
氟溴唑仑(Flub)是一种新型苯二氮䓬类精神活性物质,其成瘾性及其机制尚不清楚。本研究采用小鼠条件位置偏爱(CPP)模型,研究Flub的奖赏效应,以c-Fos表达评定神经元活性,采用病毒示踪技术追踪神经环路,通过化学遗传技术研究神经环路对奖赏... 氟溴唑仑(Flub)是一种新型苯二氮䓬类精神活性物质,其成瘾性及其机制尚不清楚。本研究采用小鼠条件位置偏爱(CPP)模型,研究Flub的奖赏效应,以c-Fos表达评定神经元活性,采用病毒示踪技术追踪神经环路,通过化学遗传技术研究神经环路对奖赏效应的调控作用。结果显示,Flub(ip 3 mg/kg)显著增加小鼠CPP评分,增加腹侧被盖区(VTA)多巴胺(DA)能神经元c-Fos表达。抑制VTA多巴胺能神经元活性,Flub小鼠CPP评分显著降低。病毒示踪显示,VTA多巴胺能神经元接受喙内侧被盖核(RMTg)γ氨基丁酸(GABA)能神经元投射。激活RMTgGABA→VTADA环路或阻断RMTg脑区苯二氮䓬受体,Flub小鼠的CPP评分显著降低。这些结果表明,Flub通过激活RMTg脑区GABA神经元中的苯二氮䓬受体,抑制RMTgGABA→VTADA环路,产生奖赏效应。 展开更多
关键词 氟溴唑仑 奖赏效应 条件性位置偏好 腹侧被盖区 喙内侧被盖核 苯二氮䓬受体
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实体器官移植术后谵妄的研究进展
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作者 梁欣 欧志宇 苗芸 《器官移植》 CAS CSCD 北大核心 2024年第6期958-963,共6页
实体器官移植术后谵妄作为影响器官移植受者预后的重要因素,目前缺乏足够的临床关注。其病理生理机制尚不明确,与移植器官的种类、受者年龄、血糖变异、大剂量糖皮质激素冲击治疗等有着紧密的联系。明确实体器官移植术后谵妄发生的危险... 实体器官移植术后谵妄作为影响器官移植受者预后的重要因素,目前缺乏足够的临床关注。其病理生理机制尚不明确,与移植器官的种类、受者年龄、血糖变异、大剂量糖皮质激素冲击治疗等有着紧密的联系。明确实体器官移植术后谵妄发生的危险因素并及早进行干预,对改善患者预后至关重要。本文通过综述国内外近年实体器官移植术后谵妄相关文献,明确术后谵妄的定义、分类、临床表现和诊断标准,汇总实体器官移植术后谵妄的危险因素,着重突出实体器官移植受者区别于其他患者的特点,并总结其预后和防治方法,旨在提升临床对实体器官移植术后谵妄的关注度,改善受者预后。 展开更多
关键词 器官移植 术后谵妄 神经系统并发症 糖皮质激素 血糖变异 右美托咪定 苯二氮䓬类
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基于FAERS数据库对艾司唑仑及阿普唑仑不良反应的研究
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作者 龚宗玉 邓秋 +1 位作者 蔡应谭 周平 《临床合理用药杂志》 2024年第14期6-10,共5页
目的挖掘艾司唑仑及阿普唑仑相关药品不良反应(ADR)的风险信号,为两种药物的临床选用及使用风险提供参考。方法收集2004年第1季度—2023年第2季度FAERS数据库中与艾司唑仑、阿普唑仑相关的ADR报告,经过去重后,采用MedDRA词典对其进行统... 目的挖掘艾司唑仑及阿普唑仑相关药品不良反应(ADR)的风险信号,为两种药物的临床选用及使用风险提供参考。方法收集2004年第1季度—2023年第2季度FAERS数据库中与艾司唑仑、阿普唑仑相关的ADR报告,经过去重后,采用MedDRA词典对其进行统计,并获得对应的系统/器官分类(SOC)和首选术语(PT),采用比值比法(ROR)和比例报告比值法(PRR)进行信号挖掘,并统计结果。结果共检索到以艾司唑仑、阿普唑仑为首要怀疑药物的ADR 30149例,其中艾司唑仑ADR 86例,阿普唑仑ADR 30063例。艾司唑仑的ADR报告中,性别无明显差异,阿普唑仑的ADR报告中男11244例(37.40%),女16370例(54.45%)。ADR报告患者的年龄主要集中在18~65岁,上报最多的年份分别是2019、2020、2018、2013、2014年,主要的上报国家为美国,主要的上报人群为医师。ADR报告中,严重报告24051例(79.77%),ADR发生时间以用药30 d内为主。两种药物ADR以精神病类、全身性疾病及给药部位各种反应为主,但艾司唑仑的ADR信号还提示了心律失常、心悸信号,阿普唑仑的ADR信号提示了药物血药浓度异常、出生后生长受限、获得性无巨核细胞的血小板减少症等特殊信号。结论临床应用艾司唑仑及阿普唑仑时,应关注患者的精神状态和生命体征,特别是特殊人群,如合并妊娠、心脏病、紫癜等疾病的患者,若发生相关的ADR临床表现,及时停药,积极采取干预措施,才能有效保障患者安全。 展开更多
关键词 FAERS数据库 艾司唑仑 阿普唑仑 苯二氮艹卓类药物 药品不良反应
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一种苯并氮杂卓类化合物的合成及抗炎活性研究
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作者 胡零 冯育林 《生物化工》 CAS 2024年第3期61-67,共7页
目的:本研究旨在通过电化学方法合成一种新型硒化的苯并氮杂环化合物,1-((4-(叔丁基)苯基)磺酰基)-5-苯基-3-((苯基硒基)甲基)-2,3-二氢-1H-苯并[b]氮杂平,并初步探讨其潜在的抗炎活性及其作用机制。方法:采用电化学方法成功合成了目标... 目的:本研究旨在通过电化学方法合成一种新型硒化的苯并氮杂环化合物,1-((4-(叔丁基)苯基)磺酰基)-5-苯基-3-((苯基硒基)甲基)-2,3-二氢-1H-苯并[b]氮杂平,并初步探讨其潜在的抗炎活性及其作用机制。方法:采用电化学方法成功合成了目标化合物,并以CCK-8法评估了其对小鼠单核巨噬细胞RAW 264.7的细胞毒性。通过使用脂多糖(LPS)诱导的体外细胞炎症模型,使用不同浓度的化合物进行干预。利用Griess法测定了细胞上清液中的NO含量,ELISA法测定了TNF-α和IL-6的水平,运用实时荧光定量PCR技术检测TNF-α、IL-1β和IL-6 mRNA表达的情况。结果:以55%的产率通过电化学方法合成了目标化合物。在1~100μmol/L,该化合物对RAW 264.7细胞无明显毒性。化合物对NO的生成具有显著的抑制效果,其半抑制浓度(IC50)为0.41μmol/L,抑制作用呈剂量依赖。在0.5~2.0μmol/L的给药浓度下,高剂量组显著降低了RAW 264.7细胞中TNF-α、IL-1β和IL-6的mRNA水平,与LPS诱导的模型组相比差异显著(p<0.01)。结论:电化学是一种绿色高效的合成苯并氮卓类化合物的方法。1-((4-(叔丁基)苯基)磺酰基)-5-苯基-3-((苯基硒基)甲基)-2,3-二氢-1H-苯并[b]氮杂平通过抑制RAW 264.7细胞释放TNF-α、IL-1β和IL-6等炎性因子,并可能通过调节NO释放的抗炎途径来发挥其抗炎效果,证实了其具有作为抗炎药物的潜力。 展开更多
关键词 电化学 苯并氮杂卓 绿色合成 抗炎活性
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1,3-苯二氮衍生物的合成
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作者 刘莹 侯梦利 白娟 《合成化学》 CAS 2024年第7期610-621,共12页
苯二氮类化合物具有强大的药理作用,是药物化学和有机合成工作者研究的热点。近几年研究发现:1,3-苯二氮类衍生物同样具有生物活性,也可作为临床药物。因此本课题利用7-endo亚硝基-烯反应构建1,3-苯二氮衍生物,从市售的含不同取代基的... 苯二氮类化合物具有强大的药理作用,是药物化学和有机合成工作者研究的热点。近几年研究发现:1,3-苯二氮类衍生物同样具有生物活性,也可作为临床药物。因此本课题利用7-endo亚硝基-烯反应构建1,3-苯二氮衍生物,从市售的含不同取代基的邻氨基苯乙酮系列化合物出发,将其转化为羟肟酸后,在CuCl_(2)/H_(2)O_(2)体系下,发生7-endo亚硝基-烯反应,生成1,3-苯二氮类衍生物。 展开更多
关键词 亚硝基-烯反应 邻氨基苯乙酮 羟肟酸 1 3-苯二氮 有机合成
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Emergency department management of acute agitation in the reproductive age female and pregnancy
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作者 Ariella Gartenberg Kayla Levine Alexander Petrie 《World Journal of Emergency Medicine》 SCIE CAS CSCD 2024年第2期83-90,共8页
BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and fetus.The safet... BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and fetus.The safety of psychotropic medications in the reproductive age female has not been well established.This review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during pregnancy.METHODS:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant female.RESULTS:While nonpharmacological management is preferred,ED visits for agitation often require medical management.Medication should be selected based on the etiology of agitation and the clinical setting to avoid major adverse effects.Adverse effects are common in pregnant females.For mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse effects.In moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on hemodynamics.Haloperidol has become the most frequently utilized psychotropic for agitation during pregnancy.Second generation psychotropics are often utilized as second-line therapy,including risperidone.Benzodiazepines and ketamine have demonstrated adverse fetal outcomes.CONCLUSION:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in utero.As the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs. 展开更多
关键词 AGITATION PREGNANCY HALOPERIDOL KETAMINE benzodiazepines
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