大安颗粒的镇静、催眠作用

目的考察大安颗粒对动物自发活动和对戊巴比妥钠催眠作用的影响,观察其潜在的镇静、催眠作用。方法观察小鼠ig给药后,自由走动的时间、举双前肢的次数及自由活动的次数,以及戊巴比妥钠的催眠剂量和阈剂量对小鼠睡眠的影响,与阴性对照组比较具显著性差异。结果小鼠1次ig大安颗粒(生药)60.3、40.5g·kg-1(高、中剂量组)后60、90min可明显减少其在XZ-4小鼠自由活动计数器内的活动次数,与阴性对照组比较有非常显著的差异(P<0.01)。ig高剂量后30、60、90、120min,与阴性对照组比较自由走动时间显著减少(P<0.01);小鼠举双前肢的次数亦明显减少,与阴性对照组比较亦有显著的差异(P<0.05);高、中剂量组小鼠的入睡时间明显缩短(P<0.01)、睡眠时间明显延长(P<0.05),高剂量组对ip阈下剂量戊巴比妥钠后的小鼠入睡只数也显著增加(P<0.05)。结论大安颗粒具明显的镇静和催眠及与戊巴比妥钠协同的作用。     

柴桂安神胶囊治疗失眠的药效学研究

目的研究柴桂安神胶囊对失眠大鼠睡眠时相变化的影响;观察柴桂安神胶囊对小鼠的镇静催眠作用;观察小鼠对催眠阈下催眠剂量戊巴比妥钠作用的影响及对小鼠自主活动的影响。方法利用电刺激诱导大鼠失眠的方法,用脑电图描记,观察给予柴桂安神胶囊后失眠大鼠睡眠时相的变化情况;将小鼠随机分为柴桂安神胶囊低、中、高剂量组(2,4和8g·kg-1),解郁安神冲剂组和空白组,观察给药后入睡潜伏期和睡眠持续时间,观察记录30min内翻正反射消失达1min以上的小鼠数以及末次给药30min后,2min内小鼠自发活动次数。结果柴桂安神胶囊可显著延长失眠大鼠的总睡眠时间(TST)、中、高剂量可明显缩短戊巴比妥钠致小鼠入睡的潜伏时间、延长睡眠持续时间、增加阈下催眠剂量戊巴比妥钠小鼠入睡率并抑制小白鼠自发活动次数。结论柴桂安神胶囊有镇静催眠作用。     

无糖型宁心安神糖浆对小鼠镇静催眠作用的研究

目的 研究无糖型宁心安神糖浆(SNAS)的镇静、催眠作用.方法 采用自主活动试验、戊巴比妥钠阈上催眠剂量试验、睡眠试验、戊巴比妥钠阈下催眠剂量试验,每个试验均选择ICR小鼠60只,随机分为6组,每组10只,分别为空白对照组,安神补脑液组,蔗糖型宁心安神糖浆组,SNAS高、中、低剂量(100、50、25 mL/kg)组,观察SNAS对小鼠的镇静和催眠作用.结果 SNAS能明显减少小鼠的自主活动次数,增加阈下剂量戊巴比妥钠致小鼠入睡数量,延长小鼠睡眠时间,缩短入睡潜伏期.结论 无糖型宁心安神糖浆具有明显的镇静、催眠作用.     

酸枣仁汤的镇静催眠作用

目的对酸枣仁汤镇静催眠药理作用进行初探。方法采用镇静催眠实验观察酸枣仁汤对小鼠自主活动的影响 ,协同戊巴比妥钠对小鼠的催眠作用。结果酸枣仁汤能明显减少小鼠自主活动次数 ,增加阈下剂量戊巴比妥钠致小鼠睡眠只数 ,延长阈上剂量戊巴比妥钠致小鼠睡眠时间。结论酸枣仁汤有明显的镇静、催眠作用。     

缬草镇静和抗惊厥药理研究

目的探讨缬草的镇静、催眠和抗惊厥作用药理特性。方法1、利用缬草的水提物对小鼠自发活动的影响以及对戊巴比妥钠致小鼠睡眠的协同作用；2、利用缬草的水提物对戊四唑诱发小鼠惊厥的影响。结果缬草水提物可增加戊巴比妥钠小鼠睡眠时间，能降低小鼠前肢上举次数；对戊四唑诱发小鼠惊厥虽无明显影响，但能明显延长其诱发惊厥的潜伏期。结论缬草的水提物具有显著的镇静和抗惊厥作用。     

缬草镇静和抗惊厥药理研究

目的探讨缬草的镇静、催眠和抗惊厥作用药理特性.方法 1、利用缬草的水提物对小鼠自发活动的影响以及对戊巴比妥钠致小鼠睡眠的协同作用;2、利用缬草的水提物对戊四唑诱发小鼠惊厥的影响.结果缬草水提物可增加戊巴比妥钠小鼠睡眠时间,能降低小鼠前肢上举次数;对戊四唑诱发小鼠惊厥虽无明显影响,但能明显延长其诱发惊厥的潜伏期.结论缬草的水提物具有显著的镇静和抗惊厥作用.     

北五味子的镇静、催眠作用

目的对北五味子水提取物镇静、催眠药理作用进行初探。方法采用镇静、催眠实验观察北五味子水提取物对小鼠自主活动的影响 ,协同戊巴比妥钠对小鼠的催眠作用。结果北五味子水提取物能明显减少小鼠自主活动次数 ,增加阈下剂量戊巴比妥钠致小鼠睡眠只数 ,延长阈上剂量戊巴比妥钠致小鼠睡眠时间。结论北五味子水提取物有明显的镇静、催眠作用。     

复方杜仲片镇静催眠的实验研究

目的:通过药理实验观察复方杜仲片的镇静催眠作用。方法:观察药物对正常小鼠的自主活动的影响以评价复方杜仲片的镇静作用;观察复方杜仲片对小鼠戊巴比妥钠催眠阈剂量所致小鼠兴奋性活动的影响以探讨复方杜仲片的催眠作用,同时观察复方杜仲片对戊巴比妥钠的协同催眠作用和复方杜仲片对抗士的宁的中枢兴奋作用。结果:复方杜仲片能明显减弱小鼠自主活动,降低小鼠戊巴比妥钠催眠阈剂量,与戊巴比妥钠有较好的催眠协同作用,可延长小鼠睡眠时间,提高小鼠的入睡率,同时可使惊厥小鼠数减少,且惊厥率随剂量的增加而降低。结论:复方杜仲片具有明显的镇静催眠作用。     

一种拟青霉菌丝体冻干粉对小鼠的镇静催眠作用

目的研究一种拟青霉菌丝体(HPC)冻干粉的镇静催眠作用.方法采用自发活动仪记录法、小鼠走动时间和举双肢法、阈下剂量戊巴比妥钠诱导小鼠睡眠法观察受试药的镇静催眠作用.结果 HPC可抑制小鼠的自发活动;缩短小鼠入睡潜伏期,延长小鼠睡眠持续时间. 结论 HPC具有一定的镇静催眠作用.     

百合知母总皂苷镇静催眠的药效学研究

目的:评价百合知母汤、百合皂苷、知母皂苷及百合知母总皂苷提取物镇静催眠药理作用。方法:观察百合知母汤水煎液,百合皂苷,知母皂苷,百合知母药材(1∶1)提取、富集的百合知母总皂苷对小鼠自主活动、戊巴比妥钠阈下剂量引起小鼠睡眠个数、戊巴比妥钠引起小鼠睡眠潜伏期、睡眠时间的影响。结果:百合知母总皂苷能显著减少小鼠自主活动次数,延长戊巴比妥钠引起小鼠睡眠时间,但对入睡潜伏期无明显影响。其余各受试药物可明显减少小鼠活动次数或站立次数,能明显延长睡眠时间,但未能增加戊巴比妥钠阈下剂量引起小鼠睡眠个数。结论:百合知母总皂苷具有显著的镇静催眠作用,呈现剂量依赖性。经大孔树脂工艺优化处理所得百合知母总皂苷提取物可用于百合知母汤的剂型开发。     

盐酸右美托咪定用于机械通气患者镇静的临床观察

目的探讨以盐酸右美托咪定为基础的镇静对重症监护病房（ICU）机械通气患者镇静效果的影响。方法 40例需机械通气的内科患者随机分为咪达唑仑组（A组）和盐酸右美托咪定＋咪达唑仑组（B组）,每组20例。记录镇静前的APACHEⅡ评分、Ramsay评分和PaO2/FiO2指标。记录镇静中4h、6h和12h的心率、血压和呼吸。镇静达12h时停止药物输注,每30min评估1次镇静深度,记录恢复时间,达到满意镇静深度的时间,镇静满意程度。结果 90%患者单独使用盐酸右美托咪定就能达到满意的镇静效果,如果联合使用咪达唑仑也只需要很低的剂量。比较咪达唑仑用量、调整泵速至镇静满意时间和恢复时间,B组均明显少于A组（P〈0.05）;B组的镇静满意程度明显高于A组（P〈0.05）。结论对机械通气的患者以盐酸右美托咪定为基础的镇静能提高咪达唑仑的镇静效果。     

瑞马唑仑在内镜检查中镇静效应有效性和安全性的Meta分析

目的 系统性评价瑞马唑仑在内镜检查中镇静效应的有效性和安全性,并与丙泊酚和咪达唑仑进行比较。方法 在PubMed、Embase、Cochrane图书馆、万方数据库、CNKI等数据库进行了检索,收集了内镜检查中瑞马唑仑用于镇静的随机对照试验文献。检索时间从2018年起瑞马唑仑获批准于临床试验开始到2022年4月。搜索策略包括以下变量关键字：瑞马唑仑、胃镜检查、支气管镜检查和结肠镜检查。通过Rev Man5.4软件对纳入文献质量进行评估和对收集的资料进行Meta分析。结果 共有10项瑞马唑仑与丙泊酚和咪达唑仑的随机对照研究,共有2076 名患者纳入分析。结果表明,瑞马唑仑镇静效应优于咪达唑仑[OR = 0.03, 95% CI: (0.02, 0.05),?I2?= 0%,?p?< 0.00001];逊于丙泊酚[OR = 11.32, 95% CI: (2.12, 60.56),??I2= 0%,?p= 0.005]。瑞马唑仑起效时间较丙泊酚慢,较咪达唑仑快;但苏醒时间快于丙泊酚和咪达唑仑。与咪达唑仑相比,其不良反应发生风险无明显差异。与丙泊酚相比,瑞马唑仑的低血压、心率减慢、低氧血症和注射痛发生风险更低,但恶心发生风险升高,二者呕吐发生风险无差异。结论 瑞马唑仑用于内镜检查时,其镇静效应和起效时间优于咪达唑仑,但不及丙泊酚。苏醒时间快于丙泊酚和咪达唑仑。瑞马唑仑对呼吸瑞马唑仑对呼吸、循环抑制发生率低于丙泊酚,与咪达唑仑相比不良反应无明显差异。     

右美托咪定和咪达唑仑复合芬太尼对ICU术后机械通气患者镇静的影响

目的观察右美托咪定和咪达唑仑复合芬太尼用于ICU术后机械通气患者的镇静效果及安全性。方法选取150例ICU术后机械通气患者,采用信封法随机分为右美托咪定组和咪达唑仑组,每组75例,两组患者均给予芬太尼持续泵入。右美托咪定组采用右美托咪定0.2～0.6μg/(kg·h)持续泵入。咪达唑仑组采用0.08～0.10 mg/(kg·h)咪达唑仑持续泵入。采用Ramsay分级标准对两组患者镇静效果进行分级评分,观察两组患者的镇静效果。详细记录两组患者芬太尼用量、达到理想镇静所需的时间、停药后苏醒时间、镇静期间呼吸及循环系统功能的变化及其他不反应发生情况。结果右美托咪定组镇静满意率为97.33%,咪达唑仑组镇静满意率为96.00%,两组镇静满意率比较差异无统计学意义(P>0.05)。右美托咪定组芬太尼用量明显低于咪达唑仑组(P<0.05),达到理想镇静所需时间及停药后苏醒时间明显短于咪达唑仑组(P<0.05)。两组患者呼吸抑制、平均动脉压下降、SpO2下降及恶心发生率比较差异无统计学意义,但右美托咪定组谵妄发生率明显低于咪达唑仑组,两组比较差异有统计学意义(P<0.05)。结论右美托咪定复合芬太尼用于ICU术后机械通气患者的镇静治疗,镇静效果满意,可以达到理想镇静时间及易唤醒时间短,谵妄发生率低,可减少芬太尼用量,而且对患者呼吸及循环系统影响小,是一种较为理想的ICU镇静剂。     

Clinical pharmacokinetic monitoring of midazolam in critically ill patients

Midazolam is a commonly used sedative in critically ill, mechanically ventilated patients in intensive care unit (ICU) settings worldwide. We used a nine-step decision-making algorithm to determine whether therapeutic monitoring of midazolam in the ICU is warranted. Midazolam has a higher clearance and shorter half-life than other benzodiazepines, and prolonged sedation is achieved with continuous infusion. There appears to be very good correlation between plasma concentrations of both midazolam and its active metabolite, alpha1-hydroxymidazolam, and the degree of sedation. However, due to high interpatient variability, it is not possible to predict the level of sedation in any given individual based on plasma concentration of midazolam or its metabolites. Moreover, no simple and practical assay is available to quantitate midazolam plasma concentrations in the acute ICU setting. Many scales are available to assess the sedative effects of midazolam. Because the plasma concentration of midazolam required to achieve a constant level of sedation is highly variable, it is usually more prudent for the clinician to monitor for sedation with a validated clinical scale than by plasma concentrations alone. Various physiologic parameters, including age-related effects, compromised renal function, and liver dysfunction affect the pharmacokinetics of midazolam and alpha1-hydroxymidazolam. Although routine drug monitoring for all critically ill patients receiving midazolam is not recommended, this practice is likely beneficial in patients with neurologic damage in whom sedation cannot be assessed and in patients who have renal failure with a prolonged time to awakening.     

Behavioral differentiation of benzodiazepine ligands after repeated administration in baboons

Baboons received repeated daily administration of saline, 5.6 mg/kg midazolam, 5.0 mg/kg flumazenil (Ro15-1788), 3.2 mg/kg 3-carboethoxy-beta-carboline hydrochloride (beta CCE) or 10 mg/kg beta CCE for 5 days. Behavioral signs of sedation and excitation were scored for 1 h after i.m. injections. Daily administration of these benzodiazepine-receptor ligands differentiated their behavioral effects; repeated midazolam resulted in tolerance to the sedative and ataxic effects; repeated beta CCE resulted in sensitization to its convulsant properties; and repeated flumazenil or saline produced no changes in behavior. In a second study, baboons received repeated injections of midazolam (5.6, 11.2 or 20 mg/kg per day) for 6 days. All three groups became tolerant to the sedative and ataxic effects of midazolam. Acute injections of flumazenil (5.0 mg/kg) on day 5 produced a dose-dependent withdrawal syndrome. This flumazenil treatment produced a slight attenuation in the degree of tolerance to midazolam on day 6, suggesting that receptor sensitivity to the benzodiazepine agonist may have partially reset.     

Behavioral effects of benzodiazepine ligands in non-dependent, diazepam-dependent and diazepam-withdrawn baboons.

Acute i.m. injections of benzodiazepine receptor ligands were administered to baboons before 1-h observational sessions. The agonist midazolam produced sedative effects, the antagonist flumazenil produced no behavioral effects, the inverse agonist FG7142 produced tremor and the inverse agonist 3-carboethoxy-beta-carboline hydrochloride (beta CCE) produced tremor, vomiting, jerks and seizures. Co-administration of these drugs (midazolam + beta CCE, midazolam + flumazenil or flumazenil + beta CCE) produced a mutual antagonism of these effects. Compared to the non-dependent condition, in the diazepam-dependent condition (baboons maintained on 20 mg/kg per day diazepam) and withdrawn condition (dependent baboons tested during withdrawal), midazolam produced decreased sedative effects, flumazenil produced increased effects (i.e., tremor, vomiting and jerks), and beta CCE produced increased frequency of seizures. Taken together, these data suggest that (1) benzodiazepine receptor ligands lie on a continuum of behavioral activity, and (2) chronic diazepam administration alters the behavioral effects of these benzodiazepine ligands, producing a shift in the direction of the inverse agonist.     

脑电双频指数监测下咪达唑仑和丙泊酚用于硬膜外麻醉镇静的临床效果比较

目的比较在脑电双频指数监测下咪达唑仑和丙泊酚做为硬膜外静脉辅助用药时,起效时间,恢复时间,使用剂量及不良反应的发生率。方法78例择期下肢手术患者,ASA分级I～II级,随机分为咪迟唑仑组（M组）和丙泊酚组（p组）,硬膜外麻醉完善后分别恒速输注0．1％的咪达唑仑和1％丙泊酚注射液,然后分别记．录两组患者达到预期镇静深度的时间,用药剂量,恢复时间,静脉用药总量,平均动脉压（MABP）,心率（HR）,脉搏血样饱和度（SpO2）,呼吸频率（RR）,不良反应（术中知晓,注射痛,烦躁,恶心呕吐）发生率。结果达到预期镇静深度的时间M组和P组分别为11．0±3．66（min）、6．2±1．88（min）。恢复时间M组和P组分别为18．6±6．50（min）、10．1±3．65（min）,M组长于P组。平均动脉压（MABP）较基础值波动〉20％M组2例（5.3％）,P组11例（28．9％）。需面罩加压给氧,M组11例（28．2％）p组8例（20．5％）。不良反应两组间差异无统计学意义。结论作为硬膜外麻醉静脉辅助用药时,咪达唑仑和丙泊酚均能达到预期的镇静深度,丙泊酚起效和恢复时间均较咪达唑仑短,但血流动力学变化较咪逸唑仑剧烈。     

Respiratory and cardiovascular effects in relation to plasma levels of midazolam and diazepam.

1. In the present study possible relationships between cardiovascular and respiratory effects and plasma concentrations were investigated after administration of midazolam and diazepam. Eight healthy volunteers were given three injections at 20 min intervals of equipotent sedative doses of midazolam (0.05 mg kg-1) and diazepam (0.15 mg kg-1) in a randomized double-blind cross-over design. Blood pressure, blood-gases and respiration measured nonivasively, were monitored throughout the experimental session of 160 min, and frequent blood samples were collected during the session. 2. Correlations between the blood pressure reduction, the increase of PaCO2 in blood, and plasma concentrations were found for both drugs. A maximal reduction of blood pressure and PaCO2 was produced after sedative doses of midazolam and diazepam. 3. A possible acute tolerance development towards the blood pressure reduction was found after the repeated administration of diazepam but not after the midazolam administration. 4. The plasma concentrations producing half the maximal effects after administration of midazolam was 50-60 ng ml-1, indicating that the influence on blood pressure and PaCO2 after drug administration is evoked at lower plasma concentrations than sedation. 5. No correlation between the respiratory effects and plasma concentrations was found for either drug.     

Intranasal administration of midazolam in a cyclodextrin based formulation: bioavailability and clinical evaluation in humans.

Intranasal administration of midazolam has been of particular interest because of the rapid and reliable onset of action, predictable effects, and avoidance of injections. The available intravenous formulation (Dormicum i.v. solution from Hoffmann-La Roche) is however less than optimal for intranasal administration due to low midazolam concentration and acidity of the formulation (pH 3.0-3.3). In this study midazolam was formulated in aqueous sulfobutylether-beta-cyclodextrin buffer solution. The nasal spray was tested in 12 healthy volunteers and compared to intravenous midazolam in an open crossover trial. Clinical sedation effects, irritation, and serum drug levels were monitored. The absolute bioavailability of midazolam in the nasal formulation was determined to be 64 +/- 19% (mean +/- standard deviation). The peak serum concentration from nasal application, 42 +/- 11 ng ml-1, was reached within 10-15 min following administration and clinical sedative effects were observed within 5 to 10 min and lasted for about 40 min. Intravenous administration gave clinical sedative effects within 3 to 4 min, which lasted for about 35 minutes. Mild to moderate, transient irritation of nasal and pharyngeal mucosa was reported. The nasal formulation approaches the intravenous form in speed of absorption, serum concentration and clinical sedation effect. No serious side effects were observed.     

Flumazenil's reversal of myoclonic-like movements associated with midazolam in term newborns

Sedation is an important aspect of care for critically ill newborns. Proper sedation reduces stress during procedures such as mechanical ventilation. Midazolam, a short-acting benzodiazepine, is widely administered as a sedative in newborn intensive care units but is not without side effects. Three term newborns developed myoclonic-like abnormal movements after receiving midazolam. In one, flumazenil controlled the abnormal movements. Flumazenil is a potent benzodiazepine antagonist that competitively blocks the central effects of benzodiazepines. It can reverse the sedative effects of benzodiazepines occurring after diagnostic or therapeutic procedures or after benzodiazepine overdose. Flumazenil may be considered in cases of abnormal movements associated with midazolam. However, further studies are needed to provide guidelines for the administration of this drug in newborns.