国产沉香化学成分及药理作用研究进展

根据国内外有关国产沉香化学成分及药理作用的文献报道,国产沉香的主要化学成分为倍半萜类和色酮类成分,除此之外,还包括芳香族类、脂肪酸类、三萜类等成分。国产沉香具有多种生物活性,其药理作用包括催眠镇静、缓解肠道平滑肌痉挛、止咳平喘、抗心肌缺血、降血糖等。根据当前研究情况,今后应对国产沉香中2-(2-苯乙基)色酮类多聚体成分进行系统研究,探索沉香化学成分与药理药效的关系,以清楚地了解各成分在各种药理作用中的具体作用机制。参考文献46篇。     

Drug withdrawal, cocaine and sedative use disorders increase the need for mechanical ventilation in medical patients

Aims   Alcohol use disorders increase the need for mechanical ventilation (MV) in critically ill medical, surgical and trauma patients. Studies examining other drug use disorders (DUD) in trauma patients have not demonstrated heightened rates of intensive care unit (ICU) complications. Patients with asthma and concurrent cocaine or heroin use disorders have an increased need for MV. The objective of this study is to determine if the presence of DUD and drug withdrawal syndromes are associated with increased need for MV in medical patients.
Design   Analysis of a national database.
Setting   The Nationwide Inpatient Sample, the largest all-payer in-patient database was utilized for the years 2002–2004.
Participants   Adult patients with one of the six common diagnoses associated with medical ICU admission were included.
Intervention   None.
Measurements   Univariate analysis and multivariate logistic regression were performed to determine if DUD and drug withdrawal were associated independently with the use of MV.
Findings   A total 1 218 875 patients fulfilled one of the six diagnoses; 22 827 (1.9%) had DUD, and 102 841 (8.4%) underwent MV. Independent of the medical diagnosis, DUD was associated with an increased risk for requiring MV by univariate analysis (relative risk = 1.50, P  < 0.0001). By multivariate analyses, sedative and cocaine use disorders remained associated with increased need for MV. Independent of medical diagnosis and substance, drug withdrawal was associated with increased odds of MV by both univariate and multivariate analysis (odds ratio = 2.94, P  < 0.0001).
Conclusions   DUD are associated with increased need for MV in medical patients. This study demonstrates the importance of screening all medical patients for DUD.     

Remimazolam: Pharmacologic Considerations and Clinical Role in Anesthesiology

Midazolam, fentanyl, and propofol are commonly used for sedation in modern anesthesia practice. These agents possess characteristics that have afforded various anesthetics to be delivered and produce relatively safe and effective outcomes. However, each agent has certain drawbacks in clinical practice. Remimazolam, a novel benzodiazepine created out of so‐called soft drug development, is an ultrashort‐acting intravenous sedative‐hypnotic currently being investigated in clinical trials. In this review, we evaluate the recent literature on the use of remimazolam in clinical practice as compared with current sedative agents, and we describe its potential roles for use in sedation. A literature search of the Medline database (2012–May 2016) was performed. Additional references were identified from a review of literature citations, manufacturer reports, and professional meeting abstracts. All premarket studies involving remimazolam as the primary study drug were evaluated. Literature describing the pharmacokinetics and pharmacodynamics of remimazolam, propofol, and midazolam was also included. Phase I and II studies in the United States have shown remimazolam to be a safe and effective option for procedural sedation. Unlike midazolam and propofol, remimazolam undergoes organ‐independent metabolism to an inactive metabolite. Because remimazolam follows first‐order pharmacokinetics, prolonged infusions or higher doses are unlikely to result in accumulation and extended effect, making it favorable for use as an intravenous anesthetic and for sedation in the intensive care unit. It is expected that phase III trials will further describe the niche that remimazolam may be able to occupy in clinical practice. Postmarket cost‐benefit analyses will need to be performed.     

右美托咪定用于慢性阻塞性肺疾病急性加重期肺肾两虚型患者无创辅助通气镇静的临床观察

[目的] 观察右美托咪定用于无创辅助通气的慢性阻塞性肺疾病急性加重期(AECOPD)肺肾两虚型患者镇静作用的临床有效性及安全性。[方法] 选取近两年内本院重症监护病房(ICU)收治的64例需无创辅助通气的AECOPD肺肾两虚型住院患者,将其随机分成观察组和对照组,每组均为32例,所有病例均按AECOPD最新指南在采取支气管扩张剂、全身糖皮质激素和抗生素等药物的常规治疗的基础上,给予患者无创通气支持,同时予观察组患者右美托咪定镇静治疗。[结果] 右美托咪定观察组的临床治疗效果总体上优于对照组,且患者依从性更好,舒适度更高,缩短带呼吸机时间,缩短ICU住院时间。[结论] 右美托咪定具有较好的临床疗效和安全性,镇静效果满意,可作为AECOPD肺肾两虚型患者无创辅助通气镇静时优先选择的药物之一。     

超高效液相色谱-质谱联用快速同时检测止痒类中药制剂中添加11种化学药物成分

摘要 目的：建立快速液相-串联质谱方法检测中药制剂中添加11种化学药物成分（马来酸氯苯那敏、氯雷他定、硝酸咪康唑、盐酸特比萘芬、酮康唑、艾司唑仑、盐酸氯丙嗪、丙酸氯倍他索、醋酸地塞米松、醋酸泼尼松、吲哚美辛）。方法：采用Waters ACQUITY UPLC BEH C18 column(2.1×100mm, 1.7μm);梯度洗脱：流动相A为乙腈,流动相B为5mmol?L-1 乙酸铵（0.1%甲酸）水溶液。通过比较样品峰与对照品峰的保留时间、一级质谱和二级质谱碎片离子,确定样品中是否掺杂化学止痒药物。结果：建立的快速液相-串联质谱方法检测上述化学药物成分不受药物辅料干扰,各色谱峰分离良好,11种待测成分最低检出限为0.01-0.46 ng?ml-1。结论：该方法简便、灵敏度高,可快速有效地判断中药制剂中是否非法掺入上述化学药品。     

Flavan-3-ol esters: new agents for exploring modulatory sites on GABA(A) receptors

BACKGROUND AND PURPOSE

Enhancement of GABAergic function is the primary mechanism of important therapeutic agents such as benzodiazepines, barbiturates, neurosteroids, general anaesthetics and some anticonvulsants. Despite their chemical diversity, many studies have postulated that these agents may bind at a common or overlapping binding site, or share an activation domain. Similarly, we found that flavan-3-ol esters act as positive modulators of GABA_A receptors, and noted that this action resembled the in vitro profile of general anaesthetics. In this study we further investigated the interactions between these agents.

EXPERIMENTAL APPROACH

Using two-electrode voltage clamp electrophysiological recordings on receptors of known subunit composition expressed in Xenopus oocytes, we evaluated positive modulation by etomidate, loreclezole, diazepam, thiopentone, 5α-pregnan-3α-ol-20-one (THP) and the flavan-3-ol ester 2S,3R-trans 3-acetoxy-4′-methoxyflavan (Fa131) on wild-type and mutated GABA_A receptors.

KEY RESULTS

The newly identified flavan, 2S,3S-cis 3-acetoxy-3′,4′-dimethoxyflavan (Fa173), antagonized the potentiating actions of Fa131, etomidate and loreclezole at α1β2 and α1β2γ2L GABA_A receptors. Furthermore, Fa173 blocked the potentiation of GABA responses by high, but not low, concentrations of diazepam, but did not block the potentiation induced by propofol, the neurosteroid THP or the barbiturate thiopental. Mutational studies on ‘anaesthetic-influencing’ residues showed that, compared with wild-type GABA_A receptors, α1M236Wβ2γ2L and α1β2N265Sγ2L receptors are resistant to potentiation by etomidate, loreclezole and Fa131.

CONCLUSIONS AND IMPLICATIONS

Fa173 is a selective antagonist that can be used for allosteric modulation of GABA_A receptors. Flavan-3-ol derivatives are potential ligands for etomidate/loreclezole-related binding sites at GABA_A receptors and the low-affinity effects of diazepam are mediated via the same site.     

颅脑损伤患者NICU镇静处置策略

目的回顾神经外科重症监护室(NICU)47例颅脑损伤患者焦虑和躁动情形下的临床处置过程,探讨适合颅脑损伤病情特点的镇静策略。方法镇静/激动(SAS)评分评判镇静效果。个体化镇静处置措施使其SAS评分稳定至2~4分。结果颅脑损伤患者镇静处置以非药物为首选;药物镇静须不得已而为之;动态定时评估镇静效果利于与脑伤恶化意识障碍区别。镇静药物宜选速效、短效药物个体化使用。结论镇静处置对于NICU的颅脑损伤患者是重要的治疗策略。     

五味子醋镇静催眠抗焦虑作用及其作用机制

目的:观察五味子醋(Schisandrae Chinensis Fructus Vinegar,SV)的镇静催眠抗焦虑作用并初步探讨其作用机制。方法:将50只ICR雄性小鼠随机分为正常组、地西泮组(镇静实验剂量为2 mg·kg-1,催眠及抗焦虑实验剂量为4 mg·kg-1)和SV低、中、高剂量组(灌胃给予相应剂量SV)。各组连续灌胃给药7 d后,采用自主活动记录仪观察SV对小鼠自主活动的影响;通过阈下剂量戊巴比妥钠协同睡眠实验观察SV对小鼠睡眠只数、潜伏期及睡眠时间的影响。采用高架十字迷宫(elevated plus maze,EPM)检测SV的抗焦虑作用;采用酶联免疫吸附实验(ELISA)检测SV对小鼠脑组织中γ-氨基丁酸(γ-aminobutyricacid,GABA)及谷氨酸(glutamate,Glu)含量的影响;应用蛋白免疫印迹法(Western blot)检测SV对小鼠脑组织中GABAAα1及GABAAγ2表达的影响。结果:与正常组比较,SV中、高剂量组小鼠自主活动次数明显减少(P0.05,P0.01),协同阈下剂量戊巴比妥钠诱导小鼠睡眠只数增加;协同阈剂量戊巴比妥钠诱导的小鼠睡眠潜伏期明显缩短、睡眠时间显著延长(P0.05,P0.01),EPM模型小鼠开臂/在臂滞留时间率(OT)和开臂/在臂进入次数比率(OE%)明显增加(P0.05);SV高剂量组小鼠脑组织中GABA含量显著增加(P0.01),Glu含量显著减少(P0.01);SV中、高剂量组小鼠脑组织中GABAAα1和GABAAγ2蛋白表达明显增加(P0.05,P0.01)。结论:SV具有镇静、催眠及抗焦虑作用,该作用与其调节小鼠脑组织中GABA,Glu含量及GABAAα1,GABAAγ2蛋白表达有关。     

灯心草镇静作用活性部位的研究

目的确定灯心草镇静作用的活性部位。方法灯心草部位提取物的制备主要采用溶剂法,灯心草全草先用95%的乙醇提取,得到的提取物进一步用石油醚、氯仿、乙酸乙酯和甲醇依次提取,得到极性由小到大的4个提取部位。活性筛选采用常规的镇静催眠实验,观察灯心草提取物对小鼠自主活动的影响以及在戊巴比妥钠协同下对小鼠睡眠时间的影响。结果灯心草95%乙醇提取物有确切的镇静和催眠作用,在乙醇提取物的4个不同极性的部位中,乙酸乙酯部分的镇静作用最为确切。结论首次确定了灯心草的乙酸乙酯部分是镇静作用的有效部位。在此基础上,可以更深入探讨灯心草镇静作用的有效成分或成分群以及镇静作用的特点。     

安神类中药及其有效成分对神经递质镇静催眠机制的研究进展

安神类中药应用于临床治疗失眠历史悠久。现代药理作用主要为镇静、催眠以及抗焦虑和抗抑郁作用。现代分子生物学研究表明,失眠症与神经递质、细胞因子等有关。该文对中药单体成分、单味中药提取物、复方安神中药提取物以及复方安神中成药通过调节神经递质而发挥镇静催眠作用进行综述。该文所涉及到的神经递质包括γ-氨基丁酸(GABA)、谷氨酸(Glu)、5-羟色胺(5-HT)、多巴胺(DA)、去甲肾上腺素(NE)及其代谢物5-吲哚乙酸(5-HIAA)、高香草酸(HVA)、二羟苯乙酸(DOPAC)。研究结果表明,目前安神药研究最多的是5-HT和GABA能神经系统。研究最多的安神药是酸枣仁,包括其单体成分、单味中药提取物、复方中药提取物及复方中成药,涉及到的安神药还有五味子、合欢花、远志、龙眼肉、灵芝等。这为安神类中药的临床研究提供参考,进而为其开发利用提供依据。