Relative efficacy of some prokinetic drugs in morphine-induced gastrointestinal transit delay in mice

AIM:To study the relative efficacy of cisapride, metoclopramide,domperidone,erythromycin and mosapride on gastric emptying(GE)and small intestinal transit(SIT) in morphine treated mice. METHODS:Phenol red marker meal was employed to estimate GE and SIT in Swiss albino mice of either sex.The groups included were control,morphine 1 mg/kg(s.c.15 rain before test meal)alone or with(45 rain before test meal p.o.)cisapride 10 mg/kg,metoclopramide 20 mg/kg, domperidone 20 mg/kg,erythromycin 6 mg/kg and mosapride 20 mg/kg. RESULTS:Cisapride,metoclopramide and mosapride were effective in enhancing gastric emptying significantly(P<0.001) whereas other prokinetic agents failed to do so in normal mice.Metoclopramide completely reversed morphine induced delay in gastric emptying followed by mosapride. Metoclopramide alone was effective when given to normal mice in increasing the SIT.Cisapride,though it did not show any significant effect on SIT in normal mice,was able to reverse morphine induced delay in SIT significantly(P<0.001) followed by metoclopramide and mosapride. CONCLUSION:Metoclopramide and cisapride are most effective in reversing morphine-induced delay in gastric emptying and small intestinal transit in mice respectively.

Nitroester drug's effects and their antagonistic effects against morphine on human sphincter of Oddi motility

AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility.METHODS: The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry.A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group,isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually.RESULTS: BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95±7.49 mmHg to 5.92±4.04 mmHg (P＜0.05) evidently after application of PTN. BPOS increased from 7.37±5.58mmHg to 16.60±13.87 mmHg, SOCA increased from 54.09±38.37 mmHg to 100.70±43.51 mmHg, SOF increased from 7.15±3.20 mmHg to 10.38±2.93 mmHg and CBDP increased 3.75±1.95 mmHg to 10.49±8.21 mmHg (P＜0.01)evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN,SOCA and SOF decreased separately from 100.64±44.99mmHg to 66.17±35.88 mmHg and from 10.70±2.76 mmHg to 9.04±1.71 mmHg (P＜0.05) markedly.CONCLUSION: The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most significant.

Differentiation of illicit drugs with THz time-domain spectroscopy

The terahertz time-domain spectroscopy(THz-TDS) was used for sensing and identifying illicit drugs.The absorption spectra of seven illicit drug samples(morphine and its hydrochloride,cocaine hydrochloride,codeine phosphate,papaverine hydrochloride,pethidine hydrochloride,and thebaine) were studied by THz-TDS at 0.3-2.0 THz at room temperature.The geometric structure and vibration frequencies of morphine were calculated by density functional theory.The four absorption features were dominated by intra-/inter-molecular collective or lattice vibration modes.Each illicit drug has a distinct signature in its THz spectra.The results indicate that the THz-TDS can be used to identify and discriminate illicit drugs by their characteristic fingerprints.

Circular RNA expression alterations are involved in incubation of morphine craving

OBJECTIVE Cue-induced drug craving progressively increase after prolong abstinence in animal and human beings.A behavioral phenomenon termed incubation of drug craving is considered as a key reason for drug relapse,but the transcriptional mechanisms that contribute to this incubation are unknown.It has been demonstrated that circular RNAs(circR NAs),act as miR NA sponges,play important roles in the regulation of gene expression and the pathogenesis of disease.The present study aims to explore the transcriptional profiles associated with incubation of morphine craving in nucleus accumbens(NAc),an important brain area previously implicated in drug seeking.METHODS The animal model of the incubation of drug craving was induced by CPP paradigms with six morphine(5 mg·kg-1) injections and 14 d drug abstinence in mice.The brain tissues of NAc were collected after the behavioral tests for circRNA-sequencing by Illumina Hiseq X sequencer.We identified differentially expressed genes(DEGs) by qRT-PCR and used bioinformatics methods for further function analysis.RESULTS The progressive increase of CPP scores during the 14 d drug abstinence indicated the establishment of animal model.The data of circRNA-sequencing reported that 16 circRNAs were significantly altered after 28 d drug abstinence in NAc of morphine treated mice(FC≥2 and P<0.05).Among those circRNAs,9 were significantly up-regulated,while 7 were down-regulated.Furthermore,we subsequently tested circRNAs expression using quantitative real-time PCR,and the consistent data were obtained.The results of KEGG pathway analysis indicated that these genes were enriched for several biological processes,including RNA transport,protein ubiquitination and histone methylation,etc.CONCLUSION These findings provide a unique resource of gene expression data for future studies examining transcriptional mechanisms in NAc that mediate opioids seeking after prolonged withdrawal.

Morphine pre-exposure facilitates reinstatement but attenuates retention of morphine-induced place preference

BACKGROUND： Drug-associated conditioned stimuli are a key factor to induce morphine relapse. To date, limited evidence is available regarding the impact of drug history on propensity or vulnerability to relapse after long-term abstinence. OBJECTIVE： To determine the effect of morphine pre-exposure on acquisition, maintenance and reinstatement of morphine-induced conditioned place preference （CPP） in rats. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Behavior Pharmacology, Institute of Psychology, the Chinese Academy of Sciences, from March to September, 2006. MATERIALS： Morphine hydrochloride was purchased from Qinghai Pharmaceutical, China; CPP software was designed and developed by Taiji Software Company, Beijing, China. METHODS： A total of 64 Sprague Dawley rats were randomly assigned to eight groups （n = 8）. Four morphine pretreatment regimens were used （subcutaneous injections, twice daily for 5 consecutive days and a total of 10 times）： （1） ＂intensive＂ （morphine injections with doses escalating from 10 to 60 mg/kg; （2） ＂moderate＂ （one morphine injection at 5 mg/kg dose and one saline injection at 1 mL/kg daily for 5 days）; and （3） ＂single＂ （nine saline injections at 1 mL/kg followed by one morphine injection at 5 mg/kg; （4） control （ten saline injections at 1 mL/kg）. At 5 days after morphine pretreatment, animals were divided into two subgroups that underwent morphine conditioned or saline conditioned training. The test for acquisition of CPP was performed 24 hours after CPP training. The retention of morphine CPP was measured by repeated tests performed weekly for 1 month after the initial test of place preference. After extinction by pairing each chamber with saline, the reinstatement of place preference by low doses of morphine （0.05, 0.15, 0.45 mg/kg） was tested. MAIN OUTCOME MEASURES： Acquisition, maintenance, and recovery response of CPP behavior. RESULTS： The acquisition magnitude of morphine-induced CPP was not affected by prior morphine exposure （F3, 56=0.17, P 〉 0.05）. However, rats treated with moderate or intensive morphine pretreatment showed a less persistent CPP （t = -1.36, P 〉 0.05; t = -1.18, P 〉 0.05）, but their place preference was reinstated by a low dose of morphine priming （t = -2.55, P 〈 0.05; t = -2.54, P 〈 0.05）. The retention and reinstatement of morphine-induced CPP did not differ between rats with single morphine pre-exposure and control rats. CONCLUSION： Morphine pretreatment enhanced reinstatement of morphine-induced CPP but with less persistence. Individuals with heavy drug exposure are more susceptible to drug relapse when re-exposed to addictive drugs.

HPTLC-MS as a Neoteric Hyphenated Technique for Separation and Forensic Identification of Drugs

Drugs are traditionally been identified on basis of chromatographic-spectroscopic hyphenated techniques in instrumental analysis. Gas chromatography (GC) and Liquid chromatography (LC) hyphenated with mass spectroscopy (MS) i.e. GC-MS and LC-MS give reliable and confirmatory results in drugs identification. In the present work the novel hyphenated technique High Performance Thin Layer Chromatography-Mass Spectroscopy (HPTLC-MS) has been used. This technique provides efficient, quick and simple method for identification and separation of Narcotic drugs and psychotropic substances. The drugs under study are Papaverine, Methadone, Cocaine, Ketamine, Caffeine, Codeine, Diazepam, Thebaine, Heroin, Methamphetamine, Carbamazepine, Morphine, Narcotine and Ephedrine. The present study comprising of sixteen drugs has been carried out on CAMAG HPTLC instrument with automatic sampling. Thin layer chromatography (TLC) plates were developed in various solvent systems, scanned under TLC scanner and the results in terms of Retention Factor (Rf value) and UV spectrum (λmax) are presented in the manuscript. Using hyphenated technique of HPTLC-MS (MS 2020 SHIMADZU) spots of these drugs from TLC plate was lifted with CAMAG TLC-MS interface and confirmed by the mass spectrum of the individual drugs by their m/z values thus delivering fast and accurate confirmatory result on the TLC plate.

Comparative Study of Solubility of Tranquilizers(Alternative Date Rape Drugs)in Stomach Acid

Date Rape Drugs are the members of tranquilizers and sedative class of drugs.These are the substances that make it easier for someone to rape or assault sexually.The person who is administrated by these drugs can cause sleepiness,slow breathing,slow heartbeat rate,trouble in muscle coordination,loss of consciousness.GHB(gamma-hydroxybutyric acid),Rohypnol(flunitrazepam),Ketamine are generally considered as date rape drugs.As Food and Drug Administration Department of Central Government of India considered this issue and placed these drugs under the schedule of Narcotic Drugs and Psychotropic Substances Act.Thereafter it is nearly impossible to get these drugs easily.But criminals have been searched new way through it.Normal tranquilizers and sedatives are also being used for committing such crimes.These drugs are also scheduled,but one can get them with prescription from a registered medical practitioner.So we carried out a comparative study of 3 tranquilizers from the benzodiazepine class that are Diazepam,Alprazolam,and Librium to check their dissolving rate in stomach acid.Estimation of action time of drug can help an investigator to identify the class of drug and time of drug injected(early phase).In our study,we found that the dissolving period of Diazepam and Alprazolam is more than conventional drugs.

An overview of management of narcotics and psychotropic drugs in China

Narcotics and psychotropic drugs are known as controlled drugs with special management and super vision due to their psychic and physiological dependence. Based on the literature review, experts interview and policy comparative analysis, our study summarized and reviewed the status of related legislation and regulations since the enactment of the Narcotics and Psychotropic Drugs Regulations in 2005. We found the problems of legal loopholes, the complexity of supervision system and the irrational use of narcotics in the treatment of chronic non-cancer. Our analysis suggested that China should reinforce legislation, strengthen the cooperation among departments, establish the information network and improve the guideline of narcotics and psychotropic drugs for clinical treatment as quickly as possible.

Drug treatment

950229 A controlled multi—center clinical trial oncisapride in treatment of functional dyspepsia.WANGBaoen(王宝恩),et al.Beijing Friendship Hosp,Bei-jing.100050.Chin J Intern Med 1995;34(3):180—184.A controlled muhi-centre clinical trial was con-ducted for evaluating the efficacy and safety of cis-apride in the treatment of 414 cases of functional dys-pepsia with 169 cases as control.Cisapride were

手术室外麻醉工作单元麻精药品同质化管理的探讨

目的探索运用同质化管理模式在手术室外麻醉工作单元麻精药品管理中的作用。方法从2021年7月开始运用同质化管理模式对手术室外麻醉工作单元麻精药品进行管理,通过制定同质化管理流程,比较和分析同质化管理模式实施后每季度麻精药品质量管理指标的比值率。结果每季度管理指标评分均有明显提升。结论运用同质化管理模式在手术室外麻醉工作单元麻精药品管理中,能有效提高麻精药品的管理质量,达到药品规范化、精细化、安全化管理的目的,值得推广。

LET CHINA STAY AWAY FROM NARCOTIC DRUGS

TO most ordinary Chinese people, July 30, 1997 was nothing unusual. But to mothers of drug addicts, it was an extraordinary day because a hotline for mothers to fight drug addiction, initiated by the China Women’s News, was officially launched, bringing an end to the mothers’ solitary efforts to help their children. The telephone number, known as the "Hotline for Mothers to Fight Drug Addiction," aims to "provide mothers who are trying to save their children an opportunity to share their bitterness,

北京市二级及以上医院麻醉科麻精药品管理现状及分析

目的调查北京市二级及以上医院麻醉科麻醉药品、精神药品管理情况,为不同级别医院麻醉科对于麻精药品管理提供依据。方法通过北京市临床麻醉质量控制和改进中心平台由专人一对一对有麻醉科建制的二级以上医院发放问卷星链接,调查问卷包括医院基本信息,目前麻醉科内麻精药品管理制度、使用现状以及建议等内容。结果本次调查共发放问卷159份,共回收有效问卷139份,其中二级医院及其他专科医院50家,三级综合医院89家,有效回收率为87.4%。调查结果显示北京市二级及以上医院麻醉科主要使用的麻精药品种类:枸橼酸舒芬太尼注射液、注射用盐酸瑞芬太尼、盐酸麻黄碱注射液、枸橼酸芬太尼注射液等。参与药品管理的人员包括麻醉科医生(63.3%)、麻醉科护士(45.3%)、手术室护士(45.3%)、临床药师(11.5%),存在交叉共管现象。在管理和使用麻精药品过程中存在的主要问题包括药品积压过期浪费(36.4%)、麻精药品无处方或处方错误(31.8%),不同药品存放问题、管理人员数量有限但身兼多职等问题。结论北京市不同级别医院麻醉科在法律规范基础上应结合自身特点建立麻精药品管理制度,明确岗位职责、规范临床人员资质,建议可引入智能化药车、设立麻醉科护士岗位,提升麻精药品管理效率。

刑法中毒品概念的再审视

为进一步加强对毒品犯罪的打击,前置性规范中麻醉药品和精神药品列管品种不断增加、范围不断扩张,这与刑法中的毒品概念应具备相对明确性、确定性之间存有内在冲突。应当重新审视刑法中的毒品概念,明晰麻醉药品、精神药品与毒品概念的关系。刑法中的毒品概念应当具备国家管制性、致瘾癖性、麻精药品和非法用途等四个基本要素。区别于前置法中麻精药品的概念,建议在刑事立法中进一步明确毒品的非法用途要素,即在毒品概念层面通过考察麻精药品的用途,将医疗、教学、科研用途的麻精药品排除出毒品的范围。

贩卖麻醉药品、精神药品行为刑法规制的困境与出路——以《昆明会议纪要》为视角

麻醉药品和精神药品具有药品、毒品和化学的多元属性,贩卖此类物品在司法认定及法律适用上需要坚持更高的要求和标准,紧扣认定罪名的构成要件。贩卖毒品罪的适用条件模糊、“代购型”贩卖等特殊贩卖行为所产生的认定争议,以及妨害药品管理罪与非法经营罪适用混乱导致的定罪偏差,是刑法规制过程中亟待解决的问题。为破解前述现实困境,应以主观目的之认定为重要依据,明确贩卖毒品罪中“明知”在先、“治疗疾病”在后的主观判断顺序,并综合考量具体行为的违法程度,坚持法律效果与社会效果协调统一理念的指引,提出相对应的路径优化建议。在具体优化路径方面,从药品性质、销售对象和方式等角度出发,为主观目的之认定提供客观参考标准;整理“代购型”贩卖、网络销售两种特殊贩卖行为的刑法规制思路,厘清所涉及的走私、贩卖毒品罪和非毒品犯罪之间的认定逻辑;妨害药品管理罪与非法经营罪中关于“许可”的具体指向不同,应以此为基点辨析两罪的适用界限,并深化构成要件的理解,为该类案件的办理提供参考。

柏拉图及鱼骨图分析法在规范麻醉药品和精神药品管理中的应用

目的分析麻醉药品和精神药品的使用情况,为麻醉药品和精神药品的规范管理和合理使用提供科学参考和依据。方法利用医院审方系统随机抽取娄底市中心医院2022年1—12月的麻醉药品和精神药品处方,利用柏拉图和鱼骨图进行统计分析,并提出有针对性的整改措施和改进方案;再将整改前(2022年7—12月)与整改后(2023年7—12月)的处方合格率进行比较,从而确定整改措施的科学合理性。结果通过对448例麻醉药品和精神药品不合理处方(医嘱)进行柏拉图分析,发现不合理处方类型主要有3种,不合理处方产生科室主要有7个;再运用鱼骨图进行根因分析,找到4个方面的主要原因,提出一系列对应整改措施;最后对整改前后处方进行对比,发现合格率从87.56%提升至98.56%,主要和次要的不合理处方类型数量皆有明显减少,差异有统计学意义(P<0.05)。结论应用柏拉图及鱼骨图对麻醉药品和精神药品处方进行分析,可有效改进医院监管措施、规范处方行为、促进合理用药,具有一定的临床价值。

1例艾司氯胺酮致围产期过敏性休克的病例分析

目的为临床工作者及时识别和治疗围产期过敏性休克提供参考。方法临床药师参与四川省妇幼保健院产科1例足月妊娠患者剖宫产麻醉中使用艾司氯胺酮致过敏性休克的救治过程,通过查阅药品说明书并检索相关文献,协助医师对过敏性休克与羊水栓塞进行区分鉴别,对所用药物与不良反应的关联性进行分析,并进行用药教育。结果该患者麻醉后出现低氧血症和低血压,且不存在凝血功能障碍,经肾上腺素对症处理后快速好转,故诊断为过敏性休克。根据该患者用药情况、不良反应发生特点,结合国家药品不良反应监测中心药物与不良反应关联性判定标准和Naranjo’s评估量表,综合判定引起过敏性休克的可疑致敏药物为艾司氯胺酮;临床药师告知患者后期就诊时务必告知医师此次严重过敏反应的相关药物。患者于剖宫产术后第6天痊愈出院。结论过敏性休克与羊水栓塞的临床表现相似,临床需要仔细鉴别。若患者发生了药物导致的全身过敏反应,临床应及时停用可疑药物,并立即采取有效的对症治疗措施,延缓或终止疾病进展,以保障患者的生命安全。

单中心纵向追踪调查分析我院麻醉药品使用情况

目的评估近五年南京市栖霞区医院(江苏省人民医院栖霞分院)麻醉药品利用情况。方法收集2019—2023年麻醉药品临床使用数据,主要分析四个指标:药物利用指标,即累计DDD值(DDDs);药物价格评价指标,限定日剂量费用(DDDc);B/A值,即药物销售总金额排序(B)与药物利用DDDs值排序(A)的比值;手术量复合增长率。结果随着我院与江苏省人民医院的深度合作,手术量不断提升,手术量复合增长率达22.28%,麻醉药品使用量呈上升趋势,2023年DDDs值为6023.39,是2019年(3031.68)的近两倍,相邻年份仅2020年与2021年之间差异有统计学意义(P<0.01)。DDDc值较高的盐酸羟考酮注射液用量呈下降趋势,瑞芬太尼自2020年开始持续稳定在首位。麻醉药品DDDc值保持稳定,最大值为盐酸羟考酮注射液(641.76),最小值为布桂嗪注射液(5.76)。大部分麻醉药品B/A维持在1左右,五年间变化较小;芬太尼注射液的B/A值由2019年的6.00下降至2023年的2.00,盐酸羟考酮注射液的B/A值由2019年的0.25上升至2023年的0.43。结论我院麻醉药品结构合理,基本可满足临床需求,在临床使用方面总体是规范的。临床医师应权衡患者受益,选择安全、有效、经济的麻醉药品。

患儿全身麻醉苏醒期躁动非药物干预的范围综述

目的 对非药物干预在患儿全身麻醉苏醒期躁动(EA)的应用的相关研究进行范围综述,为未来相关研究提供参考。方法 检索PubMed、Embase、CINAHL、Web of Science、Cochrane Library、中国知网、万方和中国生物医学数据库中的相关研究。结果 共纳入28篇文献,患儿EA的非药物干预涵盖父母的录音、父母的陪伴、母亲视频通话、围术期的心理干预、分散注意力、光疗、视听预演、蒙眼试验、术前轻饮、白噪声疗法及联合干预措施。主要评价指标是EA水平,次要评价指标为患儿术前配合相关指标、患儿苏醒期相关指标、父母态度相关指标、行为相关指标。结论 患儿EA的非药物干预措施涵盖面较广,父母参与是非药物干预措施内容的共同要素,未来的研究还需探索父母参与的最佳策略,科学地联合多种高效可行的非药物干预手段,提供有针对性的个体化医疗,同时,开展对非药物干预措施的证据总结,形成高质量的循证证据,为降低患儿EA的发生率提供依据。

药学品管圈领域研究现状及趋势的文献计量学分析

目的探讨我国药学品管圈领域的研究现状及趋势,为本领域的未来研究提供一定的参考。方法以中国知网为文献来源,并借助Microsoft Office Excel 2017进行发文趋势分析、期刊分布统计;利用VOSview 1.6.20、CiteSpace 6.3.R2软件对作者机构合作、关键词共现、聚类、突现等进行分析。结果共纳入554篇文献,本领域研究目前正处于发展缓慢期。统计表明,我国药学品管圈领域共涉及365位作者及231家机构。品管圈在药学领域的应用及其效果一直是本领域的研究重点;聚类分析得到13个有意义的聚类。关键词突现分析表明,目前本领域研究集中在药学服务和以麻醉药品为代表的用药安全方面。结论近年来我国药学品管圈领域的研究发展较为缓慢,未来应加强不同机构及学者间的交流,拓展研究深度和广度,提高研究的质量。

“临床用药”团体标准在医院麻醉药品标准化管理中的应用与实践

目的 研究中国医院协会颁布的中国《医院质量安全管理》团体标准中“第2-12部分:患者服务临床用药”标准在麻醉药品药学服务中的应用。方法 通过分解临床用药标准条款,基于药品管理、用药医嘱以及用药服务三个维度,采用修订管理制度、升级软件设施、配备硬件设施、提升用药服务、加强标准培训等方法,以保障标准应用的有效性。结果 标准应用后,某三甲医院麻醉药品处方批号登记率提升了57.1个百分点,麻醉药品住院医嘱合格率提升了6.2%,门诊处方合格率提升了2.3%,疼痛控制满意度提升了2.4个百分点,麻醉药品相关管理制度更加细化和全面。结论 标准应用后,实现了麻醉药品全流程标准化、信息化、智能化管理,增强了麻醉药品的药学服务质量。