盐城地区医疗机构基本药物合理使用情况分析

摘 要 目的：对盐城地区21家综合医疗机构的基本药物合理使用情况进行回顾性分析,以促进基本药物的合理使用。方法：随机抽取盐城地区21家综合医疗机构2015年10月～2016年9月的住院病历,对基本药物的种类、名称、剂型、用法用量、金额等进行调查,并依据药品说明书、诊疗指南等对基本药物的合理使用情况进行评价分析。 结果：共抽取一、二、三级医疗机构住院病历217,761,570份,其基本药物使用率分别为100.0%,97.1%,96.8%。各级医疗机构单个病例平均基本药物使用种数为（8.2±4.0）,（6.8±3.9）,（6.5±4.1）种,基本药物金额占药品金额比例分别为（92.9±20.9）%,（28.0±29.6）%,（19.7±21.5）%。一级医疗机构中药制剂类和头孢菌素类抗菌药物使用率较高;二级医疗机构中药制剂类和水、电解质平衡调节药使用率较高;三级医疗机构肾上腺皮质激素类药物和胃肠解痉药及胃动力药使用率较高。基本药物不合理使用问题主要体现在头孢菌素类药物、中药制剂类等药物用法用量不适宜方面。结论：盐城地区基本药物使用中仍存在一些问题,合理用药水平尚需提高。     

5073例血液系统药物相关药品不良反应报告分析

摘 要 目的:分析血液系统药物相关药品不良反应(ADR)的发生特点,为临床合理用药提供参考。方法：采用回顾性分析方法,对解放军药品不良反应监测中心数据库2009～2014年血液系统药物相关ADR报告进行统计分析。结果：5073例ADR报告中,男女比例为1.31∶1,平均年龄（51.4±19.2）岁,青年（31.45%）和中年（28.92%）患者为主;单一药引发占81.27%;抗血小板药（41.24%）、促凝血药（31.20%）、血浆及血浆代用品（11.47%）引起ADR位列前三位;注射剂占比88.76%;静脉滴注（77.86%）为主要给药途径;前列地尔（25.26%）,氨甲环酸（22.42%）,右旋糖酐40（6.63%）位列引起ADR单品种前三位;ADR导致消化系统（28.69%）,心血管系统（22.51%）、皮肤及附件（16.51%）损害列为前三位,临床表现多见恶心、呕吐、静脉炎、皮疹等;新的及严重的ADR临床表现多见血压异常,过敏性休克等。结论：血液系统药物的合理使用需重视,应加强ADR监测以防范或规避相关用药风险。     

美罗培南降低患者丙戊酸钠血药浓度的临床分析

摘 要 目的：分析美罗培南降低丙戊酸钠（VPA）稳态血药浓度的程度及变化规律,为临床合理用药提供参考。 方法: 收集我院2015年1月~2018年12月合用美罗培南和丙戊酸钠的患者信息,分析两药合用后 VPA 血药浓度下降幅度;根据患者的族别、两药合用前VPA的给药剂量和给药途径将纳入患者进行分组,比较不同族别及在不同剂量和不同给药方式下VPA与美罗培南合用,VPA血药浓度变化情况;对患者的VPA血药浓度下降百分数和年龄进行相关性分析。 结果: 17例患者在联合使用美罗培南和VPA后,VPA血药浓度均降到治疗浓度范围以下,下降幅度为37.18%~99.26%,平均（69.66±17.91）%;两药合用后,VPA使用剂量分别为0.4 g bid,0.5 g bid,0.8 g bid的3组患者的VPA血药浓度均降到了最低治疗浓度范围以下,下降幅度分别为（65.10±19.12）%,（68.15±24.18）%,（75.60±12.64）%,3组间差异无统计学意义（P＞0.05）;口服和静脉使用VPA合用美罗培南后,VPA血药浓度下降幅度分别为（68.15±24.18）%和（70.12±16.77）%,两组间差异无统计学意义（P＞0.05）;汉族与维吾尔族患者的VPA血药浓度下降百分数分别为（72.29±17.28）%和（63.60±22.86）%,两组间差异无统计学意义（P＞0.05）;VPA血药浓度下降百分数与年龄的相关系数为-0.055,两者相关性不大。 结论: VPA与美罗培南两药合用可显著降低VPA血药浓度,临床上应避免两者联用。患者的族别、年龄、VPA不同给药剂量和给药途径在两药合用后对VPA血药浓度下降幅度影响不大。     

伏立康唑白蛋白纳米粒大鼠体内药动学与组织分布

摘 要 目的：制备伏立康唑白蛋白纳米粒,并考察其在大鼠体内药动学与及组织分布。 方法: 采用超高压微射流技术制备伏立康唑白蛋白纳米粒,并评价了白蛋白纳米粒的粒径分布、Zeta电位、外观形态以及体外释药行为;考察了伏立康唑白蛋白纳米粒在大鼠体内的药动学与组织分布特征。 结果: 本研究制备的伏立康唑白蛋白纳米粒平均粒径为（121.9±41.6）nm,PdI为0.197,Zeta电位为（-42.1±0.9）mV,呈球形或类球形分布;伏立康唑白蛋白纳米粒在0.5%吐温80磷酸盐缓冲液（pH 7.4）中24 h累积释放67.5%;大鼠体内药动学研究表明,伏立康唑白蛋白纳米粒和伏立康唑注射剂的AUC0-24分别为（98.27±1.42）和（105.32±1.45）g?h?L^-1,MRT0-24分别为（4.48±0.38）和（4.86±0.51）h;伏立康唑白蛋白纳米粒能增加药物在大鼠肝、脾、脑中的靶向性。 结论:伏立康唑白蛋白纳米粒在大鼠体内具有良好的肝、脾、脑中靶向性,可以提高药物治疗疗效。     

临床药师持续干预泌尿外科清洁手术预防用抗菌药合理使用的效果评价

摘 要 目的： 调查某院临床药师实施持续干预前后泌尿外科清洁手术预防用抗菌药（简称“预防用药”）的应用情况,为临床合理预防用药提供参考。方法: 提取我院泌尿外科2010年7月~2014年6月所有行清洁手术患者,根据干预时间和干预措施分别纳入干预前组（n=141）、第1阶段干预组（n=139）、第2阶段干预组（n=162）和第3阶段干预组（n=137）,对各组患者的预防用药情况进行统计分析。结果:实施持续干预后,第1阶段干预组、第2阶段干预组和第3阶段干预组的预防用药率由干预前的100%降至34.5%,18.5%和14.6%,预防用药的选药合理率由干预前的36.9%升至58.3%,63.3%和85.0%,预防用药时间由干预前的（138.2±31.6）h缩短至（89.9±48.0）h,（72.8±32.5）h和（45.1±29.5）h,差异均有统计学意义（P<0.01）。感染发生率呈下降趋势,从干预前的2.8%分别降至2.1%,1.8%和1.4%。结论: 临床药师的持续干预措施得力,干预效果显著,明显促进了泌尿外科清洁手术围手术期预防用药合理性。     

徐州某医院2005~2016年药品不良反应报告回顾性分析

摘 要 目的：了解徐州某医院药品不良反应（ADR）报告病例的特点,为临床安全用药提供依据和参考。方法：采用回顾性调查方法,对该院2005~2016年上报的ADR病例进行分析,并按年龄、性别、药品种类等进行分类统计。结果：12年间该院共上报ADR病例1 356例,男性679例（50.1%）,平均年龄（36.4±26.1）岁。每年上报的ADR数量从18例到274例不等,以一般不良反应为主（1 169例,86.2%）,给药途径以静脉滴注为主（1 110例,81.9%）,以单一用药引发为主（1 041例,76.8%）;ADR主要累及消化系统（568例次,22.8%）和皮肤及其附件（537例次,21.6%）;ADR由抗微生物药引发最多（1 006例,55.6%）,其次是中成药（175例,10.0%）和抗肿瘤药（125例,7.1%）;抗微生物药主要以喹诺酮类（29.9%）、β-内酰胺类（27.2%）和大环内酯类（22.5%）为主;引发ADR排名前3位的药物分别是阿奇霉素、左氧氟沙星、加替沙星等。结论：该院上报的ADR病例主要由抗微生物药、中成药和抗肿瘤药引起,应加强该类药物的管理,同时积极开展ADR监测,提高医务人员上报ADR的积极性,促进临床用药安全。     

某三级甲等医院400例新的及严重的药品不良反应分析

摘 要 目的：了解某三级甲等医院药品不良反应（ADR）发生的特点,为临床安全用药、减少ADR发生提供参考。方法: 对2014～2016年收集上报的新的及严重的ADR从报告类型、年龄、性别、给药途径、药品种类、累及系统 器官方面进行分析。结果:新的及严重的ADR报告共有400例,占报告总数的64.52%;60～74岁患者所占比例最大,为34.25%;发生ADR的男女比例基本相当,男性（50.25%）略高于女性（49.75%）;静脉给药引起ADR例数最多（57.00%）;引起ADR的药品种类最多的为抗感染药物（31.25%）,其中头孢菌素类占比最多（32.00%）;主要累及系统 器官为皮肤及附件损害（33.00%）、胃肠系统损害（15.50%）及肝肾功能损害（14.00%）等。结论:全院应加强ADR监测与上报工作,从而规范药物使用,减少ADR的发生。     

血塞通注射液辅助应用对断指再植患者术后血凝指标及血栓并发症的影响

摘 要 目的： 探讨血塞通注射液辅助应用对断指再植患者术后血凝指标及血栓并发症的影响。方法: 2012年3月~2014年3月64例断指再植患者随机分为对照组和观察组各32例,对照组在常规基础治疗上加用低分子肝素,观察组在对照组基础上再加用血塞通注射液。两组疗程均为7 d。比较两组患者临床疗效、断指再植成活时间、手术前后血凝指标水平及血栓并发症发生率等。结果: 对照组和观察组患者临床总有效率分别为68.75%和93.75%,断指再植成活时间分别为（9.44±1.56）d和（6.72±2.28）d;差异均有统计学意义（P<0.05）。观察组患者术后1,4,7 d凝血指标水平均显著优于对照组（P<0.05）,术后血栓并发症发生率也明显低于对照组（P<0.05）。两组药品不良反应发生率比较差异无统计学意义（P>0.05）。结论:血塞通注射液辅助应用于断指再植患者可有效加快再植成活进程,改善术后血凝指标,并有助于降低血栓并发症发生风险。     

重楼总皂苷自微乳化颗粒剂的制备及体外溶出研究

摘 要 目的：制备重楼总皂苷自微乳化释药系统并固化成颗粒剂,考察其体外溶出情况。方法: 考察重楼总皂苷在不同辅料中的溶解度,并通过绘制由不同比例油相、乳化剂和助乳化剂组成的伪三元相图,确定重楼总皂苷自微乳化释药系统的最优处方,并将自微乳化释药系统固化制备成颗粒剂。评价自微乳化释药系统和自微乳化颗粒剂经水稀释后形成微乳的外观、微观形态、粒径分布、Zeta电位。比较重楼总皂苷自微乳化释药系统以及自微乳化颗粒剂的体外溶出情况。结果: 最终确定重楼总皂苷自微乳化释药系统的处方组成为：丙二醇单辛酸酯作为油相,吐温80作为乳化剂,丙二醇作为助乳化剂,最佳配比为7.0∶1.5∶1.5。重楼总皂苷自微乳化释药系统以及自微乳化颗粒剂经水稀释后形成的微乳外观呈微泛蓝光的澄清、透明状液体;平均粒径分别为（58.6±16.4）nm和（68.1±12.1）nm,PdI分别为（0.183±0.04）和（0.209±0.05）,Zeta电位分别为（-20.2±1.9）mV和（-18.9±1.5）mV;透射电镜下显示微乳呈圆整、规则球状分布。重楼总皂苷自微乳化释药系统以及自微乳化颗粒剂在45 min时药物的溶出度均超过85%。结论: 将重楼总皂苷制备成自微乳化颗粒剂可显著提高药物的体外溶出速度,制备工艺简单可行。     

我院门诊妊娠患者处方点评及用药合理性分析

摘 要 目的： 分析我院门诊妊娠患者处方用药的基本情况以及存在的问题,以促进妊娠期患者合理用药。方法: 抽取我院门诊2014年临床诊断中涉及妊娠但不包括“正常妊娠监督”的处方,依据美国食品药品监督管理局（FDA）妊娠分级药物使用情况、相关法规及药品说明书等,进行归纳分析及点评。结果: 共抽取处方882张,平均每张处方用药品种数为（1.3±0.1）,平均处方金额为（77.7±0.2）元,其中不合理处方31张（3.5%）。结论:需加强临床医师的相关知识培训和药师的处方审核,进一步促进妊娠患者的合理用药,提高用药安全性。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.