国家级继续医学教育项目“药物治疗的临床思维和临床决策”学习班通知

一、内容：（1）症状体征与药物治疗;（2）实验室检查与药物治疗;（3）临床信息的收集、分析、处理和判断与药物治疗;（4）病情的分析和判断与药物治疗;（5）药物治疗的临床思维;（6）药物治疗的临床决策;（7）不合理用药的表现及其判断;（8）药学监护与药物治疗;（9）循证医学与药物治疗;（10）用药学知识指导用药;（11）真性难治性疾病和假性难治性疾病;     

中山市人民医院1000例药物咨询情况分析

目的：了解中山市人民医院门诊的药物咨询情况.方法：提取2010年5月至2013年5月该院门诊药物咨询记录,按照咨询对象、咨询药物类别和咨询药物内容等进行回顾性分析.结果：咨询对象以患者居多（占48.5％）,其次为患者家属（占32.1％）、医务人员（占18.2％）;咨询药物类型主要有抗感染药（占25.3％）、心脑血管系统药（占20.1％）、消化系统药（占12.8％）和中成药（占10.2％）;咨询药物内容广泛,包括用法、用量、不良反应、药理作用、使用注意事项、相互作用等为主的药物基本信息及特殊人群用药等.结论：开展药物咨询服务,可改善患者用药的依从性,促进临床安全、合理用药,提高医院药学服务质量和水平.     

2016年3月FDA批准新药概况

2016年3月,FDA批准3个新生物制品和1个新分子实体药品（表1）,分别为治疗吸入性炭疽病药物Anthim（obiltoxaximab）、治疗银屑病药物Taltz （ixekizumab）、治疗哮喘药物Cinqair（reslizumab）和治疗严重肝静脉阻塞药物Deiftelio（去纤核苷酸钠）。     

常见抗痨药物的肝损害分析

随着临床用药种类不断增多,药物性肝炎的发生率增加。目的：对药物性肝炎患者资料进行分析,提高对该病的认识,及早做出正确诊断和治疗,分析异烟肼（INH）、利福平（RFP）、丙硫异烟胺（Th1321）、乙硫异烟胺（Th1314）、对氨水杨酸钠（PAS）以及吡嗪酰胺（PZA）和氨硫脲（TB）等药物对于不同年龄段、不同异常指标的反映。方法：对我院2011年1月～2012年12月收治典型的96例确诊为药物性肝炎的病历进行分析总结。根据患者以往的药物史、临床试验、血常规、病史以及肝功能测试、B超等综合结果进行比较,最终做出判断。结果：使用含异烟肼（INH）、利福平（RFP）、丙硫异烟胺（Th1321）、乙硫异烟胺（Th1314）、对氨水杨酸钠（PAS）以及吡嗪酰胺（PZA）和氨硫脲（TB）等抗痨药物的化疗方案时,药物性肝炎的发生率较高。结论：抗结核药物对结核病患者而言是必须采用的,但是药物引起的对肝脏的影响也是不能忽视的。对肝脏的影响大小由于个体差异引起的毒性代谢产物积累量也是不同的。但是抗结核药物引起的肝损伤问题要早期发现,及时处理,绝大部分患者是可以恢复的。     

2014年4月FDA批准新药概况

2014年4月，FDA批出3个新生物制品和1个新分子实体药品（表1），分别为治疗2型糖尿病药物Tanzeum（阿必鲁肽）、治疗癌症药物Cyramza（雷莫芦单抗）、治疗巨大淋巴结增生症药物Sylvant（司妥昔单抗）和治疗肺癌药品Zykadia（ceritinib）。     

子宫内膜癌治疗药物的研究进展

药物治疗是子宫内膜癌治疗的重要组成部分,常用药物包括激素治疗药物（孕激素、抗雌激素药物、促性腺激素释放激素激动剂）、化疗药物（紫杉醇、铂类、蒽环类）和靶向药物（表皮生长因子受体拮抗剂、哺乳动物雷帕霉素靶蛋白抑制剂等）。随着研究的深入,越来越多的抗子宫内膜癌新靶点被发现,包括血管内皮生长因子（VEGF）、聚腺苷二磷酸核糖聚合酶（PARP）、程序性死亡受体1（PD-1）和PD-1配体（PD-L1）,中药和天然单体化合物也是目前的研究热点。对子宫内膜癌治疗药物的作用机制及研究进展进行综述,以期对该病治疗及新药研发有所裨益。     

257例儿童药物咨询回顾性分析

目的了解我省儿童医院药物咨询工作情况,提高药物咨询服务的质量。方法收集本院2010年1月～2012年12月257例儿科相关药物咨询记录,对咨询者身份、咨询药物类别及咨询内容进行回顾性分析。结果咨询者以患儿家属为主（91．83％）,其次为医生、护士、药师和其他医务人员;咨询药物以抗感染药物最多（19．23％）,其次为临床各科专用药物和消化系统用药;咨询内容以药品用法用量为主（48．16％）,其次为药品不良反应和用药注意事项（14．72％）、药品适应证（11．37％）、药物相互作用和配伍禁忌（8．03％）。结论药物咨询是儿科药学服务的重要内容,是提高儿童用药安全性和合理性的重要途径;提高药物咨询服务水平,有利于提高儿童用药依从性,保证用药安全有效。     

社区获得性肺炎抗菌药物应用情况分析

目的通过对医院社区获得性肺炎（CAP）患者抗菌药物使用情况的调查分析和合理性研究，提高医院合理用药水平，增强临床医生合理用药意识。方法采用限定日剂量（DDD）、药物利用指数（DUI）、药物联合应用及抗菌药物的适应证，分析CAP患者抗菌药物使用情况。结果57.1%的抗菌药物的DUI≥1，DDD排序结果前5位依次为β 内酰胺类及其酶抑制药复合制剂（31.04%）、喹诺酮类（28.43%）、头孢菌素类（19.85%）、氨基苷类（10.66%）、抗真菌类（6.33%）。新喹诺酮类、肽类、碳青霉烯类、新氨基苷类、第3和第4代头孢菌素类被广泛使用，使用量达到全部抗菌药物用药频率（DDDs）的68.94%，联用率为100%。药品费用和住院时间，医保患者分别为（1.77±1.19）万元，（15.0±10.2）d；自费患者分别为（0.96±0.62）万元，（10.0±7.3）d，差异有显著性（P＜0.05）。结论大部分患者给予非适应证剂量的抗菌药物。新一代抗菌药物的大量使用使二重感染率偏高。药物经济学理论（序贯理论、替代疗法）在临床实践中较少被应用，临床药师在临床实践中应发挥更为积极的作用。     

放射性核素偶联药物研发的优势与挑战

<正>偶联药物将精准靶向和强效杀伤2种特性相结合,已成为近阶段受到广泛关注的一种药物形式。在“万物皆可偶联”的设计理念下,一系列偶联药物的应用让人眼花缭乱,例如抗体偶联药物（antibody drug conjugates,ADCs）、小分子偶联药物（small molecule drug conjugates,SMDCs）、多肽偶联药物（peptide drug conjugates,PDCs）、适配体偶联药物（aptamer drug conjugates,ApDCs）、病毒样药物偶联物（virus-like drug conjugates,VDCs）、抗体寡核苷酸偶联物（antibody oligonucleotide conjugates,AOCs）等。不仅如此,新的技术路线仍在被持续挖掘,比如抗体降解偶联药物（antibody degraducer conjugates,ADeCs）、前药偶联药物（Pro-antibody drug conjugates,Pro-DCs）,     

我院药物咨询情况分析

目的了解临床药物咨询情况,促进合理用药,提高药物咨询的服务质量。方法收集整理375例门诊药物咨询资料,对咨询者身份、年龄、咨询药物类别和内容进行统计分析。结果咨询者年龄以30～50岁最多,占51.5%（193/375）;咨询药种前4位分别为抗菌药（25.6%）、心脑血管药（20.5%）、消化系统药（13.3%）和内分泌系统用药（11.5%）;咨询问题以药物基本信息为主（20.3%）。结论药物咨询增进了药师与患者、医师、护理人员等之间的交流,提高患者用药的依从性,促进临床合理用药。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.