临床药师参与1例阿司匹林致小肠黏膜损伤治疗过程

摘 要 目的： 探讨临床药师在特殊类型消化道黏膜损伤治疗中的作用。方法: 临床药师运用Naranjo score和ALDEN score等分析患者疾病与阿司匹林不良反应间的关系,利用药学知识及最新研究进展,结合患者“NSAIDs引起小肠黏膜损伤”特殊性,调整患者可能引起该疾病的伴随用药以及小肠黏膜损伤治疗方案。结果: 患者肠道损伤很可能由NSAIDs药物阿司匹林引起,在药师建议下,不再恢复使用阿司匹林一级预防,减量继续使用沙美特罗替卡松吸入剂。抑酸药埃索美拉唑及黏膜保护药磷酸铝凝胶在NSAIDs相关小肠黏膜损伤中可能无治疗意义,在药师建议下,予以停用埃索美拉唑,换用对小肠黏膜损伤有作用的瑞巴派特。结论: 临床药师参与临床医疗团队合作,可发挥药学专长,优化治疗方案,提高临床治疗水平。     

质子泵抑制剂联用瑞巴派特预防双联抗血小板治疗致胃黏膜损伤的合理性

双联抗血小板治疗(DAPT)诱发的胃黏膜损伤在心血管冠脉再通抗凝治疗中较为常见。质子泵抑制剂(PPIs)是临床上预防DAPT引起相关胃黏膜损伤的首选药物,胃黏膜保护药瑞巴派特也用于预防NSAIDs或长期小剂量应用阿司匹林引起的胃肠道出血。由于PPIs长期使用的局限性及其作为心血管事件的独立危险因素,在DAPT诱导胃肠出血的高危时期可联合使用PPIs与瑞巴派特或者使用PPIs的替代性药物沃诺拉赞,序贯使用瑞巴派特或间断应用PPIs,对PPIs不耐受者可换用H_(2)RAs。尚无指南指出,接受DAPT引起消化道出血风险高的患者,应预防性使用PPIs联合瑞巴派特进行护胃抑酸治疗。本文就两药联用预防DAPT引起相关胃黏膜损伤的合理性进行阐述,希望为临床预防DAPT引起胃肠出血的用药选择提供参考。     

质子泵抑制剂临床超适应证使用的医疗大数据分析

目的 探讨国内住院患者质子泵抑制剂（PPIs）过度使用的主要原因。方法 分析20家综合性医院2015年1月1日至2018年3月31日的患者电子病历信息,统计PPIs的适应证分布,不同品种PPIs的使用分布以及超适应证用药患者的高频疾病、手术、合并用药等。结果 PPIs使用人数最高的适应证为非甾体抗炎药(NSAIDs)相关溃疡的预防,占使用患者的40.9%;34.2%的患者为超适应证用药;超适应证用药患者中,兰索拉唑使用比例最高,占48.1%;使用PPIs患者人数最高的疾病、手术和伴随用药分别是食管、胃和十二指肠疾病、胆囊胆道手术和矿物质补充剂。结论 药物性溃疡的预防和超适应证用药是PPIs用量巨大的主要原因;兰索拉唑的应用不够规范;超适应证用药通常发生在肿瘤和消化道疾病的患者,消化道不适、禁食、手术和使用糖皮质激素是其发生的主要原因。     

880例妇科手术患者应用质子泵抑制剂合理性分析

摘 要 目的：调查某院妇科手术患者质子泵抑制药（PPIs）使用情况,分析PPIs预防应激性溃疡（SU）合理性,为临床正确使用PPIs提供参考。方法: 抽取2016年首次入住妇科病区的出院患者病历1000份,回顾性分析PPIs使用情况,评价其使用合理性。结果:PPIs预防使用率为90.72%（880/970）;28.18%（248/880）的患者不具备预防用药指征,95.68%（842/880）的患者给药时机错误,91.46%（578/632）的患者用法用量错误。结论:妇科手术患者使用PPIs预防SU时,存在适应证、品种选择、用法用量等方面的不合理现象,应加强技术和行政干预,制定符合本院实际情况的PPIs使用标准,改善PPIs不合理使用现状。     

质子泵抑制药的药动学研究进展

摘 要质子泵抑制药（PPIs）为 H+/K+ATP酶抑制药,可高效快速抑制胃酸分泌,持续时间长久,是新型抑酸药物。也是目前治疗酸相关疾病如胃食管反流病、消化性溃疡及非甾体类抗炎药引起的相关胃肠病变的首选药物。对基础胃酸、夜间胃酸的分泌,胃泌素和食物刺激后的引起的胃酸分泌均有显著的抑制作用。本文就国内已上市的5种PPIs的药动学特征进行综述。     

我院骨科患者围手术期预防性使用质子泵抑制药调查

摘 要 目的：对我院骨科围手术期患者预防性使用质子泵抑制药（PPIs）的用药情况进行调查,评价PPIs预防应激性溃疡的适宜性,为促进临床合理用药提供参考。 方法：通过医院信息系统随机抽取我院骨科2018年3月~2019年2月手术患者出院病例793份,统计患者基本信息、PPIs的使用情况、手术情况等,分析PPIs的用药合理性。 结果：793例患者的手术类型主要集中在骨折内固定术（248例,31.27%）、内固定取出术（167例,21.06%）、髓核摘除术和植骨融合内固定术（88例,11.1%）。793例使用PPIs患者中,522例患者不具备预防用药指征,706例品种和剂型选择不适宜,346例患者给药时机不合理,706例患者给药频次不合理,665例患者预防用药疗程过长。 结论：骨科患者围手术期使用PPIs预防应激性溃疡存在严重不合理现象,临床医师、监督管理部门和临床药师应高度重视,避免过度使用造成不必要的资源浪费。     

PCI术后抗血小板联合抗凝治疗患者消化道出血危险因素及治疗策略分析

目的 分析抗血小板及抗凝药物致消化道出血的危险因素及治疗策略。方法 临床药师参与1例消化道出血患者的治疗过程,从具体案例着手,结合患者病情进行系统分析。结果 双联抗血小板、华法林、未系统监测INR、高龄、未预防性使用质子泵抑制剂等引起患者慢性消化道出血加重,通过对症止血、补血处理及停用抗血小板及抗凝药物,患者出血症状得到有效控制。结论 对于消化道出血高危人群,应及时加用质子泵抑制剂至少3个月预防治疗。新型胃黏膜保护剂如瑞巴匹特等对抗血小板药物导致的消化道损伤亦有显著的预防作用,可考虑作为质子泵抑制剂的替代治疗。     

砂仁水提物对5-FU致大鼠肠黏膜屏障损伤的保护作用

目的 研究砂仁水提物对5-氟尿嘧啶（5-FU）诱导的大鼠肠黏膜损伤的保护作用。方法 清洁级SD大鼠随机分成正常对照组、模型组、阳性药组、砂仁水提物48,96,192 mg·kg^-1组,每组8只。正常对照组腹腔注射生理盐水5 d,其余各组腹腔注射35 mg·kg^-1 5-FU 5 d,且从实验开始正常对照组空腹灌胃生理盐水、其余各组空腹灌胃相应治疗药物,给药12 d。实验期间记录大鼠腹泻情况、体质量、食量;实验结束后取小肠做病理切片;ELISA法检测大鼠IL-6、ROS、NF-κB、MPO、TNF-α、LPS的含量,流式细胞术检测肠道紧密连接蛋白ZO-1、occludin及caspase-3的含量。结果 砂仁水提物可显著改善5-FU导致的大鼠体质量、食量下降;显著改善5-FU诱导的大鼠肠屏障损伤及腹泻;显著降低大鼠血液中炎症因子IL-6、ROS的含量;显著抑制5-FU导致的大鼠小肠中NF-κB、TNF-α、MPO的升高与阳性药效果相当。同时砂仁水提物可增加occludin、抑制caspase-3的表达,在一定程度上抑制肠源性LPS易位,保护肠屏障功能。结论 砂仁水提物对5-FU引起的肠黏膜屏障损伤具有一定保护作用,其中96 mg·kg^-1的效果较好,推测其作用机制可能与砂仁水提物抑制肠黏膜炎前体物质ROS的产生,从而抑制核因子NF-κB通路,降低炎症反应;抑制MPO的激活及caspase-3表达,维持细胞间紧密完整性进而抑制肠源性LPS易位有关。     

PDCA循环管理法降低质子泵抑制药用药风险

摘 要 目的:探讨PDCA循环降低质子泵抑制药（PPIs）用药风险的作用。方法：随机抽取PDCA干预前应用PPIs的医嘱、处方以及应用PDCA循环干预后PPIs的医嘱、处方,对比分析PPIs用药合理性与风险。结果：应用PDCA循环干预后,PPIs医嘱和处方合格率显著增加（干预前为91.7%,干预4组为98%,P＜0.01）,超适应证应用PPIs的医嘱、处方比例（干预前为5%,干预4组为1%,P＜0.01）以及用法用量不适宜的医嘱、处方比例（干预前为3.3%,干预4组为1%,P＜0.01）均有显著下降。结论：：PDCA循环干预可降低PPIs的超适应证应用和用法用量不适宜,明显提高PPIs的医嘱和处方合格率,用药风险明显降低。但仍有少数医嘱和处方存在超适应证应用和用法用量不适宜的情况。     

300例外科手术患者预防应激性溃疡药物调查

摘 要 目的:了解外科手术患者预防应激性溃疡(SU)药物的情况,评价药物使用合理性,为临床合理用药提供参考。方法: 随机抽取2010年外科住院手术患者病历300份,对预防SU的药物使用情况进行统计、分析。结果:总的预防用药率为18.67%,其中肝胆科的预防用药率最高（63.33%）,其次为胸外科、脊柱外科和普外科;儿科和乳腺科的预防用药率为0。300例中,儿科出现应激性溃疡出血1例（0.33%）;预防SU药物中质子泵抑制药使用率最高为91.07%,H₂受体阻断药为5.36% ,黏膜保护药及其他为3.57%。结论:应激性溃疡重在预防,但应掌握适应证,防止药物不合理使用。     

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.     

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.