临床药师参与脓毒症休克患者继发泛耐药鲍曼不动杆菌感染的病例分析

摘要：本文旨在探讨临床药师参与耐药菌感染药学监护模式及在抗感染治疗中的作用。临床药师参与1例脓毒症休克患者继发泛耐药鲍曼不动杆菌（XDR-AB）感染的治疗,结合相关指南和文献报道,综合抗菌药物的药动学/药效学（PK/PD）特点,从抗菌药物品种选择、剂量、疗程、给药方式及不良反应等方面开展临床药学服务,协助临床医师制订抗感染方案,最终患者感染得到有效控制。临床药师利用药学知识,协助临床制订抗感染治疗方案,对XDR-AB感染患者实施精准药学监护,提高脓毒症休克及XDR-AB感染药物治疗的有效性和安全性,提高患者生存率,体现临床药师自身价值。     

基于PK/PD理论优化1例脓毒性休克患者抗感染治疗方案的病例分析

目的 探讨亚胺培南/西司他丁钠持续输注给药方案用于脓毒性休克合并急性肾损伤患者的疗效及临床药师参与药物治疗方案的作用。方法 临床药师参与1例脓毒性休克合并急性肾损伤且未行持续肾替代治疗患者的抗菌药物治疗,基于抗菌药物PK/PD特性及脓毒性休克患者的病理生理学改变对抗菌药物药动学(PK)/药效学(PD)参数的影响方面,分析亚胺培南/西司他丁钠持续输注给药及剂量调整对药物治疗有效性及安全性的影响。结果 结合患者病理生理学状态,并且根据亚胺培南/西司他丁钠PK/PD特性和静脉输注方法的循证医学依据,调整亚胺培南/西司他丁钠给药剂量、给药间隔和静脉输注方法,可获得满意的治疗效果。结论 临床药师依据抗菌药物PK/PD理论并结合脓毒性休克患者的病理生理学特点,参与药物治疗方案的制定及调整,可以提高药物治疗的疗效和安全性。     

1例脓毒症合并急性肾损伤患者的药学监护

摘要：临床药师参与1例脓毒症合并急性肾损伤患者的抗感染治疗,结合患者病理生理情况,在疾病治疗过程中协助制定抗感染方案,对抗菌药物的给药方式及治疗方案进行了优化,使感染得到有效控制,治疗有效。临床药师参与临床实践,优化药物治疗方案,为临床合理使用抗菌药物发挥积极的作用。     

1例尿毒症伴原发性肺淋巴瘤合并脓毒症患者的抗感染治疗分析与药学监护

临床药师参与1例尿毒症伴原发性肺淋巴瘤合并脓毒症患者的治疗，结合血液透析、残余肾功能、感染严重程度、抗菌药物的药动学/药效学、影像学与感染指标动态变化、文献资料等，制定了详细的个体化抗感染治疗方案，包括抗菌药物的选择、给药方案的优化等，使患者的感染得到有效控制。同时，通过实施药学监护，无明显不良反应发生，残余肾功能得到充分保护，患者得到安全有效的药物治疗，体现了临床药师的专业价值。     

基于药动学理论脓毒症患者替考拉宁个体化给药分析

目的 探讨临床药师利用药动学理论指导脓毒症患者替考拉宁个体化给药的可行性。方法 临床药师通过参与1例脓毒症抗感染治疗案例,结合监测结果和患者药动学分析,为临床提供药物处置对策和监护建议。结果 临床药师在2次会诊中,结合监测结果对患者进行抗菌药物药动学分析,提出替考拉宁个体化的处置对策和监护计划,保障个体化给药的实施。结论 临床药师对脓毒症患者药动学改变进行全面评估,配合治疗药物监测手段,能够辅助临床医生做好个体化用药工作。     

1例脓毒症休克合并急性肾功能不全患者使用美罗培南的药学实践

临床药师协助医师对1例脓毒症休克合并急性肾功能不全患者的美罗培南给药方案进行调整，建议采用缩短给药间隔以及采用两步滴定法给药。医师采纳临床药师建议，治疗取得良好效果，患者病情明显好转出院。     

脓毒症休克伴急性肾损伤新生儿抗菌药物剂量调整的个体化治疗实践

摘要：以1例脓毒症休克合并急性肾损伤新生儿为例,探讨临床药师在危重症患儿抗菌药物剂量调整中发挥的作用。临床药师综合分析了抗菌药物在脓毒症休克患儿体内药动学的改变及连续性肾脏替代治疗对抗菌药物清除作用的影响,协助医生上调美罗培南剂量至140 mg q12h,并延长其输注时间至4 h,同时监测万古霉素血药浓度并两次给出剂量调整建议。该患儿转归良好,未发生药品相关的严重不良反应。面对危重症新生儿抗感染治疗的挑战,临床药师发挥专长,开展治疗药物监测,给予个体化用药建议,可保障药物治疗的有效性及安全性。     

临床药师参与1例脑出血合并肺部感染患者的药学监护

目的探讨临床药师在脑出血合并肺部感染患者治疗过程中的药学服务方法。方法临床药师参与1例脑出血合并肺部感染患者的治疗过程,利用掌握的药学专业知识,与临床医师共同制定个体化给药方案。结果调整抗菌药物等药物给药方案,提高了临床药物治疗水平。结论临床药师应主动服务,根据指南,发挥药理学药动学优势开展药学监护。     

临床药师对外科髂窝脓肿患者治疗的药学监护

目的：探讨临床药师通过对髂窝脓肿患者治疗进行药学监护的要点,为临床提供合理用药建议。方法：针对1例外科髂窝脓肿病例,临床药师根据抗菌药物的抗菌谱及药代动力学特点为患者提供个体化给药及药品不良反应的分析,进行抗菌药物局部使用情况的探讨。结果：临床药师为髂窝脓肿患者选择了克林霉素联合单环口一内酰胺类抗菌药物氨曲南的抗感染治疗方案,并指出了庆大霉素＋甲硝唑局部冲洗的不规范使用,给予了合理化使用建议。结论：通过临床药师对患者的药学监护,为患者制定个体化给药方案,促进了临床合理用药。     

临床药师参与1例CRKP泌尿道感染继发血流感染患者抗感染治疗分析

摘要：临床药师在1例耐碳青霉烯肺炎克雷伯菌（CRKP）泌尿道感染继发血流感染患者的治疗过程中,根据患者病情、抗菌药物的药动学/药效学（PK/PD）特点及文献资料,为患者优化了抗感染治疗方案,包括抗菌药物的选择、给药方案的优化、药学监护等,最终患者感染得到有效控制,治疗效果较好,体现了临床药师的服务价值。     

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.