临床药物治疗学总论知识体系的构建

临床药物治疗学是为药学学生提供合理药物治疗基本知识,帮助学生了解如何合理用药,为进行临床药学服务打下基础的一门实践性课程,是医学与药学之间的桥梁。该文从培养药学学生开展药学临床服务入手,介绍对临床药物治疗学总论知识体系的构建思路,以便更好的探索临床药物治疗学的教学工作。     

临床药物治疗学创新型课程教学体系的构建

临床药物治疗学是高校临床药学专业的核心课程，在培养具有临床药学服务能力的临床药师中发挥着重要作用。但是我国临床药物治疗学引入较晚、课程体系尚不完善、所培养的学生能力与岗位要求不相匹配，这些在一定程度上制约了临床药师在临床的发展。本教研室在多年的教学过程中从师资队伍、课时安排和教学方法等方面对临床药物治疗学的课程体系进行了创新性的尝试，建立起了一套具有特色的课程教学体系。文章通过介绍这门课程的教学实践经验，以期为高素质的药学服务人才培养模式提供借鉴和参考，为完善我国临床药学人才培养提供参考和借鉴。     

药物流行病学在临床药学专业中的作用及其授课关键浅析

目的：为提高药物流行病学的教学水平,完善临床药学专业的教学体系提供参考。方法：从正确认识药物流行病学和临床药学专业的正确定位方面探讨临床药学专业学生学习药物流行病学的作用和意义,并着重讨论该课程的两个授课关键点。结果与结论：应重视药物流行病学绪论课的教学,使学生充分认识该门课程的重要性,并注重培养学生的学习兴趣,合理设置相关配套课程,充分发挥药物流行病学的学科优势,以逐步改进和完善临床药学专业的教学体系,培养适合医疗卫生发展形势的新型临床药学人才。     

临床药师在临床药物治疗学课程改革中的尝试

临床药物治疗学是一门基础药学与临床医学的桥梁学科.临床药师是连接临床和药学的专门人才,在临床药物治疗中发挥着不可或缺的作用.为了促进药学本科生学好该课程,由临床药师参与部分临床药物治疗学的授课工作,从教学内容、教学方法、课外实践等方面做出一些改革尝试.     

以“大黄”为例建立生药学教学方法

生药学是一门实践性很强的应用学科,同时也是药学专业一门骨干专业课程。同药用植物学、分析化学及天然药物化学等前置课程联系紧密。但同时生药学知识点多而繁杂,知识结构雷同。如何建立适合生药学课程特点的教学方法是提高生药学课堂教学效果,实现专业课程在药学本科专业人才培养体系中作用的关键问题。本文以大黄为例探讨了建立适合生药学课程特点的教学方法。     

基于双创教育下药学专业的临床药理学课程改革探索

临床药理学是现代医学中一门重要学科,在新药开发和临床药物治疗中发挥重要作用。临床药理学是研究药物与人体相互作用规律的一门学科,是高等院校药学专业的核心课程之一。笔者根据自己的教学过程,结合创新创业教育教育,对药学专业的临床药理学课程进行总结,通过教学时间和方式改革、增加实践教学和双创教育内容和考核方式改革等课程改革,在提高教师的创新意识的基础上,明显提高了学生的自主学习和创新能力,提高了临床药理学的教学效果。     

药学知识的横向思维在药物治疗学教学中的应用

药学知识一般按照化学结构、药效学、药动学、药物不良反应、相互作用、适应证、禁忌证和用法用量等纵向顺序进行教学,而临床上针对复杂多变的病情和个体化特征的患者,往往需要比较一类药与另一类药或一个药与另一个药之间的差别,即通过药学知识的横向思维,评估药物治疗的得失利弊,扬长避短、趋利避害,作出合理决策。为此我们在药物治疗学的教学过程中开展了药学知识横向思维的训练,以加深学生或学员对药学知识理解的深度与广度,为参加治疗团队和参与药物治疗的决策打下扎实的基础。     

对开展临床药学工作的一些看法

临床药学属于应用科学的范畴,是运用药物动力学,药效学等广泛的药学知识及临床治疗学知识,指导药物在临床合理使用的科学。它是药学的一个分支,是药学和医学相结合的科学,其内容是     

药学专业本科生的知识结构

为适应当前实施药学服务、保障公众健康的需求，药学专业本科生的知识结构和课程设置需要进一步优化。应该着重拓展基础医学、临床药学特别是临床药物治疗学的教学，强化对英语、计算机信息科学的实践教学，培养具有扎实基础知识和良好发展潜力，能够适应现代药学工作需要的药学专业人才。     

开展临床药学的体会

临床药学是药学和临床医学汇合而成的全、新、高的一门应用学。全：是指临床药学人员需要全面掌握药学知识，又有一定的临床知识。新；是说既要了解最新药学知识，又要不断补充药学专业没有学过的基础知识。高；是指治疗药物监测的开展，使经验用药转向科学用药要较高的技术与高精密的仪器设备。我院是个创办不久的儿童医院，技术力量不强，高精密仪器设备缺乏，而医院分级管理中又要求开展临床药学，临床药学工作应怎样起步，我们做了如下几件工作：     

Camptothecin accumulation and variations in camptotheca

Camptotheca (Nyssaceae) is a major source of anticancer camptothecin (CPT). It is imperative to understand CPT accumulation and variations in Camptotheca in order to develop CPT production strategies for endangered germplasm. Our study results showed that CPT is primarily accumulated in glandular trichomes of leaves and stems, and CPT content varies among species and varieties but even more significantly within the plant (with different tissues, tissue ages, and seasons). Because of higher CPT yield and desirable biological and ecological features, 'Hicksii' and 'Katie' should be considered the major management germplasm as CPT sources in the future. Young leaves and mature fruits have higher CPT contents than other tissues in the plants. Young photosynthetic leaves and stems contain higher CPT contents than old ones, but 'sink' tissues such as wood, roots, and fruits show different patterns. CPT content also shows a great seasonal change, but is less influenced by tree age. Intact clipping of young leaves and stems should be managed for harvest for CPT production. Preservation and treatment methods influence the CPT extraction. CPT is better preserved in fresh or freeze-dried material than in air or oven-dried material. CPT can be more efficiently extracted after homogenizer treatment of plant materials because more trichome walls can be broken to allow solvent extraction.     

Teaching of clinical pharmacology and therapeutics in UK medical schools: current status in 2009

AIM

To describe the current structure, delivery and assessment of Clinical Pharmacology and Therapeutics (CPT) teaching in UK medical schools.

METHODS

An online questionnaire was distributed to the person with overall responsibility for CPT teaching at all UK medical schools in June 2009.

RESULTS

Thirty of the 32 UK medical schools responded. 60% of schools have a CPT course although in 72% this was an integrated vertical theme. At 70% of schools pharmacologists have overall responsibility for CPT teaching (clinical 67%, non-clinical 33%); at 20% teaching is run by a non-specialist clinician and at 7% by a pharmacist. Teaching is commonly delivered by NHS clinicians (87%) and clinical pharmacists (80%) using lectures (90%) but additionally 50% of schools use e-Learning and 63% have a student formulary. CPT is assessed throughout the curriculum at many schools through written, practical examinations and course work. 90% of schools have specific CPT content in their written examinations. 90% of respondents believed that their students were ‘fairly’ to ‘well’ prepared for the foundation year but only 37% of schools gather data on the competence of their graduates.

CONCLUSIONS

CPT teaching in UK medical schools is very diverse. Most schools do not assess the performance of their graduates as prescribers and there is a lack of evidence that many of the teaching approaches employed are suitable for the development of prescribing skills. It is vital that developments in CPT teaching are driven by validated, real-world assessments of the prescribing skills of medical students and newly qualified doctors.     

Block Copolymer Design for Camptothecin Incorporation into Polymeric Micelles for Passive Tumor Targeting

PURPOSE: Polymeric micelles were designed for targeting of a water-insoluble anticancer agent, camptothecin (CPT). Chemical structures of inner core segment were optimized to achieve high incorporation efficiency and stable CPT-loaded micelles. METHODS: Poly(ethylene glycol)-poly(beta-benzyl L-aspartate) block copolymer (PEG-PBLA) was synthesized. The PBLA chain was modified by alkaline hydrolysis of its benzyl group followed by esterification with benzyl, n-butyl, and lauryl groups. Incorporation of CPT into micelles was carried out by an evaporation method. The stability of drug-loaded micelles was studied by gel-permeation chromatography (GPC), and their in vitro release behaviors were analyzed. RESULTS: CPT was incorporated into polymeric micelles constructed by various block copolymers. Among the esterified groups, block copolymers with high benzyl ester contents showed high CPT loading efficiency and stable CPT-loaded micelles. In chain lengths, 5-27 Bz-69 showed the highest incorporation efficiency. In contrast, 5-52 Bz-67, which had a longer hydrophobic chain, showed low incorporation efficiency. Release of CPT from the micelles was dependent on the benzyl contents and chain lengths. Sustained release was obtained when the benzyl content was high. CONCLUSIONS: CPT was successfully incorporated into polymeric micelles with high efficiency and stability by optimizing chemical structures of the inner core segment.     

卡托普利对实验性糖尿病小鼠的影响

本实验观察卡托普利(captopril,CPT)对小鼠实验性糖尿病有预防作用。CPT(160mg/kg)可降低 Alloxan 所致小鼠血清过氧化脂质(LPO)和血糖的升高幅度,CPT 的上述作用可能是通过抗脂质过氧化和抗自由基,减轻 Alloxan 对胰岛 B 细胞的损伤而实现。     

Stress reactivity: biological and subjective responses to the cold pressor and Trier Social stressors

The cold pressor test (CPT) and Trier Social Stress Test (TSST) have been shown to reliably increase HPA activity; however, little research has compared responses to these stressors. In this study, biological (plasma cortisol and ACTH levels) and subjective (e.g., stress and mood) responses were compared in 31 subjects administered both the CPT and TSST. Subjects were diagnosed with alcohol dependence and post-traumatic stress disorder (PTSD) (n = 11), alcohol dependence without PTSD (n = 10), PTSD without alcohol use disorder (n = 4), and neither PTSD nor alcohol use disorder (n = 6). All subjects completed both the CPT and TSST. In all groups, the TSST elicited higher levels of ACTH and cortisol than the CPT, and the response time course differed between tasks. The TSST also produced lower mood ratings than the CPT. A comparison of all diagnosed groups with normal controls revealed group differences in ACTH responding for the CPT but not the TSST. The results suggest that the TSST results in a greater HPA response than the CPT; however, the CPT may have utility in diagnostically heterogeneous patients.     

Pumpkin-seed oil modulates the effect of felodipine and captopril in spontaneously hypertensive rats.

Natural products like pumpkin-seed oil (PSO) may modify the potency of the calcium antagonist felodipine (FEL) or angiotensin-converting enzyme inhibitor (ACE-inhibitor), captopril (CPT) in modulating the biochemical derangement in blood, heart and kidney as well as blood pressure and heart rate of spontaneously hypertensive rats (SHR) were investigated. SHR were treated orally with FEL at a dose of 0. 45 mg kg(-1) body wt. or CPT at a dose of 9 mg kg(-1) body wt. once daily for 4 weeks. PSO was administered at a dose of 40 mg kg(-1) body wt. alone or with FEL or CPT in the previous respective dose regimen for the same period to SHR. This study showed that hypertension induced increments the content of malondialdehyde (MDA) by 55% and 38% as well as the activity of glutathione peroxidase (GSH-Px) by 26% and 23% in heart and kidney, respectively, accompanied by reductions in the activity of myocardial superoxide dismutase (SOD) from 3.40+/-0.17 to 2.42+/-0.19 U mg protein(-1)and contents of glutathione (GSH) and protein thiols (PrSHs) in different tissues of SHR as compared to normotensive rats. Treatment of SHR with FEL or CPT monotherapy or combined with PSO produced improvement in the measured free radical scavengers in the heart and kidney. Our results also showed that pretreatment of SHR with PSO for 4 weeks then i.v. administration of FEL or CPT produced a significant beneficial hypotensive action. The results were explained in the light of the antioxidant properties of PSO. Therefore, it is concluded that concomitant administration of FEL or CPT with natural antioxidants can yield a beneficial therapeutic effect and retard the progression of hypertension.     

Antitumor activity of beta-cyclodextrin polymer-camptothecin conjugates

Antitumor activity of linear, beta-cyclodextrin polymer (CDP)-camptothecin (CPT) conjugates (HGGG6, LGGG10, HG6, and HGGG10) is investigated in nude mice bearing human LS174T colon carcinoma tumors. These conjugates differ in polymer molecular mass [97 kDa (H) or 35 kDa (L)], CDP-CPT linker structure [glycine (G) or triglycine (GGG)], and CPT loading [ca. 6 wt % (6) or 10 wt % (10)]. Maximum tolerable doses (MTDs) of the three conjugates, LGGG10, HG6, and HGGG10, are determined to be 36, 9, and 9 mg of CPT/kg, respectively, while the MTD of the CDP alone exceeds 240 mg/kg (highest value investigated). The three CDP-CPT conjugates with high polymer molecular masses (HGGG6, HG6, and HGGG10) demonstrate antitumor activity at their MTDs superior to that of CPT at the same amount and to that of irinotecan at its optimal dose. They also show tumor growth inhibition that is superior to that of the conjugate containing the low-molecular mass polymer (LGGG10) at the same dose of CPT. No significant effects of CPT weight loading or linker structure on tumor growth delay are observed. However, conjugates containing G appear to be less toxic than these with GGG. These antitumor studies demonstrate that the CDP-based conjugates of CPT exhibit tumor growth inhibition superior to that of CPT or irinotecan at the conditions employed in this study. The striking observation is that a short course of treatment with the polymer conjugates gives long-term control of tumor growth that does not occur with either CPT or irinotecan. Intracellular CDPs are demonstrated by analyzing cells that were cultured in the presence of rhodamine-labeled CDP (HRhod) containing medium using both confocal microscopy and flow cytometry. The long-term therapeutic efficacy of CDP-CPT conjugates observed in mice may in part be due to the sustained release of CPT from these conjugates in the acidic, intracellular compartments since these conjugates are shown to have significantly slower release rates at acidic pH than at physiological pH.     

Ultrasound-responsive nanobubbles contained with peptide–camptothecin conjugates for targeted drug delivery

To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP–camptothecin conjugate (CPP–CPT) into nanobubble (CPP–CPT?NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP–CPT to the tumor cells. The mean particle size of the prepared CPP–CPT?NB was ～200?nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP–CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP–CPT?NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP–CPT?NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.     

A Photo-Activated Targeting Chemotherapy Using Glutathione Sensitive Camptothecin-Loaded Polymeric Micelles

Purpose  A novel photo-activated targeted chemotherapy was developed by photochemical internalization (PCI) of glutathione-sensitive polymeric micelles incorporating camptothecin (CPT) prepared from thiolated CPT (CPT-DP) and thiolated poly(ethylene glycol)-b-poly(glutamic acid) (PEG-b-P(Glu-DP)) Methods  PEG-b-P(Glu-DP) and CPT-DP were synthesized and characterized by ¹H-NMR and gel permeation chromatography, and then mixed to prepare CPT-loaded polymeric micelles (CPT/m). The CPT release from the micelle was studied by reverse phase liquid chromatography. The PCI-activated cytotoxicity of CPT/m against HeLa cells was studied in combination with a non-toxic concentration of dendrimer phthalocyanine-loaded micelles (DPc/m) as the photosensitizer. Results  The diameter of CPT/m was 96 nm and the drug loading was 20% (w/w). CPT was slowly released under the conditions reproducing the extracellular or endosomal environments. However, under the reductive conditions mimicking the cytosol, CPT was rapidly released achieving approximately 90% of the drug release after 24 h. The cytotoxicity of CPT/m was drastically increased on photoirradiation, whereas the CPT/m were not cytotoxic without PCI. Conclusions  The CPT/m released the drug responding to reductive conditions. The PCI-induced endosomal escape exposed CPT/m to the cytosol triggering the drug release. Thus, CPT/m in combination with DPc/m will behave as smart nanocarriers activated only at photoirradiated tissues. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.