Faculty of Pharmaceutical Sciences, University of British Columbia Alan C. Hayman Summer Student Research Competition 2000

Integration of the pharmacy curriculum using web-based technology

Simon P. Albon, Howard Sham, Nelson P. Kuhlen, Philip Hui, Stephanie Lee, Arthur Krumins, Kishor M. Wasan

Objective: The objective of this project was to upgrade the Web-Based Learning Centre (WBLC) prototype created in year one of the project. Based on student feedback, a re-designed user interface is expected to further integrate the pharmacy curriculum into a unified resource to enhance teaching and learning in the pharmaceutical sciences.

Methods: Enhancing the initial WBLC prototype involved strategic planning, creative development and production phases. Strategic planning consisted of extensive information gathering, consultations and concept mapping to clearly define the learning framework and the features critical for the new site design. The creative development process involved transcribing the entire resource on poster-sized paper into storyboards and site maps. The production phase focussed on the creation of a central menubar, homepages, course materials, graphic elements, animations and the interactivity of the centre using a number of software packages. Existing evaluation profiles in the form of two questionnaires, developed to determine the effectiveness of the prototype for student learning, were added to the site for on-line delivery.

Results: An upgraded WBLC prototype integrating seven core pharmacy courses and Continuing Pharmacy Education (CPE) into a seamless resource was successfully created. Components of the resource include the WBLC homepage, seven WebCT courses and the CPE website. The WBLC homepage provides an overview of the resource including instructions, tutorials and recommendations on how to use the resource. WebCT courses include a homepage built on top of the WebCT framework in addition to four common elements (Course Materials, Evaluation Tools, Communications Tools and a Resource Centre). Integration of course materials are provided through strategic linking of materials within each course (Intralinks), between courses (Interlinks) and to other sites on the internet (URLinks). Integrative problems involving literature evaluation were developed to promote the use of the resource links. An intuitive menubar was developed to link all components of the centre. The interface uses a user-centric model designed around a fundamental “three clicks to anywhere” principle. The WBLC is currently being implemented and evaluated during the 2000-2001 academic year.

Conclusions: A WWW-based educational resource was successfully created with the potential to enhance teaching and learning in the pharmaceutical sciences. The successful implementation and evaluation of this resource may provide the potential for utilizing technology-based approaches for educating students and for moving to a more learner-centered approach to pharmacy education.

Acknowledgements: The authors would like to acknowledge generous support from the University of British Columbia’s Teaching and Learning Enhancement Fund (to SPA and KMW), the Government of British Columbia’s Student Summer Works Program and the Faculty of Pharmaceutical Sciences.

The application of liquid chromatography/mass spectrometry to the qualitative analysis of illicit rave drugs.

Rahim Kanji, Keith M. McErlane

Purpose: The purpose of this study was to determine the identity of the various drug samples found during RCMP raids of Rave Parties.

Methods: Each sample was triturated using a mortar and pestle and dissolved in 10 mL of mobile phase (10% acetonitrile/0.09% formic acid). These samples were further diluted and refrigerated at 4oC until required for analysis. High Performance Liquid Chromatography (HPLC) in combination with Mass Spectrometry (MS) was used to identify the unknown drugs. HPLC/MS was used in lieu of Gas Chromatography/MS or Capillary Electrophoresis/MS because it has higher sensitivity and selectivity, does not require a derivitization step and is more suitable for thermolabile compounds. The retention times of each sample were compared to fifteen known standards to help determine their identities.

Results: Approximately 400 drug samples were analyzed. The most prevalent drug found was 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy). The second and third most prevalent drugs found, methamphetamine and 3,4-methylenedioxyamphetamine, respectively, are also amphetamine derivatives.

Conclusions: These findings suggest that amphetamines, in particular Ecstasy, are the most commonly abused drugs at Rave Parties. These results will be a valuable asset to healthcare professionals in helping them inform the public about the hazards of these illicit drugs.

Acknowledgements: The authors gratefully acknowledge the RCMP for supplying the samples analyzed in this study.

Development and integration of pharmaceutical care resources using web-based technology

Rosemin Kassam, Stephanie Lee

Objectives: The hypothesis for this project is that Web-Based Learning Centre (WBLC) will facilitate learning and communication for students participating in Pharmacy 300, 402 and 403. The project consists of two phases, the developmental phase and the evaluation phase. The development phase was initiated this summer, the evaluation phase will be implemented next year. The specific study objectives for each of the phases include: (phase 1) design and integrate the three Pharmacy Practice courses 300, 402 and 403 into the upgraded WBLC; and (phase 2) evaluate the effectiveness of the WEB CT program as a tool to facilitate learning and communication.

Methods: A plan was designed to allow for an efficient execution of the project. This planning step involved creating a fishbone diagram to identify the main components and activities to be undertaken. This was further developed into a program logic model to describe the specific activities that needed to be undertaken for each of the components, and identify objectives to help evaluate the progress of the project. Timelines and Web site maps were also proposed. The information gathering step involved consultation with the team working on WBLC and the WEB CT support group at the University of British Columbia to identify relevant WEB CT tools, and purchase of the necessary software programs. The production step consisted of designing the Pharmacy 300, 402 and 403 course web pages, drop menus, templates, course materials, resource centres and graphics. The user interface, a common menubar developed for and found on every web page in the WBLC, helped integrate these courses into the WBLC.

Results: The research project plan was very effective in helping the team stay focused on the objectives to be achieved. The program logic model and fish-bone diagrams will be presented to provide an overview of the project plan. Three WEB CT based courses, Pharmacy 300, 402, and 403, were developed and integrated into the WBLC. Each course consisted of a homepage and four common elements: Course Materials, Evaluation Tools, Communication Tools, and the Resource Centre. Course materials and pharmaceutical care resources were integrated through linking within each course (intralinks), between courses (interlinks), and to other Internet sites (URLinks). Provisions were made to incorporate evaluation tools such as quizzes, self-assessment surveys, and clerkship evaluation forms, so students may complete and submit these tools on-line. Students may correspond and discuss course topics with fellow classmates and course instructors using the WEB CT communication tools – Private E-mail, Bulletin Board and Real-time Chat. The Resource Centre consisted of links to various pharmaceutical care resources and other internet sites to facilitate learning. Students can help further develop the Resource Centre by submitting links to additional useful internet sites to the course director using the bulletin board.

Conclusions: The development of a web-based learning resource for Pharmacy 300, 402, and 403 was a success. These resources have the potential to enhance student learning and understanding of pharmaceutical care and its implementation in a variety of practice settings.

Heat treatment of amphotericin b modifies its pharmacokinetics and renal toxicity in a rabbit model, and alters its activity in the presence of human serum albumin

Evan H. Kwong, Manisha Ramaswamy, Emily A. Bauer, Scott C. Hartsel, Kishor M. Wasan

Purpose: The purpose of this project was to study the heat-treated form of Amphotericin B. Its pharmacokinetics, distribution in serum lipoproteins and tissues, and renal toxicity were determined for a single dose in rabbits. In addition, its activity against model mammalian and model fungal membranes in the presence of human serum albumin (HSA) was examined.

Methods: Fungizone (FZ) solutions were heated at 70 for 20 minutes to produce Heat-treated Fungizone (HFZ). Rabbit Study. A single intravenous dose of FZ or HFZ at 1mg/kg was administered to female New Zealand white rabbits. Blood samples were obtained before drug administration and serially thereafter. After the 48-hour blood sample, each rabbit was humanely sacrificed. Serum creatinine levels were measured before and 10 hours after drug administration. Amphotericin B levels in the serum were analyzed using High Performance Liquid Chromatography. Activity Study. Model mammalian and model fungal membranes were made by extrusion. The membrane ion channel forming activities of HFZ and FZ against these membranes were compared using an Applied Photophysics stopped flow spectrometer with fluorimeter detector.

Results: HFZ shows decreased kidney toxicity compared with FZ. HFZ follows a two-compartment model, with a similar apparent volume of distribution to FZ. However, HFZ clears faster from the system than FZ. In the presence of HSA, the activity of HFZ against model mammalian membranes is lower than that of FZ, yet it is still effective against model fungal membranes.

Conclusions: Heat-treated Fungizone is an improved low-cost Amphotericin B drug delivery system that has a potentially higher therapeutic index than regular Fungizone.

Acknowledgements: Medical Research Council of Canada (grant #MT-14484 to KMW), National Science Foundation (MCB-9603582 to SCH), Rx&D Health Research Foundation / Canadian Institutes of Health Research (to EHK), and Ronald E. McNair Scholars Program (to EAB).

Immunohistochemical analysis of endothelin (et) receptors in bosentan-treated and untreated streptozotocin-diabetic rat hearts and arteries

Inna Sekirov, Emi Arikawa, John H. McNeill

Purpose: Evidence has shown that endothelin-1 (ET-1), a 21 amino-acid vasoconstrictor-mitogen, may be involved in mediating cardiovascular complications in diabetes. Previous studies from our laboratory have demonstrated that the ET-1 level is increased in diabetic rat hearts and arteries, and that treatment with bosentan, an ETA and ETB receptor antagonist, ameliorates the impaired cardiac function and normalizes the enhanced vascular contractile responses in diabetic rats. The purpose of this study was to examine the expression of ETA and ETB receptors in diabetic rat tissues, and to determine whether the beneficial action of bosentan in alleviating diabetes-induced cardiovascular abnormalities is related to the level of ETA and ETB receptors.

Methods: Wistar rats were randomly divided into four groups: control (C), control bosentan-treated (CB), diabetic (D) and diabetic bosentan-treated (DB). Diabetes was induced with streptozotocin (STZ; 60mg/kg iv) in D and DB rats. One week after STZ-injection, CB and DB rats received bosentan treatment (100mg/kg/day po). After 10 weeks of bosentan treatment, ventricles, aortae, superior mesenteric and renal arteries were isolated from the four rat groups. Paraffin-embedded sections of those tissues were prepared and analyzed by immunohistochemistry for the levels of ETA and ETB receptors. Images of the stained tissues were obtained, and the ETA and ETB receptor immunoreactivity in each tissue was subsequently measured using Northern Eclipse computer software.

Results: In the presence of diabetes, ETA-like immunoreactivity (ir) and ETB-like ir in ventricular tissues as well as ETA-like ir in renal arteries were significantly reduced when compared to the control tissues. The level of both ETA and ETB receptors was unchanged in D aortae and superior mesenteric arteries, as was the level of ETB in D renal arteries. Bosentan did not affect the ETA level in the diabetic tissues. The level of ETB was, however, restored to control levels in both right and left diabetic ventricles by bosentan treatment. Moreover, an increase in ETB-like ir was observed in DB aorta, when compared to untreated D rat tissues, suggesting a bosentan-induced up-regulation of ETB in diabetic rats. In CB rats, a reduced ETA-like ir was found in the ventricles, and a decreased level of ETB in the aortae and renal arteries.

Conclusions: Results from this study indicate that the level of ET receptors was either decreased or unchanged in diabetic rat ventricles and arteries. The effects of bosentan on the levels of ET receptors seem to be receptor and tissue-specific. The results suggest that the corrective action of bosentan in normalization of diabetes-induced cardiac and vascular functional abnormalities may not be mediated simply by modulating the level of ETA and ETB receptors. Further studies will be required to uncover the exact mechanism(s) underlying the beneficial effects of bosentan.

Acknowledgements: This study was supported by a grant from CDA and MRC. Inna Sekirov is a recipient of a Heart and Stroke Foundation of BC and Yukon Summer Studentship.

Comparison of the effects of withdrawal following chronic administration of insulin of bmov in stz diabetic rats

Osric Sin, Violet G. Yuen, John H. McNeill

Purpose: Bis(maltolato)oxovanadium(IV) (BMOV) is an effective glucose lowering agent, as is insulin, the conventional treatment of choice in diabetes mellitus. However, while insulin treatment requires injections one or more times a day BMOV is an orally effective drug. A single acute oral administration of BMOV in diabetic rats has been found to maintain a lower blood glucose level over an extended period of time. It was of interest therefore to investigate the effects of withdrawal following chronic BMOV administration and compare it with the effects of withdrawal following chronic insulin administration.

Results: It was found that both treatments significantly decreased plasma glucose levels as compared to the non-treated diabetic rats (D=31M, DI=16M and DV=10M). At 24 hours after treatment withdrawal, plasma glucose levels in the BMOV-treated group were found to be significantly lower that the insulin-treated animals and the diabetic animals (D=30M, DI=24M and DV=14M). By 48 hours there was no difference in plasma glucose levels among the groups.

Conclusion: This study demonstrates that chronic administration of both insulin and BMOV treatment significantly lowers blood glucose in diabetic rats. At 24 hours after treatment withdrawal there is a lower rate of reversion to a diabetic state in BMOV treated animals as opposed to insulin treated animals, but within 5 days the majority of animals in both groups had reverted back to the diabetic state.

A comparison of topical anaesthetics for percutaneous for percutaneous analgesia in pediatric patients

S. Verma, L. Boshell, A. Smith, D. Blackstock, B. Miller, B. Carleton

Purpose: This study consisted of two phases. The objective of Phase 1 was to conduct a pilot assessment of the safety and effectiveness of a newly developed local anaesthetic compared to a commercially prepared product (AmetopR, Smith & Nephew) in healthy adult volunteers. The objective of Phase 2 was to determine the safety and efficacy of the new anaesthetic preparation relative to two commercially available preparations (EMLAR, lidocaine and prilocaine aa 2.5%, ASTRA Pharma, and AmetopR) prior to venous cannulation in pediatric patients undergoing daycare surgery.

Methods: Phase 1 was a double-blind cross-over trial in 40 healthy adult volunteers. 2g of tetracaine 4% w/w (AmetopR) was applied to the antecubital fossa of one arm, and 2g of the newly formulated tetracaine preparation was applied to the other arm in the same location. Efficacy of analgesia was measured using a calibrated pin-prick device at various intervals (15, 20, 25, 30, and 45 minutes after application of the cream). Study participants rated the degree of analgesia using a three-point scale. Two formulations of the study cream were tested, each with a differently formulated cream base. Phase 2 was a double-blind randomized trial in pediatric patients undergoing daycare surgery. Patients received either 2g of EMLAR, 1g of AmetopR, or 2g of the study cream, 60 minutes, 45 minutes, or 35 minutes respectively prior to venous cannulation on the dorsal aspect of their left hand. The patient’s pain was assessed using the 7 point Bieri Faces Pain Scale (1 being no pain and 7 being the greatest pain). Side effects were assessed at the time of cannulation 1-5 hours after application of the cream.

Results: With the first study cream formulation (n=22), 4 volunteers felt no anaesthesia, 7 felt partial and 11 felt full anaesthesia at 30-35 minutes after application of the cream. With AmetopR, 1 volunteer felt no anaesthesia, 5 felt partial, and 16 felt full anaesthesia at 30-35 minutes. At 45 minutes, 1 volunteer felt no anaesthesia, 1 felt partial, and 20 felt full anaesthesia with both the study cream and AmetopR. With the second study cream formulation (n=18), 1 volunteer felt no anaesthesia, 9 felt partial, and 8 felt full anaesthesia at 30 minutes after cream application. With AmetopR on for 30 minutes, 3 volunteers felt no anaesthesia, 8 felt partial, and 7 felt full anaesthesia. At 45 minutes with the study cream, 2 felt no anaesthesia, 3 felt partial, and 13 felt full anaesthesia. With AmetopR on for 45 minutes, 3 volunteers felt no anaesthesia, 1 felt partial, and 14 felt full anaesthesia. Data is still being collected for Phase 2. Thus far, the 15 patients that received the study cream reported an average Bieri Pain Measurement of 4. The 16 patients that received EMLAR also reported an average pain measurement of 4, and the 14 patients that received AmetopR reported an average pain measurement of 3. The standard deviation valves for all three study groups overlapped.

Conclusion: From Phase 1, it can be concluded that the second study cream appeared as effective as AmetopR at the 30-35 minute mark and, therefore, the 35 minute mark for the study cream could be tested on children in Phase 2. Preliminary results from Phase 2 suggest that the new formulation may be as effective as commercially available products. Further testing in pediatric patients is required to determine equivalence.

Acknowledgements: Apotex/PACE & Mount St. Joeseph’s Children’s Center Staff

The role of serum lipid levels on amphotericin b-induced nephrotoxicity in pediatric oncology patients: comparing 4-day and 7-day therapy

Titus Wong, Eunice Wong, Lorilynne Holtorf, Traci Corr, Sheila Pritchard, Kishor M. Wasan

Purpose: A previous study found several correlations between the pre-Amphotericin-B (AmpB) therapy lipid profile of subjects and AmpB-induced nephrotoxicity (as measured by Day 4 serum creatinine levels). The objective of this current study is to determine whether the relationships found during 4-day AmpB therapy also exist during 7-day therapy.

Rationale: Adult populations receiving AmpB usually exhibit AmpB-induced nephrotoxicity between days 7-10 of therapy. Since the previous study measured Day 4 serum creatinine levels, there was some concern that the values measured were not representative of normal AmpB therapy.

Methods: The target population was all patients (age<17 years) at the British Columbia Children’s Hospital receiving AmpB due to a suspected or confirmed fungal infection. Samples of patients’ plasma were separated into the a (HDL) fraction by lipoprotein precipitation. Total plasma and fraction cholesterol [C] and Triglycerides [TG] levels were determined by enzymatic colorimetric assays. Plasma creatinine levels were obtained from the patients’ charts.

Results: For 7 day therapy, a positive correlation between Cumulative Dose and % increase in serum creatinine was found in all subjects (n=10, r=0.919, p<0.001) was found. A negative correlation between % increase in serum creatinine and Total TG for all subjects (n=10, r=-0.804, p<0.01) was found. Other correlations previously found in 4-day therapy were not found in 7 day therapy.

Conclusion: Contrary to the hypothesis, LDL-C was not a predictor of AmpB-induced nephrotoxicity. However, it was found that increases in Total-TG correlated with lower AmpB-induced nephrotoxicity.

Acknowledgements: Funding for this project was provided by the Medical Research Council of Canada (grant # MT-14484) and by the British Columbia Research Institute for Women’s and Children’s Health.

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