Interactive Computer Simulated Practical Pharmacology

AWERProcedia Information Technology & Computer Science Vol 04 (2013) 964-972

3rd World Conference on Innovation and Computer Sciences 2013

Interactive Computer Simulated Practical Pharmacology Hesham Aly Salem *, Ph.D. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University Computer Center, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Suggested Citation: Salem A., H. Interactive Computer Simulated Practical Pharmacology. Interactive Computer Simulated Practical Pharmacology. AWERProcedia Information Technology & Computer Science. [Online]. 2013, 04, pp 964972. Available from: www.awer-center.org/pitcs Received December 12, 2012; revised January 15, 2013; accepted March 16, 2013. Selection and peer review under responsibility of Prof. Dr. Fahrettin Sadıkoglu, Near East University. ©2013 Academic World Education & Research Center. All rights reserved. Abstract The use of computer in education is growing, increasingly widespread and became an essential requirement for education quality. Computer assisted learning is interesting to students and best suited for them to acquire and understand the knowledge and also easier for the lecturer to deliver that knowledge. There is an obvious trend toward simulation of practical experiments, particularly those wasting animals. There is no doubt that simulation saves animals, time as well as other financial resources. Although, there are many simulation programs for some pharmacological experiments, we have designed new software to simulate in vitro experiments which are currently involved in practical pharmacology syllabus for undergraduate students of Faculty of Pharmacy, Cairo University. This software is called Interactive Computer Simulated Practical Pharmacology (ICSPP). ICSPP does not depend on a database storing figures for different responses, as it is designed to be interactive so that gives variable responses through mathematical equations that take into account; nature, concentration, dose of added drug as well as presence or absence of another drug on the isolated preparation that may affect the drug response. ICSPP also gives the possibility for coding names or concentrations of drugs allowing a coding for practical exams. In addition, it records potential procedural mistakes made by students, so that staff members can properly assess the student's work. Finally, the software can be modified to simulate other in vitro dose-response experiments according to the required educational syllabus. Keywords: Computer assisted learning, practical pharmacology, simulation, virtual lab;

*ADDRESS FOR CORRESPONDANCE: Hesham Aly Salem, Ph.D. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University Computer Center, Faculty of Pharmacy, Cairo University, Cairo, Egypt, E-mail Address: [email protected]

Salem A., H.Interactive Computer Simulated Practical Pharmacology. Interactive Computer Simulated Practical Pharmacology. AWERProcedia Information Technology & Computer Science. [Online]. 2013, 04, pp 964-972. Available from: www.awer-center.org/pitcs

1. Introduction Practical pharmacology for undergraduate students aims to consolidate some of pharmacological knowledge and principles taught in theoretical course, and to give them general practical skills. However, the category actually benefiting from those skills are those who will complete in the field of pharmacological research which undoubtedly constitute a small percentage of students; who will be employed as teaching assistances (TAs) in pharmacology department or who will register in postgraduate studies in that field. Even though, those who show interest in taking their careers further in research are usually demotivated over the fact that the devices currently used in practical pharmacology are obsolete and have no application in the future practice. On the other hand, preparing students labs with modern sophisticated devices is impractical, as it requires high financial resources that often outweigh the faculty budget especially with the surplus growing number of students. Added to the above, practical pharmacology inherently is costly, time-consuming and wastes an infinite number of animals on on-going basis. The use of computer in education is growing, increasingly widespread and even became an essential requirement for education quality (Dewhurst, 2007). This is for many reasons; the most important is that this tool is interesting to students and best suited for them to acquire and understand the knowledge, and also easier for the lecturer to deliver that knowledge. There is an obvious trend in schools, faculties and universities in many countries, especially the developed ones to simulate practical experiments, particularly those wasting animals. There is no doubt that simulation saves animals, time as well as other financial resources. Although, there are many simulation programs for some pharmacological experiments (Badyal, et al., 2009; Jukes, 2008; McGilliard, 1985), we have designed new software to simulate in vitro experiments, which are currently involved in practical pharmacology syllabus for undergraduate students of Faculty of Pharmacy, Cairo University (FOPCU). These experiments are isolated frog rectus abdominis muscle, isolated frog heart and isolated rabbit intestine. This software is called Interactive Computer Simulated Practical Pharmacology (ICSPP). ICSPP has been coded using Microsoft Visual Basic (version 6.0). Microsoft Access is applied for database creation, while Crystal Report is used for designing and printing reports. This article aims to briefly discuss and analyse different issues regarding the current undergraduate's practical pharmacology in FOPCU, general features of computer simulated practical experiments and finally, the specific features of ICSPP software. 2. Discussion 2.1. Issues regarding the current undergraduate's practical pharmacology 2.1.1. Animals-related issues 2.1.1.1. Consumption issue A large number of animals is consumed by practical pharmacology experiments. The consumption of different animal species during the last five academic years (from 2008 to 2013) in FOPCU is shown by table (1).

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Table (1): Consumption of different animal species by undergraduates' practical pharmacology experiments from 2008 to 2013 in FOPCU. Academic year 2008/9 2009/10 2010/11 2011/12 2012/13 Total

Frog 60 000 44 000 55 000 50 000 10 000 219 000

Mouse 10 000 5100 9000 8000 1255 33355

Rabbit 600 250 550 500 200 2100

2.1.1.2. Cost issue The use of experimental animals is costly. The cost includes purchase (~ 50,000 EP/year), ration and disposal costs. 2.1.1.3. Procurement-related issues 1. Tedious, time consuming purchasing procedures 2. Supplier's fail to provide the specified animals according to both the approved schedule and specifications. 2.1.1.4. Environmental issues Escape of some animals from students during the practical experiments may entail the following: 1. Death of these escaped animals somewhere which will rot and produce unpleasant odours in the department 2. Escaped rodents may also destroy the fine devices and wires of sophisticated lab devices 2.1.1.3. Procurement-related issues 3.

Tedious, time consuming purchasing procedures

4.

Supplier's fail to provide the specified animals according to both the approved schedule and specifications.

2.1.1.4. Environmental issues Escape of some animals from students during the practical experiments may entail the following: 3.

Death of these escaped animals somewhere which will rot and produce unpleasant odours in the department

4.

Escaped rodents may also destroy the fine devices and wires of sophisticated lab devices

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2.1.2. Process-related issues 2.1.2.1. Kymograph 1. Have no longer application in scientific research labs and actually are replaced with the modern sophisticated ones that connected to computer, adapters, amplifiers, etc. 2. Frequent malfunction that requires frequent maintenance and repair (added cost). 3. Sometimes do not work properly such as irregular rotation speed that leads to irregular dose cycle, or may abruptly stop during the experiment that exposes students to irritation and tension especially during exams, which leads to a general state of frustration affecting both students and TAs. 2.1.2.2. Chemicals 1. High cost. 2. Environmental pollution 3. Procurement-related issues: a. Tedious, time consuming purchasing procedures. b. Shortage or lack of certain chemicals. c. Commercial fraud practiced by some suppliers is hardly contained by the Checking Committee especially with big deliveries. As sometimes provided chemicals do not match originally approved samples. 4. Storage and disbursement procedures of stores-related problems. 2.1.2.3. Glassware 1. High cost. 2. Frequent breakage and waste due to inexperience handling as well as overloaded labs. 3. Tedious, time consuming purchasing procedures. 4. Storage and disbursement procedures of stores-related problems. 2.1.2.4. Preparation of solutions 1. Time-consuming. 2. Solutions deterioration due to conservation related issues. 3. Possible human errors in packaging exam's samples. 2.1.3. Students-related issues 1.

Negative reactions towards the use of experimental animals (fear - disgusting – inhumane feeling).

2.

Some students refuse to kill frogs according to certain religious believes.

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3.

Students complain failing to achieve experiment completion within specified lab time due to frequent Kymograph-related problems.

4.

Some students get provoked over having to deal with problems beyond their due (Kymographrelated problems - shortage of animals, etc.).

5.

Student fears of practical exam for the following reasons: a.

Fear of failure due to unrelated issues (see item 4)

b.

Fear of working individually: During the practical lab sessions, students work in groups (2 or more students/group), while in exams they work individually, which leads to a lack of confidence and irritation.

6. Performance of both students and TAs is directly affected by over-loaded labs. 7. Exploitation of some students by some lab-workers who profit over the fact that they have issues with directly dealing with animals. 8. Most students undermine the importance of practical skills due to the fact that the only category actually benefiting from those skills are those who will complete in the field of pharmacological research (TAs - researchers), which all leads to a state of indifference and carelessness while being in labs. The number of graduates, who employed as TAs in department of Pharmacology during the last five academic years (from 2008 to 2013) in FOPCU, is represented by table (2). During these years, only 36 FOPCU graduates, other than TAs, registered for postgraduate studies of master degree in the field of pharmacology. Table (2): Number of graduates employed as TAs in department of Pharmacology in FOPCU from 2008 to 2013. Graduation year 2008 2009 2010 2011 2012 Total

Total number of graduates 1121 1520 1463 1760 1450 7314

Number of TAs employed in Pharmacology Dept. 4 1 9 8 5 27 (0.37%)

9. Those who show interest in taking their careers further in research are usually demotivated over the fact that Kymographs have no application in future practice. A survey on students' related issues has been applied to the third year students of the academic year 2012/2013 after the completion of in vitro practical pharmacology course, and the results were shown by table (3). Table (3): A survey on students' related issues (applied to the third year students of the academic year 2012/2013 after the completion of in vitro practical pharmacology course). Issue % of Students Negative reactions towards the use of experimental animals 56.8 Complaining frequent Kymograph-related problems 91 Failing to complete the experiment within the assigned lab session 59.5 Reduced performance due to over-loaded labs 36.9

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Fear of exam due to possible Kymograph-related problems Fear of exam due to possible unrelated issues Fear of exam due to working individually for the first time Exploitation by some lab-workers Feel of lack of benefit from current in vitro practical pharmacological skills in future practice Prefer simulation of some of in vitro practical pharmacology experiments Prefer simulation of all in vitro practical pharmacology experiments

96.4 83.6 74.8 51.4 69.4 71.2 58.7

2.2. General features of computer simulation Using computer software that simulates practical experimentation generally overcomes all previously mentioned issues. Simulated labs have many benefits, most importantly are the following: 2.2.1. Animal preservation 1. Animal care and ethical point of view (animal rights). 2. Avoid of animal contact related issues 2.2.2. Time-saving 1. Save the time spent for purchase procedures, solutions preparation and validation, preparing and cleaning labs after experimentation. 2. Experiments that currently are performed in two-hour lab session can be done virtually in half an hour. An issue of time extension is usually faced due to students failing to complete the experiment within the assigned lab session. Such issue will seize to exist in case of computer simulation. It is worth mentioning that in the two-hour lab session, a computer lab with 25 PC units can allow for 100 students to perform a simulated experiment individually, while a lab with 25 Kymographs can only allow for 50 students to perform a practical experiment, each two students together. Accordingly, saving the practical experimentation time gives the chance for the following: a. Introducing new experiments that may add to the intended learning outcomes (ILOs). b. The possibility for the students to perform the simulated practical experiment individually, which of course gives them more experience and independency reducing their fear of exams. 2.2.3. Cost-saving Current requirements for practical experiments (animals, chemicals, glassware, devices' maintenance, animals' care, waste disposal, etc.) impose an issue of a running cost that should seize to exist in case of the use of computer-assisted labs. 2.3. Specific features of ICSPP software ICSPP has been coded using Microsoft Visual Basic (version 6.0). Microsoft Access and Crystal Report are applied for database creation and printing reports, respectively. ICSPP has simple, user friendly, self-explanatory screens that allow ease of use.

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2.3.1. In vitro experiments that can be simulated ICSPP software is designed to simulate isolated organ experiments, which are currently practiced in pharmacology labs for undergraduate students of FOPCU. These experiments are isolated frog rectus abdominis muscle, isolated frog heart and isolated rabbit intestine. ICSPP provides tutorials for isolation procedures and setting-up the preparation that permits a good comprehension of the experiment in concern. The isolated organ preparations and the experiments, which can be simulated, are shown by table (4). 2.3.2. Software capabilities 1. It is worth mentioning that ICSPP software does not depend on a database storing figures for different responses, as it is designed to give interactive and variable responses through mathematical equations that take into account the following: a. Nature of the drug b. Concentration (conc.) c. Dose d. Presence or absence of another drug on the isolated preparation e.g. presence or absence of a blocker. Table (4): Isolated organ preparations and the experiments which can be simulated by ICSPP software. Isolated organ preparation Experiment Isolated Frog Rectus 1. Dose-Response (non-cumulative, cumulative) curve for: Abdominis Muscle a. Nm-agonists(Ach – Carbachol) b. Direct: KCl 2. Indirect assay for Nm-antagonist (tubocurarine) 3. Determination of site of action of unknown drug (Ach – Carbachol – KCl) 4. Determination of susceptibility of unknown drug (Ach – Carbachol – KCl) to anticholinesterase. 5. Different techniques for biological standardization of Ach solution: a. Matching technique b. Four-point assay c. Bracketing assay Isolated Frog Heart 1. Effect of different stimulants: a. Beta agonists (Isoprenaline) b. Direct acting (CaCl2) 2. Effect of different depressants: a. M-agonists(Ach) b. Nn-agonist (Nicotine) c. Direct acting (KCl) 3. Determination of site of action of unknown drug (Isoprenaline - CaCl2 - Ach – Nicotine - KCl) using different blockers (beta blockers: propranolol – Ganglionic blocker: Hexamethonium – Muscarinic blocker: Atropine) Isolated Rabbit Intestine 1. Dose-Response (non-cumulative) curve for: a. M-agonist (Ach) b. Nn-agonist (Nicotine) c. H1-agonist (Histamine) d. 5-HT –agonist (5-Hydroxytryptamine) e. Direct (CaCl2) 2. Indirect assay for: a. Nn-antagonist (Hexamethonium) b. M-antagonist (Atropine) c. H1-antagonist (Mepyramine) d. 5-HT –antagonist (Methysergide) 3. Determination of site of action of unknown drug (Ach – Nicotine - Histamine – 5HT – CaCl2) 4. Different techniques for biological standardization of Ach solution: a. Matching technique b. Four-point assay c. Bracketing assay

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2. ICSPP software takes into consideration the concept of maximum response of the isolated preparation, as well as the time factor (contact time, dose cycle). 3. ICSPP software allows the user to process the drug at any dose or conc. When a drug is added, its data (name – conc. - dose) are automatically printed on shown screen graph paper. Once a wash order is given, the software automatically enters the produced response data (name, conc. & dose of the added drug - bath conc. – peak height) into an on-screen spreadsheet (table of results). Afterwards, the user can select certain points from such table for further processing as follows: a. Graphical presentation, with an option to select the data of X & Y coordinates i.e. can plot either dose or bath conc. of the drug versus peak height. b. Calculating the average peak height of the selected points. 4. ICSPP software gives the option to print the full experiment (chart, table and graph) with the consideration that the user's data (name, number, day/date, experiment name & technique – practical session or exam lab) are automatically printed on. 5. ICSPP software allows staff members to set the system for exams through the following features: a. Enabling the user to code drug solutions and creating a database for those codes. b. Providing a password-protected coding screen that allows only staff member to access through using his/her own password. c. Providing privacy, as each staff member’s codes are not disclosed to other staff members. d. Drafting the drugs' codes is not required as the software allows rapid random encoding, where a hard copy of codes can be printed if required. It should be noted that the software does not accept a same code for different drugs and thus avoids coding error. As far as the Exam Key (experiment number vs. unknown solution code) is concerned, it can also be processed with the same way mentioned above. e. Once a student is given an experiment number and has it entered to the system along with the date and day of the exam, the unknown solution code automatically appears on his/her screen to be processed. 6. ICSPP software records mistakes made by students while handling the experiment such as adding dose without washing the previous one (if non-cumulative addition), washing without previous stop, failure to keep regular contact time or dose cycle, etc., which enables the staff member to have the student's work and comprehension properly evaluated. 7. ICSPP software can be modified to simulate other in vitro dose-response experiments according to the required educational syllabus. 3. Conclusion Undergraduate's practical pharmacology is costly, time and animals consuming. Students who will benefit from practical skills are those who show interest in taking their careers further in research. They definitely represent a small percentage of graduates. Even though those students are usually demotivated over the fact that current devices they use have no application in future practice. Modification of current practical syllabus via replacing most of the in vitro experiments with simulated ones could be both educational and cost effective.

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Acknowledgements The author is very grateful to Eng. Tamer Ahmed Diai, senior programmer in Computer Center, FOPCU for his great and genius efforts in programming ICSPP software. References Badyal, D.K., Modgill, V., Kaur, J. (2009). Computer simulation models are implementable as replacements for animal experiments. Altern Lab Anim, 37(2), 191-195. Dewhurst, D. (2007). Is it possible to meet the learning objectives of undergraduate pharmacology classes with non-animal models? Proc. 6th World Congress on Alternatives & Animal Use in the Life Sciences, AATEX 14, special Issue, 207-212. Jukes, N. (2008). Russia: update on animal experiments and alternatives in education. ALTEX, 25(1), 56-62. McGilliard, K.L. (1985). Computer simulation of quantal dose-response relationships. Physiologist, 28, 449-450.

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