Tutors Notes on Drug Metabolism

Authors: Dr Paul Skett, Dr Suzanne Cholerton, Dr Neil Kitteringham, Mr Gavin McLellan, Ms K Huckbody.
Contact : Jeff Claudius. British Pharmacological Society, 16 Angel Gate, City Road, London, EC1V 2SG. United
Kingdom. Tel: 44 (0)20 7239 0172. Fax: 44 (0)20 7417 0114. E-mail: cal@bps.ac.uk. Internet site:
http://www.pharmaCALogy.com
Hardware and Installation
The hardware requirements and installation instructions for the program are available separately. The purpose of
these sheets is to make you aware of the program content and the ways in which the program can be used to
help you achieve particular teaching objectives.
Introduction
This courseware is designed as an introduction to drug metabolism for medical, dental, pharmacy and science
students. No prior knowledge of drug metabolism is assumed but a basic understanding of chemistry and
chemical reactions is required to make the best of the courseware. The courseware uses well-known, clinicallyused drugs as examples where possible.
Aim of Courseware
The aim of the courseware is to give the student an understanding of the basic principles of drug metabolism
including the routes of metabolism.
Objectives
The student should understand the following basic principles after using the courseware:

Where drug metabolism occurs.

Why drug metabolism is important.
Some of the major routes of drug metabolism including the principles of phase 1 and phase 2
metabolism.

Program Description
The program consists of modules covering the following material:
i. Introduction - addressing the questions:
a. Where does drug metabolism occur?
b. Why does drug metabolism occur?
c. What are phase 1 and phase 2 metabolism?
ii. Routes of Metabolism - a series of modules illustrating the different pathways of metabolism including:
a. Oxidation - cytochrome P450-mediated
b. Oxidation - others
c. Reduction
d. Hydrolysis
e. Hydration
f. Glucuronidation
g. Sulphation
h. Acetylation
i. Methylation
j. Amino acid conjugation
k. Glutathione conjugation
l. Miscellaneous

The first five groups (a-e) are explained under phase 1 metabolism and the rest under phase 2.
For each group, a series of animated reactions is given. As many or as few of these reactions as are
required can be shown. For each reaction there is a series of screens giving extra information such as the
enzyme involved, the cofactors involved and the detailed reaction mechanism (where appropriate). For certain
reactions, other information is also given as below:
For cytochrome P450 reactions :
a. The electron transport chain
b. The nomenclature of cytochrome P450 isozymes.
c. The cytochrome P450 reaction cycle.
For glutathione conjugation:
a. Further metabolism to the mercapturic acid
For all conjugation reactions:
a. The synthesis of the respective cofactor for the reaction.
There are short quizzes after each section of the courseware to test the knowledge gained during the
particular section. These can be by-passed by using the page numbers at the bottom of the page to
move to the next page. There is a more extensive quiz based on the metabolism of aspirin at the end of the
courseware - an opportunity to by-pass this quiz is given to the student.
The direct route through the courseware, looking at a few examples of routes of metabolism and only
looking at the final quiz takes approximately 45 minutes. This can be extended over 2 x 45 minutes by looking at
phase 1 and phase 2 separately and up to 6 x 45 minutes by including all of the material and all of the quizzes.

Method of Program Use

To obtain maximum benefit from computer based learning material it is essential the material is incorporated into
the module/course and integrated with other teaching/learning material. Students do not gain maximum benefit
if simply pointed at a piece of software and told to "use it to help you learn". This point cannot be overemphasised and teachers who do not integrate CAL material into courses and who do not set specific assessed
tasks associated with the use of CAL material will generally be disappointed with the effectiveness of CAL and
the students' response to it.
A Teaching and Learning Resource Pack (TLRP number 6) can be obtained from the BPS offices to be used in
conjunction with this program. This TLRP is a workbook consisting of a series of exercises for students that
utilize the CAL program with model answers for staff.
British Pharmacological Society, May 2004