|TITLE||Mechanisms of Drug Toxicity: Molecular, Cellular and Pathological|
|LEVEL||05 - Postgraduate Modular Diploma or Degree Course|
|DEPARTMENT||Clinical Pharmacology and Therapeutics|
|DESCRIPTION||This study-unit will cover basic mechanisms of drug toxicity from a molecular, cellular and pathological viewpoint. It is important that students are able to appraise these basic mechanisms to apply correct methodologies in testing chemical for toxic potential, explain teratogenicity, and the effect of mutagenic/carcinogenic impurities in pharmaceutical preparations.
It will include a discussion of the methodologies used to test chemicals for toxic potential disposition of xenobiotics in living organisms and the application of molecular biology techniques to study drug metabolism of pharmacogenetics. The role of enzyme kinetics, receptors and cell signalling pathways will be discussed. The cellular basis of cell toxicity and death are also introduced and discussed with the use of examples (e.g. reactive oxygen species) and the importance of understanding the effect of mutagenic/carcinogenic impurities in drug development. Reproductive toxicity including drugs in pregnancy and lactation will also be reviewed.
This study-unit will:
- Provide an overview of the molecular and cellular mechanisms of drug toxicity;
- Appreciate methodologies for testing chemicals for toxic potential using both in vitro and in vivo techniques;
- Review knowledge and differentiate between the molecular mechanisms involved in cellular toxicity, and iatrogenic disease;
- Provide an overview of how drug biotransformation is a mechanism of both drug elimination and toxicity, describing major drug metabolizing enzymes with examples of the formation of reactive metabolites;
- Give information on how genetic polymorphisms may predispose individuals to adverse drug reactions;
- Assess the effect of genetic polymorphisms and ADRs, since a number of these mutations are indeed toxic due to their location in the genes coding for these enzymes;
- Appreciate the pathophysiological processes underlying toxic effects and the principal aspects of target organ pathology;
- Assess the mechanisms leading to teratogenicity and eproductive toxicity including drugs in pregnancy and lactation, and organ damage due to poisoning;
- Provide an understanding of the effect of mutagenic/carcinogenic impurities in pharmaceutical preparations and Ames testing.
1. Knowledge & Understanding
By the end of the study-unit the student will be able to:
- Differentiate between the molecular, cellular and pathological mechanisms of drug toxicity;
- Evaluate the various diagnostic tools and methodologies for the testing of chemical for toxic potential;
- Outline the factors influencing the risk of toxicity in various organs;
- Appreciate how genetic polymorphisms may predispose individuals to adverse drug reactions and disease;
- Evaluate the use of chemical toxins in relation to teratogenicity and reproductive toxicity including drugs in pregnancy and lactation will also be reviewed;
- Illustrate the effect of mutagenic/carcinogenic impurities in pharmaceutical preparations and Ames testing.
By the end of the study-unit the student will be able to:
- Interpret the different molecular, cellular and pathological mechanisms of drug toxicity in drug safety;
- Plan methodologies for testing chemicals for toxic potential using both in vitro and in vivo techniques;
- Examine the molecular mechanisms involved in cellular toxicity, and iatrogenic disease;
- Explain how genetic polymorphisms may predispose individuals to adverse drug reactions;
- Link the pathophysiological processes underlying toxic effects and the principal aspects of target organ pathology;
- Predict the mechanisms involved in reproductive toxicity including drugs in pregnancy and lactation and possible teratogenicity;
- Explain the effect of mutagenic/carcinogenic impurities in pharmaceutical preparations and Ames testing.
Main Text/s and any supplementary readings:
- Curtis Klaassen, John Watkins. Casarett & Doull's Essentials of Toxicology, Third Edition. 2015. McGraw Hill ISBN 978-0071847087
- Yvonne Will, J. Eric McDuffie, Andrew J. Olaharski, Brandon D. Jeffy Drug Discovery Toxicology From Target Assessment to Translational Biomarkers 2016 Wiley ISBN 978-1119053330
- Kareen E Stine Thomas M Brown Principles of Toxicology 2015 CRS Press ISBN 9781466503427 (main library RA1211 .S75 2015)
- Abby Calvin Textbook of Pharmacology and Toxicology. 2016 Syraword Publishing House ISBN 978-1682861912.
- Klaassen, Curtis D. Casarett and Doull's toxicology: the basic science of poisons. 9th edition New York McGraw-Hill Education 2019 ISBN 978-1-259-86374-5
- Pritam S. Sahota, Robert H. Spaet, Philip Bentley, Zbigniew Wojcinski The Illustrated Dictionary of Toxicologic Pathology and Safety Science 2019 CRC Press ISBN 978-1498754712
- Gerard Marshall Raj and Ramasamy Raveendran Introduction to Basics of Pharmacology and Toxicology: Volume 1: General and Molecular Pharmacology: Principles of Drug Action 2019 Springer ISBN 978-981-329-779-1.
Journals (available in Main Library and Health Sciences Library and as e-journals subscribed by UM)
Pharmacology & toxicology
Journal of toxicology
Human & experimental toxicology
International journal of toxicology
Toxicology mechanisms and methods
Toxicology and applied pharmacology
Chemical research in toxicology.
|STUDY-UNIT TYPE||Lecture and Independent Study|
|METHOD OF ASSESSMENT||
Melissa Marie Formosa
Vanessa Petroni (Co-ord.)
The University makes every effort to ensure that the published Courses Plans, Programmes of Study and Study-Unit information are complete and up-to-date at the time of publication. The University reserves the right to make changes in case errors are detected after publication.
The availability of optional units may be subject to timetabling constraints.
Units not attracting a sufficient number of registrations may be withdrawn without notice.
It should be noted that all the information in the description above applies to study-units available during the academic year 2021/2. It may be subject to change in subsequent years.