|PCL304||DRUG DEVELOPMENT AND AND MAMMALIAN TOXICOLOGY|
|School:||School of Sciences|
To provide the students with a basic understanding of the phases of drug development from the initial concept to marketing. The concept of good quality practices will be identffied. Students will be introduced to the principles and techniques associated with the assessment of toxic potential. The mechanisms of action and the toxicological implications of exposure to selected therapeutic and environmental agents will be identified. Students will also be introduced to the relationships between micro- organisms and humans plus the current approaches to cancer chemotherapy.
On completion of this, module the student will be:
a) aware of the development cycle for the production of new drugs and of the good quality practices involved;
b) aware of the major methods used to study mammalian toxicity and of the alternative or non-mammalian procedures for assessing toxicity;
c) aware of the principles associated with clinical trials;
d) aware of the causes of major organ toxicity and the protection of;
e) aware of the factors and mechanisms involved in the onset or prevention of cytotoxicity;
f) aware of the major features associated with drug abuse and dependence.
g) aware of the significance of microbial relationships with humans and of the epidemiology of selected diseases.
h) aware of the major features of neoplastic disease states and to the current approaches to cancer chemotherapy.
An introduction into the phases involved in the discovery and development of a new medicine from the initial concept through to its eventual marketing. The systems or techniques available for assessing toxic potential will be covered with respect to mutagenicity, carcinogenicity and teratogenesis. Intracellular mechanisms of toxicity in relation to selected pharmaceutical agents and environmental contarninants will be described; with emphasis being placed on organ and systemic toxicity. Emphasis wiII also be given to drugs of social abuse including, opiates, hallucinogens, alcohol and solvents. The need for toxicity testing, the problems of drug abuse and environmental contamination will therefore be discussed. Drug development and chemotherapy in relation to microorganisms in infectious diseases plus neoplastic disease will also be covered.
Overview of the Development Cycle
Methods and procedures used for the identification of candidate drugs including preliminary pharmacological investigations, structure activity studies, medicinal chemistry, non-clinical pharmacology, biochemical pharmacology, in vivo activity and efficacy studies. Identification of approval features associated with drug licensing (i.e. quality, efficacy and safety). The role of good laboratory practice (GLP), good clinical practice (GCP) and good manufacturing practice (GMP) with respect to the evaluation and manufacture of candidate drugs.
b) Mammalian Toxicological Studies
Details regarding acute, sub-acute, chronic, special and long term toxicity studies. Identification of parameters studied with respect to man including species, routelfrequency of administration. The use of terminal investigations, haematological studies, blood chemistry and urine analysis plus histological and teratogenic studies. Information on specialised studies including those related to reproduction, mutagenicity and carcinogenicity.
c) Molecularr Toxicology Studies
Identification of molecular toxicity tests associated with mammalian and nonmammalian systems. Details regarding, bacterial mutation tests involving Salmonella typhimurium (Ames Test) and E coli, chromosome aberration tests, cytogenetic monitoring, photomutagenicity and unscheduled DNA synthesis (UDS). The use of autotradiography and isolated cells (i.e. hepatocytes and Hela) in the determination of toxic potential.
d) ADME Study programmes
The relationship and importance of administration, distribution, metabolism and excretion (ADME) with respect to the metabolism of therapeutic agents and environmental contaminants/pollutants. Relevance of cytochrome P-450, enzyme induction, pharmacokinetics and pharmacogenetics to the development of toxicity.' The mechanism and controlling factors associated with cytotoxicity; the role played by reactive species and cofactors.
e) Clinical Pharmacology and Trials
Phase 1 studies in health volunteers relationship to the identification of initial safety limits, pharmacokineties, bioavailability, initial efficacy drug metabolism and interactions. Phase II and III with respect to patients and parameters used to determine the need to continue development and further proof of efficacy.
|Teaching, Learning and Assessment:||
Lectures: 45 hours
Practical Work: 12 hours
Computer Aided Learning: 6 hours
Seminars and Tutorials: 9 hours
Written examination (3 hours): 60 marks
Coursework (seminar presentation; MCQ test; and two practical exercises): 40 marks