Aims

To introduce the principles of toxicology and drug metabolism; to understand the chemical basis of drug metabolism and its importance in drug discovery; to equip students with a knowledge and understanding of the mechanism of toxicity of drug molecules and other environmental toxins.

To introduce the basic concepts of the aetiology of cancer and pathogenic disease; to develop the concepts of selective toxicity and resistance; to equip students with an understanding of the principles of chemotherapy of cancer and infectious disease; to provide an understanding of the molecular mechanisms underpinning the action of common anticancer and anti-infective drugs.

Outline Of Syllabus

Pharmacokinetics and Drug Metabolism

Pharmacokinetics
Processes and mechanisms of drug metabolism
Selected case studies in drug metabolism

Toxicology

Principles of Toxicology and toxicokinetics
Critical toxicological issues for drug discovery
Allergens and reactive metabolites;
Ion channels – hERG and acetyl choline signaling;
Carcinogenesis

Basic Principles of Enzymology

Overview of the role of amino acid side-chains, metal ions and coenzymes in catalysis
Characteristics of enzymes: stability, substrate specificity, stereospecificity,
catalytic groups, factors affecting catalysis, enzyme kinetics
Model systems for enzymes (probing proximity effects, solvation, strain), acid-base
and nucleophilic catalysis
Overview of selected enzyme mechanisms including those with no cofactor/metal (e.g.
glutathione transferases)
Redox cofactors
Small molecule activation by non-metallic cofactors
Radical enzymes

Cancer Chemotherapy

Introduction to cancer
Cytotoxic chemotherapeutic agents: DNA reactive drugs
Antimetabolites
DNA Ttopoisomerase inhibitors
Mitotic poisons
DNA Repair Enzymes
Antiendocrine drugs
Current approaches to cancer chemotherapy
New therapies: Targeting receptor tyrosine kinase signalling and kinase inhibitors
case studies

Chemotherapy of Infectious Diseases

Introduction and historical overview
Principles of antimicrobial chemotherapy
Antibacterial agents: – Penicillin and related β-lactams
Glycopeptidesglycopeptides, quinolones, oxazolidinones and metronidazole
Antifungal agents: – Polyenes, azoles and other antifungals
Antimalarials
Antiviral chemotherapy:
Acyclovir and maraviroc

Teaching Rationale And Relationship

Lectures will present relevant, research-focused course material, allowing students to gain a greater appreciation of the research activities undertaken by academic staff. Students will be further encouraged to develop their critical thinking skills to participate in advanced discussions of the primary literature relevant to the topics covered.

Assessment Rationale And Relationship

The written examinations will assess the level of knowledge and understanding of all aspects of the module, including student reading.

Formative assessment to aid students' understanding during the module.