Core Curriculum in Pharmacology for BSc courses
Introduction
The desirable set of attributes, skills and areas of knowledge for science pharmacology graduates is likely to appear rather nebulous and variable compared to those for graduates of professional courses like medicine and pharmacy where a definable set of skills and areas of knowledge are desirable for accreditation and safe practice. The following outline of core areas for science pharmacology is intended to circumvent that problem through being based on a reasonable answer to the question “What might an employer of our graduates expect them to understand?” Four broad areas of understanding are specified: dose-response relationships; sites of drug action; drug selectivity; drug discovery and development. Specific topics are arranged under those headings, but no attempt has been made to arrange them in order of importance or size. The outline is not intended to be directly the basis of course design.
One feature that is notably absent from the listing of core areas is any specification of particular drugs and receptors. The vexing issue of a drug list was raised, and no doubt will be raised in the future. However, it is likely that list of important drugs would be subject to disputation, need continual updating, and would inevitably inappropriately imply low importance of drugs omitted.
It is expected that different courses in pharmacology will have different emphases and strengths and it is also likely that students might not cover all of the listed areas in any particular pharmacology course.
A. An understanding of dose-response relationships
Pharmacokinetics
1. Absorption and distribution
- influence of physicochemical properties of drugs
- bioavailability
- volume of distribution
2. Elimination
- clearance
- half-life
- hepatic and renal elimination mechanisms
- metabolism
- excretion
- variability (pharmacogenomics)
3. Bioavailability
Concentration-response relationships
1. Affinity
- Molecular determinants of affinity
- Binding assays
2. Antagonism
+ Competitive
- Analytical approaches: Schild et al.
+ Noncompetitive
- Allosteric inhibitors (and enhancers)
- ‘Mechanistic’ antagonism by inhibitors of signaling pathways
- Functional/physiological antagonism
3. Efficacy
+ Agonist fullness and partiality
- Tissue (assay) stimulus-response sensitivity, receptor reserve
+ Conceptual and theoretical models of efficacy
- Stephenson/Furchgott, multi-state models, Operational model
B. An understanding of the sites of drug action
Receptors
1. Classes
2. Molecular regulation of receptors
+ Desensitization and resensitization
- Modulation of expression levels
- Receptor modification and internalization
+ Signaling pathways
- Generic signaling for each class of receptor
- Signaling pathways for specific receptors
- GPCRs as monomers and polymers
Enzymes and transporters
1. Similarities and differences from receptors
2. Modes of inhibition
C. An understanding of drug selectivity
Selectivity
1. Selective affinity
2. Selective delivery
+ Concentrations: sources and sinks
- Drug removal (e.g. neuronal uptake)
- Restricted diffusion (e.g. blood-brain barrier)
- Prodrug conversion (e.g. AngI in tissues)
3. Functional selectivity
- Efficacy
- Combination of effects
Whole organism influences on drug selectivity
1. Simplicity of assay vs relevance
2. Reflexes and other feedback processes
3. Functional redundancies
4. Side-effects
- From primary drug action or from other actions
D. Drug discovery and development
Drug categories
1. Small molecules
2. Proteins
- antibodies
3. Gene therapies
Screening candidates
1. Screening approaches
2. Natural sources of drugs
- Toxins, hormones etc.
- ‘herbal’ vs ‘drug’
Rational drug design strategies
1. Structure-activity series
2. Starting from a candidate (e.g. a natural product)
4. Starting from target structural information (e.g. relenza)
Biotechnological drug discovery
1. Bioinformatics
2. Transgenic approaches
In vivo assays
1. Complications of integrated systems
2. Clinical trials
- Placebo
Drug regulation and legal/ethical issues