4. Principles Of Drug (& Hormone) Action Flashcards
What is pharmacology?
The study of how drugs affect biological systems.
Describe the branches of pharmacology.
- Pure pharmacology -> Identification and study of chemically sensitive sites and their mechanisms
- Applied pharmacology
- Chemical physiology -> How do these sites play a role in normal function?
- Therapeutics -> Can these sites be exploited in treatment?
- Toxicology -> Do these sites mediate toxic effects of chemicals?
Define a drug.
- Any chemical agent which affects any biological process.
- Generally organic chemicals of small molecular weight (<500g/mol)
Do drugs have to be synthetic?
No, the term also encompasses bodily chemicals.
What are some examples of biopharmaceuticals?
- Therapeutic proteins from genetic engineering (e.g. hormones, blood clotting factors, enzymes)
- Nucleic acids
- Vaccines
- Monoclonal antibodies
- Cell-based therapies
What are the different methods of drug classification?
Based on:
- Chemical structure
- Main effect (e.g. analgesics)
- Therapeutic use (e.g. antidepressants)
- Mechanism of action
What are pharmacodynamics and pharmacokinetics?
- Pharmacodynamics -> What the drug does to the body (e.g. drug receptors, efficacy, responses, toxicity, etc.)
- Pharmacokinetics -> What the body does to the drug
What mnemonic is used to remember the branches of pharmacokinetics?
ADME:
- Absorption
- Distribution
- Metabolism
- Excretion
How can drugs cause a toxic effect on a molecular and cellular level?
On a molecular level, chemicals can:
- Interact with proteins, lipids and DNA
On a cellular level, chemicals can:
- Interfere with receptor-ligan binding
- Interfere with membrane function
- Interfere with cellular energy production
- Bind to biomolecules
- Perturb homeostasis (e.g. calcium levels)
Define a receptor.
A protein or macromolecule in or on a cell that is a recognition site for endogenous ligands or drugs. When a drug binds it initiates or blocks a response to an endogenous chemical.
Define endogenous.
Originating from within an organism.
What are main subtypes of drugs that bind to a receptor and what do they do?
- Agonists -> May ctivate more than one type of receptor (e.g. ACh activates nicotinic and muscarinic receptors)
- Antagonists -> Selectively block one type of receptor subtype (e.g. curare)
What are some criteria for a receptor?
- Recognition -> Receptor protein must exist in a conformational state that allows for recognition
- Saturability
- Reversibility
- Stereoselectivity -> Receptor must recognise only one of the optical isomers
- Agonist specificity -> Structurally related drugs should bind well
- Tissue specificity -> Binding should occur in the correct tissues
- Transduction -> The binding of the agonist must be transduced into some sort of functional response
Give some examples of endogenous agents that act on receptors.
- Hormones
- Neurotransmitters
- Growth factors
- Vaso-active factors
Why are drugs so potent?
Their action is amplified by, for example, second messenger systems.
Define affinity.
The tenacity by which a drug binds to its receptor.
State the primary assumption of receptor theory.
A single ligand is binding to a homogenous population of receptors.
Describe the concept of receptor kinetics.
[L] + [R] -> [LR]
- kon is the rate of the forwards reaction
- koff is the rate of the backwards reaction
- At equilibrium, the rate of formation equals the rate of dissociation, so: [L][R]kon = [LR]koff
- KD is the equilibrium dissociation constant: KD = koff / kon = [L][R]/[LR]
- KD is the [L] which produces 50% receptor occupancy
What is KD in receptor kinetics? What are the units?
- It is an inverse measure of receptor affinity for a particular ligand
- It is the concentration of the ligand that produces 50% receptor occupancy
- Units: M/L
What does a high KD value indicate?
A low receptor affinity for a certain drug.
Describe the idea behind drug binding studies.
- Measure the affinity not efficacy
- No need for intact cells or tissues
- Need a radio-ligand
- Saturation binding curve may be plotted, where the drug concentration producing 50% binding is the KD value
How do agonists work?
Bind to receptor causing a change of conformation, leading to a cellular response.
Do agonists and antagonists have both an affinity and efficacy?
- Agonist -> Affinity and efficacy
- Antagonist -> Affinity but no efficacy
How do antagonists work?
- Prevent agonist-mediated response by preventing a drug from binding and eliciting its normal response.
- They may be competitive or non-competitive.

