Pharmacodynamics Flashcards
Affinity
Attractiveness of ligand for receptor. Dependent on chemical structure. Forces mediating affinity: van Der waals, ionic, hydrogen bonds, hydrophobic, covalent bonds.
Pharmacodynamics
What drug does to the body. Characterizes relationship of drug concentration at site of action to intensity of biological effect.
Major concepts: mechanism of action, site of action, receptor, agonist, antagonist
Specificity
Lock and key analogy. How narrow or broad the effect of the drug is in relation to number of kinds of receptors the ligand interacts with.
What are 3 characteristics of binding?
- Concentration dependent (Kd)
- Responses are graded
- Binding is saturable
Kd, equilibrium dissociation constant
Measure of affinity of ligand for receptor. Kd = concentration of ligand yielding 50% occupancy of all receptors.
What are the methods of signal transduction?
- Bind to receptors of regulatory elements in genome, increase transcription and expression of proteins (eg: steroids)
- Bind to enzymes, altering activity on physiology of cell
- Bind to cell surface proteins, ion channels
- Bind to cell surface proteins, second messengers
What are the second messengers used in signal transduction?
- Adenylyl cyclase -> cAMP (eg: β agonist)
- Guanylyl cyclase -> cGMP (eg: organic nitrates)
- Phospholipase C -> PIP, DAG (eg: histamine)
- Tyrosine kinases -> phosphorylate tyrosine residues (eg: growth factors)
Potency
ED50, measure of potency, half maximum effect. Potency = concentration of ligand required to yield an effect.
Efficacy
Emax, measure of efficacy. Ability to produce a biological effect.
How do spare receptors shift potency and/or efficacy?
Up-regulation of receptors increases potency but does not change efficacy.
Therapeutic index
TI = LD50/ED50
LD50 = lethal dose for 50% of population
ED50 = effective dose for 50% of population
Higher TI means safer
