From binding to response
Pharmacodynamics of a drug in practice are usually expressed by the relationship between dose and response. It is obvious that the ligand-receptor binding plays an important role in this dose-response relationship.
The response to a drug is proportional to the concentration of receptors that are bound by the drug.
According to traditional receptor theory, the magnitude of an effect (E) produced when an agonist at a specified concentration ([L]) interacts with a receptor depends upon 4 factors (see the equation in the illustration):
Two of these are chemical properties of the agonist itself unique for each ligand-receptor pair:
- Kd: the equilibrium dissociation constant, a receptor-affinity related parameter
- ε: "intrinsic efficacy" (ε describes the capacity of a drug to produce a receptor "stimulus" which is transmitted to the signal transduction components of the cell)
The remaining two parameters are cell or tissue dependent properties:
- RT: receptor density
- ƒ: a function that describes the efficiency of signal transduction.