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Yuandani
LEARNING OBJECTIVES
Theory of Receptor
Drug-Receptor Interaction
Definition
Concept of Receptor
Theory of Receptor
Drug-Receptor Interaction
Concept of Agonist and Antagonist
DEFINITION
DRUG
RECEPTOR
“orphan” receptors
their ligands are presently unknown, which may prove to
be useful targets for the development of new drugs.
regulatory proteins
which mediate the actions of endogenous chemical signals
such as neurotransmitters, autacoids, and hormones.
This class of receptors mediates the effects of many of
the most useful therapeutic agents.
enzymes
which may be inhibited or activated by binding a drug
transport proteins
eg, Na + /K + -ATPase, the membrane receptor for
cardioactive digitalis glycosides
structural proteins
tubulin, the receptor for colchicine, an anti-inflammatory
agent
RECEPTOR CONCEPT
Rate Theory
•Agonist or stimulant activity is proportional to the rate of drug-receptor
combination rather than the number of occupied receptors
•Agonist activity is the result of a series of rapid association and
dissociation of the drug and the receptor
•An antagonist has a high association rate but a low rate of dissociation
Drug-Receptor Interactions
Occupancy:
fraction of receptors occupied to the
total number of receptors
Agonist
Full Agonist
AGONIST
Partial Agonist
Full Agonist
Competitive
Antagonist
Pharmacologic
ANTAGONIST
Irreversible
Antagonists
Competitive Antagonist
In the presence of a fixed concentration of agonist, increasing
concentrations of a reversible competitive antagonist
progressively inhibit the agonist response; high antagonist
concentrations prevent response completely.
Conversely, sufficiently high concentrations of agonist can
surmount the effect of a given concentration of the antagonist.
Because the antagonism is competitive, the presence of
antagonist increases the agonist concentration required for a
given degree of response, and so the agonist
concentrationeffect curve is shifted to the right
Most antagonistic drugs are competitive
Competitive Antagonist
physiologic antagonism
It occurs between endogenous regulatory pathways
mediated by different receptors
example: glucocorticoid hormone >< insulin
Allosteric
Agonist Receptor
Agonist-Receptor
Interaction
Antagonist
Antagonist Receptor
Antagonist-Receptor
DENIED!
Complex
Competitive and Irreversible Antagonist