Antagonism Flashcards
What is antagonism?
The process of inhibiting retarding or preventing agonist-induced receptor response.
What are the mechanisms of antagonism?
- Orthosteric:- both agonist and antagonist compete for the same binding site.
- Allosteric:- different binding sites for agonist and antagonist on the receptor
Classify antagonism.
- Competitive antagonism:- agonist and antagonist compete for the same binding site on receptor. May be surmountable and reversible.
E.g. Losartan at angiotensin receptor site - Non-competitive antagonism:- Different binding sites. Binding of antagonist retards agonist activity but doesn’t affect binding of agonist. May be insurmountable and irreversible.
Explain surmountable and insurmountable antagonism.
Surmountable antagonism:- results in a parallel shift to the right with no reduction in maximum response
Insurmountable antagonism:- results in a depression of maximum response.
The activity of an antagonist depends on:
- Its concentration
- Its affinity for the receptor
How is antagonism reversed?
- Increasing agonist conc
- antagonist dissociation with decreasing conc.
Derive Gaddum’s equation for competitive antagonism.
p = [A]/([A] + KA (1+[B]/KB)
What is Schild’s simplified equation for competitive antagonism?
[A’]/[A] - 1 = [B]/KB
What is PAx?
The negative log of the molar conc of the antagonist that shifts the dose-response curve by a factor of x.
What are possible reasons why Schild’s slope may not be unity?
- Multiple binding sites
- Pharmacokinetic interactions
- Multiple drug properties are expressed in the concentration used to take the measurements
- Competitive antagonism of heterogenous receptor population enhancing the same observed response
What is Gaddum’s equation for non-competitive antagonism?
PA = ([A]/KA)/([A]/kA +1) (1-PB)
