Antagonists Flashcards
(15 cards)
What is an antagonist?
A drug which binds to a receptor and blocks th e effect of agonists (aka blocker or inhibitor)
What is the efficacy and slope in an antagonist?
EFFICACY IS THE LOWEST (MAX) RESPONSE, ANTAGONISTS BLOCK RESPONSE
A slope greater than one thus indicates positively cooperative binding between the receptor and the ligand, while a slope less than one indicates negatively cooperative binding
What is the difference between an antagonist and inverse agonist?
Antagonist binds to receptor inhibiting its activation
Inverse agonists actively turns off the receptor/reduces activity below the baseline.
What is competitive antagonism?
No change in Hill coefficient
no change in efficacy
Reduced potency=parallel shify to the right
=reversible antagonism (summountable)
(Look at the lecture to see the graphs)
What is reversible competative antagonism? give example
A reversible competitive antagonist is a drug that binds reversibly to the same receptor as the agonist, competing for the same binding site and preventing activation. However, its effects can be overcome by increasing the concentration of the agonist.
No change in Emax, but higher agonist conc is needed to reach the same response
Graph shifts to the right
Higher EC50=higher dose of agonist needed
i.e.Propranolol, beta adgrenergic receptor, competes with adrenaline ut does not activate the receptor. adrenaline increases, overcomes propanolol effect.
What is a Schild plot?
Is used to confirm reversible competative antagonism and measure an antagonists potency (pA2 value).
Straight line with a slope 1 confirms competitive antagonisM
pA2 value tells how strong the antagonist is.
Used to study drugs like propranolol vs. adrenaline.
What is an irreversible competative antagonism?
When the antagonist dissociates very slowly from the receptor e.g. covalent binding
Reduced Hill coefficient
Reduced efficacy
Reduced potency- non-parallel shift to the right
Irreversible antagosim, insummountable
What is Non-competitive antagonism?
Antangist binds to the receptor at a different sites than the agonist:
Orthosteric site=location of agonist binding
Allosteric site=alternative binding site
Can be reversible or irreversible
What is reversible/surmountable non-competitive antagonism?
When theantagonist reduces the affinity of the agonist for the receptor (confirm with binding studies) potency reduced, emax stays the same.
What is a irreversible/insurmountable non competative antagonist?
When the antagonist reduces the affinity (interferes with binding) and efficacy (interferes with activation) of the agonist.
potency and efficacy decreases.
What is a positive modulation of? Allosteric modulation
POTENCY INCREASES EMAX STAYS CONSTANT
What is the neagtive modulation? allosteric modulation
Potency decreases
What is the Agonist modification? allosteric modulation
Potency and Efficay increased
What is non-competitive antagonism? allosteric modulation
Decreased Potecny and Efficacy
Explain how uncompetitive antagonism works? i.e ketamine block of NMDA receptor
- No agonist: channel closed, antagosit binding site inside pore so inaccessible
- agonist binds: agonist binding opens channel, antagosit enters pore
- Antagonist binds: antagonist causes channel to be blocked, ions cant pass through.
