Drug-Receptor Interactions 2 Flashcards
Affinity
A measure of the concentration range over which a drug binds to its receptor.
Kd
Efficacy
The ability of a drug to generate/initiate a stimulus once bound to its receptor
Function of partial agonists
Reduce the response to a full agonist because some receptors will be occupied by partial agonist molecules.
This gives a smaller response than if all the receptors were occupied by full agonist molecules.
What is a competitive antagonist ?
A drug which interacts/binds REVERSIBLY with receptors to form a complex, but this complex doesn’t evoke a response.
[D]
Concentration of drug
State the competitive antagonist equation
[D] + [R] + [A] = [DR] + [AR]
[R]
Concentration of receptor
[A]
Competitive antagonist
[DR]
Only [DR] gives rise to a response
[AR]
Receptors which are occupied by not activated
Ka
The equilibrium dissociation constant for an antagonist
Describe log dose-response curves for a competitive antagonist
Displaced to the right
Maximum response to agonist remain the same (linear sections are parallel)
What does the log dose response curve moving to the right in response to an antagonist mean ?
More of the receptor sites are being occupied
r
Ratio by which [D] must be increased to overcome competition by [A]
Describe Ka
The concentration of antagonist that makes it necessary to add twice as much agonist to produce a response as would be needed in the absence of the antagonist
pA2
-log10(Ka)
Compares the affinity of an antagonist
Describe the log dose-response curve of irreversible competitive antagonism
Slope is decreased
Maximum response to agonist is decreased
Allosteric Modulators
Bind to sites on the receptor other than the agonist binding site and can modify agonist activity.
Describe allosteric binding sites
Allosteric binding sites are regulatory, not active binding sites.
Function of allosteric binding sites
Can modify the affinity or efficacy of a receptor’s endogenous ligand or drug.
Potentiate or inhibit
Non-competitive antagonist
These are an example of allosteric modulation
The antagonist blocks access of the agonist to its binding site through steric hinderance.
How quickly does an irreversible competitive antagonist dissociate from the receptor ?
Very slowly (if at all)
What effect does a non-competitive antagonist have on efficacy ?
Efficacy is lowered
What effect does a non-competitive antagonist have on affinity ?
Receptor can alter conformation and binding affinity of agonist so affinity is lowered.
What is an inverse agonist ?
An agonist that decreases the activity of the receptor from basal level
Homeopathy
The dilution and potency of medicines is inversely proportional.
Higher dilution, the more potent the medicine
If drug A has a Kd value of 8nM, and drug B has a Kd value of 100nM
Which drug has the greatest affinity for the receptor ?
Drug A
Drug A has a pD2 value of 2 and drug B has a pD2 value of 6
Which has the greatest affinity for the receptor ?
Drug B
(higher pD2 value means lower Kd)
Both drug A and drug B have a pD2 value of 2.
At the same concentration, drug A produces 50% of the effect seen with drug B.
Which has the greatest affinity ?
Neither
Concerning drug receptor interactions, the Kd refers to ?
The drug concentration required to occupy 50% of receptors at equilibrium.
State the true statement :
Competitive inhibition is based on reversible drug/antagonist binding at receptor sites.
With competitive inhibition, the dose-effects curve is shifted to the left
With competitive inhibition, maximal drug effect cannot be obtained, even at high agonist concentrations.
All of the above
Competitive inhibition is based on reversible drug/antagonist binding at receptor sites.
Non-competitive antagonists can be surmounted with high concentrations of agonist
True or False
False
AKA Allosteric Modulators
