Drug Receptor Interactions 2 Flashcards
What are the two key properties of drugs?
Affinity and
Efficacy
What is drug affinity?
(KD or KA) is a measure of the concentration range over which a drug binds to its receptor
What is drug efficacy?
the ability of the drug to generate/initiate a stimulus once bound to its receptor
What are partial agonists?
Partial agonists can ↓ the response to a full agonist because some receptors will be occupied by partial agonist molecules, giving a smaller response than if all the receptors were occupied by full agonist molecules
What is competitive antagonism?
A competitive antagonist may be regarded as a drug which interacts/binds reversibly with receptors to form a complex but this complex does not evoke a response
[D] + [R] + [A] = [DR] + [AR]
Where [A] is a competitive antagonist
Only [DR] give rise to a response
[AR] are receptors which are occupied but not activated
What similarities do competitive antagonists have with competitive agonists?
Like agonists, antagonists have affinity for receptors:
KA = Equilibrium dissociation constant for an antagonist.
Log Dose-response curves displaced to the right by a competitive antagonist
Maximum response to agonist remains the same
“Linear” sections are parallel
What is the Schild equation?
r = ([A]/KA) + 1 r = Ratio by which [D] must be increased to overcome competition by [A] in a competitive antagonist
What is Ka in a competitive antagonist?
KA is 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
What equation for competitive antagonists involve KA?
pA2 = -log10(KA)
What is pA2 in competitive antagonists?
The pA2 value is a way of comparing the affinity of an antagonist (similar to the pD2 of an agonist)
What are irreversible competitive antagonists?
Competitive antagonists that bind, but dissociates very slowly (if at all)
What effects do irreversible competitive antagonists have on a slope of Log Donee-response curve?
Slope of Log Dose-response curves decreased by an irreversible competitive antagonist
Maximum response to agonist decreased
What are allosteric modulators?
Bind to sites on the receptor other than the agonist binding site and can modify agonist activity
What are allosteric binding sites?
Allosteric sites are regulatory, not ‘active’ binding sites
Can modify the affinity or efficacy of a receptor’s endogenous ligand or drug
Potentiate or inhibit
What is a non competitive antagonist?
Non competitive antagonists are an example of allosteric modulation - The antagonist blocks access of the agonist to its binding site through steric hindrance
