drug receptor interactions 2

Question 1

drugs have two properties:

define affinity!
define efficacy!

Answer 1

1. AFFINITY (Kd - measure of affinity for the agonist or Ka - measure of affinity for the antagonist) is a measure of the concentration range over which a drug binds to its receptor (the lower the Kd the higher the affinity for the drug)
2. EFFICACY is the ability of the drug to generate/initiate a stimulus once bound to its receptor

Question 2

describe the efficacy in partial agonists

how can partial agonists affect a response to a full agonist?

Answer 2

• Partial agonists has low intrinsic efficacy - irrespective of the concentration of drug used, it will never illicit a full maximal response (can have same affinity but be less efficacious than a full agonist)
• partial agonists can decrease (dampen the response) the response to a full agonist because one receptor will be occupied by partial agonist molecules, giving a smaller response than if all the receptors were occupied by full agonist molecules

Question 3

what are competitive antagonists?

how do competitive antagonists affect agonists?

Answer 3

• competitive antagonists may be regarded as drugs which interact/bind reversibly with receptors to form a complex but this complex does not evoke a response, whereas a drug evokes a response
• competitive antagonists bind to the same site as the agonists so in order to achieve a maximal response, the number of agonists must outcompete the number of competitive antagonists
• competitive antagonists decrease the maximum response of an agonist as it binds to the same active site and dissociates very slowly (or at all)

Question 4

what do allosteric modulators do?

what do allosteric bind sites do?

what is an example of an allosteric modulation?

Answer 4

they bind to sites on the receptor other than the agonist binding site and can modify agonist activity (allosteric sites)

• they are not regulatory (not active binding sites) but instead they can modify the affinity or efficacy of a receptor’s endogenous ligand or drug
• they can either potentiate (positive allosteric modulators) or inhibit (negative allosteric modulators)
• non-competitive antagonists in which the antagonist blocks access of the agonist to it’s binding site through steric hindrance

Question 5

describe the roles of inverse agonists?

Answer 5

when an inverse agonist binds to receptors which are constitutively active, it gives a response, but the response is to reduce the activity of the receptor