Pharmacodynamics

Question 1

Define ligand

Answer 1

Molecule that binds to a receptor

Question 2

Define agonist

Define antagonist

Answer 2

Ligand that activates a receptor and produces a measurable biological response

Ligand that inactivates or prevents an agonist from activating a receptor, producing no measurable biological response

Question 3

Define partial agonist and state it’s values for Emax, intrinsic efficacy, affinity, and potency

Answer 3

Ligand that activates a receptor and produces a measurable biological response but one that is lower than the response of a full agonist
Lower Emax
Lower intrinsic efficacy
Same potency
Same affinity

Question 4

Define:
Affinity
Intrinsic efficacy
Ligand efficacy
Agonist potency

Answer 4

Affinity: Ability of a ligand to bind to a receptor
Intrinsic efficacy: Ability of an agonist to generate the active form of a receptor
Ligand efficacy: Ability of the agonist-receptor complex to produce a measurable biological response after activation of the receptor
Potency: Ability of an agonist to produce its maximum biological repsonse

Question 5

Define:
Kd
EC50

Answer 5

Kd: conc. of ligand that binds to half the available receptors
EC50: conc. of agonist that produces half of its max response

Question 6

What is potency dependent upon?

Answer 6

Affinity
Efficacy
Cell specific components

Question 7

What is Kd also known as?

Answer 7

Dissociation constant: strength of the interaction between ligand and receptor

Question 8

How does the Kd affect the selectivity of a ligand?

Answer 8

Ligands have different affinity’s for different receptors

Greater difference in Kd, more drug is available to administer without side-effects

Question 9

What are spare receptors?

Answer 9

Tissues contain an excess number of receptors than what is needed for the Emax
Therefore, tissues have an increased sensitivity to ligands (signal amplification or multiple signals)
Allows an equivalent response following the loss of receptors

Question 10

Describe how changes in the number of receptors will affect the response of a cell

Answer 10

Change in the number of receptors will cause a reciprocal change in Emax, EC50, Bmax, Kd

Question 11

Explain the terms down-regulation and up-regulation and their causes

Answer 11

Down-regulation: receptor numbers decrease due to high activity
Up-regulation: receptor numbers increase due to low activity

Question 12

How do partial agonists allow a controlled response and what is an example?

Answer 12

Can act as an antagonist in the presence of a full agonist
Buprenorphine is a partial agonist with a higher affinity than heroin for (micro-)opioid receptors causing withdrawal symptoms

Question 13

Describe what functional antagonism is

Answer 13

An antagonist that uses a different pathway (to the agonist) to oppose the effects of the agonist

Question 14

What are the different types of conventional antagonism?

Answer 14

Competitive (reversible and irreversible)

Non-competitive

Question 15

Describe the action of reversible competitive antagonists

Answer 15

Non-covalent binding to the receptor
Dynamic equilibrium of antagonist and agonist (inhibition only when [Antagonist] > [Agonist])
Increases Kd

Question 16

Describe the action of irreversible competitive antagonists

Answer 16

Covalent binding to the receptor
Slow dissociation (inhibition when antagonist is present)
Increases Kd and EC50

Question 17

Describe the action of non-competitive antagonists

Answer 17

Binding at allosteric site
Antagonists allosterically modulate Active site of receptor
Reduce orthosteric (natural site) ligands affinity and intrinsic efficacy
Increases Kd and EC50