MnR S8 - Drugs and receptors

Question 1

What is meant by the term affinity?

Answer 1

Likelihood of a ligand binding to a receptor site

Question 2

What is meant by the term intrinsic efficacy?

Answer 2

The ability of an agonist to produce an active receptor

Question 3

What does overall efficacy depend on, other than intrinsic efficacy?

Answer 3

Cell/tissue dependent factors

Question 4

What is the definition of efficacy?

Answer 4

Ability to activate a receptor and produce a response

Question 5

What is meant by the term potency and what can be used as a measure of potency?

Answer 5

• Combination of both affinity and efficacy

- Measured by EC50 - effective concentration giving half the maximal response

Question 6

What is a partial agonist and give one clinically used partial agonist drug?

Answer 6

• A drug that binds to receptors but cannot produce a maximal response even at 100% occupancy
• Buprenorphine (used to treat heroin addiction)

Question 7

What is Kd?

Answer 7

Measure of affinity of the receptor for a drug

Question 8

What is IC50 a measure of?

Answer 8

Inhibitory concentration of an agonist giving 50% maximum inhibition

Question 9

Why is EC50 equal to Kd for partial agonists?

Answer 9

No spare receptors

Question 10

What is the function of spare receptors in tissue?

Answer 10

Increases sensitivity as they enable responses at low concentration of agonist

Question 11

When may a partial agonist become a full agonist?

Answer 11

Different tissues have different numbers of receptors, more receptors means maximum response can be achieved by a partial agonist

Question 12

How can the differences in efficacies of full agonists be determined from a graph of drug concentration against binding or response?

Answer 12

Response curve will be shifted to the left, the greater the efficacy

Question 13

What is reversible competitive antagonism?

Answer 13

Antagonist binds to orthosteric site, relies on the dynamic equilibrium between ligands and receptors, can be overcome with increasing agonist concentration

Question 14

Give a clinical use of reversible competitive antagonists

Answer 14

Naloxone acts on mew-opioid receptors

Question 15

What is irreversible competitive antagonism?

Answer 15

Occurs when antagonist dissociates slowly or not at all from the receptors orthosteric binding site, cannot be overcome by increasing antagonist concentration and at high concentrations suppress maximal response

Question 16

Give an example of a clinical use of irreversible competitive antagonists

Answer 16

Phenoxybenzamine used in treatment of pheochromocytoma as non-selective alpha 1-adrenoceptor blocker

Question 17

What is non-competitive antagonism?

Answer 17

Antagonist binds to allosteric site and effects cannot be overcome by increasing agonist concentration

Question 18

Give an example of a clinical use of non-competitive antagonist

Answer 18

Ketamine acts on NDMA inotropic glutamate receptors

Question 19

What governs drug-receptor binding interactions and which law does this relationship obey?

Answer 19

• Association and disassociation rates

- Obeys law of mass action

Question 20

Outline the difference between Bmax and Emax

Answer 20

Bmax - maximum binding capacity, information on number of receptors

Emax - effective drug concentration giving maximum response