Lecture 2

Question 1

What is affinity?

Answer 1

The binding of a drug to a receptor.

Question 2

Describe Kd?

Answer 2

Affinity constant - this is the concentration of the ligand that will bind to 50% of the substrate.

Question 3

What happens if affinity is high?

Answer 3

You will need less concentration of ligand to bind to the substrate - therefore concentration will be low. This is known as a smaller Kd.

Question 4

Describe affinity vs Biological response?

Answer 4

When you look at biological response curve you are not getting a measure of direct drug binding to the receptor. This is due to occupancy and effect are not always completely proportional. Affinity and ability to produce an effect don’t always line up. Biological effect could be measuring anything (the further away from a receptor then you have other systems interacting with the drug).

Question 5

Describe Biological Response curves?

Answer 5

A biological response can be anything - change in BP, ion channel opening or the activation of an enzyme. These can be measured and plotted as a concentration response curve. We look at the

Question 6

Describe the effect of a drug?

Answer 6

This is defined by the maximal effect (EMAX) and the EC50 (the concentration in which the drug produces a 50% result).

Question 7

Describe potency?

Answer 7

EC50 is the effective concentration of an agonist that produces 50% of the maximal response. When potency is high EC50 will be low (due to less drug that is needed to produce an effect).

Question 8

Describe efficacy?

Answer 8

This is the maximum affect a drug can produce.

Question 9

What is an agonist drug?

Answer 9

A drug with positive efficacy will activate a receptor to promote cellular response.

Question 10

What is an inverse agonist drug?

Answer 10

A drug which produces a decrease response.

Question 11

What is an antagonist drug?

Answer 11

A drug that binds to the receptor but does not produce a conformational change. This is to prevent the natural agonist at the receptor.

Question 12

What is the difference between full and partial agonists?

Answer 12

Full - drugs that produce the maximum tissue response.
Partial - drugs that produce less than the maximum response. These agonists cannot produce the maximal response even at 100% receptor occupancy. Basically the ligand binds to the receptor but does not cause the full drive of conformational change. on the receptor.

Question 13

Describe antagonism?

Answer 13

Bind to a receptor but don’t activate or inactivate a receptor. Have affinity but zero efficacy.

Question 14

Describe reversible competitive antagonism?

Answer 14

Binds non-covalently to the receptor. Competes for the orthosteric binding site. This will stop the agonist ligand binding to the receptor.

Question 15

What happens to the antagonist if you continue to add agonist?

Answer 15

The agonist will outcompete the antagonist. Will see an effect. You will continue to move the curve to the right.

Question 16

Describe irreversible antagonism?

Answer 16

This drug reduces the number of receptors available to the agonist. It doesn’t matter how many drugs you have, the antagonist never lets go of the receptor.

Question 17

Why do you only inhibit an enzyme, but you can activate or inactivate a receptor?

Answer 17

With a receptor drug, the drug is not using a ligand to make something.

Question 18

Describe the inhibitors of AChE?

Answer 18

This will increase neurotransmission. As ACh can reach more receptors. Stronger cholinergic response. Short and immediate duration inhibitors.

Question 19

Describe the Serotonin Transporter?

Answer 19

Serotonin (5HT) is involved in many functions. Very similar to ACh neurotransmitter. However there isn’t an enzyme to break down 5HT in the synaptic cleft, instead there is a transporter. The transporter binds to 5HT, and returns it back to the pre-synaptic terminal. There are 12 transmembrane domains. Have to have sodium bound first then serotonin, then chloride binds. Conformational change happens and 5HT is then moved.

Question 20

What are SSRI’s?

Answer 20

Selective Serotonin Reuptake Inhibitor. Binding to the serotonin transporter and selectively preventing the transport of 5HT across the cell membrane so that it is staying in the synapse. There is enhanced serotinergic activity and enhanced neurotransmission. And example is fluoxetine. Increase serotonin results in improvement of mood - in a slightly controlled transmission.