14. Drugs and Receptors

Question 1

Order the following in decreasing size: molar, micro molar, picomolar, nanomolar and millimolar.

Answer 1

Molar, millimolar, micro molar, nanomolar, picomolar.

Question 2

Why are drugs concentrations considered in molar?

Answer 2

To show how many molecules are at the site of action.

Question 3

What is drug binding governed by?

Answer 3

Association and dissociation.

Question 4

What is the difference between agonists and antagonists?

Answer 4

Agonists activate the receptor, antagonists block the binding of an endogenous agonist.

Question 5

What is receptor activation governed by?

Answer 5

Intrinsic efficacy, how good an agonist is at generating the activated state of the receptor.

Question 6

What is the difference between intrinsic efficacy and efficacy?

Answer 6

Intrinsic efficacy is just activation of the receptor, efficacy I how good it is at generating a response from that activation.

Question 7

Describe agonists and antagonists in terms of affinity, intrinsic Africans and efficacy.

Answer 7

Agonists have all three.

Antagonists only have affinity.

Question 8

How can drug-receptor interactions be measured?

Answer 8

By binding radioactive labelled ligand (radioligands) to cells or membranes prepared from cells. Low [ligand] = low binding, high [ligand] = high binding.

Question 9

What is Kd/ dissociation constant a measure of?

Answer 9

Affinity. It’s the concentration of ligand needed to bind to 50% of the receptors.

Question 10

What does a high or low Kd value tell you about affinity?

Answer 10

High Kd = low affinity.

Low Kd = high affinity.

Question 11

What is EC50?

Answer 11

Effective concentration giving 50% of the maximal response of a drug.

Question 12

What happens to the shapes of plotted graphs with drugs when [drug] is converted to [drug]log10?

Answer 12

The graph changes from a rectangular hyperbole to a sigmoidal curve.

Question 13

What is the difference between concentration and dose?

Answer 13

Concentration is the known concentration of drug at the site of action. Dose is where the concentration at the site of action is unknown.

Question 14

What is EC50 a measure of?

Answer 14

Potency.

Question 15

What does EC50 depend on?

Answer 15

Affinity and intrinsic efficacy and efficacy.

Question 16

On a [Drug]Log10 (M) vs binding/response curve of two drugs, how would two drugs of equal affinities but different efficacies appear?

Answer 16

Their binding curve would be in the same position, with the same sigmoidal curve. The difference between the binding and response curve shows the efficacy, a bigger difference is a bigger efficacy. So the drug with a greater efficacy will have a response curve further to the left, and further away from the binding curve than the lower efficacy drug.

Question 17

What is the problem of treating asthma with adrenaline on B2-adrenoceptors?

Answer 17

The treatment can act on other B-adrenoceptors elsewhere, like on B1-adrenoceptors in the heart. This will increase the force and rate of contraction.

Question 18

How is salbutamol a selective treatment for asthma?

Answer 18

It has poor selectivity for B1 and B2-adrenoceptors but it has a much higher B-selective efficacy. So the drug may bind to all the receptors but it only produces a big response on the B2-adrenoceptors, and so is selective.

Question 19

How is salmeterol a selective treatment for asthma?

Answer 19

It has a good Kd selectivity for B2-adrenoceptors over B1-adrenoceptors. Once it has bound, it does not have a selective efficacy. So it is selective but only based on affinity, it won’t bind easily to heart B1-adrenoceptors.

Question 20

Why do spare receptor exist?

Answer 20

Because of amplification in the signal transduction pathway. Also response is limited by a post-receptor event.

Question 21

Rearrange the following equation to calculate molarity. MWt (molecular weight) X molarity = g/L.

Answer 21

M = (g/L)/MWt.