ICPP 6

Question 1

Why is it important to consider drugs in molarity rather than concentrations?

Answer 1

Same concentrations of different compounds can be totsally different concentrations of molecules

Question 2

What is intrinsic activity?

Answer 2

The ability for a ligand to activate a receptor

Question 3

What governs the efficacy of a drug?

Answer 3

Intrinsic efficacy plus cell/tissue-dependent factors such as receptor number

Question 4

What is Kd and what can it be used to show?

Answer 4

Dissociation constant, a measure of AFFINITY.

The amount of drug needed to occupy 50% of receptors

Question 5

What does a low Kd indicate?

Answer 5

High affinity

Question 6

What can you use to assess binding?

Answer 6

Radioligands

Question 7

What is Ec50

Answer 7

Concentration of drug that gives 50% of maximal response

Question 8

What does EC50 value indicate?

Answer 8

Potency - depends on both affinity and efficacy.

Question 9

What shape is a concentration - response curve?

Answer 9

Sigmoidal

Question 10

What are the properties of Salbutamol?

Answer 10

Selective efficacy for B2 receptors over B1 adrenoceptors, less selective affinity than salmeterol

Question 11

What are the benefits of salmeterol?

Answer 11

It has much higher selective efficacy for the B2 receptor, but equal efficacy for both receptors.
insoluble so cannot be given IV

Question 12

How can you tell if spare receptors are present?

Answer 12

If 100% binding gives 100% response then no spare receptors.

If <100% binding gives 100% response then must be spare receptors.

Question 13

Why do spare receptors exist?

Answer 13

Amplification in signal transduction pathway, one receptor can cause a big response
Increase specificity - allow responses at low conc of ligand
Lower drug conc needed - fewer side effects

Question 14

How does increasing receptor number alter specificity?

Answer 14

Increased receptors means increased specificity

Question 15

how can partial agonists become full agonists?

Answer 15

Increase in receptor number

Question 16

Give an example of a partial agonist

Answer 16

buprenorphine

Question 17

What are the 3 types of antagonist?

Answer 17

1. Competitive reversible
2. Irreversible competitive
3. Non-competitive (allosteric)

Question 18

What is IC50?

Answer 18

The concentration of antagonist which inhibits 50% of the response.

Question 19

How do competitive antagonists alter the % reponse?

Answer 19

Can still achieve maximal response but higher concentration of ligand required. Right shift.

Question 20

Give an example of a competitive antagonist.

Answer 20

Naloxone at mu-opioid receptors to reverse respiratory depression

Question 21

How does the agonist/response curve differ for irreversible antagonists?

Answer 21

After spare receptors have bound, 100% response cannot be achieved and begins to decrease.

Question 22

Give an example of an irreversible antagonist and its therapeutic effect.

Answer 22

Phenoxybenzamine.
Tumour of chromaffin cells in adrenal medulla results in excessive adrenaline production. Phenoxybenzamine inhibits the alpha1-adrenoceptor no matter how much adrenaline is produced.