Session 8

Question 1

How do all drugs exert their effects?

Answer 1

By binding to a target, majority are proteins.

Question 2

Do drugs bind reversibly or irreversibly?

Answer 2

Reversibly with receptors.

Question 3

What governs drug binding?

Answer 3

Association and dissociation rates.

Question 4

What is the importance of concentration of drug molecules?

Answer 4

Concentration around the receptor is critical in determining drug action.
Drugs with equivalent molar concentrations have the same concentration of drug molecules.
Drugs with equivalent concentrations by weight may not.

Question 5

What is the equation for grams per litre?

Answer 5

Molecular weight x Molarity

Question 6

What is affinity?

Answer 6

The likelihood of a ligand binding to its target

Question 7

What is efficacy?

Answer 7

Likelihood of activation.

Question 8

Do Antagonists have affinity or efficacy?

Answer 8

Affinity only.

Question 9

Do Agonists have affinity or efficacy?

Answer 9

Both.

Question 10

How can binding information be found out?

Answer 10

By the binding of a radioligand.

Question 11

What is Bmax?

Answer 11

The maximum binding capacity

Question 12

What can the Bmax tell you?

Answer 12

The number of receptors

Question 13

What is Kd?

Answer 13

The dissociation constant and concentration needed for 50% occupancy

Question 14

What can you measure with the dissociation constant?

Answer 14

Affinity.

Question 15

What does a low Kd value relate to?

Answer 15

A higher affinity.

Question 16

When are concentration response curves used?

Answer 16

Measuring a response in cells/tissues.

Question 17

When are dose response curves used?

Answer 17

When measuring a response in a whole animal.

Question 18

What is Emax?

Answer 18

The maximum response.

Question 19

What is EC50?

Answer 19

The effective concentration giving 50% of the maximal response.
It can be used to measure Potency

Question 20

What is Potency?

Extra point - What governs it?

Answer 20

A combination of affinity and efficacy.

Extra point - The number of receptors.

Question 21

If an agonist has the same Emax value, will the efficacy be the same? What id the efficacys were different?

Answer 21

Not necessarily. If the efficacys are different then the Emax value will be different.

Question 22

What is the goal of treatment in asthma?

Answer 22

To activate Beta 2 adrenoceptors to relax the airways.

Question 23

What is Salbutamol?

Answer 23

A beta 2 adrenoagonist. It is high affinity and Beta 2 selective efficacy. It has side effects and limits Beta 1 activation.

Question 24

What is Salmeterol?

Answer 24

A longer acting Beta 2 adrenoagonist.No selective efficacy and prevents Beta 1 activation and side effects through difference in affinity only.

Question 25

When can less than 100% receptor occupancy give 100% response?

Answer 25

When EC50 is smaller than Kd = 50% of the maximal response needs less than 50% of the receptor occupancy.

Question 26

What effects the relationship between receptor occupancy and response?

Answer 26

It is non linear response and influenced by both transduction system and amplification (produced by second messengers) and properties of the tissue.

Question 27

How do spare receptors increase the response of a cell?

Answer 27

They increase sensitivity and allow responses at low concentrations of agonists.

Question 28

What does number of receptors have an effect on?

Answer 28

Potency

Question 29

What are partial agonists?

Answer 29

An agonist that cannot produce a maximal effect even with full receptor occupancy.

Question 30

What is the EC50 of a partial agonist equal to?

Answer 30

Kd

Question 31

How can partial agoniosts be more or less potent than full agonsits?

Answer 31

Because potency is dependent on affinity and efficacy.

Question 32

Is a partial agonist always a partial agonist?

Answer 32

No, it depends on the tissue and biological response.

Question 33

Is Morphine a full or partial agonist?

Answer 33

A full agonist.

Question 34

What is Buprenorphine and why is it used?

Answer 34

It is a partial agonist used for pain relief where possible as it doesn’t have the respiratory depression associated with morphine.

Question 35

What are the 3 types of antagonists?

Answer 35

Reversible competitive
Irreversible competitive
Non competitive

Question 36

What is the most common form of antagonism used in therapeutics?

Answer 36

Reversible competitive antagonism. It relies on a dynamic equilibrium between ligands and receptors.

Question 37

What is IC50?

Answer 37

The concentration of antagonist that gives 50% inhibition.

Question 38

How can reversible competitive antagonists be overcome?

Answer 38

By high concentrations of agonist so cause a parallel shift to the right of the agonist concentration response curve

Question 39

What is a therapeutic example of a reversible competitive antagonist?

Answer 39

Naloxone - high affinity to opioid receptors. It is used to reverse respiratory depression caused by opioids.

Question 40

When does irreversible competitive antagonism occur?

Answer 40

When the antagonist dissociates slowly or not at all. They cause a parallel shift to the right of the agonist concentration response curve.

Question 41

What do irreversible competitive antagonists cause at high concentrations?

Answer 41

They suppress the maximal response as the spare receptors are filled by the antagonist so not enough are left free to create a response.

Question 42

Give a therapeutic example of irreversible competitive antagonism.

Answer 42

Phenoxybenzamine is a non selective alpha 1 adrenoceptor blocker used in hypertension episodes in pheochromocytoma.(Tumour of the adrenal gland that released excessive adrenaline –> vasoconstriction)

Question 43

What is non competitive antagonism?

Answer 43

The allosteric binding of an antagonist to a receptor that IS NOT the ligand binding site.