Session 6 (Pharmacodynamics)

Question 1

What is critical in determining drug action?

Answer 1

Concentration of drug around receptor

Question 2

Give an equation relating molarity, concentration and molecular weight

Answer 2

Molarity(M)= MWt x conc(g/L)

Question 3

What drugs activate receptors?

Answer 3

Agonists

Question 4

In order to be an agonist what must a drug have in addition to affinity for the receptor?

Answer 4

Intrinsic efficacy (ability to switch receptor on)

Question 5

What is the drug’s ability to cause a response called?

Answer 5

Its efficacy

Question 6

What type of drug is said to have efficacy?

Answer 6

Agonists

Question 7

What is efficacy governed by?

Answer 7

Intrinsic efficacy (receptor activation) + things happening to generate a measurable response

Question 8

What do agonists have to have in order to work?

Answer 8

Affinity, intrinsic efficacy and efficacy

Question 9

What do antagonists have to have in order to Work?

Answer 9

Affinity alone

Question 10

How do we measure drug-receptor interactions by binding?

Answer 10

Bind a radioactively labelled ligand to cells or membranes

Change [ligand] and observe the binding patterns

Question 11

What is Bmax?

Answer 11

The max binding capacity of a receptor (like Vmax but this is about receptors)

Question 12

What is Kd?

Answer 12

Indicates ligand affinity (like Km)

[ligand] at which half of the receptors are saturated

Question 13

What does a low Kd mean?

Answer 13

The ligand has a high affinity

Question 14

How else can affinity of substrates be measured?

Answer 14

Ka (assay)

Question 15

What is Emax?

Answer 15

Effect max of drug, (max response of drug)

Question 16

What is EC50?

Answer 16

Effective concentration of drug giving 50% of max response

Question 17

What is the difference between concentration and dose?

Answer 17

Conc- amount of drug known at site of action

Dose- conc unknown at site of action

Question 18

What is potency?

Answer 18

Equal to EC50

Question 19

What does potency depend on?

Answer 19

Affinity + intrinsic efficacy + efficacy

Question 20

What is functional antagonism?

Answer 20

Going against an effect using a different mechanism from the one that cased the effect in the first place

Question 21

What happens to the response and binding curves when there are spare receptors?

Answer 21

The response graph would shift to the left because <100% binding is giving 100% response

Question 22

When are spare receptors seen?

Answer 22

When the receptors are catalytically active (GPCR/tyrosine kinase)

Question 23

Why aren’t all receptors always needed?

Answer 23

Because there is amplification systems (eg GPCRs)

Question 24

What is a benefit of spare receptors?

Answer 24

Increases sensitivity (ability of cell to respond to a lower [ligand])

Question 25

Why would a cell decrease its receptor number?

Answer 25

To decrease sensitivity

Question 26

What effect does changing receptor number have?

Answer 26

Changes agonist potency + maximal response if 100% occupancy produces an insufficient response

Question 27

What are partial agonists?

Answer 27

Ligands giving partial responses even with 100% occupancy

Question 28

What kind of intrinsic efficacy do partial agonists have?

Answer 28

Insufficient

Question 29

If a line plotted on a response/[drug] graph shifts to the left what does this mean in terms of potency?

Answer 29

The drug has increased potency (EC50 is lower)

Question 30

If a line plotted on a response/[drug] graph no longer goes up as far on the y axis what does this mean in terms of the drugs intrinsic efficacy?

Answer 30

The intrinsic efficacy is reduced because its not able to activate the receptor as well and therefore responses are reduced also (if response is less that 100%=partial agonist)

Question 31

Why is it sometimes beneficial to use partial agonists?

Answer 31

They give more controlled responses and can sometimes act as antagonist (if they have better affinity)

Question 32

What are partial agonists dependent on?

Answer 32

Both the compound itself and the system in which it is working on (It may not always be a 'partial agonist)

Question 33

If you plot both the binding and response curves on the same graph, what does the gap between the two lines show?

Answer 33

Indicative of efficacy (shows how good drug is at kicking cell into life, bigger gap=better efficacy)

Question 34

What happens if you increase [antagonist] for a reversible competitive antagonists?

Answer 34

Receptors more likely to be bound to antagonist (greater inhibition)

Question 35

What is the concentration of antagonist that gives 50% inhibition called?

Answer 35

IC50 (index of antagonist potency)

Question 36

What kind of inhibition do you get with reversible competitive antagonists?

Answer 36

Surmountable (increasing conc of agonist can overcome antagonist)

Question 37

What happens when antagonists dissociate slowly or not at all?

Answer 37

Irreversible competitive antagonism occurs (non surmountable)

Question 38

What do you call antagonists that bind to other areas of a receptor?

Answer 38

Non competitive antagonists

Question 39

Where do normal/natural ligands bind?

Answer 39

Orthosteric site

Question 40

Where do non-competitive antagonists bind?

Answer 40

Allosteric sites

Question 41

What modulation of allosteric sites do non-competitive antagonist do?

Answer 41

Negative allosteric modulation

Question 42

What is potency?

Answer 42

It is a measure of how good a ligand is at evoking a response (defined as EC50)