Lecture 31 and 32 - Drugs working through receptors

Question 1

Affinity

Answer 1

Strength of drug-binding at a specific receptor

Question 2

Determinants of affinity:
1)
2)

Answer 2

1) Shape

2) Forces (electric charge)

Question 3

Law of mass action

Answer 3

K^1
[A] + [R] [AR]
K^-1

Question 4

R total

Answer 4

[R] + [AR]

Question 5

Ka (Dissociation constant)

Answer 5

K^-1/K^1

Question 6

Fractional receptor occupancy

Answer 6

[AR]/[R]

Question 7

When [A]=Ka, [AR]/[R]=

Answer 7

0.5

Question 8

What is Ka a a measure of?

Answer 8

Affinity

Question 9

EC50

Answer 9

[Drug] that results in 50% of total tissue response

Question 10

Ka=affinity, EC50=

Answer 10

Potency

Question 11

EC50=Potency, Ka=

Answer 11

Affinity

Question 12

Factors determining EC50:
1)
2)

Answer 12

1) Ka

2) Intrinsic efficacy. Receptor activation upon binding

Question 13

Intrinsic efficacy

Answer 13

Receptor activation upon drug binding

Question 14

Full agonist

Answer 14

Causes full effect upon binding

Question 15

Partial agonist

Answer 15

Causes lesser response upon binding

Question 16

Antagonist

Answer 16

Causes no effect upon binding, or opposite effect (inverse agonists)

Question 17

Response is a function of:

Answer 17

efficacy[A][R]/[A]Ka

Question 18

Receptor reserves

Answer 18

% of receptors not required for a given response

Question 19

Can conclusions about affinity (Ka) be drawn from concentration/response curves?

Answer 19

No. Insufficient data.

Question 20

Isoprenaline

Answer 20

Beta-adrenoceptor agonist.

Selective for beta- over alpha-adrenoceptors

Question 21

Congestive heart faliure

Answer 21

1) Compensatory sympathetic baroreceptor reflex increases heart rate to compensate for lower blood pressure.
2) Overexposure of beta-adrenoceptors to noradrenaline leads to decrease in sensitivity.
3) Increase EC50

Question 22

Chemical antagonism

Answer 22

Antagonist molecule that binds to, or destroys another molecule

Question 23

Examples of chemical antagonists

Answer 23

Antibodies

Protamine antagonism of heparin

Question 24

Protamine chemical antagonism of heparin

Answer 24

Protamine is a polycation

Heparin is a polyanion

Question 25

Effect of heparin

Answer 25

Inhibits coagulation cascade

Question 26

Competitive antagonism - Reversible

Answer 26

Concentration-related antagonism

Moves stimulus-response curve to the right in parallel. Maximum effect unchanged

Question 27

Competitive antagonism - Irreversible

Answer 27

Covalent binding to active site

Response decreases with time

Question 28

Non-competitive antagonism - At receptor

Answer 28

Orthosteric agonist

Allosteric inhibitors or enhancers

Question 29

Non-competitive antagonism - Mechanistic

Answer 29

Effect isn’t agonist-specific
Interferes with another part of a system that reduces the effect of agonist
EG: In smooth muscle, calcium-channel blockers

Question 30

Antagonism by a partial agonist

Answer 30

A form of competitive inhibition

Question 31

Functional antagonism

Answer 31

A system is affected by two different mechanisms
EG: ACh (decrease) and noradrenaline (increase) effect on heartrate
EG: Blood pressure: Angiotensin increases peripheral vascular resistance
Parasympathetic release of ACh decreases heart rate

Question 32

Duty cycle of beta-adrenoceptors:
1)
2)
3)

Answer 32

1) GPCR binding makes part of receptor phosphorylated
2) Phosphorylation causes GPCR to be internalised, where it can be recycled or degraded
3) Example of desensitisation

Question 33

Buprenophine uses

Answer 33

Pain relief, withdrawal form heroin

Question 34

Buprenophine effects

Answer 34

1) Mu opioid partial agonist
2) Protects against dysphoria in withdrawal
3) Partial agonist, so doesn’t stop respiraiton like full agonists (EG: heroin)
4) Decreases the reward of heroin

Question 35

PIndolol effects

Answer 35

1) Beta1 selective adrenoceptor partial agonist
2) Decreases exercise capacity
3) Adrenaline can’t increase heartrate