MR 8 Drugs and Receptors

Question 1

How do drugs exert their effects?

Answer 1

By binding to a target, often protein, occasionally DNA (some antimicrobial and antitumour drugs). Most bind reversibly with receptors, binding governed by association and dissociation rates

Question 2

What can be targets of drugs?

Answer 2

Enzymes, GPCRs, ion channels, transporters, nuclear hormone receptors, other receptors

Question 3

How much is a mole?

Answer 3

6x10^23 particles.

Question 4

What is a molar solution?

Answer 4

Solution containing 1 mole in 1 litre

Question 5

Are drugs of equivalent concentrations by weight, always the same concentration?

Answer 5

No but drugs of equivalent molar concentrations are

Question 6

What are drugs that bind to receptors and cause a response called? What qualities do they have?

Answer 6

Agonists

Both efficacy and affinity

Question 7

What are drugs that bind to receptors but don’t cause a response called? What qualities do they have?

Answer 7

Antagonists

Affinity only

Question 8

What is affinity?

Answer 8

Likelihood of a ligand binding to its target

Question 9

What is intrinsic efficacy?

Answer 9

Likelihood of activation

Question 10

How is binding information often obtained?

Answer 10

through binding of a radioligand

Question 11

What is Bmax?

Answer 11

Maximum binding capacity

Gives info about number of receptors

Question 12

What is Kd?

Answer 12

The concentration needed for 50% occupancy

This is a measure of affinity and a lower Kd indicates higher affinity

Question 13

What are concentration response curves used for?

Answer 13

Measuring a response in cells/tissues

Question 14

What are dose response curves used for?

Answer 14

Measuring a response in whole animal

Question 15

What is Emax?

Answer 15

The maximum response

Question 16

What is EC50?

Answer 16

Effective concentration giving 50% of maximal response.

Measure of potency

Question 17

What is potency?

Answer 17

depends on affinity, intrinsic efficacy and efficacy.

Efficacy + affinity= potency

Question 18

What is efficacy?

Answer 18

Likelihood of response

Question 19

If two agonists have identical Emax do they have equal efficacy?

Answer 19

No, may differ in affinity

Question 20

What does salbutamol do and why is salbutamol effective?

Answer 20

beta adrenoagonist used to relax the airway via the b2 receptors there.
There are b1 adrenoceptors in the heart which could be affected by salbutamol but as salbutamol has higher affinity for b2 (kd b1=20um Kd b2=1um), because of its B2 SELECTIVE EFFICACY and because of administration route b1 activation and side effects are limited

Question 21

How are side effects prevented using salmeterol?

Answer 21

(Longer acting than salbutamol)
No selective efficacy
Prevents b1 activation through huge difference in affinity
kd b1=1900nm b2=0.55nm

Question 22

What are spare receptors?

Answer 22

These occur when the maximal 100% response does not need 100% receptor occupancy (Ec50<Kd so 50% of max resp takes less than 50% occupancy) so some receptors appear spare

Question 23

What influences whether there will be spare receptors or not?

Answer 23

transduction system/amplification and properties of tissue

Question 24

How do spare receptors affect sensitivity?

Answer 24

Increase sensitivity allowing responses at low agonist concentrations therefore also affecting potency

Question 25

What is a partial agonist?

Answer 25

Drug that cannot produce a maximal effect even with full receptor occupancy

Question 26

What is the relationship between Kd and EC50 in partial agonists?

Answer 26

Kd=EC50

Question 27

Can partial agonists be more potent than full agonists?

Answer 27

Yes as potency involves both efficacy and affinity

Question 28

Is a partial agonist a partial agonist in all tissues?

Answer 28

No can differ as tissue with more receptor would give more of a response

Question 29

What are the three types of antagonists?

Answer 29

Reversible competitive
Irreversible competitive
Non-competitive

Question 30

How common is reversible competitive antagonism and can it be overcome?

Answer 30

Commonest and most important form in therapeutics

Yes, overcome by high agonist concentration

Question 31

Why will a heroin(morphine-full agonist) addict who then takes (partial agonist)buprenorphine become ill?

Answer 31

Buprenorphine has higher affinity than heroin so occupies the receptors anatgonising the heroin. The buprenorphine is only a partial agonist so doesnt give maximal response so addict feels withdrawal symptoms

Question 32

Give an example of a reversible competitive antagonist

Answer 32

Naloxone- antagonises u-opioid receptors. Used to reverse opioid mediated respiratory depression. Its high affinity means it competes effectively with other opioids like heroin

Question 33

How do reversible competitive antagonists affect a concentration response curve?

Answer 33

Parallel shift to right

Question 34

How do irreversible competitive antagonists affect a concentration response curve?

Answer 34

Parallel shift to right and at high concentrations suppresses maximal response as spare and needed receptors filled by antagonist

Question 35

Give an example of an irreversible competitive antagonist?

Answer 35

Phenoxybenzamine
a1 adrenoceptor blocker used in hypertension episodes in pheochromocytoma (tumour of adrenal gland causing excessive NA secretion and vasoconstriction

Question 36

What is non-competitive antagoniism?

Answer 36

Allosteric binding of an antagonist to a receptor