Drugs And Receptors (8)

Question 0

What’s the most common drug target?

Answer 0

• Proteins

- GPCRs

Question 1

How do drugs exert their effects?

Answer 1

• By binding to a target.

Question 2

What is the equation for molarity?

Answer 2

• Molarity= g/L / MWt

Question 3

How many atoms are thee in a mole?

Answer 3

• 6x10^23

Question 4

Drug action on a receptor is dictated how?

Answer 4

• Affinity and intrinsic efficacy

Question 5

How is binding governed?

Answer 5

• Association and dissociation

- Affinity

Question 6

The activation of a drug and receptor is governed how?

Answer 6

• Intrinsic efficacy

Question 7

How do antagonists work in respect to affinity and intrinsic efficacy?

Answer 7

• Have affinity only
• No intrinsic efficacy
• Blocks effects of agonists

Question 8

How can drug-receptor interactions by binding be measured?

Answer 8

• Via binding of radioactively labelled ligand to cells/membranes prepared from cells.
• Low ligand conc = low binding
• High ligand conc = high binding

Question 9

What is Kd?

Answer 9

• Dissociation constant
• Measure of affinity
• Concentration of ligand required to occupy 50% of the available receptors
• Lower Kd = higher affinity

Question 10

What is B max?

Answer 10

• Max binding capacity - gives information about receptor number

Question 11

What are examples of responses from drugs?

Answer 11

• Change in signalling pathway

- Change in cell/tissue behaviour (e.g. Conc)

Question 12

What is meant by EC50, what is it a measure of and what is it dependent on?

Answer 12

• Effective concentration giving 50% of maximal response
• Measure of potency
• Affinity+efficacy=potency

Question 13

What is meant by concentration?

Answer 13

• Known concentration of drug at site of action e.g. Cells and tissues

Question 14

What is meant by dose?

Answer 14

• Concentration at site of action unknown (don’t know how body will react)

Question 15

What are the characteristics of drugs that need to be taken into account in a clinical setting?

Answer 15

• Affinity
• Efficacy
• Selectivity (off target effects?)
• Drug metabolism/pharmacokinetics (how body deals with it)
• Physicochemical properties (solubility/pH/stability/crystallinity)

Question 16

Why may selectivity be a problem?

Answer 16

• If isn’t selective then will have effects on other receptors
• e.g adrenaline on B adrenoceptors, useful for asthma but may also increase heart rate.

Question 17

What is selectivity based on?

Answer 17

• Affinity

Question 18

In some cases <100% occupancy leads to 100% response why is this?

Answer 18

• Spare receptors

Question 19

Why may spare receptors exist?

Answer 19

• Amplification in signal transduction pathway response limited by post-receptor event.

Question 20

What do spare receptors allow for in terms of sensitivity?

Answer 20

• Increases

- Allows responses at low concentrations of agonist

Question 21

A change in receptor number can lead to what?

Answer 21

• Change in agonist potency (max response)

- E.g. 10,000 is full response. If only have 5000 receptors means can’t get full response

Question 22

How does tolerance to drugs arise?

Answer 22

• Receptor number decreases when there’s a high activity

- Too high=no receptors available.

Question 23

When is buprenorphrine used and why?

Answer 23

• Adequate pain relief but no respiratory problems

- Higher affinity but lower efficacy than morphine

Question 24

What role can a partial agonist act as?

Answer 24

• Act as an antagonist to a full agonist

- Has a higher affinity but doesn’t turn on receptor as well

Question 25

What are partial agonists dependent on?

Answer 25

• Compound and systemic
• Increase receptor number can change a partial agonist into a full agonist, still has a low intrinsic efficacy but there are sufficient receptors to contribute to a full response

Question 26

What are the types antagonists?

Answer 26

• Reversible/irreversible competitive antagonism

- Non-competitive antagonism (allosteric/post-receptor)

Question 27

Describe what reversible competitive antagonism is.

Answer 27

• Competitive inhibition
• Relies on dynamic eqm between ligands and receptors
• As antagonist concentration concentration increase response decreases

Question 28

What is irreversible competitive antagonism?

Answer 28

• When agonists slowly dissociate or not at all
• With more time or antagonist concentration more receptors are blocked by antagonist. Non-surmountable
• At higher conc suppresses max response

Question 29

What effect does irreversible competitive antagonist have on an agonist - conc response curve?

Answer 29

• Parallel shift to the right as spare receptors filled by antagonist

Question 30

What is non-competitive antagonism?

Answer 30

• No competition for binding site but affects orthosteric affinity and or efficacy
• Non competitive inhibition