Pharmacodynamics: Drugs and Drug Targets

Question 1

What type of proteins are the main drug targets?

Answer 1

GPCRs

Question 2

What is critical in determining drug action?

Answer 2

Concentration of drug molecules around receptors

Question 3

What is the equation of molarity?

Answer 3

Molarity (M) = g/L / molecular weight

Question 4

What is drug binding governed by?

Answer 4

Association and dissociation

Question 5

Which law is related to concentrations of reactants and products?

Answer 5

Law of mass action

Question 6

What is the difference between an agonist and an antagonist?

Answer 6

Agonist - Activates a receptor

Antagonist - Blocks the binding of an endogenous agonist

Question 7

Describe the term ‘affinity’

Answer 7

• How well a drug molecule interacts with a receptor

Higher Affinity = Stronger Binding

Question 8

What is intrinsic efficacy?

Answer 8

Degree to which a ligand enables a receptor to adopt a fully or partially activated state

Question 9

What is efficacy?

Answer 9

Ability of a ligand to cause a response

Question 10

What do agonists have that antagonists don’t?

Answer 10

Efficacy

Question 11

How can binding of ligand to receptors be measured?

Answer 11

Using radioactive labelling of ligand

Question 12

What is Bmax and what does it indicate?

Answer 12

• Maximum binding capacity

- Informs about the number of receptors

Question 13

What is Kd?

Answer 13

• Dissociation constant showing ligand affinity

- Ligand concentration at which 50% of receptors are occupied

Question 14

How are Kd and affinity related?

Answer 14

Low Kd = High affinity

Question 15

What is Emax?

Answer 15

• The maximal response of the system to a ligand binding

- 100% of the measured response

Question 16

Which curve represents Emax?

Answer 16

Concentration-Response curve

Question 17

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

Answer 17

• Potency

- Dependent on affinity and intrinsic efficacy

Question 18

How is EC50 determined?

Answer 18

Concentration of the ligand required to cause 50% of its own maximal response

Question 19

Do all receptors have to be occupied to reach a maximum response?

Answer 19

No there can be spare receptors

Question 20

What other factor can limit response other than the number of receptors?

Answer 20

Post-receptor response

E.g. a muscle has a limit to its contraction

Question 21

What do spare receptors increase?

Answer 21

Sensitivity

Question 22

Why do spare receptors exist?

Answer 22

Due to amplification in the signal transduction pathway

Question 23

What can change the number of receptors?

Answer 23

• External influences (drugs)

- Physiological/pathological circumstances

Question 24

What stimulus do receptor numbers increase and decrease in response to?

Answer 24

• Increase in response to low activity

- Decrease in response to high activity

Question 25

Name 2 differences between full and partial agonists

Answer 25

Full - high efficacy and intrinsic activity - high Emax Partial - low efficacy and intrinsic activity - low Emax

Question 26

What is a partial agonist?

Answer 26

A substance which cannot produce maximal effect even with full receptor occupancy

Question 27

Why are partial agonists commonly used as drugs?

Answer 27

- Allow a more controlled response - Work in absence of endogenous ligand - Can act as an antagonists

Question 28

What is a clinical example of a partial agonist as a drug?

Answer 28

buprenorphine use instead of heroin

Question 29

What are the effect of partial agonists dependent on?

Answer 29

- Compound | - Target cell/tissue

Question 30

What are the 3 methods of action that antagonists have as drugs?

Answer 30

- Reversible competitive antagonism - Irreversible competitive antagonism - Non-Competitive Antagonism

Question 31

What is reversible competitive antagonism dependent on?

Answer 31

- Concentration of agonist and antagonist | - Dynamic equilibrium between ligands and receptors

Question 32

How can reversible competitive antagonism be overcome?

Answer 32

By adding more agonist

Question 33

What is IC50?

Answer 33

Concentration of antagonist giving 50% inhibition

Question 34

Give an example of reversible competitive antagonism

Answer 34

Effect of naloxone on mew-opioid receptors

Question 35

What is the result of irreversible competitive antagonism?

Answer 35

Causes depression of the maximal response

Question 36

Give an example of irreversible competitive antagonism

Answer 36

Treatment of thrombosis with clopidogrel

Question 37

Which 2 sites are utilised in non-competitive antagonism?

Answer 37

- Orthosteric | - Allosteric

Question 38

What can allosteric antagonists influence?

Answer 38

- Effect of the orthosteric ligand | - Binding at the orthosteric site

Question 39

What effect does non-competitive antagonism on receptor subtype selectivity?

Answer 39

Increases

Question 40

Give an example of non-competitive antagonism

Answer 40

- Maraviroc in HIV | - Prevents HIV entering the cell