Drug Testing

Question 1

What are the 2 types of gating in ion channels?

Answer 1

1. Ligand gating
2. Voltage gating

Question 2

How do ligand gating ions channels work?

Answer 2

The binding ligand induces change in the channel’s shape

Question 3

How do voltage gating ions channels work?

Answer 3

Change in ion concentration triggers opening

Question 4

What is a full agonist?

Answer 4

Molecules which mimic the effects of a ligand, achieve up to the same mazimum effect as a ligand

Question 5

What is a partial agonist?

Answer 5

Do not achieve 100% effect of a ligand

Question 6

What are the leaky receptors?

Answer 6

Receptors which trigger an activity even when nothing is bound to them

Question 7

What are inverse agonists?

Answer 7

Switch off the natural activity of leaky receptors

Question 8

What are antagonists?

Answer 8

Competes with the natural ligand, so it can’t bind to the cite to activate the receptor

Question 9

Define Affinity

Answer 9

How strongly the ligand/drug binds to receptor

Question 10

How can affinity be tested?

Answer 10

Using radiolabelling

Question 11

What does the value of KD mean

Answer 11

Concentration at which 50% of the receptors are occupied

Question 12

Define efficacy

Answer 12

Measure of the maximum bological effect that a drug can produce as a result of binding to the receptor

Question 13

Define potency

Answer 13

A measure of the concentration of a drug to cause a specific effect

Question 14

How is potency of antagonist determined?

Answer 14

By measuring agonist efficacy in the presence of different antagonist

Question 15

Define Desensitisaiton

Eg opioid abuse

2 points

Answer 15

• Agonist that bind strongly to a receptor switch it on, but then may block the receptor for a long period of time.
• They are acting as agonists and then antagonists.

Question 16

Define Sensitisation

Giving beta blockers for a prolonged period of time

2 points

Answer 16

• Antagonists tend to be slow to add and slow to leave
• The cell synthesises more receptors to compensate for the receptors that are blocked.

Question 17

What is Lipinski rule of 5?

Answer 17

1. Molecular weight < 500
2. HBD max 5
3. HBA max 10
4. log P < 5

Question 18

What is Verber’s rule?

Answer 18

Rotatable bonds < 10

Question 19

What is eflux?

Answer 19

Process of removing waster from the brain

Question 20

3 ways of transporting a drug to the brain

Answer 20

1. Passive diffusion
2. Active transport (attaching to a transport protein)
3. Receptor-mediated transcytosis

Question 21

What is Receptor-mediated transcytosis?

Answer 21

Receptor attaches to a molecule and travels with the molecule through BBB

Question 22

What is free drug hypothesis?

Answer 22

Free drug concentration at the cite of action is responsible for pharmacological activity in vivo and at steady state and in the absence of active transport the free drug concentration is the same on both sides of any biomembrane (except BBB)

Question 23

What drugs for CNS need special consideration of lipophilicity?

Answer 23

Lipophilicity helps CNS penetration but too much will result in a high efflux

Question 24

What is the rule of 4?

Answer 24

• Compounds of Mr < 400
• Total number of N and O atoms < 4
• Basic pKa < 8
• Those are unlikely to be P-gp substrates

Question 25

How does H-bonding affect drugs accessing CNS?

3 points

Answer 25

• H bondng = lower Kp
• Lower rate of permeation: poorer lipid solubility, increased P-gp binding
• Lower K_{p,uu}

Question 26

2 main stategies in antagonist design

Answer 26

1. Design a drug that is the right shape & main interactions to bind to the receptor binding site - prevents binding of agonist
2. Make new interactions with different parts of the binding site that are not used by the agonist

Question 27

What do protein kinases do?

Answer 27

Catalyse the transfer of phosphate group from ATP to a specific molecule