Intro to Drug Discovery

Question 1

What is a drug?

Answer 1

A substance that has a physiological effect when introduced to the body

Question 2

what can a drug be used for?

Answer 2

Diagnosis, treatment, prevention of disease

Question 3

Can drugs vary in sizes?

Answer 3

YES- some drugs have Mr as small as 7- lithium all the way to 150000

Question 4

How is dimorphic different to morphine?

Answer 4

has acetyl groups- allows better brain penetration

Question 5

what is dimorphine metabolised to in the body?

Answer 5

Morphine

Question 6

Des codeine have a similar structure to morphine?

Answer 6

YES- smaller

Question 7

Is naltrexone similar to morphine chemically?

Answer 7

YES- increased in size of methyl group

Question 8

Which overdose can Naltrexone treat and how?

Answer 8

opioid OD

• works as an antagonist for the receptor opioids bind to as agonists
• competitive inhibition–> opioids cant bind

Question 9

Is Naloxegol similar to Morphine and what does it do?

Answer 9

YES

prevents constipation in patients with opioid use- reduces absorption in the GIT

Question 10

What is loperamide and what does it do?

Answer 10

• Immodium
• Extremely potent opioid agonist
• treats diarrhoea- has very little systemic exposure so mostly absorbed in GIT

Question 11

Drug discovery can be split into 2 parts?

Answer 11

1. drug discovery- finding a compound suitable for clinical trials
2. drug dev- testing this agent for use in clinic

Question 12

What are the 8 steps in drug development?

Answer 12

1. target ID
2. hit ID
3. lead ID
4. Lead optimisation
5. pre-clinical dev
6. clinical dev 1,2,3
7. launch
8. post launch- pharmacovigilance

Question 13

What must the drug demonstrate tone progressed into clinical trials?

Answer 13

1. desired biological effect
2. suitable pharmacokinetics e.g. solubility, permeability
3. likely to be well tolerated by patients

Question 14

What do severe toxicological effects do to the drug process?

Answer 14

stop the whole project

Question 15

What is NOAELs?

Answer 15

No Observable Adverse Effects Limits

Question 16

What do phase 1 of clinical dev involve?

Answer 16

phase 1- demonstration of exposure + assessment of safety

Question 17

What does phase 2 of clinical dev involve?

Answer 17

2a- proof of principle- does the drug alter the target

2b- prof of concept- does drug have impact on disease progression

Question 18

what does phase 3 of drug dev involve?

Answer 18

demonstration of efficacy & safety

Question 19

What % of compounds are likely to be approved for clinical use?

Answer 19

10%

Question 20

What is multi- parameter optimisation?

Answer 20

1. dissolution
2. absorption
3. interactions with target proteins
4. interactions with other proteins
5. metabolism
6. distribution
7. excretion

Question 21

What is DMTA cycle?

Answer 21

Design compound
Make compound
Test compound
Analyse compound

Question 22

what is a Hit compound?

Answer 22

a compound with biological activity in a bias model

Question 23

what is a Lead compound?

Answer 23

a comp with biological activity in in vitro models

Question 24

What is a Candidate drug?

Answer 24

a comp with an overall profile consistent with the target product profile