Intro to Drug Discovery Flashcards
What is a drug?
A substance that has a physiological effect when introduced to the body
what can a drug be used for?
Diagnosis, treatment, prevention of disease
Can drugs vary in sizes?
YES- some drugs have Mr as small as 7- lithium all the way to 150000
How is dimorphic different to morphine?
has acetyl groups- allows better brain penetration
what is dimorphine metabolised to in the body?
Morphine
Des codeine have a similar structure to morphine?
YES- smaller
Is naltrexone similar to morphine chemically?
YES- increased in size of methyl group
Which overdose can Naltrexone treat and how?
opioid OD
- works as an antagonist for the receptor opioids bind to as agonists
- competitive inhibition–> opioids cant bind
Is Naloxegol similar to Morphine and what does it do?
YES
prevents constipation in patients with opioid use- reduces absorption in the GIT
What is loperamide and what does it do?
- Immodium
- Extremely potent opioid agonist
- treats diarrhoea- has very little systemic exposure so mostly absorbed in GIT
Drug discovery can be split into 2 parts?
- drug discovery- finding a compound suitable for clinical trials
- drug dev- testing this agent for use in clinic
What are the 8 steps in drug development?
- target ID
- hit ID
- lead ID
- Lead optimisation
- pre-clinical dev
- clinical dev 1,2,3
- launch
- post launch- pharmacovigilance
What must the drug demonstrate tone progressed into clinical trials?
- desired biological effect
- suitable pharmacokinetics e.g. solubility, permeability
- likely to be well tolerated by patients
What do severe toxicological effects do to the drug process?
stop the whole project
What is NOAELs?
No Observable Adverse Effects Limits
What do phase 1 of clinical dev involve?
phase 1- demonstration of exposure + assessment of safety
What does phase 2 of clinical dev involve?
2a- proof of principle- does the drug alter the target
2b- prof of concept- does drug have impact on disease progression
what does phase 3 of drug dev involve?
demonstration of efficacy & safety
What % of compounds are likely to be approved for clinical use?
10%
What is multi- parameter optimisation?
- dissolution
- absorption
- interactions with target proteins
- interactions with other proteins
- metabolism
- distribution
- excretion
What is DMTA cycle?
Design compound
Make compound
Test compound
Analyse compound
what is a Hit compound?
a compound with biological activity in a bias model
what is a Lead compound?
a comp with biological activity in in vitro models
What is a Candidate drug?
a comp with an overall profile consistent with the target product profile
