L2: Sources of drugs & their nature Flashcards
Learning Objectives: • List some key points in the history of the pharmaceutical industry • List the main sources of drugs, giving examples from each source • Describe the key stages in the drug discovery process • Explain what is meant by the term “structure-activity relationship” and why it is important in drug development List the four phases of clinical trials and explain the main purpose of each phase
What did Paul Ehrlich do in 1909 that showed syphilis can be treated with arsenical compounds?
Dying bacteria
What was developed in 1932 used to treat syphilis?
‘Protonsol’- the 1st sulphonamid antibacterial
What did Sir James Black lead in 1960s,70s & 80s?
The era of ‘rational drug design’
What drug was withdrawn in 1961?
Thalidomide- drug used to treat morning sickness in pregnant women
What was developed to revolutionise the drug discovery process in the 1990s?
High throughput screening & combinatorial chemistry
When was the human genome mapped?
2002
What is used now (<2000) to increase development of ‘biologicals’
Using antibodies instead of small molecules
First stage of the drug discovery process
Basic research
2nd stage of the drug discovery process
Identification of potential drug targets
3rd stage of the drug discovery process
Hypothesis generated
What are assay systems?
Way of measuring something
Considerations during the drug discovery process
Safety issues, ethical issues, cost, intellectual property
What is a chemical library?
A collection of chemicals that can be used for high throughput screening for drug development
What is high throughput screening?
Large quantities of chemical compounds put through robotic assay systems to test initial activity
What is combinatorial chemistry?
Synthesis process that enables the production of large numbers of related compounds
What is the 1st stage of combinatorial chemistry?
Molecular skeleton with 2 attachment points
What is the 2nd stage of combinatorial chemistry?
1st attachment point reaches with 3 different substituents
What is the 3rd stage of combinatorial chemistry?
Products of 1st reaction are mixed, then 2nd attachment reacted the same with the substituents
What is structure activity relationships (SARs)?
Used to predict biological activity from molecular structure
What is pre-clinical development?
Before drug has been administrated to humans
What is Phase 1 in clinical trials?
(Exploratory, first in human)
Chronic toxicity of drug assessed in at least 2 mammalian species
How many people does Phase 1 involve?
40-60 healthy people
Where is the location & placebo of phase 1?
- Location: Specialised clinical facilities
- Placebo: controlled, randomised, double-blind
What is Phase 2 in clinical trials ?
Efficacy, proof of concept & safety
Determine how clinically effective the drug is in patients to confirm safety
What does efficacy mean?
Power to produce a desired result
What is Phase 2a?
Exploratory
What is Phase 2b?
Confirmatory that efficacy is statistically significant
How many people involved in Phase 2a?
50-200
How many people involved in Phase 2b?
200-500
Length of time of Phase 2a?
Approx 1 year
Length of time of Phase 2b?
Approx 2 years
Importance of Phase 2b?
To confirm dose for Phase 3
What is Phase 3 of the clinical trials?
Confirmatory
Full scale evaluation of how EFFECTIVE & SAFE it is
Number of patients in Phase 3 ?
200-10,000
What is Phase 4 of clinical trials?
Ongoing
Continues after drug is licensed & on the market to monitor
