Drug discovery & development Flashcards
Properties of arecoline…
- intense SM contraction
- acetylcholine agonist
- natural alkaloid
- chewed by humans as stimulant
Properties of penicillin…
- Mould on bread used to treat wounds in ‘ancient’ times
- 1870 England mould covered culture did not produce bacteria
- Joseph Lister described AB property on human tissue
- 1928 Alexander Fleming isolated penicillin from A. notatum
- 1938 Howard Florey produced stable form of ‘penicillin’
- 1941-1943 industrial production of penicillin began
- 1952 acid stable oral penicillin developed
What is curare?
paralysing poison (Sth American Indians) acts on voluntary muscles -> asphyxiation
How did the development of curare come about?
1596 - 1st reported by Walter Raleigh
1825 - shown if animal kept breathing, would not die
1850 - shown to be effective in tetanus & strychnine poisoning
modern med. - used in anaesthesia as muscle relaxant
Why didn’t American Indians die after eating animals killed with curare?
because molecule too big to cross gut mucosa
Why is herion useful?
it gets converted to morphine in the body -> powerful analgesic
When was morphine 1st made synthetically? Use?
1874, to treat severe pain
The discovery of ivermectin…
- 1975 Merck lab workers studied soil samples (golf course) from Japan
- soil had high [macrocyclic lactone] produced by fungus Streptomyces avermitilis - antihelmintic (killed round worms)
What was invermectin initially developed to treat?
African River Blindness (Onchocerca volvulus) - very effective & used in mass drug treatments
First step in drug development…
Screening, examining & synthesising 10,000 - 25,000 chemical entities ~ 3 years
Development and testing involves what? How many years?
Preclinical tests (animals) using 10 - 20 chemical entities ~ 7 years. Also includes phase I, II & III
Phase I of drug development…
5 - 10 compounds 1 year. Small group of exp. animals to assess SAFETY, TOLERABILITY & PHARMOKODYNAMICS
Phase II of drug development…
2 - 5 drugs Tests EFFICACY (how well drug works) larger group of animals test & control groups are same age, sex, weight randomised, blinded (single), placebo
Phase III of drug development…
2 drugs ~ 2 years
larger group - field trials 100 - 1000’s subjects
different countries, geo. areas, climatic zones
Phase IV of drug development…
postmarketing surveillance
ongoing safety monitoring etc.
reporting adverse reactions
What is the APVMA?
Australian Pesticide and Veterinary Medicines Authority
Adverse reactions to drugs get reported to who? What actions may be taken?
APVMA - may cancel or review registration of drug, and/or change conditions of use of product
What are some roles of Independent Research consultants…?
- specialists in defined area
- hired by companies to undertake specific studies (eg. efficacy)
- have their own facilities
- consultants run study under Good Clinical Practice (GCP) protocols
What is GCP? Which organisation is it closely associated with?
Good Clinical Practice closely associated with the Veterinary International Committee for Harmonisation (VICH)
What principles does the VICH uphold?
Internationally accepted guidelines for the study of veterinary therapeutics (includes Aus, USA, EU and Japan)
What are some other guidelines of GCP?
- rigid recording requirements
- reduce repeats of similar/same studies for international registrations
- reduce no. of animals used in product development
- minimise costs
- minimise ethical dilemmas
What are some of the approvals/regulations required for consultants undertaking GCP efficacy studies?
- Animal Experimentation Ethics Committee (AEEC)
- conform to Universities Federation for Animal Welfare (UFAW)
- obtain quarantine authority approval (AQIS-Approved Premesis & Personnel)
What are the 4 different roles of peeps involved in GCP studies?
- Sponsor (funding clinical study undertaken by independent consultant)
- Monitor (company rep. to make sure investigator adheres to GCP)
- Investigator (scientist with specialist skills on behalf of the company. NOT a company employee)
- Regulator (member of independent organisation assessing applications for new drug registration. In Aus it’s the APVMA)
GCP recording mantra…
“If it has not been written down, then it never happened”
