week 8 Flashcards
identify two common bush medicines
- red bloodwood
2. emu
use of redwood as medicine
oil - antiseptic, astringent, parasiticide
dry resin & gum = tannin = diarrhoea & inflammation
use of emu
oil - high omeg-3 = dry skin = anti-inflammatory
recognising importance of bush medicine
kakadu plum = ownership = highest natural source of VC
List the stages of modern drug development
- drug discovery
- preclinical development
- clinical development
- regulatory approval
- phase 4
define rational drug design
involves systemic approach of using protein-structure techniques for the discovery of new drug ligand against drug targets = functional role in cellular processes & 3D structural information may be known or unknown
- find medicine based on knowledge of target
steps in drug discovery (2–5yrs)
- target selection
- identification; is it drugable?
- validation; test hypothesis = understand cellular mechanism in disease process
- hit/lead identification
= testing millions of compounds at single dose concentration against a target using HTS
= hit compound optimised by changing chemical structure to produce lead compound
- lead optimisation
= desired characteristics optimised such as better efficacy, potency & pharmacokinetics & file intellectual property claims
define structure based drug design (SBDD)
design of new drugs based on the knowledge of the structure characteristics of the target protein of nucleic acid = using x-ray crys.. or NMR etc
what are the three types of drug design
- rational drug design
- structure based drug design
- ligand based drug design (more specific than rational)
define ligand based drug design
= used in the absence of the receptor 3D information
- relies on the knowledge of molecules that bind to the biological target of interest
- structure activity relationships & pharmacophore modelling are used
factors to consider before human trials = pre-clinical trial
- toxicological tests to eliminate genotoxicity = chromosomal damage
- PK/PD studies to link plasma conc to pharmacological & toxicological effects
- chemical & pharm development for large scale synthesis, drug stability & formulation
- safety pharmacology i.e. any hazardous acute effect
requirements for pre-clincal trials to be able to move to clinical trials
- at least 2 animal species
- important stage to study the suitability of safety profile & determine if it can be tested in humans
how many stages in clinical development
3
4 possible objectives of clinical trials
- To diagnose or detect disease
- To treat an existing disorder
- To prevent disease or early death
- To change behaviour, habits or other lifestyle factors
what must clinical trials be approved by
Human Research Ethics Committee (HREC)
7 principles of clinical studies
- social & clinical value
- scientific validity
- fair subject selection
- favourable risk benefit ratio
- independent review
- informed consent
- respect for potential & enrolled subjects
number of participants in phase I clinical trials
20-40
how many people in these stages
phase i
Phase ii
phase iii
phase iv
toxicity: 20 - 40
efficacy: 30 - 100
confirmatory: greater than 100
postmarking: greater than 10 000
aim phase I of clinical trials
- Identify max tolerated dose (MTD)
- dose-limiting toxicities (DLTs)
- recommended phase II dose (RPTD)
Phase II clinical trial aim
-At recommended phase II dose, the efficacy is tested & the toxicity profile of the agent is refined
oScreen out ineffective drugs
oSending promising agents to Phase III
aim of Phase III of clinical trial
study the efficacy in large groups or participants
- randomised & controlled
- double blinded
- monitor adverse affects
- compare treatments
- then TGA approves
how does a randomised control trial work
- The experimental group = receiving the intervention that is being tested
- Comparison group/ control = receiving an alternative treatment
aim of phase IV
= post-marketing surveillance
- after registration & marketing
- monitor in general population e.g., collect info on adverse effects
- monitor efficacy & safety
summary of phases
Phase0 - effect on body
Phase I - safety in humans
Phase II - effectiveness at treating diseases
Phase III - larger scale safety & effectivness
Phase IV - long term safety = ongoing
