week 8

Question 1

identify two common bush medicines

Answer 1

1. red bloodwood

2. emu

Question 2

use of redwood as medicine

Answer 2

oil - antiseptic, astringent, parasiticide

dry resin & gum = tannin = diarrhoea & inflammation

Question 3

use of emu

Answer 3

oil - high omeg-3 = dry skin = anti-inflammatory

Question 4

recognising importance of bush medicine

Answer 4

kakadu plum = ownership = highest natural source of VC

Question 5

List the stages of modern drug development

Answer 5

1. drug discovery
2. preclinical development
3. clinical development
4. regulatory approval
5. phase 4

Question 6

define rational drug design

Answer 6

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

Question 7

steps in drug discovery (2–5yrs)

Answer 7

1. target selection

• identification; is it drugable?
• validation; test hypothesis = understand cellular mechanism in disease process

2. 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

3. lead optimisation

= desired characteristics optimised such as better efficacy, potency & pharmacokinetics & file intellectual property claims

Question 8

define structure based drug design (SBDD)

Answer 8

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

Question 9

what are the three types of drug design

Answer 9

1. rational drug design
2. structure based drug design
3. ligand based drug design (more specific than rational)

Question 10

define ligand based drug design

Answer 10

= 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

Question 11

factors to consider before human trials = pre-clinical trial

Answer 11

1. toxicological tests to eliminate genotoxicity = chromosomal damage
2. PK/PD studies to link plasma conc to pharmacological & toxicological effects
3. chemical & pharm development for large scale synthesis, drug stability & formulation
4. safety pharmacology i.e. any hazardous acute effect

Question 12

requirements for pre-clincal trials to be able to move to clinical trials

Answer 12

• at least 2 animal species

- important stage to study the suitability of safety profile & determine if it can be tested in humans

Question 13

how many stages in clinical development

Answer 13

3

Question 14

4 possible objectives of clinical trials

Answer 14

• To diagnose or detect disease
• To treat an existing disorder
• To prevent disease or early death
• To change behaviour, habits or other lifestyle factors

Question 15

what must clinical trials be approved by

Answer 15

Human Research Ethics Committee (HREC)

Question 16

7 principles of clinical studies

Answer 16

1. social & clinical value
2. scientific validity
3. fair subject selection
4. favourable risk benefit ratio
5. independent review
6. informed consent
7. respect for potential & enrolled subjects

Question 17

number of participants in phase I clinical trials

Answer 17

20-40

Question 18

how many people in these stages

phase i
Phase ii
phase iii
phase iv

Answer 18

toxicity: 20 - 40
efficacy: 30 - 100
confirmatory: greater than 100
postmarking: greater than 10 000

Question 19

aim phase I of clinical trials

Answer 19

• Identify max tolerated dose (MTD)
• dose-limiting toxicities (DLTs)
• recommended phase II dose (RPTD)

Question 20

Phase II clinical trial aim

Answer 20

-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

Question 21

aim of Phase III of clinical trial

Answer 21

study the efficacy in large groups or participants

• randomised & controlled
• double blinded
• monitor adverse affects
• compare treatments
• then TGA approves

Question 22

how does a randomised control trial work

Answer 22

1. The experimental group = receiving the intervention that is being tested
2. Comparison group/ control = receiving an alternative treatment

Question 23

aim of phase IV

Answer 23

= post-marketing surveillance

• after registration & marketing
• monitor in general population e.g., collect info on adverse effects
• monitor efficacy & safety

Question 24

summary of phases

Answer 24

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

Question 25

define placebo

Answer 25

= a substance, pill, or other treatment that appears to be a medial intervention but isn’t one e.g., sugar pill

Question 26

define nocebo effect

Answer 26

=based on negative expectations to the intervention e.g., if the participant is told that the tablet may cause headache & dizziness, the participant will feel the adverse effects even if allocated to the control arm (receiving placebo). Therefore, differently from placebo effect which is the positive effect, nocebo effect causes the negative effect

Question 27

define active placebo

Answer 27

no efficacy but can cause expected adverse effect = good way to avoid bias

Question 28

who approves vaccine

Answer 28

TGA

Evidence requirements are based on international guidelines developed by the European Medicines Agency (EMA)

Question 29

what advice does TGA use to register vaccine

Answer 29

Advisory Committee on Vaccines (ACV)

Question 30

list properties of promising drug target

Answer 30

• ability to bind to the drug
• the reaction produced
• specificity
• abundance target & location
• affinity
• function can me modulated by therapeutic agent