Please enable JavaScript.
Coggle requires JavaScript to display documents.
Theme Four (Making a drug (Discovery (4-8)
Therapeutic concept to…
Theme Four
Making a drug
Discovery (4-8)
- Therapeutic concept to molecule
Development
- Molecule to registered product
- Pre-clinical (1)
- Clinical trials (6.5)
- Registration (1-2)
-
-
Generics
- Bio equivalence = everything is the same, comparable
- Biosimilars =bioequivalence for biological shit
Try for one indication first and then trial later
- Post-marketing studies (docetaxel)
- TGA approval
- Scheduled
- ARTG
TGA
Quality
- Quality = formulation (design),
synthesis, storage life, pharmacokinetics
- Synthesis = sources
E.g. Taxol from ancient tree treating cancer = no solubility,
low yield, habitat destruction :
Efficacy and safety
- Pharmacokinetics = dosing, metabolism,
elimination, administration, effects, VD, drug-drug
- Animal models = transgenics (put in genes)
E.g. ACV1
= not great in humans
Toxicity
- Exploratory = see what can happen
- Regulatory toxicity = satisfies requirements,
needs licences, etc.
Thalidomide
- pregnancy
- no limbs
- changed regulatory stuff
Teratogenic effects = unmasked
many species testing
Roaccutane
- needs to take contraception
- teratogenic
-
-
Clinical Development
Good clinical practice
- Quality control standards
- Outlines responsibilities =
sponsors, investigators, ethics
Informed consent = GCP
- Know whats gonna happen to you
- Free - willed consent
- Comprehensive language (yr 6 lang)
-
-
-
Feasibility
- Medical need
- Are they new ideas
- Rate of success
- Competitors
- Current reputation
- Epidemiology
Orphan diseases
- Drug use in the treatment of rare diseases
Patents
- Owner has exclusive marketing rights
- 20 yrs + 5 yr extension
Natural sources
- Plants and animals sometimes
synthesise shit normally
= no work needed
Secondary metabolites
- Primary metabolite = something used for metabolism
- Secondary = not essential for growth and development
- contributes to 'survival' tings. venom etc.
Plants
- Plants make for
25% of clinical drugs
Alkaloids
- basic nitrogen
- bitter
- -ene
-
-
Minerals
- Iodine = thyroid
- Copper = reduce microbes
Animals
- Hormones
(insulin derived from pigs)
- Heparin (anti-coagulant)
- Venoms and toxins
Snakes
E.g. Captopril
- Drops blood pressure
- Brazilian pit viper
- ACE inhibitor
Bradykinin
- Drops BP
- Slow contraction of other
smooth muscles
- Bradykinin not inactivated
Neurotoxic
- Nervous system
- Paralysis leading to respiratory failure
Cone snails
- ziconotide
- non-opioid drugs
- N-type calcium blocker
Minoxidil
- Hypertension meds
- Serendipity = hypertrichosis = hair growth
Rational design
- knowledge of target and ligand to create
a compound to achieve effect
- beta-blockers = treats angina from
not enough oxygen
- b1 receptor = decrease sympathetic
- isoprenaline > adrenaline > NA
- Propranolol = blocked b1 but not b2
- Practolol
- Atenolol = b1-selective
The PBS
- PBS listing happens after registration
- cost effectiveness
- 8-12 months
History
- 100 yrs ago
- RPBS = repatriation (war veterans)
- 1944 = Pharmaceuticals benefits act
Submissions
- Cost minimisation = drug has same
standard of care as another
- Cost effectiveness = argue that one
is better than another
Sections of submission
- Disease area, main
comparator, advantages etc.
- Clinical trial data
- Economic model/translation
= model income etc.
- Pricing and utilisation
-
-
-
- Branded medicine in first yr = 45% = 50 a pack
- Goes down to 37 a pack
- 10 to 12 billion dollars
-
-