Drug Discovery & Development

Question 1

Earliest traces on veterinary diseases

Answer 1

18th century
Rinderpest in cattle (1709)
Anthrax in cattle and humans (1712)
Foot & mouth disease in cloven-hooved animals (1755)

Question 2

What is the one-health initiative?

Answer 2

One-health recognises the inter-relationship between animal health, human health and environmental health

Question 3

What are economic factors to drug discovery?

Answer 3

Profit
Importance of diseases
Diseases in the developing world

Question 4

What are the approaches to drug discovery?

Answer 4

Bioassay-based
- Suitable bioassays
- Screening extracts
Target-based
- Drug target (receptor, enzyme, nucleic acid)
- Understanding biomacromolecules in disease
- Synthesis (agonists/antagonists or inhibitors)

Question 5

Process of Bioassay-based drug discovery

Answer 5

• Raw material
• Crude extract
• Bioactive extract
• Semi-purified fraction
• Pure compound
• Medicinal chemistry
• Clinical trials
• Licensing and marketing

Question 6

Stages of biological evaluation during bioassay-based drug discovery

Answer 6

• Bioactive extract
• Semi-purified fraction
• Pure compound

Question 7

Stages of bioassay-based drug discovery allowing chemical identification and characterisation

Answer 7

• Bioactive extract
• Semi-purified fraction
• Pure compound

Question 8

What raw material can be assessed through bioassay-based drug discovery?

Answer 8

• Medical Folklore
• Plants
• Microorganisms
• Marine sources
• Animals
• Venoms
• Toxins

Question 9

What is Artemisinin?

Answer 9

• Medical folklore ad plant kingdom
• Traditional Chinese medicine
• Herbal plant - Artemisia annua
• Crude extract effective against malaria parasite Plasmodium falciparum
• was isolated as active component in 1972 by Tu YouYou

Question 10

What is Cephalosporins?

Answer 10

• Bacteria and Fungi are good sources of bioactive compounds
• Cephalosporin C was derived from a fungus (Acremonium chrysogenum) found in the sewers in Sardinia
• Giuseppe Brotzu identified the compound responsible for the antibacterial action of the fungus
• 1948

Question 11

Example of venom and toxins bioassay drug discovery

Answer 11

• Animals, plants, snakes, spiders, insects, microorganisms
• Often extremely potent, with specific interactions with macromolecular target

Question 12

What is Teprotide?

Answer 12

• A nonapeptide in the venom of Bothrops jararaca
• In 1970, Sergio Ferreira discovered that the venom had antihypertensive effects compromised by teprotide
• Teprotide inhibits angiotensin-converting enzyme (ACE)
• Captopril developed from teprotide

Question 13

Purification and screening methods include…

Answer 13

Chemical extractions (methanol, dichloromethane, hexane)
Semi-purification (removes sugars and amino acids)
Screening for biological activity (screening of crude extracts for antimicrobial activity)

Question 14

What procedures are included in biological assays

Answer 14

Purification
Pre-clinical testing

Question 15

What is biological assay purification?

Answer 15

Separation and purification of individual compounds from the extract; screening for biological activity

Question 16

What is biological assay Pre-clinical testing?

Answer 16

Biological evaluation in vitro and in vivo; identification of mode of action

Question 17

What is chemical characterisation?

Answer 17

Structural elucidation

Question 18

What does high-performance liquid chromatography - mass spectrometry (HPLC-MS/MS) provide results for?

Answer 18

Gives the molecular weight and the molecular formula of chemical substrate

Question 19

What does nuclear magnetic resonance (NMR) spectrometry provide results for?

Answer 19

• Gives the carbon framework of the molecular and the environment of the hydrogens
• Gives information of the shape (conformation) of the molecule
• Can give information on how the compound binds to its target biomolecule

Question 20

What does lead optimisation develop?

Answer 20

Structure-Activity Relationships (SARs)

Question 21

What is an effective dose?

Answer 21

• Dose or amount of drug that produces a therapeutic response

Question 22

What is efficacy?

Answer 22

• Ability of the drug to elicit a response when it binds to the receptor

Question 23

What responses are established through clinical trials?

Answer 23

Toxicity
Efficacy

Question 24

Why is a marketing authorisation required?

Answer 24

• Is needed to sell or supply veterinary medicine

Question 25

What animal medications do not require a marketing authorisation?

Answer 25

• Small animals exclusively kept as pets
  -> Aquarium animals (in closed systems only)
  -> Cage birds
  -> Homing pigeons
  -> Terrarium animals (including reptiles, amphibians, arthropods free-living in domestic gardens)
  -> Small rodents
  -> Ferrets
  -> Rabbits

Question 26

What animals are not exempt from needing a Marketing authorisation?

Answer 26

• Chickens
• Ducks
• Turkeys
  (regarded as food animals)

Question 27

Medications which require marketing authorisation include…

Answer 27

• Antibiotics
• Psychotropic drugs

Question 28

Advantages of drugs from natural structures…

Answer 28

Novel structures
Possibly safer than synthetic drugs

Question 29

Disadvantages of natural product drugs…

Answer 29

Some products only available in small doses
Not every product drug can be synthesised
Semisynthesis