Drug Discovery and Development

Question 1

What is the typical drug development timeline?

Answer 1

Discovery/Basic research
Preclinical studies (animal)
-- [Regulatory Review: request to do on humans] --
Clinical Testing (phase 1, 2, 3)
-- [Regulatory Review: request to market drug] --
Pre-launch activities
LAUNCH
Post-Marketing Studies (phase 4)

Question 2

What are two examples of drug-drug interactions that have been withdrawn from the market?

Answer 2

1. Sorivudine: Antiviral, stopped 5-fluorouracil metabolism (15 deaths in Japan)
2. Terfenidine: antihistamine when with ketoconazole. Leads to cardiotoxicity

Question 3

What are two examples of unexpected toxicity reactions that caused the drugs to be withdrawn from the market?

Answer 3

1. Troglitazone: for non-insulin dependent diabetes (severe hepatotoxicity)
2. Rofecoxib: selective COX-2 inhibitor for chronic pain relief. (Increased heart attack and stroke).

Question 4

What are the two main reasons for failure during drug development?

Answer 4

1. Inappropriate pharmacokinetics

2. Lack of efficacy

Question 5

What are the 6 ways a drug may be discovered?

Answer 5

1. From herbal/traditional remedies
2. Empirical Approach
3. Rational Drug design
4. Prodrugs/analogs/metabolites of existing drugs
5. Serendipity-chance observation
6. Genomics

Question 6

What are 3 example s of herbal remedies?

Answer 6

Morphine (Opium poppy)
Digoxin/digitoxin (foxgloves)
Salicylic acid (willow bark)

Question 7

What are anti-cancer drugs and Cyclosporin (an immunosuppressant) an example of?

Answer 7

An empirical approach to drug discovery.

Question 8

Describe what rational drug design involves.

Answer 8

Understanding the cellular/molecular basis of diseases then using computer technology to determine 3D structure of receptor to design agonist drug.
E.G: Propranolol (beta-blocker), Cimetidine (Hydrogen-antagonist)

Question 9

What is aspirin and paracetamol an example of?

Answer 9

Prodrug. Aspirin is salicylic acid with an acetyl group (or else it is a gut irritant). Paracetamol is a derivative of phenacetin which is an irritant to the kidneys.

Question 10

Describe serendipiity drug development.

Answer 10

By chance observation.

Penicillin, valproate, sildenafil (viagra)

Question 11

Describe the 2 main phases of a drug development process.

Answer 11

Pre-clinical:
- animal studies

Clinical:
- Phases 1-4

Question 12

In pre-clinical studies, what is assessed?

Answer 12

Pharmacology, ADME, toxicology.

Then using this info, does the drug need to be re-designed?

Question 13

Describe the clinical phases process.

Answer 13

Phase 1: Small number of healthy volunteers/patients

Phase 2: Several hundred patients with the specific disease

Phase 3: Several thousand patients
- help to refine dose, safety and efficacy

Phase 4: Post-marketing surveillance