Lecture 11.1: Drug Discovery

Question 1

What are New Compounds?

Answer 1

• Newly synthesised compounds or
  isolates from natural sources
• High throughput screening

Question 2

Hoe can Existing Analogues give rise to new drugs? Why is it done?

Answer 2

• Modification of existing molecules
• Structural activity relationships
• May improve potency or selectivity or
  bioavailability

Question 3

What is Informed Design of a New Drug?

Answer 3

When a new drug is designed to target a particular biological function

Question 4

Timeline of the development of new
drugs (4 Stages)

Answer 4

• Drug Discovery (3-5 yrs)
• Pre-clinical (1-2 years)
• Clinical Trials: Phase I, II & III (6-7 yrs)
• Regulatory Approval (1-2 years)

Question 5

What is covered in Pre-clinical Studies? (3)

Answer 5

• Pharmacology (in-vitro and in-vivo studies)
• Pharmacokinetics (metabolites, bioavailability, route of
  administration, rate of elimination)
• Toxicology

Question 6

What happens in Phase I Studies?

Answer 6

• Basic parameters established e.g. route of admin,
  tolerability
• Generally healthy individuals involved
• First doses very small
• Standard haematology, clinical biochemistry, ECG etc
• C14 or H3 studies to identify metabolism

Question 7

What happens in Phase II Studies?

Answer 7

• Investigation of detailed pharmacology, in volunteers
  with the intended condition
• Looking to establish a dose-response effect
• Studies may identify a beneficial effect – but placebo
  not necessarily given
• Additional studies for complex drug interactions/
  polypharmacy

Question 8

What happens in Phase III Studies?

Answer 8

• Large, multicentre, placebo-controlled (or the existing
  gold-standard)
• Randomisation
• Identify side effects (Type A = unwanted, Type B =
  idiosynchratic)

Question 9

What is a Crossover Study?

Answer 9

A longitudinal study in which subjects receive a sequence of different treatments

Question 10

What is a Parallel Group Study?

Answer 10

A type of clinical study in which two or more groups of participants receive different interventions

Question 11

What happens in Phase IV Studies?

Answer 11

• Post-marketing systematic surveillance (efficacy and
  ADRs)
• Benefits and risks may only become fully established
  after a drug has been marketed
• Pharmacovigilance in the UK

Question 12

In the EU, new medicines have to be approved by?

Answer 12

European Medicines Agency (EMA)– analogous to FDA in USA

Question 13

EMA receives advice from the…?

Answer 13

Committee for Medicinal Products for Human Use (CHMP)

Question 14

What was established to replace the Medicines Commission (MC) and the Committee of Safety of Medicines (CSM) in the UK?

Answer 14

UK Commission on Human Medicines (CHM)

Question 15

What is the MHRA?

Answer 15

Medicines and Healthcare products Regulatory Agency