Lecture 9 - drug development and discovery 1

Question 1

Key stages of drug development

Answer 1

1. basic research and target selection
2. pre-clinical research
3. clinical research (phase 1,2 and 3)
4. regulatory review

Question 2

what is the target selection for drugs?

Answer 2

includes receptors, enzymes and transport proteins

Question 3

what is lead finding?

Answer 3

• finding the lead compounds of the drugs by cloning target protein in human form

Question 4

what is primary screening?

Answer 4

used to prepare sets of homologues by combinational chemistry to identify structural features for selective binding to the target

Question 5

Exploratory safety measures (lead selection)

Answer 5

• predicting safety concerns by selecting a candidate
• this helps in the next steps towards study designs

Question 6

Regulatory safety measures (preclinical and clinical)

Answer 6

• provides a safety margin
• defines dose to start human trials and the max dose
• obtain regulatory approval of clinical

Question 7

What is LD50

Answer 7

experiment conducted in mice to determine the dose of a chemical that causes 50% death rate called median lethal dose.

Question 8

common rodent study

Answer 8

rat because it is easier to manipulate and has greater blood volumes

Question 9

common non-rodent study

Answer 9

beagle because it has consistent quality of health and low background pathologies

Question 10

what are the three dose groups for toxicology study?

Answer 10

1. low (no toxicology)
2. intermediate
3. high (toxicology expected in target organ)

Question 11

clinical pathology

Answer 11

• haematology/ clinical chemistry
• kidney and liver function
• coagulation

Question 12

what is histopathology?

Answer 12

• studying structural manifestation of disease under a microscope where these results are one of the most important parts on non-clinical safety measurements.

Question 13

what is pathology?

Answer 13

• large organ toxicity
• determining which organs are affected

Question 14

goal of preliminary toxicology?

Answer 14

tests eliminates genotoxicity and determines the non-toxic dose of the drug.

Question 15

goal of pharmacokinetic testing?

Answer 15

includes studies of absorption, metabolism, distribution and elimination in lab animals

Question 16

what does chemical and pharmaceutical development assess?

Answer 16

feasibility of large-scale synthesis and purification. assess stability of the compound under various conditions to develop a formula suitable for clinical studies

Question 17

what happens in the phase 1 clinical trial?

Answer 17

• tests if the drug is safe to humans and checks for any potential problems in physiological systems.
• sees if drug produces any unpleasant symptoms and pharmacokinetic properties
• conducted on small group of healthy volunteers

Question 18

what are the smaller groups within a clinical trial called?

Answer 18

cohorts
- first cohort given a small dose of the drug and dose adjusted for other groups

Question 19

where is phase 1 clinical trial conducted?

Answer 19

done in labs to investigate if the drug is hitting its target or changing at the level of a protein.
looks into how the drug will interact with other drugs or food

Question 20

what happens in phase 2?

Answer 20

• tested on 100-300 patients to test the efficacy in clinical situation and then establish a dose used for phase 3
• these studies cover several distinct clinical disorders to identify possible therapeutic indications for new compound.

Question 21

what happens in part 2 (part a)?

Answer 21

• exploratory study that has clinical efficacy
• tests pharmacodynamics or biological activity
• explores dose range
• conducted on patients or healthy volunteers

Question 22

what happens in phase 2 (part b)

Answer 22

• more definite dose range study in patients
• efficacy as the main focus
• used as pivotal trials for drugs treating life-long illnesses

Question 23

what happens in phase 3?

Answer 23

• double-blind and randomised trial
• performed on thousands of patients to compare the new drug with an alternative.
• these are very expensive to organise

Question 24

what happens in phase 3 (part a)?

Answer 24

• designed and executed to get statistically significant evidence of efficacy and safety as required by world organisations.
• includes post marketing study commitments
• presents data to the regulatory agencies to decide if drug is approved.

Question 25

what happens in part 3 (part b)

Answer 25

• study prior to approval with intended support of publications rather than registration

Question 26

what happens in phase 4?

Answer 26

• obligatory post marketing surveillance to detect any rare or long-term side effects from using drug in clinical environment for thousands of patients
• could limit use of drug in certain groups

Question 27

withdrawing drugs

Answer 27

• to do with risks of patients or commercial reasons
• risks or harms is the main reason with unexpected side effects that were not detected