drug development

Question 1

what are contract research organisations?

Answer 1

companies performing specific parts of the drug development process e.g. organising and running clinical trials

Question 2

what is a lead compound?

Answer 2

molecule that acts specifically and selectively with protein target

Question 3

what are some optical approaches used to determine receptor activity?

Answer 3

• measuring fluorescent emissions

- measuring light absorption

Question 4

Lead finding

Answer 4

high frequency + automated screens against chemical libraries
screen = performing assay on cloned gene generating target

Question 5

what is combinatorial chemistry?

Answer 5

synthesising multiple drugs that are derivatives of an initial molecule of interest

Question 6

what does exploratory toxicology consist of?

Answer 6

• general toxicity –> in silico and in vitro
• preliminary genotoxicity - predict whether drug will cause dna mutations?
• preliminary toxicity -> in vivo

Question 7

what does exploratory safety consist of?

Answer 7

• off target binding profile –> any unpredicted side effects?
• preliminary cvs safety
• preliminary cns safety - toxicity of small molecules that may enter cns?

Question 8

describe the ames test

Answer 8

1. isolate strains of salmonella that cannot grow on a medium missing histamine
2. apply drug on medium
3. bacteria grows? - may have acquired mutation reversing effect
   so drug has potential to cause mutations

Question 9

arrhythmia biomarker

Answer 9

drugs that can bind to hERG k+ channel give rise to long QT syndrome in patients = electrophysiology
so drug can give rise to cardiac arrhythmia

Question 10

how long do preclinical studies for small molecules take?

Answer 10

4-4.5 years

Question 11

how long do preclinical studies for biomolecules take?

Answer 11

2-2.5 years

Question 12

what is exaggerated pharmacology

Answer 12

drug having a more extreme reaction than expected. relates to high specificity and effectiveness.

Question 13

what is a cytokine storm?

Answer 13

massive immune reaction after injecting drug for 1st time

leads to massive organ failure

Question 14

what is the irwin activity screen for rats?

Answer 14

• test if drug has entered cns and exerted any effects there

observing behaviour, respiratory rate, heart rate, muscle tone, motor coordination etc.

Question 15

what is a major metabolite

Answer 15

metabolite accounting for >10% of parent compound - may have to synthesise and test separately

Question 16

DEFINE: pharmacodynamics

Answer 16

study of the ability of a drug to exert its effect on intended target

Question 17

phase I of clinical development

Answer 17

8-20 healthy volunteers 
minimal dose 
how safe is the drug?
how well is the drug tolerated? - any side effects
pharmacokinetics

Question 18

phase II of clinical development

Answer 18

low 100s of patients/volunteers
test effectiveness
test concentration needed for effectiveness

Question 19

phase III of clinical development

Answer 19

lasts for several years
1000+ patients
multi centre + multinational
broadening patient groups to which the drug is administered
toxic side effects, tolerance, pharmacokinetics?
compare to standard treatment
randomised and blind trials

Question 20

what is hydromorphine?

Answer 20

narcotic painkiller

taking with alcohol -> respiratory depression -> overdose

Question 21

what are the causes of drugs failing to be registered?

Answer 21

• not economically viable
• drug metabolism and pharmacokinetics - decreased strength of drug
• no improvement in efficacy in patients