pharmacodynamics - bioassays

Question 1

bioassay definition

Answer 1

tests to establish if a particular candidate molecule interacts with the target identified

Question 2

what are the 2 types of bioassay?

Answer 2

in vitro and in vivo

Question 3

what are in vitro bioassays + what do they test for?

Answer 3

tests carried out on isolated target molecules, cloned cells, tissues, organs or microorganisms
this measures the interaction of the drug with the target

Question 4

give 2 advantages of in vitro bioassays

Answer 4

• more suitable for routine testing (used in HPT screening)
• results are easier to rationalise as less factors are involved

Question 5

give 3 disadvantages of in vitro bioassays

Answer 5

• doesn’t demonstrate a physiological/clinical effect
• cannot identify side effects
• cannot be used to test prodrugs

Question 6

how can in vitro bioassays on enzymes be useful?

Answer 6

can identify competitive/non competitive inhibition - strength of inhibition can be measured as IC(50), based on concentration
- smaller concentration of inhibitor needed to reduce enzyme activity by 50% (hence IC50) = better inhibitor

Question 7

how can in vitro bioassays on receptors be useful?

Answer 7

allows investigation of affinity, efficacy and potency of drug

Question 8

how are in vitro bioassays on receptors normally carried out?

Answer 8

it is difficult to isolate membrane bound receptors, many denature/lost 3D shape, so typically these tests are done on whole cells/tissues/organs

Question 9

what are in vivo bioassays + what do they test for?

Answer 9

tests are carried out on live animals/humans (clinical trials)
these test the effectiveness of the molecules as drugs, as a physiological effect can be observed, as well as drugs ability to reach + interact with target
this is also the only way to find side effects

Question 10

how has modern technology improved patient testing?

Answer 10

transgenic animals/genetically modified animals are used to replicate drug tests on patients, by genetically modifying the animals to develop particular conditions that are treated in the trial

Question 11

therapeutic ratio/index definition

Answer 11

compares the dose level of a drug that is lethal to 50% of the sample (LD(50)) vs dose level required to produce a desired effect in 50% of sample (ED(50))
therapeutic ratio = LD(50) / ED(50)

Question 12

what is the ideal therapeutic ratio?

Answer 12

larger therapeutic ratio = safer drug, means effective dose is very low, fatal dose is very high

Question 13

give a disadvantage of drugs with low therapeutic ratios?

Answer 13

often more expensive to administer as it needs to be done by a trained professional e.g. dr or nurse, and in a hospital, requires careful monitoring

Question 14

why is in vivo testing important for determining therapeutic ratio?

Answer 14

this is how ED(50) must be determined (not LD(50)!!)