Term
| what are the general steps in new drug synthesis |
|
Definition
discovery and synthesis of new molecule
in vitro studies determine effective dose
animal testing
IND
clinical trials (3 phases)
data gathering phase
approval |
|
|
Term
| what is the information gathered for pre-clinical safety and toxicity (8) |
|
Definition
acute toxicity
subacute toxicity
chronic toxicity
effects on reproduction: cellular and behavorial
carcinogenicity: 2 years looking into prolonged use
mutagenicity: effect on genetically stable bacteria or mammal cell culture
investigaive toxicology: determine MOA of toxic actions
quantative estimates |
|
|
Term
|
Definition
| efects of large single dose up to lethal dose. max tolerated dose |
|
|
Term
|
Definition
| effects of multiple doses over time in ratio to the expected clinical duration |
|
|
Term
| what are the wuantative estimates in teh pre-clinical safety and toxicity assessment |
|
Definition
no-effect dose: max dose at which toxic effect is not seen
minimal leathl dose: smallest dose that is observed to kill any animal
median lethal dose (LD50): dose tha tkills approx 50% of animals |
|
|
Term
| what are limitations during the pre-clinical safety and toxicity testing |
|
Definition
toxicity testing is time consuming and expensive
large numbers of animals are used which is mean
extrapolation of toxicity from all species tested has a high perdictive value to statistical reasons, rare adverse effects are unlikley to be detected |
|
|
Term
| what drug testing design must be used for human approval, explain it |
|
Definition
| crossover: alternating periods of administration of test drug, placebo, and standard treatment |
|
|
Term
| how must human test subjects be chosen |
|
Definition
large enough population over sufficient period of time
presence of other diseases and lifetyle choices can affect the study so you have to randomize
minimize subject and observer bias and weed out placebo effect results. double blind can help this out |
|
|
Term
| what does the FDA mandate about drugs, what is concerning about this |
|
Definition
drugs must be safe and effective
safe means different things to doc, patient, and society. complete absence of risk is impossible
public assumes FDA approval means free of serious or all side effects |
|
|
Term
| what is IND, when does it happen, what must be done by this point |
|
Definition
new drug is ready for trial in humans and must be filed with the FDA
need acute and subacute animal toxicity studies
chronic safety testing can be done in animals and humans at the same time
volunteers and patients informed of status of drugs and risk and be allowed to decline at any time |
|
|
Term
| what happens in clinical trial phase 1, what is the goal |
|
Definition
effect of drug dose in a small number of healthy volunteers unless drug has a toxic risk (then use sick volunteers) non-blind
determine if humans and animals have the same response, show perdictable toxicities |
|
|
Term
| what are the chances of getting past clinical trial phase 1 |
|
Definition
| you can usually find a non toxic dose so pretty good |
|
|
Term
| what happens in phase 2, how is it done, what is the goal |
|
Definition
drug is studied in a small number of patients with the disease to determine EFFICACy
single bind with placebo or older active drug usually in a university hospital
find a broader range of toxicities |
|
|
Term
| what are the chances of getting past clinical trial phase 2 |
|
Definition
| not so much most drugs fail here |
|
|
Term
| what happens in clinical trial phase 3, how is it done |
|
Definition
evaluation of a large population to judge safety and efficacy
double blind cross over study performed in the natural setting for the drug future use
goal is to have success and get permission to market in a controlled setting |
|
|
Term
| what happens in clinical trial phase 4, what is the goal |
|
Definition
begins after marketing approval
postmarking surveillance program
important side effects at incidence f 1:10,000 or less are formed |
|
|
Term
| what are the considerations when evaluating a clinical drug study |
|
Definition
ethical considerations: adequate safegaurds, proper concent
statement of objectives: what are they? are they clear?
experimental methods: were they ok? were they sensitive?
statistical methods: how were patients selected? were placebo positive controls used?
conclusions: does the data justify them? does the drug have a cost, efficacy, or safety advantage over the old drug?
look at peer reviews |
|
|
Term
| define an orphan drug, what is the problem, how was it fixed |
|
Definition
drugs for rare diseasees
difficult to research, develop, and market
kids diseases, not as cost effective, less people buying the drug, pathology gets little attention
orphan act is incentive to develope these drugs |
|
|
Term
|
Definition
| required when drug is intened for prolonged use. tested for 2 years |
|
|
