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15 Cards in this Set
- Front
- Back
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What is the main reason for drug failure at lower phases of clinical trials |
toxicity |
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What are the other reasons for drug failure as clinical trials advance? |
- Efficacy
- Clinical Safety
- Marketing potential |
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Why are toxicology tests perfomed? |
- injury type
- mechanism of toxicity
- whether toxicity is reversible
- intrinsic factors of patient and drug that leads to toxicity e.g. age, sex, formulation |
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What are the levels of toxicology testing |
1. species/strain of animal 2. end point (response) 3. dose 4. route 5. duration of toxicity test |
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Describe the (1) species/strain level of toxicology testing |
- affects ADME
- different metabolites, proteins, enzymes etc in species
- hugely different internal environments such as organ function, structure even number |
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Describe the (2) End point (response) level of toxicology testing |
- what are the pharmacodynamic(/kinetic) responses
- type of toxicity e.g. direct, geno, immuno? |
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Describe the (3) dose level of toxicology testing |
- dosages can be predicted using dose-reponse curves (extrapolate data?)
- or parameters like ED50 and LD50
- repeated doses may not be given since effects may be cumulative => studied using population |
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Describe the "no effect level" of (3) dose level of toxicology testing |
- at the extreme left of the dose-response curve it is possible that the drug has no effect
- from there it's possible to determine a NOAEL - no observable adverse effect level. |
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In population dose testing at (3), what three types of doses can be investigated? |
1. pharamcology activity dose - dose for drug to have efficacy
2. sub-lethal toxicity dose
3. lethal dose |
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What factors affect the shape of dose frequency (bell-shape) curves? |
endogenous & exogenous factors
- cellular defence mechanisms
- saturation of the biochemical process that produces the toxic effect may induce a plateau |
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What are the two levels of the (5) duration of toxicology testing |
Two levels:
1. Acute toxicity test
2. Chronic toxicity test |
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Describe acute toxicity tests of the (5) duration of toxicology testing |
- find effects within short ttime of drug exposure
- usually single dose given @ various routes
- determine dose-reponse relationship / end points (response) e.g. LD50 |
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Describe sub-acute toxicity testing |
- exposure to drug for around 1~3 months
- exposure is frequent
- provide information on target organs & major toxic effects
- detect slow onset toxic effects |
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What are the consequences of sub-acute testing |
- indicates development of possible pathological lesions
- complete necropsy tests canbe performed
- a full analysis of bodily functions can be performed e.g. blood chemistry, haematology
- helps design experiments for chronic toxicity studies |
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What is the therapeutic index |
- ratio of dose that is required to produce a toxic effect and a therapeutic effect.
TI =(LD50)/(ED50)
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