Flashcards in Drug Toxicity II: Treatment and Prevention Deck (17):
How many stages of drug development are there? And what are there names?
1. Phase 1
2. Phase 2
3. Phase 3
4. Phase 4
4 Stages altogether
What is looked at in phase 1 of drug development?
1. Safety in humans
2. Body do to the drug (pharmacokinetics)
3. Drug do to the body (pharmacodynamics)
4. Might it work in patients
What is looked at in phase 2 of drug development?
1. Does it seem safe in patients
2. Does it seem to work in patients
What is looked at in phase 3 of drug development?
1. Does it seem really safe in patient
2. Does it really work?
3. Does it seem safe in a different group of patients?
4. Does it really work in a different group of patients?
What is looked at in phase 4 of drug development?
1. Is it truly safe?
2. How does it compare with similar other drugs?
What is the purpose behind Preclinical drug development testing?
1. Access genotoxic (toxicity) potential
2. Evaluation of chromosome damage in response to the drug
3. Carcinogenicity testing
4. Reproductive testing: pregnant female rabbits
What is measured in the preliminary toxicity testing?
1. Maximum non toxic dose (given for 28 days to 2 species)
2. LD50 examined
3. NOAEL and LOAEL tested
Lethal Dose- the dose to kill 50% of treated animals within a short amount of time
How do you work out the LD50?
1. Measure midway the toxic response curve
2. To where it measures the amount of Log [drug]
What does NOAEL mean and represent?
1. No observed adverse effect level
2. Highest concentration that does not cause toxic response
What does LOAEL mean and represent?
1. Lowest observed adverse effect level
2. Lowest concentration that produces toxic response
How do you calculate the HED (human equivalent dose) if the NOAEL of a rat was 100mg/kg for a 70kg man?
1. 100/6.2= 16mg/kg
(6.2 appears from animal dose based on surface area)
2. Therefore lowest HED= 16mg/kg
3. Apply ten fold safety margin
112mg in 70kg man
What is the therapeutic index?
The ratio of the dose of the drug that produces an unwanted (toxic) effect to that producing a wanted (therapeutic) effect
How do you work out the therapeutic effect?
Give an example of a drug with a small therapeutic index?
Give an example of a drug with a large therapeutic index?