Drug Toxicity II: Treatment and Prevention

Question 1

How many stages of drug development are there? And what are there names?

Answer 1

1. Phase 1
2. Phase 2
3. Phase 3
4. Phase 4

4 Stages altogether

Question 2

What is looked at in phase 1 of drug development?

Answer 2

1. Safety in humans
2. Body do to the drug (pharmacokinetics)
3. Drug do to the body (pharmacodynamics)
4. Might it work in patients

Question 3

What is looked at in phase 2 of drug development?

Answer 3

1. Does it seem safe in patients

2. Does it seem to work in patients

Question 4

What is looked at in phase 3 of drug development?

Answer 4

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?

Question 5

What is looked at in phase 4 of drug development?

Answer 5

1. Is it truly safe?

2. How does it compare with similar other drugs?

Question 6

What is the purpose behind Preclinical drug development testing?

Answer 6

1. Access genotoxic (toxicity) potential
2. Evaluation of chromosome damage in response to the drug
3. Carcinogenicity testing
4. Reproductive testing: pregnant female rabbits

Question 7

What is measured in the preliminary toxicity testing?

Answer 7

1. Maximum non toxic dose (given for 28 days to 2 species)
2. LD50 examined
3. NOAEL and LOAEL tested

Question 8

Define LD50?

Answer 8

Lethal Dose- the dose to kill 50% of treated animals within a short amount of time

Question 9

How do you work out the LD50?

Answer 9

1. Measure midway the toxic response curve

2. To where it measures the amount of Log [drug]

Question 10

What does NOAEL mean and represent?

Answer 10

1. No observed adverse effect level

2. Highest concentration that does not cause toxic response

Question 11

What does LOAEL mean and represent?

Answer 11

1. Lowest observed adverse effect level

2. Lowest concentration that produces toxic response

Question 12

How do you calculate the HED (human equivalent dose) if the NOAEL of a rat was 100mg/kg for a 70kg man?

Answer 12

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
4. Therefore:
   112mg in 70kg man

Question 13

What is the therapeutic index?

Answer 13

The ratio of the dose of the drug that produces an unwanted (toxic) effect to that producing a wanted (therapeutic) effect

Question 14

How do you work out the therapeutic effect?

Answer 14

LD50/ED50

Question 15

Give an example of a drug with a small therapeutic index?

Answer 15

1. Warfarin

2. Theophylline

Question 16

Give an example of a drug with a large therapeutic index?

Answer 16

1. Penicillin

2. Aspirin

Question 17

What can the LD50 show us?

Answer 17

1. Useful to show the short term poisoning potential

2. Lethal Dosage when injected