09 - Drug Response: Individual Variation

Question 0

47) Relationship between age and pharmacokinetics.

Answer 0

1. Renal excretion:
   
   • Glomerular Filtration Rate (GFR)
   • Newborns (20% of adult value)
   • Decrease with age (25% lower at 50yrs, 50% lower at 75yrs)
   • Reduced drug clearance = Elevated plasma conc. and prolonged drug actions.
2. Drug metabolism:
   (a) Neonates (esp premature)
   - Reduced activity of drug metabolizing enzyme
   (b) Elderly
   - Reduced activity of drug metabolizing enzyme
   - Slower and more variable elimination
   - altered drug distribution (increased in body fat)
   - Drug accumulation over time (repeated dosing)

    - Reduced cardiac output = 
              - Reduced metabolism
              - Reduced renal clearance

Question 1

46) Causes of drug response variability

Answer 1

1. Age
2. Disease state (kidney or liver disease)
3. Pregnancy
4. Genetic factors
5. Drug interactions
6. Lifestyle

Question 2

48) What is the effect of giving Chloramphenicol to neonates?

Answer 2

Toxicity. “grey baby syndrome”

due to reduced glucuronyl conjugation, hence reduced clearance

Question 3

49) What is the effect of giving Morphine to neonates?

Answer 3

Toxicity. (prolonged respiratory depression)

due to reduced glucuronyl conjugation, hence reduced clearance

Question 4

50) How does hepatic disease affects pharmacokinetics?

Answer 4

• Reduced metabolic activity, clearance and protein synthesis
• Higher and prolonged (free) plasma levels

Question 5

51) How does cardiovascular disease affects pharmacokinetics?

Answer 5

• Reduced cardiac output
• Reduced metabolism
• Reduced renal clearance
• Higher and prolonged (free) plasma levels

Question 6

52) How does renal disease affects pharmacokinetics?

Answer 6

• Reduced filtration and reabsorption

- Higher and prolonged (free) plasma levels

Question 7

53) How does pregnancy affects pharmacokinetics?

Answer 7

1. Maternal plasma albumin is reduced
   
   • more free drug in plasma
2. Cardiac output is increased
   
   • increased renal blood flow + GFR
   • increased renal elimination
3. Selectivity of placental barrier
   
   • lipophilic molecules readily pass
   • hydrophobic molecules doesnt pass

Question 8

54) Plasma cholinesterase deficiency

Answer 8

• Autosomal recessive disorder
• Carrier healthy until exposed to suxamethonium
• Carriers experience prolonged paralysis with suxamethonium