Bv: Explain the difference & clinical relevance of zero and first order kinetics (60 marks)

Give an example relevant to ICU

Zero & First Order Kinetics = terms used to describe elimination of drugs from the body

First Order

  • A CONSTANT PROPORTION OF DRUG IS REMOVED PER UNIT OF TIME
    • Rate of elimination ∝plasma [ ] (Cp)
    • Enzymes exceed substrate
    • Most drugs obey First Order Kinetics
    • KA­ ‘First Order’ because elimination is dependent on drug concentration Cp1 = Cp
First Order
  • If the drug [ ] ↑ so too will the elimination as long as the Cp is well below the KM
  • KM = the [ ] at which ½ the max rate of elimination is reached

AKA ‘MICHELIS CONSTANT’

Zero Order

  • CONSTANT AMOUNT OF DRUG ELIMINATES PER UNIT TIME
    • When a drug [ ] exceeds KM
    • Enzyme systems become saturated
    • Elimination is not dependent on drug Cp
Zero Order

Example in ICU

  • 1st order → Cp rises proportionally with dose
  • 0 order → Cp rise is disproportional with ↑dose (because the body can’t remove a constant proportion, just a constant amount)
  • Drugs which have therapeutic Cp KM have narrow therapeutic index & need monitoring
Example in ICU
  • Phenytoin KM = 7mg/L
    • Therapeutic range 10 – 20mg/L
    • Metabolism is saturated at therapeutic range
    • Zero order kinetics
    • Requires monitoring