# 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**Cp^{1}= Cp

- If the drug [ ] ↑ so too will the elimination as long as the Cp is well below the K
_{M} **K**= the [ ] at which ½ the max rate of elimination is reached_{M}

_{AKA} ‘MICHELIS CONSTANT’

## Example in ICU

- 1
^{st}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 K
_{M}have narrow therapeutic index & need monitoring

**Phenytoin K**_{M}= 7mg/L- Therapeutic range 10 – 20mg/L
- Metabolism is saturated at therapeutic range
- Zero order kinetics
- Requires monitoring