Pharmacokinetics in practice (metabolism and excretion) Flashcards
What is first order kinetics?
- Rate of elimination is PROPORTIONAL to the plasma drug concentration (processes involved in elimination do not become saturated)
- A constant % of the plasma drug is eliminated over a unit of time
- If plasma concentration ↑ clearance capacity ↑ too
What is zero order kinetics?
- Rate of elimination is NOT proportional to the plasma drug concentration (metabolism processes become saturated)
- A constant AMOUNT of the plasma drug is eliminated over a unit of time
What is Cmax?
Maximum plasma concentration
What is Tmax?
Time taken to reach Cmax
What is clearance (CL)?
rate of drug elimination by all eliminating organs
What is half life?
time taken for plasma drug concentration to fall 50%
What is half life dependent on?
- Dependent on clearance (CL) of drug from body by all eliminating organs (hepatic, renal, faeces, breath)
- Dependent on volume of distribution (Vd):
- A drug with large Vd will be cleared more slowly than a drug with a small Vd
- The better a drug distributes = will have a longer half life
-t1/2 is not dependent on drug dose or drug formulation
If a drug is given at 50% of its concentration what will happen to its half life?
Stays the same
After how many half lives is a drug basically (97%) cleared from the body?
5
What is the steady state in continuous IV infusion?
rate of drug input is equal to rate of drug elimination
What is Css in continuous IV infusion?
drug plasma concentration at steady state
What does a 50% dose reduction do to Css?
50% reduction (time to Css is unchanged)
What does reduced clearance mean for half life?
Reduced clearance means prolonged half life
Therefore Css increases
Need dose reduction
How is Css calculated?
rate of infusion/ CL
What does repeat IV dosing aim to do?
Aim for Css which lies between the Maximum safe concentration (MSC) and minimum effective concentration (MEC)
Why would we need to reduce time to steady state?
In some conditions waiting for steady state could be detrimental
What could speed up time to steady state?
A loading dose will speed up time to steady state
Which drugs require a loading dose?
- Digoxin
- Vancomycin
- Teicoplanin
- Amiodarone
- Heparin
When does zero order kinetics occur?
If an enzyme system that removes a drug is saturated the rate of removal of the drug is constant and unaffected by an increase in concentration
What order kinetics does ethanol follow?
Ethanol follows zero order kinetics once alcohol dehydrogenase has been saturated
Describe drugs with a narrow therapeutic window
Drugs with a narrow window between MEC and MSC
