Studied by 2 people
what types of drugs require TDM
narrow therapeutic index + variable PK (inter- and intra-patient variability) + known concentration-effect relationship (efficacy and/or toxicity)
T/F: therapeutic window and therapeutic index are not the same thing
true
what does ED50 mean
the dose where 50% of the patients get the desired therapeutic effect
what does TD50 mean
the dose where 50% of the patients get unwanted side-effects
how does therapeutic window differ from therapeutic index?
concentration based and usually based on individual not populations
what are some indications for TDM?
PK dose individualization, monitor compliance, monitor for drug interactions, and ensure efficacy/prevent toxicity
TDM definition:
monitoring drug concentrations to ensure efficacy and minimize toxicity
common drugs that require therapeutic drug monitoring
vancomycin, gentamicin/tobramycin, phenytoin, and warfarin
therapeutic range for vancomycin:
trough 10-20 mcg/mL or AUC 400-600 mg*h/L
therapeutic range for gentamicin/toobramycin:
peak 6-8 mcg/mL and trough 1-2 mcg/mL
therapeutic range for phenytoin
random 10-20 mcg/mL
therapeutic range for warfarin:
INR 2-3
what is clearance
volume of plasma that is cleared of drug per unit time
what is apparent volume of distribution (Vd)?
PK rate constant - NOT A PHYSIOLOGIC TERM and may be represented as a fraction of weight
Ke =
Cl/Vd
half-life =
0.693/ke
define Cmax
highest concentration of drug in blood
define half-life
time at which drug has lost half its maximum concentration
define Cmin
lowest concentration of drug in blood
define AUC
overall drug exposure
how many half-lives to steady state?
4-5 half-lives
define steady state
amount of drug into the system = amount of drug out of system
what is true regarding the peak and trough concentrations at steady state?
consistent for each dose
T/F: time to steady state is independent of dosage
true
when is it ideal for TDM to be performed?
at steady state
initial dose of vancomycin
15-20 mg/kg
what value correlates with efficacy of vancomycin
AUC/MIC > 400
what value correlates with toxicity (nephro) correlates with vancomycin
trough > 15 mg/L or AUC > 600
what value correlates with efficacy of aminoglycosides
peak concentrations 5-10 mg/L for gentamicin/tobramycin and peak concentrations of 20-30 mg/L for amikacin
what value correlates with toxicity of aminoglycosides?
concentrations greater than target trough of < 2 mg/L for genta/tobra and < 10 mg/L for amikacin
what is a pearl of phenytoin TDM?
interpretation of concentration data is obscured in renal dysfunction due to alterations in protein binding, volume of distribution, and free drug available
target total phenytoin concentration?
10-20 mcg/mL
target free phenytoin concentrations
1-2 mcg/mL
what can occur if INR is too high
bleeding side effects more likely
what can occur if INR too low
blood clots more likely
onset of action for warfarin
2-3 days
duration of effect for warfarin
2-5 days
half life of factor II:
72 hours
target INR range for mechanical heart valves
2.5-3.5
