Pharmacokinetics Flashcards
TDM
Therapeutic drug monitoring
- predicts a physiologic response of the concentration:response relationship
- individualizes a patient’s dosage regimen based on serum drug concentrations, serving to improve efficacy and minimize toxicity
When is TDM used?
When the pharmacokinetics and pharmacodynamics are understood, and when the drug has a low therapeutic index
- ex: electrolytes (bicarb)
Elimination is composed of both ______ and ______
Excretion and metabolism
- follows zero-order and first-order processes
Zero-order process
Removes a constant amount of drug
- saturated process
- CRI’s, many transdermals and sustained release formulations
First-order process
Remove a constant proportion of drug
- applies to most oral and extravascular administrations
- elimination rate constant primarily determines terminal drug concentrations
What is dose proportionality?
Occurs when first-order processes exist and as such a change in dose results in a proportional change in plasma concentrations
- ex: 2x increase in dose = 2x increase in plasma concentration
Lack of dose proportionality
- saturation (zero order) of absorptive processes –> ex: 2x increase in dose = 1.5x increase in plasma concentration
- saturation (zero order) of elimination processes leading to drug accumulation beyond proportionality –> ex: 2x increase in dose = 3x increase in plasma concentration
What does it mean when a drug is said to have “flip-flop” kinetics
Occurs when absorption rate is slower than the elimination rate
- absorption rate constant primarily determines terminal drug concentrations
- many sustained release formulations have flip-flop kinetics
What is an elimination half life and how can it be used to estimate the time required to eliminate a drug?
Time it takes for the body to remove 1/2 of the drug present
- zero order processes: half life changes with changing drug concentrations
- first order processes: half life is constant
Clinical implications of first order half life
- predict time to nontoxic concentrations after poisoning or accidental overdose
- predict slaughter and milk withdrawal times
What is the purpose in pharmacokinetics of a volume of distribution (Vd) term?
The proportionality constant between C and A is the volume of distribution (Vd) of the drug in the body
- units of L/kg or mls/kg
Does Vd have physiologic significance?
Mathematical term that may or may not have physiologic significance
What does a Vd>1 L/kg signify?
Associated with tissue binding (concentration) of drug
Explain the plateau principle (steady state)
When peak and trough concentrations do not vary between dosing intervals
How does changing the dose or the dosing interval affect time until steady state?
Dosage changes result in differing peak and trough values, but it still takes the same amount of time to reach steady-state
Dosage interval changes result in differing peak and trough values, but it still takes the same amount of time to reach steady-state
Drugs with ______ reach steady state rapidly
Short half-lives
- no or minimal accumulation from prior doses
Drugs with ______ take a long time to reach steady state
Long half-lives
To reach desired concentrations rapidly for a drug with a long half life, give a ________
Loading (priming) dose
- applicable to IV or rapidly absorbed extravascular routes
Assumptions for ratio (proportionality) method
- no change in interval will occur
- kinetic processes are all first-order (dose proportionality exists)
- for drugs with a long half-life one must wait for steady state to occur thru the plateau principle
Ratio formula
Old dose/existing concentration = new dose/ desired concentration
OR
New dose = (old dose x desired concentration)/ existing concentration
Clearance
Volume of fluid (plasma) totally cleared of drug in a given time
CL = rate of elimination/concentration in plasma
What is total body clearance (TBC) the best parameter for describing the overall disposition of a drug
CL addresses both the elimination rate and the Vd
