Flashcards in Pharmacokinetics Deck (51):
What does drug clearance tell you?
it describes the body's efficiency of drug removal (theoretical volume of fluid from which a drug is removed per unit time)
What is the equation for drug clearance (CL)?
CL= rate of elimination/concentration
In order to maintain a steady-state concentration of a drug within the therapeutic window, what must a physician do?
administer the drug at the same rate that it is eliminated
What is the equation for rate of elimination from an organ?
Rate of elimination= Q(Ca-Cv)
What is the value "Q" in the rate of elimination equation?
Q= blood flow to the organ
*this is the LIMITING VARIABLE
What is the value "Ca-Cv" in the rate of elimination equation?
it is the concentration gradient of drug from the arterial side to the venous side
What concentration do you divide the rate of elimination by to get the clearance?
Ca (concentration on the arterial side)
What is the extraction ratio?
the fraction of drug presented on the arterial side that is removed by the organ
What is the mathematical representation of the extraction ratio(E)?
What is another way to calculate clearance?
True or false: most drugs obey second order kinetics.
FALSE: most drugs obey first order kinetics
What does a concentration versus time plot look like for first order kinetics?
exponential decay function
How do you get a "straight line" from a graph of first order kinetics?
make Y axis (concentration) a log
keep X axis linear
What does the slope of a first order kinetics reaction (straight line type) tell you?
elimination rate constant (Ke)- means that constant FRACTION of the drug is eliminated per unit time
Ex. every 2 hours the concentration is halved (hour0=8, hour2=4, hour4=2, hour6=1)
The absolute amount of drug removed per unit time (in first order kinetics) depends on what factor?
What does half-life mean in first order kinetics?
the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%
What is another name for 0 order kinetics?
True or false: few drugs obey zero order kinetics.
List examples of drugs that obey zero order kinetics.
What does a concentration versus time plot look like for zero order kinetics?
a straight line
True or false: zero order kinetics uses saturable enzymes that make an early plateau in activity.
FALSE: zero order kinetics uses enzymes that get saturated at usual levels of drug in the body. The SAME amount of drug is metabolized regardless of the level of drug
True or false: half life of drugs in zero order kinetics varies with the DOSE of the drug.
TRUE: the larger the dose, the longer the half life
What is the volume of distribution?
fluid volume that would be required to contain all of the dose at the same concentration as exists in the blood or plasma
What is the equation for the volume of distribution?
Vd= amount of drug in body/C (blood concentration)
What drug has a Vd very close to plasma (~4L)?
What drug has a Vd very close to total body water (~40L)?
What drug has a Vd very close to extracellular fluid (~12L)?
What is the equation for elimination rate?
What is the equation for elimination half life?
T1/2= 0.7/Ke or 0.7(Vd)/CL
True or false: the greater the clearance, the longer the halflife.
FALSE: the greater the clearance, the shorter the half-life
True or false: if a drug has a large volume of distribution, it will have a longer halflife.
Drugs with short half-lives are ideally given by what route of administration?
IV or sustained release tablets
What does half-life help a physician decide?
Dosing interval (drugs often given at half-life intervals)
What is a one compartment open model good to model?
drugs that are distributed fairly uniformly throughout the body (because it assumes the entire body is a 1 compartment, open system)
What type of kinetics does a one compartment open model follow?
first order kinetics (linear decrease)
What does a two compartment open model assume?
-drug is in a particular compartment
-equilibrium exists between the blood and other areas
What are the "phases" of a two compartment open model?
distribution phase: drug drops in blood rapidly when first administered
elimination phase: drug follows first order kinetic model (linear)
What do multicompartment models measure?
area under the curve
What is the relationship between clearance and area under the curve?
What is the equation for dosing rate?
Dosing Rate= CL * Css
Dosing rate= Dose/dosing interval (T)
What is Css?
steady-state concentration of the drug (plateau)
How is the dosing rate equation modified to account for the loss of drug?
incorporate bioavailability (F)
Dosing rate= (CL * Css)/F
What is the "plateau principle"?
The plateau principle says that the time to steady state is independent of dose or dosing interval. It is strictly dependent on half-life
Around how many half-lives does it take to reach steady state?
What is the equation of Css considering dose and dosing rate?
What is the Css equation for an IV infusion?
Css= infusion rate/total body clearance
How long does it take an IV infused to reach steady state?
around 5 half-lives (not different)
When should you use a loading dose?
when you cannot wait 5 half-lives to achieve therapeutic range
What is the equation for a loading dose?
What is a maintenance dose?
dose given after a loading dose that helps maintain the Css in a desired therapeutic window