Pharmacokinetics

Question 1

What does drug clearance tell you?

Answer 1

it describes the body’s efficiency of drug removal (theoretical volume of fluid from which a drug is removed per unit time)

Question 2

What is the equation for drug clearance (CL)?

Answer 2

CL= rate of elimination/concentration

Question 3

In order to maintain a steady-state concentration of a drug within the therapeutic window, what must a physician do?

Answer 3

administer the drug at the same rate that it is eliminated

Question 4

What is the equation for rate of elimination from an organ?

Answer 4

Rate of elimination= Q(Ca-Cv)

Question 5

What is the value “Q” in the rate of elimination equation?

Answer 5

Q= blood flow to the organ

*this is the LIMITING VARIABLE

Question 6

What is the value “Ca-Cv” in the rate of elimination equation?

Answer 6

it is the concentration gradient of drug from the arterial side to the venous side

Question 7

What concentration do you divide the rate of elimination by to get the clearance?

Answer 7

Ca (concentration on the arterial side)

Question 8

What is the extraction ratio?

Answer 8

the fraction of drug presented on the arterial side that is removed by the organ

Question 9

What is the mathematical representation of the extraction ratio(E)?

Answer 9

E=(Ca-Cv)/Ca

Question 10

What is another way to calculate clearance?

Answer 10

CL= Q*E

Question 11

True or false: most drugs obey second order kinetics.

Answer 11

FALSE: most drugs obey first order kinetics

Question 12

What does a concentration versus time plot look like for first order kinetics?

Answer 12

exponential decay function

Question 13

How do you get a “straight line” from a graph of first order kinetics?

Answer 13

make Y axis (concentration) a log

keep X axis linear

Question 14

What does the slope of a first order kinetics reaction (straight line type) tell you?

Answer 14

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)

Question 15

The absolute amount of drug removed per unit time (in first order kinetics) depends on what factor?

Answer 15

concentration

Question 16

What does half-life mean in first order kinetics?

Answer 16

the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%

Question 17

What is another name for 0 order kinetics?

Answer 17

saturation kinetics

Question 18

True or false: few drugs obey zero order kinetics.

Answer 18

True

Question 19

List examples of drugs that obey zero order kinetics.

Answer 19

Ethanol
Aspirin
Heparin

Question 20

What does a concentration versus time plot look like for zero order kinetics?

Answer 20

a straight line

Question 21

True or false: zero order kinetics uses saturable enzymes that make an early plateau in activity.

Answer 21

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

Question 22

True or false: half life of drugs in zero order kinetics varies with the DOSE of the drug.

Answer 22

TRUE: the larger the dose, the longer the half life

Question 23

What is the volume of distribution?

Answer 23

fluid volume that would be required to contain all of the dose at the same concentration as exists in the blood or plasma

Question 24

What is the equation for the volume of distribution?

Answer 24

Vd= amount of drug in body/C (blood concentration)

Question 25

What drug has a Vd very close to plasma (~4L)?

Answer 25

indocyanine green

Question 26

What drug has a Vd very close to total body water (~40L)?

Answer 26

ethanol

Question 27

What drug has a Vd very close to extracellular fluid (~12L)?

Answer 27

aspirin

Question 28

What is the equation for elimination rate?

Answer 28

Ke= CL/Vd

Question 29

What is the equation for elimination half life?

Answer 29

T1/2= 0.7/Ke or 0.7(Vd)/CL

Question 30

True or false: the greater the clearance, the longer the halflife.

Answer 30

FALSE: the greater the clearance, the shorter the half-life

Question 31

True or false: if a drug has a large volume of distribution, it will have a longer halflife.

Answer 31

True!

Question 32

Drugs with short half-lives are ideally given by what route of administration?

Answer 32

IV or sustained release tablets

Question 33

What does half-life help a physician decide?

Answer 33

``` Dosing interval (drugs often given at half-life intervals) Dose ```

Question 34

What is a one compartment open model good to model?

Answer 34

drugs that are distributed fairly uniformly throughout the body (because it assumes the entire body is a 1 compartment, open system)

Question 35

What type of kinetics does a one compartment open model follow?

Answer 35

first order kinetics (linear decrease)

Question 36

What does a two compartment open model assume?

Answer 36

- drug is in a particular compartment | - equilibrium exists between the blood and other areas

Question 37

What are the "phases" of a two compartment open model?

Answer 37

distribution phase: drug drops in blood rapidly when first administered elimination phase: drug follows first order kinetic model (linear)

Question 38

What do multicompartment models measure?

Answer 38

area under the curve

Question 39

What is the relationship between clearance and area under the curve?

Answer 39

CL= dose/AUC

Question 40

What is the equation for dosing rate?

Answer 40

Dosing Rate= CL * Css OR Dosing rate= Dose/dosing interval (T)

Question 41

What is Css?

Answer 41

steady-state concentration of the drug (plateau)

Question 42

How is the dosing rate equation modified to account for the loss of drug?

Answer 42

``` incorporate bioavailability (F) Dosing rate= (CL * Css)/F ```

Question 43

What is the "plateau principle"?

Answer 43

The plateau principle says that the time to steady state is independent of dose or dosing interval. It is strictly dependent on half-life

Question 44

Around how many half-lives does it take to reach steady state?

Answer 44

4-5

Question 45

What is the equation of Css considering dose and dosing rate?

Answer 45

Css= (F*Dose)/(CL*T)

Question 46

What is the Css equation for an IV infusion?

Answer 46

Css= infusion rate/total body clearance

Question 47

How long does it take an IV infused to reach steady state?

Answer 47

around 5 half-lives (not different)

Question 48

When should you use a loading dose?

Answer 48

when you cannot wait 5 half-lives to achieve therapeutic range

Question 49

What is the equation for a loading dose?

Answer 49

LD= (Css*Vd)/F

Question 50

What is a maintenance dose?

Answer 50

dose given after a loading dose that helps maintain the Css in a desired therapeutic window

Question 51

What is the equation for the dosing rate of a maintenance dose?

Answer 51

Dosing rate= (target Css* CL)/F