Pharmacokinetics I & Ii

Front 1

What term is given to the difference between MEC and MTC?

Back 1

therapeutic window

Front 2

The effect of a drug depends on what 2 factors?

Back 2

rate of absorption & rate of elimination

Front 3

Zero Order Kinetics is not related to what?

Back 3

ZOK is not related to the concentration of the drug

Front 4

Why is ZOK important clinically?

Back 4

(1) little reserve is available in teh body (2) small additional doses may cause large increses in plasma levels

Front 5

How do elimination rates compare in ZOK vs. MMK?

Back 5

(1) ZOK: elimination rate is constant & is independent of concentration
(2) MMK: elimination rate depends on concentration, specifically Km

Front 6

In the case of MMK, if the measured concentration of the drug is much greater than the Km, are kinetics more indicative of ZOK or FOK? What if the concentration is much less than Km?

Back 6

(1) if C>>Km, then kinetics are approaching ZOK
(2) if C << Km, then kinetics are approaching FOK

Front 7

The decrease in concentration in ZOK is constant. The decrease in concentration in MMK depends on Km and Vmax. What does the decrease in concentration in FOK depend on?

Back 7

(1) concentration of the drug (2) Ke, elimination rate constant

Front 8

In FOK, how do elimination rates change as the drug concentration decreases? as the drug concentration increases?

Back 8

in FOK, elimination rates decrease as conc decreases & rates increase as conc increases.

Front 9

What does Ke mean anyway?

Back 9

Ke is the fraction of available drug eliminated per unit time.

Front 10

What helps determine Ke?

Back 10

(1) Vd (2) clearance

Front 11

How are elimination half-life and Ke related?

Back 11

they are inversely related

Front 12

What is AUC used for?

Back 12

AUC values used to measure bioavailability of a drug & used to measure bioequivalence of generic drugs

Front 13

If you are trying to determine AUC but don't know the concentration-time function, how do you estimate AUC?

Back 13

(1) give a drug (2) plot changes in concentration over a 24 hr period (3) use trapezoidal rule to determine AUC from time 0-24 (4) use Ke to determine additional AUC after 24h (5) add this additional AUC to what you got in (3) to estimate AUC from time 0 to infinity

Front 14

What is the clinical significance of bioavailability?

Back 14

used to increase dosage to offset amt of drug lost as it enters systemic circulation

Front 15

What exactly is bioavailability?

Back 15

it's the fraction of the dose that enters the systemic circulation

Front 16

What can help you determine the bioavailability of a drug?

Back 16

AUC - it measures systemic drug presence over time

Front 17

What does the variable "S" mean?

Back 17

it is the fracion of a salt that is the active drug

Front 18

What is "S" used for?

Back 18

used to calculate loading dose

Front 19

What are the limitations of Vd?

Back 19

(1) initial drug concentration before elimination can be inaccurate if 2 compartment kinetics are at work (2) bioavailability of a drug - the fraction that enters systemic circulation - can be uncertain in cases of orally admin'd drugs due to elimination-absorption lag issues

Front 20

What 2 parameters does Vd relate?

Back 20

Vd relates dose to initial drug concentration before elimination

Front 21

Describe clearance in FOK.

Back 21

Clearance - in the case of FOK - is independent of [drug] and remains constant.

Front 22

Is clearance the same thing as "the amount of drug removed during any given time interval"?

Back 22

Nope. Clearance is the portion of the Vd that is cleared of a drug per unit time. Clearance is NOT the amt of drug that is removed during a given time interval.

Front 23

what does Ke help you to determine? what does Ka help you to determine?

Back 23

(1) Ke helps you to determine how quickly a drug will be eliminated from the body
(2) Ka helps you to determine when drug levels will peak (a more rapid absorption means the peak level occurs sooner & the peak concentration is greater)

Front 24

In considering the plasma concentration of a drug after a single dosage, what 5 variables become very important? How does changing any one of these variables affect plasma concentration?

Back 24

(1) Bioavailability, F: increase will increase [plasma]
(2) Dose: increase will increase [plasma]
(3) Vd: increase will decrease [plasma]
(4) Ka: increase will increase [plasma]
(5) Ke: increase will decrease [plasma]

Front 25

The time at which the plasma concentration following a single oral dose peaks (Tmax) is dependent on what 2 variables?

Back 25

(1) Ka
(2) Ke

Front 26

If you know the Ka and Ke, you can calculate the Tmax for a single oral dose. And if you know the Tmax for that dose, what are you then able to calculate?

Back 26

Cmax, the peak plasma level

Front 27

What is the loading dose?

Back 27

initial quantity of drug that has to be given to a patient in order to achieve the desired **initial* plasma level

Front 28

What factors/variables do you need to know to calculate the loading dose for your patient?

Back 28

(1) desired initial plasma concentration
(2) Vd
(3) bioavailability if it is less than 1
(4) fraction of active drug in a salt, S, if it is less than 1

Dl = (C x Vd) / (F x S)

Front 29

Calculating a loading dose is best for (blank) and will underestimate (blank).

Back 29

Calculating a loading dose is best for IV dosage and will underestimate oral dosage. This is because elimination occurs during the time required for complete drug absorption.

Front 30

How is a plasma drug level plateau, or steady state concentration, achieved?

Back 30

A plateau is achieved when a drug that is eliminated by first order kinetics is administered at a constant rate.

(first order kinetics output & zero order kinetics input)

The drug level *AND* the elimination rate rise until elimination rate equals the rate of administration. At this point, a steady state concentration has been achieved

Front 31

If you know the desired steady state plasma level and if you know the renal clearance, what then can you calculate to help you maintain that desired blood level?

Back 31

drug infusion rate

Dir = C x Clearance

(where C is the desired steady state concentration)

Front 32

It is important to realize that the time required to reach a steady state concentration depends on the drug half-life. Would a drug with long half-life reach a steady state slowly or quickly? What about a drug with a short half-life?

Back 32

Drugs with long half-lives reach steady state slowly. Drugs with short half-lives reach steady state quickly.

Front 33

Approximately how many half-lives does it take for a drug to reach its steady state concentration?

Back 33

4-5 half lives

Front 34

If it takes 5 half-lives for a drug to reach its steady state concentration and the drug that you want to give to your patient has a half-life of 9 hours, what does that mean and what can be done to change it?

Back 34

It means it will take 45 hours for the drug to reach therapeutic levels. A way around this is to (1) use a loading dose or (2) use fast initial infusion rate

Front 35

If you are going to use a fast initial infusion rate, what adjustments will have to be made once the duration of that fast infusion is over?

Back 35

Steady state infusion rate must be used once the drug reaches its steady state concentration.

Front 36

In the cases of infusions in which a drug's half-life is long, there are ways to achieve a steady state concentration in a shorter amount of time (loading dose or rapid infusion rate). But what happens if you give too much of that drug with a long half-life? Is there a way to eliminate it quickly?

Back 36

Nope. Drugs with long half-lives require long times for elimination.

Front 37

All this talk about loading doses and infusion rates and time it takes to reach steady state levels is discussed primarily in the context of IV administration. What about oral dosage?

Back 37

Oral dosing can be managed with the same principles that govern IV dosing steady state concentrations: constant rate of dosing and constant rate of elimination. But drug levels will fluctuate between doses in the case of oral drugs.

Front 38

Rule of thumb when considering repetitive maintenance dosing of an oral drug: use of dosing intervals equal to (blank) will result in maximum levels that are twice the minimum levels.

Back 38

use of dosing intervals equal to the drug's half-life will result in maximum levels that are twice the minimum levels.

Front 39

In considering the plasma concentration approach to steady state after oral dosage, what 6 variables become very important?

Back 39

(1) Bioavailability
(2) Maintenance Dose
(3) Vd
(4) Ka
(5) Ke
(6) Dosing interval

Front 40

Let's say your patient is taking a drug with a half-life of 8 hours and he takes 20mg of the drug every 8 hours. Predict what the minimum and maximum levels will be relative to each other. How can you adjust your patient's dosing?

Back 40

The maximum levels will be twice the minimum levels. To bring these levels closer to one another, you could give your patient 10mg every 4 hours.

Front 41

Let's say your patient takes 10mg of a drug every 5 hours and that drug has a half-life of 10 hours. On this regimen, your patient's drug levels are right where they should be. What if your patient - on his own - decided to only take half of a pill (5mg) every 5 hours - would the drug be therapeutic?

Back 41

Your patient's average drug concentration will fall by half. If his previous levels while on 10mg every 5 hours were therapeutic, then 5mg every 5 hours would probably not produce therapeutic levels.

Front 42

Let's say your patient takes 20mg of a drug every 6 hours and that drug has a half-life of 12 hours. On this regimen, your patient's drug levels are right where they should be. What if your patient - on his own - decided to take 40mg every 12 hours (morning & night time) - would the drug levels remain the same?

Back 42

Average plasma concentrations will be the same if the patient takes 20mg every 6 hours or if the patient takes 40mg every 12 hours. However, the difference between minimum concentrations and maximum concentrations will be greater in the case of 40mg per 12 hours (remember the drug's half-life is 12 hours).

Front 43

Let's say your patient takes 20mg of a drug every 6 hours and that drug has a half-life of 12 hours. On this regimen, your patient's drug levels are right where they should be. What if the bioavailability dropped by half (perhaps due to a problem with the liver)? In relative terms how would the average concentration level change?

Back 43

A 50% decrease in bioavailability will decrease the average concentration level by half (considering all other factors remain the same).

Front 44

Let's consider a drug with a half-life of 12 hours. Patient A takes 20mg of the drug every 6 hours and Patient B takes 10mg of the drug every 3 hours. Will their average concentrations be different? Will patient A reach his average concentration first?

Back 44

Their average concentrations are the same and they will both reach those concentrations in the same amount of time - about 60 hours (half-life x 5).. The only difference between Patient A and Patient B is their minimum and maximum concentrations. Patient A's min & max will be farther apart.

Front 45

In determining an infusion rate that will PRODUCE AND MAINTAIN a desired drug level, what 3 factors become very important?

Back 45

(1) desired steady state plasma level
(2) Vd
(3) Ke
(4) Clearance (determined by Vd & Ke)

Front 46

Let's say you are infusing a patient at the rate of 2 mg per kg per hour. Your patient's blood levels are at the desired concentration. What might have happened if you miscalculated and infused the patient at 4mg per kg per hour?

Back 46

The plasma concentration would have been double that of the desired concentration. (20mg/kg rather than 10mg/kg for example).

Front 47

In the case of a drug that exhibits a saturated elimination process, how will the half life be affected by administering a dose of the drug?

Back 47

Drug will accumulate on repeated dosings and the elimination will be independent of plasma concentration.

Front 48

2 typical physiological processes that might combine to give a biphasic exponential are:

Back 48

(1) initial drug distribution from plasma into peripheral tissues

(2) concurrent elimination from plasma

these processes have different rate constants and duration in a multi-compartment model

Front 49

TRUE or FALSE

AUC is useful for determining parameters dependent on the amount of drug absorbed and/or persisting in the body over time

Back 49

TRUE

Front 50

How do you mathematically compare the bioavailability of a generic formulation and a brand name formulation?

(answer is an equation)

Back 50

AUC* & Dose* are the values for the generic drug.

AUC' & Dose' are the values for the brand name drug.

F = (AUC*/Dose*) / (AUC'/Dose')

Front 51

Why are some drugs engineered as pharmaceutical salts?

Back 51

salt forms are often more stable for storage & more soluble for absorption

Front 52

You give your patient a drug that is a pharmaceutical salt. The pharmaceutical salt has a MW of 200.

The fraction of the salt that is the active drug, or "S", is 0.8.

What is the MW of the base that was added to the active drug if the ratio of
active drug: base = 1:1?

Back 52

S = 0.8
pharmaceutical MW= 200

0.8 = (x) / (200)

x = 160

200 - 160 = 40

The active drug MW = 160

So the base that was added to the active drug has a MW of 40.

Front 53

You give your patient a drug that is a salt preparation. The pharmaceutical salt has a MW of 400.

The active drug in that salt has a MW of 120.

Calculate the fraction of the salt that is the active drug if the ratio of
active drug : salt = 2:1

Back 53

active drug MW = 120
base MW = 400

ratio of active drug: base = 2:1

S = (240) / (400) = 0.6

The fraction of the salt that is the active drug is 0.6

Front 54

Vd = Dose / C

The above equation has limitations due bioavailability issues, absorption lag issues, etc.

What is a better equation for determing Vd? Especially in the case of oral dosing.

Back 54

Vd = (Dose) / (Ke x AUC)

Ke = elimination rate constant
AUC = area under the curve

Front 55

How do you use AUC to calculate clearance?

Back 55

Clearance = Dose / AUC


similar equation for Vd:

Vd = Dose / (Ke x AUC)

Front 56

Drug A has a Ka = .693
Drug B has a Ka = .231

How will their Concentration vs. Time plots differ?

Back 56

Drug A has a larger Ka value. Thus, Drug A will

(1) be more rapidly absorbed
(2) reach its peak concentration sooner
(3) have a greater peak concentration

see Fig. 8 on page 58

Front 57

You calculate the steady state infusion rate for a drug with a half-life of 2 hours.

The drug finally reaches the desired concentration.

How long did it take for the drug to reach this steady state concentration?

Back 57

10 hours

Front 58

In the setting of constant-rate infusion, making the following changes depends on what?

(1) achieving inital steady state concentration

(2) changing form one steady state level to another by altering infusion rate

(3) time of total elimination of drug

Back 58

In the setting of constant-rate infusion, these things depend solely on Ke, or drug half-life.

Front 59

You calculate the steady state infusion for a drug. However, it will take too long for the drug to reach the desired concentration.

You decide to use a fast initial fusion rate.

You determine the duration of the fast infusion (say 20 minutes) and calculate the fraction of change during that 20 minutes to be 0.1

Based on the information above, how will the fast initial fusion rate compare to the too-slow steady state infusion rate ?

Back 59

The much quicker fast initial infusion rate will be in proportion to the inverse of the fraction of steady state achieved during that 20 minutes.

It was already mentioned that the fraction of steady state achieved during the 20 minutes was 0.1

Thus, the fast initial infusion rate should be rougly 10x the too-slow steady infusion rate.