Module 6

Question 1

What is the underlying principle of clinical pharmacokinetics?

Answer 1

A relationship exists between the effects of a drug and the concentration of drug in the body.

Question 2

What are the most important parameters determining drug disposition in humans?

Answer 2

Clearance, volume of distribution, elimination half-life, bioavailability

Question 3

Ideally, drug concentrations would be measured from _______, however this is not feasible (generally, and thus drug concentrations are usually measured in ________.

Answer 3

the site of action

plasma

Question 4

Why is the plasma a good site to measure drug concentrations?

Answer 4

1 - Relatively non-invasive

2 - Good correlation between plasma concentration and therapeutic/toxic effects (generally)

Question 5

How is plasma obtained?

Answer 5

Phlebotomy (take blood from pt) –> centrifuge blood sample –> obtain plasma

Question 6

What is measure in terms of drug concentration, in plasma.

Answer 6

Total drug concentration (since free drug concentration is difficult)

Question 7

Describe the oral administration plasma concentration vs. time curve.

Answer 7

A >> E
Cmax - A = E
A << E
A - absorption
E - elimination

Question 8

What are the different characteristics of plasma concentration time curves?

Answer 8

MEC - minimum effective concentration
Duration
Toxic concentration
Therapeutic range

Question 9

The minimum concentration required to have a therapeutic effect.

Answer 9

MEC - minimum effective concentration

Question 10

Length of time the drug is above the MEC.

Answer 10

Duration

Question 11

Above which, toxic side effects will occur.

Answer 11

Toxic concentration

Question 12

Range at which the plasma drug concentration is between the toxic concentration and the MEC.

Answer 12

Therapeutic range

Question 13

The ________ of the therapeutic range is an index for how ________ a drug can be used.

Answer 13

width

safely

Question 14

Drugs with a narrow therapeutic range often undergo ________ _________ to ensure that drug concentrations are within the target range.

Answer 14

Therapeutic monitoring

Question 15

Describe therapeutic monitoring.

Answer 15

Typically performed on troughed blood samples

= Take a blood sample just prior to patient’s next dose

Question 16

What is another word for therapeutic range?

Answer 16

Therapeutic window

Question 17

Why do oral drugs have a lag time before they reach the MEC?

Answer 17

They have to be absorbed first, and rise in plasma concentration to have therapeutic effects

Question 18

Using IV administration, there is no drug ________.

Answer 18

absorption

Question 19

Describe the different phases of the IV plasma drug concentration time curve.

Answer 19

I >> E
Steady state - I = E
I << E = infusion stopped
I - infusion rate
E - elimination rate

Question 20

The elimination of a drug given by IV bolus follows what type of kinetics?

Answer 20

First order - the rate of elimination is dependent on the blood concentration

Question 21

When patients take repeated dosing of drugs, ___________ occurs.

Answer 21

accumulation

Question 22

Repeated dosing of drugs results in ________ in the body until a ________ is reached. This is called the _______ _______.

Answer 22

accumulation
plateau
steady state

Question 23

When drugs are repeatedly administered orally or as an IV bolus, drug concentrations fluctuate. The high level is called the ______, and the low level is called the _________. The goal of drug therapy is for the fluctuations at steady state to be within the ________ _______.

Answer 23

peak
trough
therapeutic range

Question 24

Steady state is reached in repeated dosing when?

Answer 24

When the peak and trough concentrations are the same between doses.

Question 25

What are the ways to reduce fluctuations in plasma drug concentrations?

Answer 25

Use continuous IV infusion
Use depot preparations
Change the dosing interval

Question 26

Describe a depot preparation.

Answer 26

Depot preparations release drug at a slow and constant rate - minimizes peaks and troughs

Question 27

Describe how changing the dosing interval can reduce peaks and troughs.

Answer 27

Giving the same daily dose, but split up throughout the day reduces the size of peaks and troughs

Question 28

Describes the efficiency of irreversible drug elimination from the body.

Answer 28

clearance

Question 29

Volume of blood cleared per unit time.

Answer 29

Clearance

Question 30

What are the units of clearance?

Answer 30

mL/min

L/hr

Question 31

Sum of clearance from all routes.

Answer 31

Total clearance (note clearance can also be described based on specific routes of elimination - e.g. renal clearance)

Question 32

Why is total drug clearance important?

Answer 32

Because it determines the dosage rate required to maintain a certain blood concentration of a drug.

Question 33

What is the relationship between drug concentration and clearance?

Answer 33

Dosing rate = plasma concentration * Clearance

Question 34

Time it takes for the plasma concentration to decrease by 50%.

Answer 34

Half-life

Question 35

How is half-life related to Vd and Cl?

Answer 35

T1/2 = ln2Vd/Cl
ln2 = 0.693

Question 36

When the SAME dose of a drug is administered repeatedly, it takes approximately ___ half-lives to reach steady state.

Answer 36

5

Question 37

If the dose of the drug remains constant, the time to reach steady state is independent of the ______ of the dose

Answer 37

size/concentration

Question 38

If a drug has a long half-life, it will take a long time for a patient to reach steady state. What can be done to circumvent this?

Answer 38

Loading doses

Question 39

How is the loading dose calculated? What is the assumption of this equation?

Answer 39

Loading dose = target plasma concentration * Vd

This assumes 100% bioavailability

Question 40

The time it takes for plasma concentration to decline from steady state is dependent on a drug’s ________, but not on its _______.

Answer 40

half-life

dose

Question 41

It takes ___ half-lives for most of a drug (97%) to be eliminated from the body.
It takes ____ half-lives to eliminate every molecule of a drug from the body.

Answer 41

5

9

Question 42

________ reactions will persist, even when drug concentrations are very low.

Answer 42

allergic