Pharmacokinetics - steady state

Question 1

What is the drug half-life?

Answer 1

The time required for the drug concentration to change by 50%.

Question 2

What are the two half-lives for a drug?

Answer 2

Distribution half-life

Elimination half-life

Question 3

Half-life follows what order kinetics?

Answer 3

First order

Question 4

What is the equation for Ct?

Answer 4

Ct = C0e^-kt
Ct - concentration of drug at various times
C0 - initial concentration of drug at time zero
k - elimination rate constant

Question 5

What is the equation for half-life, first order elimination?

Answer 5

t1/2 = 0.693/k
i.e.
t1/2 = 0.693Vd/CL

Question 6

How is k determined?

Answer 6

k = CL/Vd

Question 7

The rate constant in the half-life equation is dependent on what two parameters?

Answer 7

Clearance and Vd.

Question 8

A drug that is cleared quickly will have a _____ half-life.

A drug with a ____ Vd value has a ____ half-life value.

Answer 8

low
low
low

Question 9

Drug half-life is used in the determination on what?

Answer 9

1 - The duration of action after a single dose
2 - Time required to reach steady state
3 - The frequency of drug administration
4 - Time required to clear and free of drug

Question 10

One drug (A) reaches the therapeutic range quickly but the Cp drops quickly after that.
Another drug (B) takes longer to reach the therapeutic range but stays there for longer.
Both are taken orally.
There are two patients, one has difficulty falling asleep but, once asleep stays asleep.
The other, can fall asleep easily, but wakes up many times during the night.
Which drug is better for which patient?

Answer 10

Drug A is better for patient 1 since he just needs to reach the therapeutic range to fall asleep.
Drug B is better for patient 2 since he can easily fall asleep but needs a longer therapeutic range to stay asleep.

Question 11

A higher Cl value means what?

Answer 11

It takes longer to clear out the drug (think backwards).

Question 12

Oftentimes, when a drug is given to a patient, it is not given in a single dose to maintain the therapeutic concentration.
For an orally administered drug, for each half-life there is an increase, then a decrease. What do each correspond to?

Answer 12

increase - absorption/distribution

decrease - elimination (/metabolism)

Question 13

Steady state is attained after how many half-lives?

Answer 13

5-6

Question 14

The time to reach the steady state is independent of _______.

Answer 14

dosage

Question 15

Fluctuations (on the Cp/half-life graph) are proportional to what?

Answer 15

dosage interval/half-life

Question 16

The steady state concentration is proportional to what?

Answer 16

dose/dosage interval

Question 17

Determination of the time needed to reach steady state is determined when?

Answer 17

Phase 1 - clinical trial

Question 18

When a drug has a short half-life, what is done to compensate?

Answer 18

Increase dosage.

Question 19

Steady state is achieved when _____ _______ is equal to ____ _________.

Answer 19

drug elimination = drug administration

Question 20

Ideally, we want the drug plasma concentration (CP) to be (________) within the ________ range.

Answer 20

fluctuated

therapeutic

Question 21

What is the equation to determine the maintenance dose rate?

Answer 21

DR = CL * Css
DR - maintenance dose rate - mg/hr
CL - clearance (L/hr)
Css - plasma drug concentration at the steady state condition - mg/L

Question 22

For a drug that is rapidly eliminated, will give a _____ dose to maintain it longer.

Answer 22

larger

Question 23

The frequency of drug administration is ultimately completed to what?

Answer 23

Keep the drug within the therapeutic range

Question 24

To keep a drug within the therapeutic range, what does this depend on?

Answer 24

• The property of the drug (i.e. physico-chemical properties, interaction with other macromolecules in body comparments)
  (i. e. bioavailability)
• elimination

Question 25

The frequency of drug administration is also referred to as what?

Answer 25

interval

Question 26

How is the interval of administration determined?

What are the units?

Answer 26

Interval (h) = (Bioavailability * Dose(mg))/Css (mg/L) * Clearance (L/hr)

Question 27

What do these commonly used terms mean?
stat
B.i.d.
t.i.d.
q.i.d.
q.h.
Q4H

Answer 27

stat - immediately
B.i.d - twice a day
t.i.d. - three times a day
q.i.d. - four times a day
q.h. - hourly
Q4H - every 4 hours

Question 28

Both clearance and bioavailability are _____ properties.

Answer 28

drug

Question 29

How many half-lives does it take for the body to be clear of a drug?

Answer 29

5-6 half lives after administration has been stopped

Question 30

Which organ is most responsible for drug metabolism?

Answer 30

the liver

Question 31

Where are blood clot factors made?

Answer 31

liver

Question 32

What are some functions of the liver?

Answer 32

Glycogen storage
Plasma protein synthesis
Drug detoxification

Question 33

What capillary type does the liver have?

Answer 33

Sinusoidal

Question 34

What is the portal triad of the liver?

Answer 34

Vein, artery, bile duct

Question 35

What does the gallbladder store? What is it used for?

Answer 35

Stores bile, important for fat digestion

Question 36

What does the portal triad do related to drugs?

Answer 36

Blood flow can go from one part of the triad to another.
Due to this intermingling, some drugs absorbed by the portal vein can go to the gallbaldder and get secreted back to the Gi and absorbed back again.

Question 37

What is the hepatic portal system’s function?

Answer 37

Gather/monitor nutrients (Drugs) from the GI tract.

Question 38

What is the entero-hepatic circulation?

Answer 38

Secretion of bile

Absorption and reabsorption of nutrients (Drugs) and drugs from the GI tract

Question 39

Where are drugs metabolized?

Answer 39

Mostly in the liver, but also in the GI tract, kidney and lungs

Question 40

Describe how a drug goes through the liver.

Answer 40

Drug taken orally, asborbed passively from the GI and directed to the liver.
First pass metabolism occurs.
The drug either goes to the blood or is actively secreted by the gallbladder back into the GI, where the drug undergoes a later pass metabolism.