4 - Pharmacokinetics 2b

Question 1

What is the goal of drug therapy?

Answer 1

To maintain a concentration of drug in the body that is enough to produce the desired efect with minimal toxicity.

Question 2

On a graph of plasma concentration of an orally administered drug by time in hours, what does the area under the curve tell us?

Answer 2

the extent of absorption (ie bioavailability).

Question 3

What is the therapeutic window?

Answer 3

The range of concentrations that allow you to have a desired effect but below the level of minimum toxicity.

For useful drugs this is a range.

Question 4

Drugs can be in body compartments other than the blood, so how do we tell how much is in these places? How is this calculated? What do we assume for this calculation?

Answer 4

The parameter of volume of distribution (Vd).

Vd = amount of drug in the body (dose) /plasma concentration of the drug at time 0

We assume that the concentration is the same throughout the circulation and we use the total PLASMA concentration (ie bound and unbound).

Question 5

How would you determine the volume of a container that you placed a drug into?

Answer 5

Volume of container = amount of drug/concentration

Question 6

How do we calculate the concentration of blood in the body at time 0 (C0)?

Answer 6

By extrapolating the elimination phase of the drug.

Question 7

What does it mean if Vd is very small? Large?

Answer 7

If volume of distribution is small: drug stays almost entirely in the plasma

Larger Vd indicates that the drug can move as water and the Vd is equal to the total body volume (70L).

Question 8

What does it mean if the Vd is even larger than the body volume?

Answer 8

It means that the drug is sequestered in a non-plasma compartment in a much higher concentration than what’s present in the plasma.

Question 9

What can the Vd equation be rearranged to help solve for?

Answer 9

To calculate the dose.

D = Vd * C0

C0 = concentration at time 0
Vd = volume of distribution (can be looked up in a table)

Question 10

What needs to be considered when giving a drug orally and determining the dosage?

Answer 10

Bioavailability (F) because we cant assume that the entire dose gets into the plasma.

D = Vd * C0/F

Question 11

What effects does bioavailability have on the log based serum concentration vs time graph of a drug?

Answer 11

Reduction in the peak drug concentration and the area under the curve.

No effect on the kinetics of elimination - bioavailability just effects the absorption.

Question 12

How do you calculate drug clearance?

Answer 12

Clearance = Rate of elimination / concentration

They are additive too:
CL total = CL renal + Cl liver

Question 13

Most drugs are cleared through first order decay process. What does this tell us about elimination?

Answer 13

The clearance is constant.

When graphed on a Ln graph, the slope is equal to -Kelimination (rate constant for elimination).

Question 14

How do you calculate the slope on a log based 10 graph of a first order elimination? What does a higher slope mean?

Answer 14

Slope = -Kelim/2.3

The higher the slope, the higher the Kelim (quicker the elimination from the body).

Question 15

What is the half life and how do you calculate it? How does half life change in a first order process?

Answer 15

Amount of time needed to reduce the amount of drug by one half.

T1/2 = 0.69/Kelimination

Half life is constant for a first order process.

Question 16

About how many half lives does it take to completely eliminate a drug from the body?

Answer 16

4 - 5 half lives.

Question 17

How do you calculate the slope for the drug during the accumulation phase for a first-order process?

Answer 17

Slope = Kabsorption/2.3

Question 18

What are the two phases for IV administered drugs? What are the characteristics of each?

Answer 18

Alpha phase: distribution - loss of drug out of circulation as a result of being distributed to other places. Short and quick.

Beta phase: elimination with a slope of -Kelim/2.3. Can be used to give us the valid C0 because it’s when we assume equal distribution.

Question 19

What happens when the elimination process is saturated at therapeutic concentrations?

Answer 19

Clearance is not a constant because the rate of elimination cannot increase with increasing concentration.

Clearance goes down as the concentration goes up.

Question 20

How do you calculate the rate of elimination when the concentration (C) is very large compared to the Km such as seen with a drug that follows zero order kinetics?

Answer 20

Rate of elimination = Vmax*C/(Km + C)

If the concentration is high, the rate of elimination will reach Vmax but can’t go any higher.

Question 21

What occurs with zero order kinetics? What happens as concentration increases?

Answer 21

AKA capacity-limited, dose-dependent, and Michealis-Menton elimination.

As concentration increase: clearance decreaes, Kelimination decreases, half-life increases.

In other words, half life and clearance as not constants.

Question 22

What happens when elimination is saturation (zero order kinetics)? What are some examples of drugs that display zero order kinetics?

Answer 22

Drugs accumulate.

Ethanol, aspirin, and phenytoin.

Question 23

How is clearance calculated in first order kinetics? How does this equation allow us to calculate half life?

Answer 23

CL = Kelimination * Vd

Half life = 0.69 * Vd/CL

Question 24

The time a drug stays in the body is directly proportional. to what? What is it inversely proportional to?

Answer 24

Directly related to its volume of distribution

Inversely proportional to its clearance.

Question 25

Drugs will accumulate in the body until when?

Answer 25

Until the amount added into the body and the amount eliminated are equal.

At this point the concentration of the drug in the plasma reaches a steady state (Css)

Question 26

What is clearance?

Answer 26

The rate of elimination / concentration

Question 27

What is Css? How can it be used to calculate the dose?

Answer 27

Dose/dosing interval = CL * Css/F

Question 28

The desirable concentration at steady state should be _______?

Answer 28

In the therapeutic window.

Question 29

What does it take for a drug to reach a steady state in the body? What else does this tell us?

Answer 29

About 4-5 half-lives when the same dose is given at regular intervals.

This is the same about of time to completely eliminate a drug because absorption = elimination.

Question 30

What can you do to reach the steady state of a drug more quickly? How do you calculate this?

Answer 30

Use a loading dose: a large dose of a drug that allows for therapeutic levels ot be reached immediately without waiting the 4-5 half lives.

Dose = Vd * C0/F

Any concentration can be used to calculate the loading dose but if you’re using this to calculate Vd you have to use time 0.

Question 31

Changing the dose/dose interval affects the peaks and valleys of a plasma concentration vs time graph but _____ stays the same.

Answer 31

The concentration at the steady state.

Question 32

What is a maintenance dose? How do you calculate this?

Answer 32

The dose needed to maintain the concentration at a steady state (Css).

Maintenance dose = Css *CL *DI/F

DI is the dosing interval? for example if something is given twice a day the DI is 12 hours.

Question 33

How do you calculate a loading dose?

Answer 33

Loading dose = Vd * C0/F

Question 34

How do you calculate a half life?

Answer 34

T1/2 = 0.69 * Vd/CL

CL is clearance

Question 35

How do you calculate Clearance?

Answer 35

CL= 0.69 * Vd / T1/2

Question 36

How do you calculate a maintenance dose?

Answer 36

Css * CL * DI / F

DI is dose interval