Pharmacokinetics 5 & 6 (Kyle)

Question 1

What are the 4 aspects of clinical pharmacokinetics?

Answer 1

q. Clearance- bods efficenty at removal
2. Volumeof Distribution- apparent space the drug resides in
3. Elimination Half Life- rate of drug removal
4. Bioavailability- fraction of drug absorbed

Question 2

What is clearance?

Answer 2

(CL) is defined as the theroretical volume of fluid (ie blood and plasma ) from which a drug is removed per unit of time

Question 3

What needs to happen to maintain a steady state of drug in the therapeutic window?

Answer 3

You need to administer the drug at the same rate at which it is eliminated. Dosing Rate= CL x Css
Css= steady state concentration of drug
CL=clearance

Question 4

How would you calculate clearance?

Answer 4

CL= rate of elimination / concentration

Question 5

What is system clearance?

Answer 5

The sum total of clearance by the various organs. CL = CLrenal + CLhepatic + CLother

Question 6

Which type of elimination kinetic displays enzyme saturation?

When graphing concentration vs hours which displays linear elimination?

Answer 6

Zero Order Kinetics are saturation kinetics

Vero Order Kinetics will display a linear regression.

Question 7

How would you calculate the rate of elimination in an organ?

Answer 7

Elimination = Q x Ca - Q x Cv = Q (Ca - Cv)

Q= blood flow to an organ
Ca= concentration arterial 
Cv= concentration venous

Question 8

Then how would you calculate the clearance of that organ?

Answer 8

CL = Q[(Ca - Cv) / Ca] = Q x E

E= Extraction ratio

Question 9

How do you determine which organ’s clearance is most important?

Answer 9

Drugs handeled by the kidney, renal clearance is most important
Drugs metabolized by the liver- hepatic clearance is most important
Drug excreted by the lung- lung clearance is most important.

Question 10

What is the limiting reagent for drug clearance by a particular organ?

Answer 10

Blood flow to that organ

Question 11

What type of kinetics is rate limiting?

Answer 11

Zero Order- It is rate limiting because the enzyme responsible gets saturated

Question 12

Which order of drug elimination shows a linear decay?

Answer 12

Zero Order Kinetics

Question 13

When you plot concentration against time what will the slope of the connecting you data points be?

Answer 13

The slope is the elimination rate constant. This means that a constant fraction if drug is eliminated per unit time.

Question 14

Is the absolute amount of drug removed from per unit time concentration dependent?

Answer 14

Yes

Question 15

What is the half life of a drug (t1/2)

Answer 15

Half life is the time it takes for the plasma concentration or the amount fo drug in the body to be reduced by 50%

Question 16

What is the volume of distribution ?

Answer 16

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

Question 17

How would you calculate the volume of distribution?

Answer 17

Vd = [amount of drug in the body] / C[blood concentration]

Question 18

What is the significance of Vd?

Answer 18

For some drugs the Vd describes the primary fluid compartments in which the drug is distributed. For others Vd means nothing.

Question 19

What is the elimination half life?

Answer 19

CL / Vd= (ml/min) / ml = 1/min = elimination constant ( Ke)

Question 20

What is the definition of elimination half life?

Answer 20

The half life is the time it takes for the plasma concentration of a drug to be reduced by 50%

Question 21

What is the clinical importance of half-life determination?

Answer 21

1. Determines the dose interval. A drug is given at half life intervals
2. A factor deterining dose
3. May determine route. Short half life is often given IV or by sustained release tabs.
4. Provides a good indication of thme required to reach a steady state dose.

Question 22

What is the one compartment open model (pharmacokinetics)

Answer 22

It assumes the entire human body is one compartment. This works for durgs that are distributes fairly uniformly throughout the body. Assumes an open system and degradation is linear (zero order)

Question 23

What is the two compartment open model of pharmacokinetics?

Answer 23

It assumes that much of a drug is in a particular compartment and that an equilibrium exists between the blood and other areas.

Question 24

Describe the elimination of drug from a two compartment open model.

Answer 24

There is an initial distribution phase followed by an elimination phase. The elimination is zero order showing a linear degradation.

Question 25

What is the multi-compartment model for drug elimination?

Answer 25

Measures area under the curve (AUC)

CL= dose / AUC

Question 26

Due to first pass metabolism what is one obsticle of mantaining a steady state dose of drug in the body?

Answer 26

You must account for the bioavailability of a drug. This is compensated for by using the Bioavailability factor (F) .

Question 27

What is the dosing equation that incorporates F to correct for first pass metabolism ?

Answer 27

F x Dosing Rate = CL x Css

Dosing rate = dose / T Where T is the dosing interval

Question 28

How can you calculate Cssin regard to steady state concentrations?

Answer 28

Css= [ F x Dose ] / [ CL x T ]

F = Bioavailability
T = Dose Interval

Question 29

How can you calculate Dose in regard to steady state concentrations?

Answer 29

Dose = [ Css x CL x T ] / F

Question 30

In multiple dosing how many administrations of a drug does it take to achieve steady state?

Answer 30

5 half lives.

Question 31

What is the plateu principle ?

Answer 31

With multiple doses, after time, a steady state maximum and steady state minimum are reached. The time to steady state is endependent of dose or dose intercal

Question 32

Below the therapeutic minimum what will the drug do?

Answer 32

Below its therapeutic range the drug will have no effect.

Question 33

What happens if the drug gets above its therapeutic range?

Answer 33

Toxicity

Question 34

How do you calculate clearance rate in the multi-compartment model ?

Answer 34

This requires computer assistance but….
CL= dose / AUC
*You plot the Linear clearance of the IV administration and the Clearance of oral administration and calculate the area under the curve.

Question 35

What relationship is necessary to understand to determine the infusion rate? Hint: Css =

Answer 35

Css = Infusion Rate / Total Body Clearance

Question 36

What happens if you can not wait for 5 half lives to achieve a therapeutic range of a drug?

Answer 36

Give a loading dose

Question 37

What is the formula for calculating the loading dose?

Answer 37

(LD) = (Css x Vd) / F

Question 38

What is dangerous about using loading doses?

Answer 38

You can achieve relatively high concentrations of drug in the blood system

Question 39

After the loading dose what is required to mantain the therapeutic window of drug concentration?

Answer 39

Following the loading dose you will hace to give the patients a maintenance dose

Question 40

How do you calculate the maintenance does?

Answer 40

Dosing rate = target Css x CL / F

Question 41

Describe zero order kinetics

Answer 41

If the enzymes that metabolize a drug are rate limiting i.e. the enzyme is saturated at usual levels of drug in the body then the same amount of drug is metabolized regardless of the level of drug. No plateau is observed.

Question 42

Work the practice problems that were given in lecture .

Answer 42

Have you done it yet?