PHARM: Clinical Pharmacokinetics

Question 1

True or False: IV administration is the fastest route of drug absorption.

Answer 1

False- when administered via IV, there is no drug absorption

Question 2

How can the rate of elimination of a drug be calculated in a one-compartment model?

Answer 2

Rate of Elimination (Vel)= Inherent rate of Elimination (Kel) * [Drug] in the body ([A]c)

Question 3

What does it mean if a drug follows a 1st order process of elimination?

Answer 3

The drug elimination is proportional to the drug concentration in the body

Question 4

True or False: Kel is a constant for a particular drug.

Answer 4

False: Kel can be different from individual to individual and can be different in the same individual at different times

Question 5

How can Kel be determined from a Semi-log plot of [drug] vs. time?

Answer 5

Kel is the slope of the line

Question 6

What is the half life of a drug?

Answer 6

The time it takes for half of the drug to be eliminated from the body

Question 7

What is the relationship between half-life and the elimination rate constant for first order drugs?

Answer 7

Kel=0.693/T(1/2)

Question 8

What sorts of drugs are zero order drugs?

Answer 8

Drugs whose metabolism or elimination is mediated by proteins, and thus, is saturable

Question 9

What is the appearance of a regular and semi-log plot of a zero order drug?

Answer 9

Regular plots show a linear decrease, and semi-log plots are concave downward until the rxn is no longer is zero order

Question 10

How can the rate at which a drug is absorbed be calculated for a drug administered extravascularly in a one compartment model?

Answer 10

Rate of absorption (Vabs)= absorptive rate constant for the drug (Kabs) * concentration of the drug at the absorptive site ([A]a)

Question 11

How can a drug following a one-compartment model and in a first order process be identified by looking at a semi-log plot?

Answer 11

The semi-log plots for these drugs will simply be a straight line

Question 12

Following administration into a two compartment model via intravascular bolus and accumulation in the central compartment what two process can happen to the drug?

Answer 12

Elimination or Distribution to peripheral compartment

Question 13

How can distribution from the central to peripheral compartment be calculated?

Answer 13

Vcp= Kcp (rate constant for drug describing ability to distribute from central to peripheral compartments) * [A]c (conc. of drug in central compartment)

Question 14

How can distribution from the peripheral to central compartment be calculated?

Answer 14

Vpc= Kpc * [A]p

Question 15

On a regular plot of a two compartment model drug what is alpha and what is beta? What is happening to the drug during those periods?

Answer 15

Alpha is the distribution phase that consists of the rapid decrease in [drug] from initial concentration. Beta is the disposition phase, which consists of distribution, redistribution, and elimination of drug

Question 16

How can beta be calculated for a two-compartment model drug?

Answer 16

Beta= 0.693/T(1/2)beta, where T(1/2)beta can be determined by using the linear portion of a semi log plot (indicating the cessation of distribution/redistribution)

Question 17

What are the three phases of a semi-log plot of a drug administered extravascularly into a 2 compartment system?

Answer 17

Absorption, Distribution, Disposition

Question 18

What is the utility of apparent volumes of distribution?

Answer 18

Gives an idea on where a drug goes once it enters the body

Question 19

How can apparent volumes of distribution be calculated?

Answer 19

Give a patient a drug of a known amount, take blood levels (concentration) over time and then extrapolate the concentration to time point 0 prior to any elimination. Dividing the amount of drug by the concentration at time 0 will give the apparent volume of distribution

Question 20

A drug is given to a patient and has a calculated apparent volume of distribution equal to 5.5 L. Where is the drug primarily located?

Answer 20

Within the vasculature

Question 21

A drug is given to a patient and has a calculated apparent volume of distribution equal to 14.6 L. Where is the drug primarily located?

Answer 21

In the vasculature and ECF

Question 22

A drug is given to a patient and has a calculated apparent volume of distribution equal to 105.5 L. Where is the drug primarily located?

Answer 22

Some tissue compartment of the body

Question 23

What is bioavailability?

Answer 23

The fraction of drug that reaches systemic circulation- essentially a measure of absorption of a drug and how effectively it is absorbed

Question 24

How can bioavailability be determined?

Answer 24

First administer a drug via IV, measure drug concentration over time and measure the area under the curve of a regular plot. Next administer the drug via extravascular route and obtain the area under the curve. Bioavailability (F)= AUCx/AUCiv

Question 25

What is the interpretation of “When administered sublingually, THC has an F of 1?”

Answer 25

All of the THC that would have entered into systemic circulation directly via IV is the same amount that would get into circulation via sublingual administration

Question 26

What is clearance?

Answer 26

The theoretical volume of fluid from which a drug is completely removed in a given period of time

Question 27

What two equations can be used to determine total clearance?

Answer 27

Clt=Kel * Vd; =Xo/AUC

Question 28

What is the extraction ratio and how is it calculated?

Answer 28

E is the efficiency at which an organ extracts a drug and is =(Cin - Cout)/(Cin)

Question 29

How could one determine clearance of a drug from the liver?

Answer 29

Clh= Q (rate of blood flow) * E

Question 30

What are the three processes that contribute to renal clearance of a drug?

Answer 30

Glomerular filtration, Active secretion, passive reabsorption

Question 31

How is renal clearance of a drug calculated?

Answer 31

Clr=Clglomfilt + Cl (actsec) - Cl(tubReab)

Question 32

What is the minimum effective concentration?

Answer 32

The concentration of a drug needed to produce its pharmacological effect

Question 33

What is the steady state concentration?

Answer 33

The concentration at which a drug administered continuously has a dose rate = rate of elimination such that the blood concentration of a drug remains stable

Question 34

How can steady state concentration be calculated

Answer 34

Css=dose rate/ Ct or dose rate/ Kel * Vd

Question 35

When administering a drug via IV infusion how long does it take for a drug to reach half of its steady state concentration?

Answer 35

One half life

Question 36

When administering a drug via IV infusion how long does it take for a drug to reach its steady state concentration?

Answer 36

4-5 Half lives

Question 37

How does increasing the frequency of a smaller dose of a drug effect its pharmacokinetics?

Answer 37

There is smaller fluctuations in the concentration level

Question 38

What is a loading dose? When is it needed? How can it be calculated?

Answer 38

A loading dose is a higher first dose given when the therapeutic window must be reached quickly. Loading dose (X*)=Css *Vd

Question 39

How would a graph of multiple IV administrations differ from a graph of multiple extravascular administrations?

Answer 39

The spikes on the fluctuations would be more rounded due to absorption slowing down the process

Question 40

How can the steady state concentration of a drug administered multiple times be calculated?

Answer 40

Css= (F*dose rate)/Clt