Drug Distribution - Protein Binding

Question 1

fu

Answer 1

Fraction unbound in plasma

Question 2

Fu, T

Answer 2

Fraction unbound in Tissues

Question 3

Cu

Answer 3

Free drug concentration in plasma

Question 4

Cu, T

Answer 4

Free drug concentration in tissue

Question 5

Kp

Answer 5

Tissue-to-plasma equilibrium distribution ratio

Question 6

Vp

Answer 6

plasma volume

Question 7

VT

Answer 7

tissue volume

Question 8

Drug distribution is broken up into what two different categories?

Answer 8

extent of distribution and rate of distribution

Question 9

Determinants of “extent of distribution”

Answer 9

PROTEIN BINDING
plasma volume
tissue volume

Question 10

Determinants of “rate of distribution”

Answer 10

BLOOD FLOW (perfusion)
PERMEABILITY
tissue volume

Question 11

T/F - (plasma) Protein-bound drug molecules are available to exert pharmacologic effect and can be eliminated.

Answer 11

False - bc they are bound, they can NOT be used to exert a pharmacologic effect nor can they be eliminated.

Question 12

Concerning plasma protein binding drugs, acidic drugs usually bind to ______ while basic drugs usually bind to ______.

Answer 12

plasma albumin; alpha1-acid glycoprotein

Question 13

__________ drug is pharmacologically active.

Answer 13

unbound

Question 14

Plasma protein binding of a drug are ________.

Answer 14

not selective

Question 15

Fu is defined as…

Answer 15

the extent to which a drug is bound to plasma/blood proteins or tissue components

Question 16

What is fraction bound and fraction unbound related to?

Answer 16

1

Question 17

What is total drug concentration equal to?

Answer 17

unbound drug conc. + bound drug conc.

Question 18

The Fu value of a drug is determined by:

Answer 18

The plasma protein conc.

Question 19

The total conc. of Drug A is 100mcg/L and its fu is 70%. The bound conc. of Drug A is ________. When the total conc. of Drug A is halved, its fu should be___________.

Answer 19

30 mcg/L; 70% (no change)

Question 20

There is relationship between fu and fu,T.

Answer 20

F - there is no relationship between fu and fu, T. They are two different compartments and have no correlation to one another. The binding proteins in plasma are different from those in tissues so the change in fu should have no effect on fu,T and vice versa.

Question 21

What is the PRIMARY determinant of the magnitude of volume of distribution of a drug?

Answer 21

ratio of fu to fu,T -> tissue to plasma equilibrium distribution ratio (Kp = fu/fu,T)

Question 22

F/T = Free/unbound drug conc. in plasma (Cu) and tissue (Cu,T) are equal under distribution equilibrium.

Answer 22

True

Question 23

Cu =

Answer 23

fuC

Question 24

Cu,T =

Answer 24

fu,T CT

Question 25

T/F - highly plasma protein bound drugs have small volume of distribution value.

Answer 25

F - The volume of distribution value is not dependent on the plasma protein binding alone. It depends on its binding affinity for tissue components as well. Volume of distribution value represents the relative distribution of a drug between plasma and tissue.

Question 26

T/F - Displacement of drug from its plasma protein binding site results in a decrease in volume of distribution.

Answer 26

F - Based on V = Vp+Vt*(fu/fu,T), displacement of drug from its plasma protein binding sire results in increase in fu value and thus an increase in V.

Question 27

T/F - fu and V have an indirect relationship with one another.

Answer 27

F - there is a direct relationship

Question 28

What is V magnitude determined by?

Answer 28

It is determined by Kp value

Question 29

Lower V value means more drug in plasma

Answer 29

true

Question 30

Greater V value means more drug in the tissue

Answer 30

True

Question 31

Under distribution equilibrium, when a drug is displaced from its plasma protein binding site, its bound fraction in plasma should __________.

Answer 31

decrease (fb=1-fu)

Question 32

Under distribution equilibrium, when a drug is displaced from its plasma protein binding site, its unbound conc. in tissue should ___________.

Answer 32

increase (Cu,T=Cu)

Question 33

Under distribution equilibrium, when a drug is displaced from its plasma protein binding site,

Answer 33

decrease (the free drug molecules move plasma to tissue causing a decrease in the total drug conc. in plasma)

Question 34

Under distribution equilibrium, when a drug is displaced from its plasma protein binding site, its unbound fraction tissue should _________.

Answer 34

have no change (fu and fu,T have no relationship)

Question 35

Under distribution equilibrium, when a drug is displaced from its plasma protein binding site, its volume of distribution should _________.

Answer 35

increase (the increased fu/fu,T or CT/C ratio)