Drug Distribution - Protein Binding Flashcards
fu
Fraction unbound in plasma
Fu, T
Fraction unbound in Tissues
Cu
Free drug concentration in plasma
Cu, T
Free drug concentration in tissue
Kp
Tissue-to-plasma equilibrium distribution ratio
Vp
plasma volume
VT
tissue volume
Drug distribution is broken up into what two different categories?
extent of distribution and rate of distribution
Determinants of “extent of distribution”
PROTEIN BINDING
plasma volume
tissue volume
Determinants of “rate of distribution”
BLOOD FLOW (perfusion)
PERMEABILITY
tissue volume
T/F - (plasma) Protein-bound drug molecules are available to exert pharmacologic effect and can be eliminated.
False - bc they are bound, they can NOT be used to exert a pharmacologic effect nor can they be eliminated.
Concerning plasma protein binding drugs, acidic drugs usually bind to ______ while basic drugs usually bind to ______.
plasma albumin; alpha1-acid glycoprotein
__________ drug is pharmacologically active.
unbound
Plasma protein binding of a drug are ________.
not selective
Fu is defined as…
the extent to which a drug is bound to plasma/blood proteins or tissue components
What is fraction bound and fraction unbound related to?
1
What is total drug concentration equal to?
unbound drug conc. + bound drug conc.
The Fu value of a drug is determined by:
The plasma protein conc.
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___________.
30 mcg/L; 70% (no change)
There is relationship between fu and fu,T.
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.
What is the PRIMARY determinant of the magnitude of volume of distribution of a drug?
ratio of fu to fu,T -> tissue to plasma equilibrium distribution ratio (Kp = fu/fu,T)
F/T = Free/unbound drug conc. in plasma (Cu) and tissue (Cu,T) are equal under distribution equilibrium.
True
Cu =
fuC
Cu,T =
fu,T CT
T/F - highly plasma protein bound drugs have small volume of distribution value.
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.
T/F - Displacement of drug from its plasma protein binding site results in a decrease in volume of distribution.
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.
T/F - fu and V have an indirect relationship with one another.
F - there is a direct relationship
What is V magnitude determined by?
It is determined by Kp value
Lower V value means more drug in plasma
true
Greater V value means more drug in the tissue
True
Under distribution equilibrium, when a drug is displaced from its plasma protein binding site, its bound fraction in plasma should __________.
decrease (fb=1-fu)
Under distribution equilibrium, when a drug is displaced from its plasma protein binding site, its unbound conc. in tissue should ___________.
increase (Cu,T=Cu)
Under distribution equilibrium, when a drug is displaced from its plasma protein binding site,
decrease (the free drug molecules move plasma to tissue causing a decrease in the total drug conc. in plasma)
Under distribution equilibrium, when a drug is displaced from its plasma protein binding site, its unbound fraction tissue should _________.
have no change (fu and fu,T have no relationship)
Under distribution equilibrium, when a drug is displaced from its plasma protein binding site, its volume of distribution should _________.
increase (the increased fu/fu,T or CT/C ratio)
