Drug Distribution Flashcards
Vd allows determination of the necessary dose (_____) to fill the distribution volume with enough drug to achieve desired steady state plasma level (Cp).
(loading dose [LD])
Most drugs are absorbed into and eliminated from one central body compartment, _______.
the plasma
When the ____ is lower than the pKa of the drug, there are relatively more _____ and the protonated form of the weak acid [unionized-lipophilic] or weak base [ionized] drug will predominate.
pH; protons
Dissociation of a proton from an acid produces an _____ drug, whereas dissociation of a proton from a base produces an _____ drug.
ionized; un-ionized
Acidic drugs are trapped in the more ____ solutions.
basic
When the pH is lower than the pKa of the drug, there are relatively more protons and the protonated form of the weak acid _____ or weak base _____ drug will predominate.
[unionized-lipophilic]; [ionized]
Ionized drugs can enter the plasma circulation following _____ and can enter the urine tubular fluid following ______.
parenteral administration; filtration at the glomerulus
How is excretion enhanced by the kidney?
there is reduced reabsorption of the drug from the urine into the blood after glomerular filtration
_____ drug forms are more readily absorbed.
Non-ionized
_____ bind primarily to albumin; ____ bind to alpha-1 acid glycoprotein.
Acidic drugs; basic drugs
Name 4 effects of protein binding to drugs.
1) reduces conc of active, free drug 2) hinders metabolic degradation and reduce rate of excretion –> prolongs drug action 3) decreases volume of dist 4) decreases ability to enter CNS
What does Vd stand for?
volume of distribution
Vd gives an indication of the extent to which a drug passes from _____ to ______.
plasma; extravascular tissue
Ionized forms do not cross ______.
lipid membranes
Dissociation of a proton from an ____ produces an ionized drug, whereas dissociation of a proton from a ____ produces an un-ionized drug.
acid; base
At pHs where the unionized form predominates, drug ______is favored; at pHs where the ionized form predominates, ______ is possible.
absorption; ion-trapping
Name 3 examples of clinical ion trapping.
1) urine traps aspirin (weak acid) in ODs 2) Basic drugs (opiods) are trapped and concentrate in acidic breast milk 3) Weak base toxins (PCP, meth) are found concentrated in the acidic stomach contents.
What must be present for ion trapping to occur?
ions
Vd will vary between patients depending on ____, _____ and ______.
body size (weight), composition (fat vs lean), changes in protein binding
Acids become non-ionized in _____.
acid medium
Vd = ?
amount of drug in body (Ab) / concentration of drug in plasma (C0)
_____ allows determination of the necessary dose (loading dose [LD]) to fill the distribution volume with enough drug to achieve desired steady state plasma level (Cp).
Vd
At equilibrium, un-ionized concentration of drug is the same on both sides of the membrane, but total concentration of drug is ______.
greater on the side where ionization is greater
Vd allows the prescriber to determine the effect any given dose [D] will have on the _____.
plasma concentration [Cp]
