Drug Distribution

Question 1

Vd allows determination of the necessary dose (_____) to fill the distribution volume with enough drug to achieve desired steady state plasma level (Cp).

Answer 1

(loading dose [LD])

Question 2

Most drugs are absorbed into and eliminated from one central body compartment, _______.

Answer 2

the plasma

Question 3

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.

Answer 3

pH; protons

Question 4

Dissociation of a proton from an acid produces an _____ drug, whereas dissociation of a proton from a base produces an _____ drug.

Answer 4

ionized; un-ionized

Question 4

Acidic drugs are trapped in the more ____ solutions.

Answer 4

basic

Question 5

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.

Answer 5

[unionized-lipophilic]; [ionized]

Question 6

Ionized drugs can enter the plasma circulation following _____ and can enter the urine tubular fluid following ______.

Answer 6

parenteral administration; filtration at the glomerulus

Question 7

How is excretion enhanced by the kidney?

Answer 7

there is reduced reabsorption of the drug from the urine into the blood after glomerular filtration

Question 8

_____ drug forms are more readily absorbed.

Answer 8

Non-ionized

Question 8

_____ bind primarily to albumin; ____ bind to alpha-1 acid glycoprotein.

Answer 8

Acidic drugs; basic drugs

Question 9

Name 4 effects of protein binding to drugs.

Answer 9

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

Question 10

What does Vd stand for?

Answer 10

volume of distribution

Question 10

Vd gives an indication of the extent to which a drug passes from _____ to ______.

Answer 10

plasma; extravascular tissue

Question 10

Ionized forms do not cross ______.

Answer 10

lipid membranes

Question 11

Dissociation of a proton from an ____ produces an ionized drug, whereas dissociation of a proton from a ____ produces an un-ionized drug.

Answer 11

acid; base

Question 12

At pHs where the unionized form predominates, drug ______is favored; at pHs where the ionized form predominates, ______ is possible.

Answer 12

absorption; ion-trapping

Question 12

Name 3 examples of clinical ion trapping.

Answer 12

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.

Question 12

What must be present for ion trapping to occur?

Answer 12

ions

Question 13

Vd will vary between patients depending on ____, _____ and ______.

Answer 13

body size (weight), composition (fat vs lean), changes in protein binding

Question 14

Acids become non-ionized in _____.

Answer 14

acid medium

Question 15

Vd = ?

Answer 15

amount of drug in body (Ab) / concentration of drug in plasma (C0)

Question 16

_____ 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).

Answer 16

Vd

Question 17

At equilibrium, un-ionized concentration of drug is the same on both sides of the membrane, but total concentration of drug is ______.

Answer 17

greater on the side where ionization is greater

Question 19

Vd allows the prescriber to determine the effect any given dose [D] will have on the _____.

Answer 19

plasma concentration [Cp]

Question 20

Basic drugs are trapped in the more _____ solutions.

Answer 20

acidic

Question 21

At equilibrium, un-ionized concentration of drug is ____, but total concentration of drug is greater on the side where ionization is greater.

Answer 21

the same on both sides of the membrane

Question 22

At pHs where the _____ form predominates, drug absorption is favored; at pHs where the _____ form predominates, ion-trapping is possible.

Answer 22

unionized; ionized

Question 23

_____ can enter the plasma circulation following parenteral administration and can enter the urine tubular fluid following filtration at the glomerulus.

Answer 23

Ionized drugs

Question 24

Where can selective accumulation occur?

Answer 24

in the kidney, eye, lung, bone, ear

Question 25

When the ____ is higher than the pKa of the drug, there are relatively ____ protons and the unprotonated form of the weak acid [ionized-hydrophilic] or weak base [unionizedlipophilic] drug will predominate.

Answer 25

pH; fewer

Question 27

Which drugs cannot pass through membranes?

Answer 27

those of large size, protein bound, highly charged, or high water solubility

Question 28

When the pH is higher than the pKa of the drug there are relatively fewer protons and the unprotonated form of the _____ [ionized-hydrophilic] or _____[unionizedlipophilic] drug will predominate.

Answer 28

weak acid; weak base

Question 30

______ drug forms do not cross lipid membranes.

Answer 30

Ionized

Question 31

When the pH is ____ than the pKa of the drug, there are relatively fewer protons and the unprotonated form of the weak acid [ionized-hydrophilic] or weak base [unionizedlipophilic] drug will ______.

Answer 31

higher; predominate

Question 33

Drugs that can’t pass through membranes will be unable to move between ____ and _____.

Answer 33

tissues with tight junctions compartments and the blood

Question 35

What does the Vd tell?

Answer 35

the size of compartment needed to account for the total amount of drug in the body if it were found in the same concentration throughout the body

Question 36

____ will vary between patients depending on body size (weight), composition (fat vs lean), and changes in protein binding.

Answer 36

Vd

Question 37

____ allows the prescriber to determine the effect any given dose [D] will have on the plasma concentration [Cp].

Answer 37

Vd

Question 38

Most drugs are absorbed into and eliminated from _____, the plasma.

Answer 38

one central body compartment

Question 40

Most drugs are _____ or weak bases.

Answer 40

weak acids

Question 41

Acidic drugs bind primarily to _____; basic drugs bind to ______.

Answer 41

albumin; alpha-1 acid glycoprotein

Question 43

Only non-ionized drug can _____.

Answer 43

diffuse through the membrane

Question 43

At equilibrium, ______ 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.

Answer 43

un-ionized

Question 44

Only _____ drug can diffuse through the membrane.

Answer 44

non-ionized

Question 45

Which tissues have tight junctions?

Answer 45

GI mucosa, BBB, placenta, renal tubules

Question 46

_____ drugs are trapped in the more basic solutions.

Answer 46

Acidic

Question 47

_____ drugs are trapped in the more acidic solutions.

Answer 47

Basic

Question 48

_____ gives an indication of the extent to which a drug passes from plasma to extravascular tissue.

Answer 48

Vd

Question 49

Bases become nonionized in _____.

Answer 49

alkaline medium

Question 50

Nonionized forms are _____ absorbed.

Answer 50

more readily

Question 51

When the pH is _____ than the pKa of the drug, there are relatively more protons and the protonated form of the weak acid [unionized-lipophilic] or weak base [ionized] drug will ______.

Answer 51

lower; predominate