Lecture 3: Distribution

Question 1

Drug Transport Process

Answer 1

-paracellular
-transcellular
-carrier mediated

-go from lumen to blood

Question 2

passive diffusion

Answer 2

-down concentration gradient
-not saturated
-most common

Question 3

Facilitated Diffusion

Answer 3

-down concentration
-carriers
-saturable

Question 4

Active transport

Answer 4

-AGAINST concentration
-via TRANSPORTER
-use ATP
-saturable

Question 5

Passive transport

Answer 5

-diffusion
-faciliatated diffusion (carrier mediated)

Question 6

Factors determining diffusion

Answer 6

-molecular size
-lipophilicity
-charge

Question 7

Smaller molecules permeability

Answer 7

high

Question 8

lipophilic molecules permeability

Answer 8

high

Question 9

Log P

Answer 9

-higher = more lipophilic

Question 10

charge molecule permeability

Answer 10

POOR

Question 11

(True/false) Salicylic acid will exhibit better crossing through the lipid bilayer at higher pH (e.g., in a
basic condition)

Answer 11

-FALSE
-it is charged at higher pH

Question 12

Rate-limiting factors

Answer 12

-perfusion-rate limiting
-permeability-rate limiting

Question 13

perfusion rate-limiting factors

Answer 13

-lipophilic compounds
-limited by amount of blood carrying drugs away
-faster distribution

Question 14

Permeability-rate limiting factors

Answer 14

-hydrophilic compunds
-limited by slow rate of passing the cell membrane
-will not distribute as well

Question 15

Would brain (0.5 perfusion rate) or muscle (0.025 perfusion rate) show faster distribution of propofol (nonpolar lipophilic compound with perfusion-rate limitation)

Answer 15

brain

Question 16

major drug binding plasma proteins

Answer 16

-albumin
-a1-acid glycoprotein
-lipoproteins

Question 17

albumin

Answer 17

-most abundant plasma protein (50%)
-produced in liver
-binds fatty acids, hormones, and weakly acidic drugs

Question 18

albumin function

Answer 18

-maintain oncotic pressure of blood

Question 19

albumin serum levels

Answer 19

decreased in liver and kidney disease

Question 20

a1-acid glycoprotein (AAG)

Answer 20

-aka orosomucoid
-produced in liver
-binds weakly basic drugs (3’ or 4’ amines)

Question 21

a1-acid serum levels

Answer 21

-increase during acute phase reaction (inflammation and. burns)
-DECREASED in liver and kidney disease

Question 22

Lipoproteins

Answer 22

-lipophilic protein or complex of protiens and lipids
-HDL, LDL
-binds hydrophobic drugs
-altered in heart disease state

Question 23

Free drug Hypothesis

Answer 23

-only free drugs:

-exit capillaries
-cross membrane via diffusion
-bind transporters

Question 24

Plasma protein-binding

Answer 24

is reversible

Question 25

Free drug concentration

Answer 25

-same on both sides of membrane at equilibrium

Question 26

Plasma

Answer 26

-liquid component of blood where blood cells are suspended (yellow) -makes up 55% blood volume -contains fibrinogen, globulins, albumin

Question 27

Serum

Answer 27

-blood allowed to coagulate, clot, and settle at bottom of tube -supernatant fluid -devoid of blood cells, fibrins, and clotting factors -contains plasma proteins

Question 28

Unbound fraction (fu)

Answer 28

Free drug concentration (Cu)/Total drug concentration (C)

Question 29

Ultrafiltration

Answer 29

-allow only free drug to be filtered -allow estimate of unbound fraction

Question 30

Determinants of Vd

Answer 30

-increase when fu increases -decrease when FuT increases

Question 31

Ionized compounds show poorer membrane permeability than un-ionized compounds

Answer 31

TRUE

Question 32

Lipophilic compounds tend to show greater membrane permeability

Answer 32

TRUE

Question 33

Lipophilic compounds tend to show permeability rate-limited distribution

Answer 33

-FALSE -PERFUSION rate-limited

Question 34

Decreased plasma protein binding of high protein-bound drugs will likely increase Vd

Answer 34

TRUE

Question 35

Vd is expected to be small for a drug that exhibits strong binding to tissue components

Answer 35

FALSE -it will be large

Question 36

fut

Answer 36

-unbound drug fraction in tissues -Vd will be smaller for more unbound franstion