Lecture 1 part 3

Question 1

is drug permeation a pharmacokinetic or dynamic principle

Answer 1

kinetic

Question 2

drug permeation proceeds by how many mechanisms?
name them

Answer 2

4:

-aqueous diffusion
-lipid diffusion
-special carriers
-exocytosis and endocytosis

Question 3

give an example of a molecule that needs a special carrier to permeate

Answer 3

glucose

Question 4

true or false

passive diffusion in an aqueous or lipid medium is common

Answer 4

true

Question 5

active processes play a role in the movement of drugs, especially with what kind of molecules —

Answer 5

those that are too large to diffuse readily

Question 6

what is aqueous diffusion driven by?

Answer 6

usually by the concentration gradient of the drug

-downhill movement described by FICK’S LAW

Question 7

Where does aqueous diffusion occur (3 places)

Answer 7

within larger aqueous compartments of the body

across epithelial tight membrane junctions

across the endothelial lining of blood vessels (through pores that permit 20,000-30,000 MW)

Question 8

true or false

drug molecules that are bound to large plasma proteins like albumin will not permeate through aqueous pores

Answer 8

true

Question 9

what is the most important RATE LIMITING FACTOR for drug permeation and why?

Answer 9

lipid permeation

bc there are a large number of lipid barriers that separate aqueous compartments of the body

Question 10

what determines how readily the drug molecule moves between the aqueous and lipid media?

Answer 10

the lipid:aqueous partition coefficient

Question 11

the higher the partition coefficient……..

Answer 11

the higher the lipid solubility

Question 12

special carriers exist for what kind of substances?

Answer 12

that are important for cell function but too big or too insoluble in lipid to passively diffuse through membranes

-peptides
-amino acids
-glucose

Question 13

how do these special carriers bring about movement

Answer 13

active transport or facilitated diffusion

Question 14

special carrier transport mechanisms are ___ and ____

Answer 14

saturable and inhibitable

Question 15

how is it that drugs can use special carriers used for endogenous substances like glucose, amino acids, and peptides, for their own transport?

Answer 15

because many drugs resemble these molecules

Question 16

a few substances are so large that they can only enter cells how?

Answer 16

by endocytosis

Question 17

define endocytosis

Answer 17

process in which the substance is engulfed by the cell membrane and carried into the cell by pinching off the newly formed vesicle inside the membrane

substance then released inside the cytosol bc of breakdown of vesicle membrane

Question 18

endocytosis is responsible for the transport of what?
explain the transport mechanism

Answer 18

iron and vit B12

each forms a complex with binding proteins. they cross the wall of the gut and get into the blood

Question 19

what is the reverse process of endocytosis? what is it responsible for?

Answer 19

exocytosis

the secretion of many substances from cells

Question 20

give a specific example of exocytosis

Answer 20

many neurotransmitters are stored in membrane-bound VESICLES in nerve endings to protect them from metabolic destruction in cytoplasm.

therefore, only when the nerve ending is activated the storage vesicle fuses with the cell membrane and expulses the contents into the extracellular space

Question 21

define Fick’s law and give the formula

Answer 21

passive flux of molecules DOWN a concentration gradient

flux = C1(higher conc)-C2 * [Area (where diffusion happening * permeability coefficient] / thickness of diffusion path

flux = number of molecules diffusing/unit time

Question 22

in the case of _____ diffusion, the lipid: aqueous partition coefficient is a major determinant of the mobility of the drug.

why?

Answer 22

lipid diffusion

it determines how readily the drug enters the lipid membrane from the aqueous medium

Question 23

true or false

the ionization of drugs reduces their ability to permeate through membranes

Answer 23

true

due to the electrostatic charge – attracts water dipoles and results in a polar, relatively water-soluble and lipid insoluble complex

Question 24

true or false

a small fraction of drugs today are weak acids/bases

Answer 24

false - large fraction

Question 25

what is the best buffer

Answer 25

the body

Question 26

define a weak acid

Answer 26

acids that do not completely dissociate into their constituent ions when dissolved in solution

Question 27

give 5 examples of weak acids

Answer 27

phosphoric acid
nitrous acid
methanoic acid
acetic acid
ascorbic acid

Question 28

define a weak base

Answer 28

base that, when dissolves in water, does not dissociate completely. the resulting solution contains only small proportion of hydroxide ions

Question 29

give 6 ex of weak base

Answer 29

ammonia (NH3)
aluminum hydroxide
lead hydroxide
ferric hydroxide
copper hydroxide
zinc hydroxide

Question 30

what is the most important application of the principle of the ionization of weak acids/bases

Answer 30

the manipulation of drug excretion by the kidney

Question 31

where are almost all drugs filtered?

Answer 31

the glomerulus

Question 32

what will happen if a drug is too lipid-soluble when passing through the renal tubule

Answer 32

a significant fraction will be reabsorbed by simple passive diffusion back into the body

Question 33

if the goal is to ACCELERATE the excretion of the drug, what is important?

how can it be accomplished?

Answer 33

prevent the reabsorption of the drug from the tubule and back into the body

can be done by adjusting the urine pH to make most of the drug ionized. The drug will be trapped in the urine

Question 34

true or false

weak acids are usually excreted faster in acidic urine

Answer 34

false

alkaline

Question 35

true or false

weak bases are usually excreted faster in acidic urine

Answer 35

true

Question 36

in metabolism, lipophilic drugs are metabolized to form relatively more hydrophilic metabolites.

what can you say about these metabolites

Answer 36

they are more easily excreted (harder to be reabsorbed into the body)

Question 37

true or false

lipophilic substances are harder to be reabsorbed than hydrophilic

Answer 37

false

hydrophilic are harder to be reabsorbed and more easily excreted from the kidney