Lab 3

Question 1

A drug must do what 3 things to produce a biological response?

Answer 1

1. cross the biological membrane
2. interact with biological fluids
3. reach its site of action

Question 2

name 3 properties that influence the ADME and biological activity of a drug

Answer 2

solubility, ionization, and stability

Question 3

the environment in the biological tissue must be favorable to facilitate ___ and ____ and maintain the characteristics necessary to do what?

Answer 3

environment must be favorable to facilitate ABSORPTION AND DISTRIBUTION and maintain the characteristics necessary to INTERACT WITH THE BIOLOGICAL RECEPTOR TO PRODUCE BIOLOGICAL EFFECTS

Question 4

Before it is absorbed, the drug must be….

Answer 4

soluble in the local biological fluid

Question 5

the solubility of a drug depends on what?

Answer 5

its ability to form hydrogen bonds and/or ionize in water

Question 6

changes in ionization are influenced by _____

Answer 6

pH

Question 7

name 2 things that can REDUCE the amount of drug absorbed in the GI tract

Answer 7

1. changes in ionization
2. complex formation through interaction with the GI tract contents

Question 8

true or false

when a drug is in circulation, it is post absorption and IV administration

Answer 8

TRUE

Question 9

when the drug is in circulation, what can delay or prevent the drug from reaching the site of action?

Answer 9

protein binding

Question 10

drugs must partition between the ___ phase and the ____ phase to _____________

Answer 10

drugs must partition between the AQUEOUS PHASE (GI, blood) and lipid phase (cell membrane) to ENTER TISSUE CELLS

Question 11

true or false

partition coefficient is measured at a specific temperature

Answer 11

TRUE

Question 12

When partition coefficient is being measured, it is assumed that there is….

Answer 12

a SINGLE SPECIES OF THE DRUG partitioning between the lipid and aqueous phase

Question 13

as mentioned, when measuring partition coefficient, it is assumed that there is a single species of the drug partitioning between the lipid and aqueous phase.

what is an important consideration about this?

Answer 13

most drugs are weak acids or weak bases and the number of different species and their concentrations will VARY with pH

unionized (neutral), zwitterions (neutral), and charged (positive or negative ions) species may be present depending on the pH

Question 14

true or false

as mentioned, unionized (neutral), zwitterions (neutral), and charged (positive or negative ions) species may be present depending on the pH.
each species will have the SAME partition coefficient characteristics

Answer 14

FALSE - each species may differ in partition coefficient characteristics

Question 15

define distribution coefficient

Answer 15

the ratio of the drug partitioning between the lipid and aqueous phases pf the various species present

Question 16

it is assumed that ______ species do NOT partition in the lipid phase

Answer 16

IONIC

Question 17

the partition coefficient of neutral drugs is equivalent to its ________.

why?

Answer 17

for neutral drugs, partition coefficient is equivalent to its distribution coefficient.

this is because a neutral drug does not ionize and contains a SINGLE SPECIES, regardless of pH

Question 18

drugs with weak acid or weak base properties exhibit what kind of ionization?

Answer 18

pH dependent

Question 19

Distribution coefficients consider what factors?

Answer 19

consider the pH, concentration, and partitioning properties of both the ionic AND non-ionic species

Question 20

which is more relevant to predict drug permeability and aqueous of weak acids and bases and why? – partition coefficient or distribution coefficient?

Answer 20

distribution coefficient because it considers the pH, concentration, and partitioning properties of the ionic and nonionic species

Question 21

true or false

the percent ionization does not vary with pH for weak acids and bases

Answer 21

FALSE - it does vary for weak acids and bases

Question 22

is the distribution coefficient higher for ionizable drugs or nonionizable drugs?

explain

Answer 22

the distribution coefficient is higher in nonionizable drugs.

this is because for ionizable drugs, a fraction of the drug is ionized at biological pH and does not partition into the lipid phase

Question 23

what has to exist in order to predict the distribution coefficient at a specific pH using the hendersen hasselbach equation?

Answer 23

-if only the non-ionic species partitions in the lipid phase

-the partition coefficient for the free form is known

Question 24

the Henderson-Hasselbalch equation expresses the relationship of…..

Answer 24

pka, the ratio of the acid:conjugate base and the pH

Question 25

write the Henderson-Hasselbalch equation

Answer 25

pH=pka + log (base/acid)

Question 26

the partition coefficient value of acid and basic drugs is affected by what 3 things? (besides % ionization)

Answer 26

pH, intrinsic solubility in the organic solvent, solvent volume

Question 27

the _______ the solubility of a drug in a solvent, the better the extraction efficiency in that solvent

Answer 27

the MORE soluble the drug is in the solvent, the better the extraction efficiency in that solvent

Question 28

how do you get the most effective extractions?

Answer 28

several smaller extractions are more effective than 1 large extraction with the same volume

Question 29

for extraction in the organic solvent, the drug must be in what form?

Answer 29

UNIONIZED

Question 30

______ is also known as the free form (ionized or unionized)

Answer 30

unionized

Question 31

as mentioned, for extraction in the organic solvent, the drug must be in unionized form. HENCE..........

Answer 31

the pH must be adjusted to more than 4 pH units away from the pka of the drug so that almost all the drug is in unionized form

Question 32

ephedrine is a ___ ____

Answer 32

sympathomemetic amine

Question 33

ephedrine may enhance the release of _______ through what?

Answer 33

ephedrine has alpha- beta- adrenergic agonists that may enhance the release of norepinephrine

Question 34

compare the water solubilities of ephedrine and baclofen

Answer 34

ephedrine is much more soluble in water (56,900mg/L) than Baclofen (2090mg/L)

Question 35

what kind of drug is baclofen?

Answer 35

a muscle relaxant

Question 36

true or false baclofen is stable under normal conditions

Answer 36

TRUE

Question 37

Explain the structure of baclofen

Answer 37

it is amphoteric and exists as a zwitterion at ph 7 has 2 pkas because of this (3.85 and 9.25)

Question 38

does baclofen bind to serum proteins?

Answer 38

no - not significantly

Question 39

how is baclofen excreted?

Answer 39

mainly in the urine (90%)

Question 40

which enantiomer of baclofen is more active?

Answer 40

the l (-) enantiomer is more active -- but it also is related to toxicity

Question 41

can drugs with both acid and amino groups exist as neutral zwitterions?

Answer 41

yes -- when basic and acidic groups are nonionized at the pH

Question 42

what is P0

Answer 42

the distribution coefficient that involves the partitioning of both neutral (unionized) species P0 = [sum of the conc of neutral species] octanol/[sum of the conc of neutral species]water

Question 43

what is P1

Answer 43

the distribution coefficient that involves the partitioning of charged (ionized) species P1 = [sum of the concentration of the microspecies with charge "i"] octanol/[sum of the concentrations with charge "i"]water

Question 44

the distribution coefficient involves the partitioning of.....

Answer 44

both neutral (unionized) species and charged (ionized) species

Question 45

the distribution coefficient is represented as the......

Answer 45

sum of P0 and P1 D = [sum of the concentrations of ALL microspecies] octanol/[sum of the concentration of ALL microspecies]water

Question 46

AH <-------> A- + H+ the partition coefficient of unionized Kpc0 can be represented as......

Answer 46

Kpc0 = [AH]octanol/[AH]water

Question 47

AH <----> A- + H+ the partition coefficient of ionized Kpc1 =...

Answer 47

Kpc1= [A-]octanol/[A-]water

Question 48

therefore, distribution coefficient =.... give full formula

Answer 48

D = Kpc0 + Kpc1 therefore, this is equivalent to [AH]octanol/[AH]water + [A-]octanol/[A-]water

Question 49

% ionization =.....

Answer 49

10 ^(pH-pka) / 10 ^(pH-pka) + 1 * 100