Lab 3 Flashcards
A drug must do what 3 things to produce a biological response?
- cross the biological membrane
- interact with biological fluids
- reach its site of action
name 3 properties that influence the ADME and biological activity of a drug
solubility, ionization, and stability
the environment in the biological tissue must be favorable to facilitate ___ and ____ and maintain the characteristics necessary to do what?
environment must be favorable to facilitate ABSORPTION AND DISTRIBUTION and maintain the characteristics necessary to INTERACT WITH THE BIOLOGICAL RECEPTOR TO PRODUCE BIOLOGICAL EFFECTS
Before it is absorbed, the drug must be….
soluble in the local biological fluid
the solubility of a drug depends on what?
its ability to form hydrogen bonds and/or ionize in water
changes in ionization are influenced by _____
pH
name 2 things that can REDUCE the amount of drug absorbed in the GI tract
- changes in ionization
- complex formation through interaction with the GI tract contents
true or false
when a drug is in circulation, it is post absorption and IV administration
TRUE
when the drug is in circulation, what can delay or prevent the drug from reaching the site of action?
protein binding
drugs must partition between the ___ phase and the ____ phase to _____________
drugs must partition between the AQUEOUS PHASE (GI, blood) and lipid phase (cell membrane) to ENTER TISSUE CELLS
true or false
partition coefficient is measured at a specific temperature
TRUE
When partition coefficient is being measured, it is assumed that there is….
a SINGLE SPECIES OF THE DRUG partitioning between the lipid and aqueous phase
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?
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
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
FALSE - each species may differ in partition coefficient characteristics
define distribution coefficient
the ratio of the drug partitioning between the lipid and aqueous phases pf the various species present
it is assumed that ______ species do NOT partition in the lipid phase
IONIC
the partition coefficient of neutral drugs is equivalent to its ________.
why?
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
drugs with weak acid or weak base properties exhibit what kind of ionization?
pH dependent
Distribution coefficients consider what factors?
consider the pH, concentration, and partitioning properties of both the ionic AND non-ionic species
which is more relevant to predict drug permeability and aqueous of weak acids and bases and why? – partition coefficient or distribution coefficient?
distribution coefficient because it considers the pH, concentration, and partitioning properties of the ionic and nonionic species
true or false
the percent ionization does not vary with pH for weak acids and bases
FALSE - it does vary for weak acids and bases
is the distribution coefficient higher for ionizable drugs or nonionizable drugs?
explain
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
what has to exist in order to predict the distribution coefficient at a specific pH using the hendersen hasselbach equation?
-if only the non-ionic species partitions in the lipid phase
-the partition coefficient for the free form is known
the Henderson-Hasselbalch equation expresses the relationship of…..
pka, the ratio of the acid:conjugate base and the pH
write the Henderson-Hasselbalch equation
pH=pka + log (base/acid)
the partition coefficient value of acid and basic drugs is affected by what 3 things? (besides % ionization)
pH, intrinsic solubility in the organic solvent, solvent volume
the _______ the solubility of a drug in a solvent, the better the extraction efficiency in that solvent
the MORE soluble the drug is in the solvent, the better the extraction efficiency in that solvent
how do you get the most effective extractions?
several smaller extractions are more effective than 1 large extraction with the same volume
for extraction in the organic solvent, the drug must be in what form?
UNIONIZED
______ is also known as the free form
(ionized or unionized)
unionized
as mentioned, for extraction in the organic solvent, the drug must be in unionized form.
HENCE……….
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
ephedrine is a ___ ____
sympathomemetic amine
ephedrine may enhance the release of _______ through what?
ephedrine has alpha- beta- adrenergic agonists that may enhance the release of norepinephrine
compare the water solubilities of ephedrine and baclofen
ephedrine is much more soluble in water (56,900mg/L) than Baclofen (2090mg/L)
what kind of drug is baclofen?
a muscle relaxant
true or false
baclofen is stable under normal conditions
TRUE
Explain the structure of baclofen
it is amphoteric and exists as a zwitterion at ph 7
has 2 pkas because of this (3.85 and 9.25)
does baclofen bind to serum proteins?
no - not significantly
how is baclofen excreted?
mainly in the urine (90%)
which enantiomer of baclofen is more active?
the l (-) enantiomer is more active – but it also is related to toxicity
can drugs with both acid and amino groups exist as neutral zwitterions?
yes – when basic and acidic groups are nonionized at the pH
what is P0
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
what is P1
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
the distribution coefficient involves the partitioning of…..
both neutral (unionized) species and charged (ionized) species
the distribution coefficient is represented as the……
sum of P0 and P1
D = [sum of the concentrations of ALL microspecies] octanol/[sum of the concentration of ALL microspecies]water
AH <——-> A- + H+
the partition coefficient of unionized Kpc0 can be represented as……
Kpc0 = [AH]octanol/[AH]water
AH <—-> A- + H+
the partition coefficient of ionized Kpc1 =…
Kpc1= [A-]octanol/[A-]water
therefore, distribution coefficient =….
give full formula
D = Kpc0 + Kpc1
therefore, this is equivalent to
[AH]octanol/[AH]water + [A-]octanol/[A-]water
% ionization =…..
10 ^(pH-pka) / 10 ^(pH-pka) + 1 * 100
