Ch6 DRUG ABSORPTION Flashcards
absorption
when the drug moves from its site of application to the blood
lipid bilayer
usually allows other lipids to dissolve into and then pass through the membrane. Lipid bilayers are not easily penetrated by molecules that are charged (ionized).
Therefore, to cross the plasma membrane and get into the bloodstream,
the drug molecule had to be lipophilic and uncharged.
ionization
depends on whether the drug is an acid or a base and on the pH of the solution
acids
is composed of molecules that produce hydrogen (H+) ions when dissolved in water
bases
composed of molecules that produce hydroxyl ions (OH-) and cations and that are not H+ when dissolved in water. Because OH- ions will often take on H+ ions from the water molecule, bases are often thought of as hydrogen (H+) acceptors.
pH of bodily fluids - gastric juice, urine, saliva, milk blood
gastric juice - 2.5-3
Urine - 5.0 to 8.0
saliva - 6.0 to 7.4
Human milk - is alkaline but slightly acidic compared with blood
blood - 7.35 to 7.45 (7.42-7.4 in pregnancy)
Blood pH of a pregnant person
typically have a blood pH of 7.42 or 7.40, so they are actually on the top
side of the normal range of pH.
b/c preg people hyperventilate -> low CO2 in the blood -> causes a shift in the bicarb buffer system away from H+ -> creating a more alkaline environment
Why does a fetus have a lower (more acidic than adult) blood pH?
normal fetal blood pH - 7.25-7.33
the fetus produces CO2 which can only be cleared by the placenta by moving it into the preg person’s blood stream - the transfer can’t keep up leaving a more acidic environment
A weak base
has an amino functional group (NH2) that is a proton acceptor (H+) and doesn’t fully ionize in an aqueous solution
A weak acid
contain a carboxyl group that will give up its H+ to form a carboxylate anion
The Henderson-Hasselbach equation
used to predict the degree of ionization at a particular pH as long as the pKa of the acid or base is known.
a formula that predicts drug absorption and distribution
association constant (Ka)
The tendency of an acid to dissociate
Ka = [A-] x [H+] / [HA]
pKa
is the negative log of Ka and helpful when relating Ka to pH
a drug with a high Ka (strong acid) will have a very low pKa
Since pKa is a constant for each drug, the amount of A- (ionized drug) and HA (lipophilic drug) varies with pH.
Each drug has its own particular pKa, so the transition from mainly water soluble to mainly lipid soluble is specific to the drug
an acidic drug in an acidic condition
If the pH is low, the ratio between A and HA must also be low; thus under acidic conditions, there will be lots of HA and not much A-. If the drug is largely in the HA (lipophilic) form, then it could easily be absorbed and would tend to penetrate tissues and leave the bloodstream.
an acidic drug in an alkaline condition
there will be little of the HA, and the A- form will predominate. Consequently, the drug will move easily in the aqueous environment of the bloodstream but will not be readily absorbed or penetrate tissues
basic drugs
Most drugs are bases; in an acidic environment, they accept H+ ions
and become ionized, which makes them water soluble. Most basic drugs
are water soluble in the stomach and thus are not readily absorbed there.
As the drug moves into the basic environment of the small intestine, it
will give up H+ ions gained in the stomach and thus become lipid soluble
amides
have pKas from 7.6 to 8.1
amide LAs, are most likely to cross the placenta. Relatively large amounts of the
non-ionized LAs—as much as 25% of them are in lipophilic form—cross
the placenta to the baby. There they will convert into the ionized form
(because of the relatively acidic environment) and get trapped because
they are no longer lipophilic. Every time one of these lipophilic molecules
picks up an H+ ion to become BH+, it becomes unable to cross back to
the preg person. The more acidotic the baby is, the more this is a problem.
Only the amide LAs have a pKa close to physiological pH levels, so only
the amide LAs will cause this problem
esters
have pKas from 8.7 to 9.0
At the pH of blood and tissue, esters will be
much more ionized than amides and will not penetrate as rapidly
ion trapping
a nonionized, lipophilic molecule enters an area of different pH and becomes
ionized and thus cannot leave as easily as it entered. As a result, the
amount of drug in this area builds up. For this to occur in a clinically
significant way, the pKa of the drug has to be close to the pH of the two
different areas
