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okay let's talk about a new topic
something called PKA now look at this
question spend a little bit of time
reading it and then we'll try and go
through the answer together okay so
hopefully you've read the question what
I want to do is I want to focus a skill
that you need for your exam when you're
writing an exam and you see a long stem
like this especially for the USMLE exam
look at the last sentence first because
what that's going to do it's going to
focus your attention now in this
particular question the last sentence
says that it has a pKa of 3.8 and what
percentage of the drug will be
hydrophobic well all of a sudden you've
realized that the first half of that
question is completely useless to
getting your answer so you can actually
just ignore a lot of that clinical
information and get to the answer much
quicker so now what we do is we want to
pick between the answers 100 percent 50
percent 10 percent and 1 percent so what
percentage of the drug will be
hydrophobic at a pH of 4.8 if the pKa is
3 paint 3.8 well what is PKA let's go
over that together so aspirin has a pKa
of 3.8 so what is PKA the pKa is that pH
level at which a drug is 50% protonated
and 50% non protonated so the Roche
ratio of protonated and non protonated
forms is 1 to 1 for weak acids and you
can see that because the pKa is 3.8
which is less than 7 that's an acid so
for all weak acids the ratio changes to
1 to 10 or 10% at one pH unit more
alkali than the pH and the ratio changes
to 1 to a hundred or 1% at two pH units
so remember that pH is a logarithmic so
one unit is 10 two units is a hundred
three units is a thousand so if you have
a pKa of 3.8
and the pH of 5.8 you've got a pretty
significant difference in ratio so two
pH units is one to one hundred so let's
take a look at pyramid Amin
pyramid Amin is another drug that has a
pKa of seven point four two that makes
it a weak base right because the 7.42 is
actually higher than seven point zero so
anything above seven point zero is a
base the pKa is the point at which a pH
that gives you 50% protonated and 50%
non protonated drug so the ratio is one
to one for weak acids and bases the
ratio changes by one to ten or one to a
hundred for each one or two pH units you
are from your PKA now because it's a
base the more alkali the pH is it makes
it less soluble or less polar in the
protonated form so to go over it again
for weak bases they are ionized they are
more polar when protonated and more
soluble when protonated with weak acids
they are not ionized they are less polar
when protonated and less soluble when
when protonated that's really hard to
remember so I have a mnemonic for you to
memorize this there's bits and there's
pan so bases are ionized polar
protonated and soluble and pan means
that protonated acids are non ionized
nonpolar and non soluble so if you
remember these two acronyms that'll help
you with some questions so speaking of
questions let's go back to our our
question in our case the ratio changes
from 1 to 1 to 1 to 10 at one pH unit
more alkaline than the pKa and it
changes to a ratio of one to a hundred
at two pH units that are more alkaline
than the pKa so in the case of this
question we were saying the bottle label
says that the substance has a pKa of 3.8
what percentage of the drug will be
hydrophobic or lipid soluble or Lippo
fight lipophilic in the small bowel at a
pH of 4.8
what's the answer so the answer is C 10%
one pH unit difference 10% 1 to 10 ratio
now why do you care about a PKA this
sounds like a lot of chemistry that you
left behind in pre-med well the reason
why we need to know this is because we
need to know how to enhance excretion of
excretion of a toxin so for example an
aspirin over overdose we want to
alkalinize the urine when we alkalinize
the urine with sodium bicarb we trap the
aspirin molecules in the urine so it
can't get reabsorbed back into the body
that's how we treat an aspirin overdose
it's also useful when we want to design
a drug and when we want to mix
medications so in the pharmacy world
it's also something that's very
important
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