well welcome to another MedCram lecture with bored vitals question this question
comes from the NA ple X question Bank and the question is about digoxin so
let's get into it here a seventy year old male with a history of diabetes GERD
and COPD develops atrial fibrillation with a rapid rate after cardioversion
he begins treatment with digoxin which of the following is true of treatment
with digoxin select all that applied there could be more than one or maybe
just one so it's basically true/false so let's just review briefly what it is
that the johnson does so if you can imagine a myocardial cell and as you
recall in just about every cell of the body there's something called a sodium
potassium ATPase and this is a enzyme that is in the cell surface and
basically what it does is it maintains the fact that there's a lot of potassium
inside the cell and a lot of sodium outside the cell so the way it does that
is by pumping in potassium and pumping out sodium so that's what maintains this
now interestingly what digoxin does is it actually blocks that pump it slows it
down so as a result of that sodium starts to build up inside the cell
relative to what it would be of course there's still a lot more outside the
cell but sodium starts to build up inside the cell and as it turns out
there's another way of sodium to get out of that cell and that's something called
the sodium calcium exchanger so here sodium can leave the cell in this
direction and as a result of that what comes in is calcium
of course it's two positive charges and that increase in calcium because of this
blockage of the sodium potassium ATP leads to increase in inotrope e that
just means the strength of contraction so let's go over this one more time so
normally the ATPase this is an enzyme that uses ATP pumps in potassium pumps
out sodium however digoxin blocks this or slows it down and as a result of that
the amount of sodium leaving is slowed down
therefore the sodium concentration in the cell increases and as a result of
that goes down this concentration gradient and at the same time brings in
calcium increasing the calcium concentration inside which leads to
increased in a trophy so that's how the jocks in actually makes your heart beat
stronger the other thing that digoxin does is if you recall we've got the SA
node here and we've got the AV node here and those of course are connected and
then you've got the hiss Purkinje system this is the electrical conduction system
of the heart these two areas here are susceptible and are innervated by the
vagus nerve and the digoxin levels or digoxin actually stimulate the vagus
nerve and up regulates it so as a result of that you've got up regulation here of
vagal stimulation using acetylcholine and as a result of that it should slow
down the SA node and also slow down the AV node conduction especially apropos
when you've got a situation here where you have atrial fibrillation and all of
these electrical conduction coming down the AV node will slow down the
conduction so you don't have RvR or rapid ventricular response so digoxin
not only increases intracellular calcium but it also improves vagal nerve
stimulation which in fact slows the heart rate down
now as it turns out digoxin has a pretty narrow therapeutic window what does that
mean that means if we were to look at a dose range of digoxin there would be a
very small area where we would actually get the good benefit of digoxin and if
we went too high we would get deleterious effects of the digoxin and
if we went too low we would get not enough concentration to do the things
that we would want it to do so in other words what we try to do is we try to get
the concentration of the jocks in high enough for it to work but not too high
that it actually causes cardiac arrhythmias that's what we've referred
to when we say that it has a very narrow therapeutic window and exactly what is
that therapeutic window well several different publications and guidelines
have said that that narrow therapeutic window
for congestive heart failure is 0.5 to 0.9 and this is of course in units of
nanograms per milliliter so 0.5 0.9 is that narrow therapeutic window that
we're looking at and this goes along with the guidelines that are seen in
up-to-date and also the American College of Cardiology typically this can be
achieved via intravenous loading or it can be done by oral loading the key
though that you've got to remember is it's typically about seven days until
you get to steady states can be longer in some cases but at least seven days is
the key now as we mentioned this upper limit of therapeutic window of 0.9 which
is what we see right about here if we go above that we can see things like
arrhythmias and the interesting thing about that is
that having a low potassium can actually increase that risk so what you have to
do is if you have a low potassium is you've got to watch this level very very
carefully it doesn't mean that you can't use the jock sin' if you have
hypokalemia it just means you have to make sure that you're not super
therapeutic because the risk of arrhythmias goes up in that sort of a
situation the other thing that's interesting about digoxin itself is that
when it's ingested there are some medications that can interact with it
now there are of course like things like amiodarone and verapamil which can
increase the risk of arrhythmias but in terms of medications for
gastroesophageal reflux disease which our patient has there can be interaction
with digoxin now the one of the things that I want you to be aware of is the
difference between antacids and actually medications like proton
pump inhibitors now antacids neutralize the stomach pH and that has the effect
of increasing the pH in the stomach proton pump inhibitors shut down the
ability of your stomach to make acid by blocking this proton pump and that also
increases the pH the thing that's interesting though is that there's
actually differences in how this interacts with digoxin and obviously
it's not through the pH a proton pump inhibitor will actually increase the
levels of digoxin because of drug interaction however antacids because of
what they contain and these are over-the-counter antacids they can
actually decrease the bioavailability of the Jackson and so as a result of that
you would have to take more digoxin to compensate for the decreased
bioavailability when taking antacids so let's go back to our question and as you
can see we've got them correct here and correct here let's go through them
though with a an oral with the jocks and results in
steady-state concentration in three to four days actually that's incorrect it's
more like seven to ten days be patients who take antacids may require an
increase in dosage that is correct we actually just talked about that where
there are actually things in the antacids themselves that will reduce the
bioavailability of digoxin the Jackson has a broad therapeutic window that's
not the case it actually has a narrow therapeutic window and specifically that
narrow therapeutic window is 0.5 to 0.9 nanograms per ml and so that's the
second correct answer and we skip D and let's read D patients with hypokalemia
should not take the jocks until the serum potassium is normal well we know
that hypokalemia can increase the arrhythmia s'ti of digoxin it's not a
reason to not take the jock sin' until the level is normal
we just need to watch and make sure that the patient doesn't become too high on
the ditch levels so the answers here are B and E well thanks for joining us