well welcome to another MedCram lecture we're going to talk about
pulmonary hypertension treatment and there's actually several different types
of treatments remember there are different waho groups there's Group 1 2
3 4 & 5 now group 1 we said was idiopathic
pulmonary arteriolar hypertension and the other ones for instance the collagen
vascular diseases the drugs the toxins those sorts of things number one is
where most of the work in terms of drugs specifically for pulmonary hypertension
have centered there's also one that is FDA approved for four which we'll talk
about but remember why this is is because
group two is almost exclusively is exclusively due to left ventricular
failure Group three has to do with lung disease and group five is kind of a
grab-bag so these already have their treatments specifically for them one has
a whole bunch which we're going to talk about and there is one that is indicated
for for remember four is for venous thromboembolism or chronic pulmonary
hypertension or as it's officially called chronic thromboembolic pulmonary
hypertension and that's abbreviated C T e pH okay so let's talk about number one
and the different types of treatments okay so there's some things that all
groups would do well to start and we're going to make this as simple as possible
and explain it as clearly as possible as we normally do so because of the fact
that they get this lower extremity diuretics is something that you want to
do the other thing that you want to do if they need it is oxygen therapy and
they've noticed on autopsies that there are a lot of blood clots not just in
group chronic thromboembolic pulmonary hypertension
but also in the other groups after many studies anticoagulation was found to be
definitely something that you want to do in group 4 and maybe in group number one
other medications that might be beneficial is the Jackson and exercise
definitely beneficial so these are ones that can go really to just about all
classes let's talk about group one now and the different classes now before we
start with the advanced medications that some of you are familiar with we have to
do something called a vaso reactivity test and the reason why we do this is
because those who respond to the vaso reactivity test are more likely to
respond to ordinary medications like calcium channel blockers like the
dihydropyridine and diltiazem calcium channel blockers so if they respond if
that's a positive response calcium channel blockers if it's negative then
we go on down to the more advanced medications so what is the Rays of
reactivity test looking at well there's a number of ways you can do it you can
use nitric oxide to see whether or not the patient's mean pulmonary artery
pressure drops by 10 millimeters of mercury the other thing that you can do
is you can use equal Pross on all
finally the other thing that you can use is adenosine so all of these are
medications that can be used to see whether or not the patient is reactive
and once again it's considered positive if the main pulmonary artery pressure
decreases by at least 10 millimeters of mercury and goes to less than 40
millimeters of mercury this is assuming that the cardiac output actually gets
better or it's unchanged and as we mentioned patients with a positive
reactivity test are ones that could improve with calcium channel blockers
those that are of will not respond to calcium channel
blockers so once we do this and I'll tell you it's a very small percent or
actually reactive most of these are going to go into the negative category
and so most of them are going to be having to be put on advanced medications
if we're dealing with a group one so let's talk about those things but before
we do the thing that's going to determine what medication they get is to
determine how sick they really are and that's determined by a w-h-o again
functional class and so there's functional class one which is the most
mild and they typically don't need medications that can be monitored and
then there's class - and there's class three and these are
where most of the medications are actually started and then there's class
four which is the most severe and these are usually given IV so the way I
remember it is that class IV should be given IV class one doesn't need to be
giving any medications orally and the ones in the middle are given Pio
meds and those Pio meds we'll talk about very shortly
most of these medications haven't been around for more than fifteen years
that's how new they are and if you're lucky enough to have a patient who is
responsive to Veysel reactive medication then you can just give a calcium channel
blocker which is dirt cheap and has been around for many years if on the other
hand they don't respond and they're a w-h-o class two or three then you're
going to be starting them on some Pio meds which we're going to talk about
right now the first category is the prostacyclin agonists so this is like
equal process in all IV which is indicated for stage 4 IV as we talked
about there's tree procced Annelle which can come IV sub-q or inhaled there's
isla Pross which is comes inhaled and then there's these prostacyclin agonists
which are not really prostacyclin 's like celexa peg which all of these
things stimulate the prostacyclin receptor and in effect caused an
increase in cyclic AM P and therefore vaso dilation
okay so those are the prostacyclin agonists the next group are the endo
feelin receptor antagonists so endothelium one is a hormone that
basically circulates around and is extremely potent vasoconstrictor so if
we could possibly block these receptors potentially we could get some basal
dilation that's exactly what we see there's two types of receptors is the a
and B and so both senton and massive 1010 is basically a drug that blocks
these receptors it's non selective and it seems to reduce the PA pressures it
also like a lot of the other medications improves the quality of life extends the
length of time before decompensation and increases exercise capacity one of
the selective ones is amber senton so these are the receptor field and
receptor antagonists these are a list of medications that are fda-approved for
pulmonary hypertension specifically sildenafil and Tel dalla fill the
purpose of these things is to inhibit the breakdown of these medications which
basically increase the amount of nitric oxide so there is cyclic GMP and that
cyclic quantity monophosphate is broken down by phosphodiesterase well these
medications inhibit the ability of this phosphodiesterase to break down the cmp
and so these are why they're called pde5 inhibitors and so what happens is cyclic
GMP goes up which stimulates an increase in nitric oxide and it's nitric oxide
which is a vasodilator okay so there's a couple of other things that
also increase vasodilation and that would be like an alpha blocker or a
nitrate so you should not be on these medications at the same time these PB v
inhibitors cause vasodilation the pulmonary vasculature by increasing
nitric oxide and they do it specifically by inhibiting the breakdown of cyclic
GMP the last mechanism that we're going to
look at is the guanylate cyclase direct stimulants and this riociguat is one of
the medications that is fda-approved is the medication that is FDA approved to
do this and it's a direct stimulator of the nitric oxide receptor so it
increases nitric oxide just like the phosphodiesterase inhibitors do but they
do it in a different way and they have a dual mode of action not only do they
increase the nitric oxide receptor they also increase the sensitivity of the SGC
to endogenous nitric oxide which is a pulmonary vasodilator and so they also
directly stimulate the receptor to mimic the action of nitric oxide so this is a
little different and not only is it approved in a PH group w-h-o group
number one but it's also approved for w-h-o group number four which remember
is the chronic thromboembolic disease so just be aware of that
now all of the medications that we've just talked about can be used in
combination but you've got to be careful make sure again that you are using these
in combination after you have done a right heart cath and made sure that they
are not reactive so you could add for instance tadalafil and amber senton you
could use sildenafil and both senton you could use both senton added to either
Ypres process in all or triple prosthetic or you could do triple
Prasanna added to either both sent in or sildenafil so there's different ways of
doing this and this is very similar to how we increase blood pressure
medication for systemic hypertension we can also do this for pulmonary
hypertension so the key points again are that if you suspect somebody of having
pulmonary hypertension make sure that you classify them in the w-h-o group if
they are group 1 or 4 there may be medication specifically designed for
these types of diseases if it is group 2 you need to look at
the underlying cause of the left heart disease and treat that if it is three
you have to look at the underlying cause for the hypoxemia and treat that whether
it's lung disease or sleep apnea for you need to anticoagulate them generally and
they may need to go to surgery where they actually have the clot removed or
if that's not feasible they may have to consider a medication like we just
talked about here and then five is kind of the grab bag it should be looked at
in terms of the other causes so that is a very brief primer in pulmonary
hypertension how it is diagnosed how it is looked at how it is treated and and
what are the medications that are involved so thanks for joining us
you