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 arterial or 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 for 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 p h 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
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 Jaques in' 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 the 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
base 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 process in 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 tests are ones that could improve with calcium channel blockers
those that are Nega will not respond to calcium channel
blockers so once we do this and I'll tell you it's a very small percent are
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 1 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 3 and these are
where most of the medications are actually started and then there's class
4 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 1 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 15 years that's how new they are and if you're lucky enough to
have a patient who is responsive to a 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 there are w-h-o class
2 or 3 then you're going to be starting them on some Pio meds which we're gonna
talk about right now the first category is the prostacyclin agonists so this is
like equal process and 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 x' 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 endo feelin 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 Tenten 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 pb5 inhibitors
cause vasodilation in 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 and all or triple process Annelle or you
could do triple process Annelle 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 a 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
get 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