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let's start off with looking at a
platelet so a platelet is a very
important part of the blood clot it's
like the brick in a wall and platelets
if they don't adhere to each other
aren't going to form very good clots for
us so the glycoprotein to be three a
molecule is central to the function of a
platelet you can see here I have a
picture of a platelet next to me and you
can see in blue the glycoprotein to be
three a molecule which is also called
the alpha to be beta three molecule in
Europe allows that platelet to adhere to
the collagen substrate of any particular
tissue the other thing that this
glycoprotein to be three a molecule
allows us to do is adhere to other
platelets so you can see that there's
another platelet attaching to the first
platelet through fibrinogen this
cross-linking and activation of platelet
adhesion and aggregation are important
components of the glycoprotein to be
three a molecule the third component of
platelet function is its release
function now thromboxane a2 plays a very
important component in the release
function ATP is released when platelets
mind--to damaged tissue and adp is
another important component in platelet
function this brings us to our first
drug aspirin aspirin is an irreversible
inhibitor of cyclooxygenase it is used
to manufacture thromboxane a2 and
platelets when you inhibit thrombus
cyclooxygenase with aspirin actually are
permanently inhibited that means that
the anti platelet function of aspirin is
going to last for the entire life of
this platelet and that means that only
replacement platelets will be functional
and that means that the aspirin is going
to last anywhere between three and seven
days interactions of aspirin are very
important because the aspirin is going
to interact with nonsteroidal
anti-inflammatory pain agents they
impair platelet function on their own
and when combined with aspirin you
actually have an enhanced anti platelet
effect
the next group of drugs that I want to
talk about are the glycoprotein 2 B 3
inhibitors we've already spoken about GP
2 B 3 a before and we've Illustrated how
important it is in platelet adhesion and
aggregation so we have reduced adhesion
with the 2 B 3 inhibitors and we have
reduced platelet aggregation these are
the drugs that are commonly used in this
drug class you don't need to know them
so much as you need to know that they're
used in the cath lab to inhibit platelet
aggregation after catheterization the
ADP inhibitors are another drug class
you need to know this for your exam so
pay close attention okay so pretty girl
and pricey girl are the two drugs that
we're using right now in in clinical
practice
they require hepatic conversion to be
active so they don't act right away they
take some time to actually work they are
also irreversibly inhibited of platelet
function there are some new drugs that
have come out take a glow or brew lanta
is a very commonly used drug in the cath
lab it does not require hepatic
activation and it is a reversible
inhibitor of adp receptors so tyke hag
role or is a reversible inhibitor
clopidogrel and praise you gal are not
reversible they are irreversible drugs
it's really important I want you to
remember the distinction between the two
because guaranteed I'm going to put it
on an exam let's talk about the next
class of drugs diaper to mole is a very
commonly used agent that has a dual
mechanism of action the first action is
that it inhibits phosphodiesterase that
reduces cyclic am p mediated degradation
and cyclic a and p is an inhibitor of
platelet aggregation so there's a double
negative there pay attention more cyclic
a.m. P means less platelet aggregation
so in other words these drugs inhibit
platelet aggregation the second effect
of this class of drugs is that inhibits
the uptake of adenosine so it increases
your plasma concentration of adenosine
adenosine acts to that a2 receptor on
the platelet surface and the a2 receptor
activation causes increases in
cyclic EMP levels once again more cyclic
A&P
means less platelet aggregation so we
have less platelet aggregation through
adenosine mediated action so this brings
us to the actual uses in clinical
practice aspirin is the most commonly
used anti platelet that we have it
reduces heart attacks an aspirin a day
keeps the cardiologist away it also
reduces stroke so we use it all the time
in preventing stroke activity and it
reduces peripheral arterial ischemia so
the three areas are heart brain and the
legs or peripheral arterial supply the
direct
inhibitors also prevent restenosis after
angioplasty it's used in acute coronary
syndrome we spoke about clopidogrel
remember that it's an irreversible
inhibitor it prevents cia's or mini
strokes it prevents strokes and it
reduces restenosis of stents so a lot of
time we will use clopidogrel or pricey
gal for about a year after we put in a
drug-eluting stent diaper animal is
often often used in combination we
sometimes use as an adjunct to warfarin
in patients who have have who have
artificial mechanical heart valves and
we use it in combination with aspirin
for secondary prevention of stroke so
the thing that you want to remember is
that if a person has a stroke we give
them aspirin if a person on aspirin has
a stroke so we give them aspirin plus
diaper animal or we switch them to one
of the other drugs and finally there's a
new drug that's out on the market that
is used to treat intermittent
claudication in terms of the toxicity
these drugs there they're not
insignificant so aspirin has a bleeding
of rate of about 0.3% or three four 1000
tike klaapa dean has a bleeding rate of
about 5% but a 1% rate of severe
neutropenia ty klaapa Dean is a drug
that you only need to know because we
don't use it anymore
so thrombocytopenic thrombotic purpura
is a rare complication severe
neutropenia is a common complication at
1%
on your exams they're going to talk
about the side effects of this drug but
in real world clinical practice we don't
use this drug anymore we spoke a bit
about the direct inhibitors the side
effects of course are bleeding and
thrombocytopenia with chronic use we
only use these drugs short-term so it's
not as much of an issue with it
clopidogrel the bleeding rate is less
than 1%
it is certainly pretty is certainly
present and when you combine clopidogrel
and aspirin together the bleeding rate
increases diaper animal is that adjunct
of drug that we were talking about it
adds between one and two percent
bleeding risk to your drug that already
has a bleeding risk and then in terms of
the peripheral drugs they are
contraindicated in heart failure this is
going to be on your exams no this this
particular drug it is contraindicated in
heart failure
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