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let's talk in detail about aspirin or a
sa a sa is your prototypical
cyclooxygenase inhibitor and in fact it
was probably one of the first drugs that
was commercially available in the world
now coxswain is found in
non-inflammatory 8 s l's
and cox-2 is found in activated
lymphocytes polymorphonuclear cells and
other inflammatory cells aspirin reduces
thromboxane and prostaglandin formation
in the body aspirin irreversibly
inhibits cox-1 and co2 so nonsteroidal
anti-inflammatory agents a reversible
aspirin is irreversible and I'm gonna
say this again because I want you to get
that into your brain aspirin
irreversibly inhibits Cox 1 & 2 low-dose
aspirin less than 325 milligrams works
on platelet aggregation medium dose
aspirin between 325 and 1,250 milligrams
a day have antipyretic and significant
analgesic effects and high dose that's
twelve hundred and fifty to four
thousand milligrams a day have a strong
anti-inflammatory effect I was
hospitalized with pericarditis after my
trip to the Amazon and the thing that
worked the best for me was 650
milligrams twice daily of aspirin it was
a very effective anti-inflammatory agent
and I use it almost exclusively in
severe inflammatory conditions like
pericarditis
now aspirin works quite well to reduce
inflammation without reducing immunity
it does not affect regular tissues which
is why we like it so much it reduces
prostaglandin synthesis in the central
nervous system so that's why it has an
anti fever or antipyretic activity it's
also a great analgesic we don't know why
it works so well as an analgesic but we
know that patients who take aspirin have
a reduced pain sensor activity through
prostaglandin it may work through a
central mechanism as well but we haven't
quite figured it that out yet that's
surprising considering the drug is a
hundred and eighty years old the drug
has a half-life of about five
and it's really excreted now remember
that type of kinetics that we were
talking about it's a first order
connecticut low doses and zero order at
high doses in terms of adverse events
with aspirin they're quite significant
and we need to know them well in terms
of the long duration treatment we use it
usually for antiplatelet activity but it
does cause an increased bleeding risk
there's an increased level of GI
toxicity and that's because aspirin
works to reduce gastric protection so in
the stomach we release mucus to protect
the lining of the stomach aspirin
reduces that protective layer through
prostaglandin and that's how you get
more stomach ulcers because now the
stomach acid is able to attack the
lining of the stomach there's increased
renal risk once again that is a
prostaglandin mediated if issue so you
can precipitate acute renal failure and
one of the more common causes of
interstitial nephritis is actually
aspirin you can develop nasal polyps
that are associated with
hypersensitivity asthma exacerbations
and a small drop in prostaglandin result
in increased leukotriene synthesis so
you have to be aware of that seesaw
action that I was talking about and
aspirins effect in it now the other
adverse events that I want to talk about
with respect to aspirin at high doses
tinnitus is often seen vertigo is a
hallmark of aspirin toxicity
hyperventilation is often seen because
the patients are acidotic and you
develop a secondary respiratory
alkalosis so by the time you usually see
these patients in the emergency
department they have developed they have
developed a respiratory alkalosis at
exceedingly high doses these are
patients who have ingested bottles of
aspirin you'll see dehydration
hyperthermia that's high temperatures
cardiovascular collapse metabolic
acidosis coma seizure death Reye's
syndrome is a is a syndrome that we
actually don't see anymore
it's a progressive in calf allopathy and
liver djay
that we saw in children who were exposed
to aspirin aspirin consumption with a
virus viral illness in age four to
twelve was routinely treated with
aspirin when I was a child and so lots
of kids were hospitalized with Reye's
syndrome in the 60s and 70s now that we
know about rice syndrome we actually say
that aspirin is contraindicated in
children and the old children's aspirin
is now given to adults as eighty-one
milligram aspirin for platelet
protection
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you