00:00
Let's talk in detail about aspirin or ASA. ASA is your
prototypical cyclooxygenase inhibitor
and in fact it was probably one of the first drugs that was
commercially available in the world.
00:13
Now COX-1 is found in non-inflammatory cells, and COX-2 is
found in activated lymphocyte, polymorphonuclear cells
and other inflammatory cells.
00:25
Aspirin reduces thromboxane and prostaglandin formation in
the body. Aspirin irreversibly inhibits COX-1 and 2.
00:34
So, non-steroidal anti-inflammatory agents are 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 and 2.
00:46
Low-dose aspirin, less than 325 milligrams, works on platelet aggregation.
00:52
Medium dose aspirin, between 325 and 4000 milligrams a day, has antipyretic and significant analgesic effects.
01:01
In high doses, that's 4000 to 8000 milligrams a day; there is a strong anti-inflammatory effect.
01:07
Keep in mind these are not hard cutoffs, and there is overlap in the effects of low, medium, and high doses.
01:13
Additionally, the usual maximal dose of aspirin is 4500 mg per day due to the potential for toxicity.
01:20
However, some circumstances may require higher doses for limited periods.
01:24
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.
01:34
It was a very effective anti-inflammatory agent, and I use it almost exclusively in severe inflammatory conditions like pericarditis.
01:43
Now, aspirin works quite well to reduce inflammation without
reducing immunity. It does not effect 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 reduced pain
sensor activity through prostaglandin.
02:14
It may work through a central mechanism as well but we haven't
quite figured that out yet. That's suprising considering the drug
is a 180 years old. The drug has a half life of about 5 hours.
And it's renally excreted. Now remember that type of kinetics
that we were talking about. It's a first order kinetic drug
at low doses, and zero order at high doses.
02:38
In terms of adverse events with aspirin, they are quite
significant and we need to know them well.
02:43
In terms of the long duration treatment, we use it usually
for antiplatelet activity, but it does cause an increased bleeding risk.
02:51
There is an increased level of GI toxicity. And that's
because aspirin works to reduce gastric protection.
02:59
So in the stomach we release mucous 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.
03:16
There is increased renal risk. Once again that is a prostaglandin
mediated issue. So you can precipitate acute renal failure
and one of the more common causes of interstitial nephritis
is actually aspirin.
03:30
You can develop nasal polyps that are associated with
hypersensitivity asthma exacerbations.
03:36
And a small drop in prostaglandin results in increased
leukotriene synthesis. So you have to be aware of that
seesaw action that I was talking about and aspirin's
effect in it.
03:47
Now, the other adverse events that I want to talk about
with respect to aspirin. At high doses, tinnitus is often seen.
03:56
Vertigo is a hallmark of aspirin toxicity. Hyperventilation
is often seen because the patients are acidotic.
04:04
And you develop a secondary respiratory alkalosis. So by the
time you usually see these patients in the emergency department
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.
04:31
Reye's syndrome is a syndrome that we actually don't see
anymore. It's a progressive encephalopathy and liver degeneration
that we saw in children who are exposed to aspirin. Aspirin
consumption with a viral illness in age 4 to 12,
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.
04:55
Now that we know about Reye's syndrome, we actually say that
aspirin is contraindicated in children,
and the old children is now given to adults as 81 milligram
aspirin for platelet protection.