Commonly used drugs as well are
The great grandfather of all these drugs
is aspirin, ASA. The newer drugs tend to
be either relatively short acting
and low potency like ibuprofen,
or they can be very long acting
and have very profound effects on
the cyclooxygenase enzymes,
COX-1 and COX-2, and reduce
the production of prostaglandins, which are
present in inflamed tissues. So,
the reduction in inflammation reduces pain,
so that's where they become analgesics.
They also reduce the recruitment of leukocytes,
white blood cells, which produce inflammatory
mediators. So they both
go in and help moderate
inflammation and prevent further inflammation
from forming. So, side-effects
of non-steroidals are not inconsequential
And gastric hemorrhage is still a relatively common
event in people who were taking high doses of these
drugs. They're very irritating
to the gastric mucosa. In addition,
they interfere with platelet function, so they
interfere with clotting. So once bleeding starts,
they tend to cause a lot of bleeding.
They also cause renal toxicity. And
one of the more common causes of renal failure
in the western world is excessive use of non-steroidal
anti-inflammatory agents. Specific drugs,
ASA, even though it's the original
non-steroidal, has virtually no effect on the kidney,
but it has lots of effect, bad, on the stomach.
Acetaminophen, which falls into the same
family, interestingly has virtually
no anti-inflammatory effect. It
does not cause bleeding, it does
not have any negative effect on the kidney. But it's unfortunately
becoming one of the commonest reasons
for liver transplant in North America, as people
overdose on it or take too much for their
pain management, because it's directly toxic to the liver.
So, as I already mentioned, Ibuprofen is relatively short
acting. Other drugs such as Naproxen,
or Ketorolac, or Diclofenac are
longer lasting. They all have the same
negative renal and gastric effects,
but they also likely have cardiac effects that we
haven't really been aware of in the past. And we
didn't really learn much about this until a class
of drugs called COX-2 inhibitors were introduced,
with the expectation of fewer side effects,
particularly gastric, but also less bleeding.
And this was, these drugs were pushed
incredibly aggressively, particularly to orthopedic
surgeons, and were extremely widely used.
The one that you may have heard of was Vioxx.
And, after about five years of use,
it was discovered that the incidence
of ischemic cardiac events, myocardial infarctions
and death, in people taking these drugs
was quite high. And they were finally stopped.
And the interesting thing from a historical perspective
is that one of the drug, not regulatory
bodies, but examination bodies at
my own university, actually published the problem with,
the potential problem with cardiac disease
years in advance of this drug being taken, these drugs
being taken off the market, and it was largely ignored.