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E-DRUG: Last Posting about Nimesulide
Nimesulide has not been licensed by the FDA for use in the United States.
Prostaglandins are synthesized from arachidonic acid by the enzyme
cyclo-oxygenase.
There are two isoforms of cyclooxygenases: Cox-1 is expressed
constitutively in most
tissues and helps maintain gastric mucosal integrity; Cox-2 is inducible
and is
associated with cellular growth and differentiation. In a recently
published study,
PGE2 was shown, for the first time, to up-regulate the MRNA levels of its own
synthesizing enzyme, Cox-2, in four human cells lines. In this regard, it is
conceivable that cells continuously sustain their growth in part by using
extra
cellular PGE2 that they themselves produce and release to up-regulate the
expressions
of Cox-2 and possibly other growth related genes. Elevated Cox-2 expression
may make
cancer cells resistant to apoptosis. Inhibition of excess activity with Cox-2
specific non-steroidal anti-inflammatory drugs might restore the cell�s
ability to
die by apoptosis and so cause tumor regression.
Super aspirins that selectively inhibit Cox-2 are being developed by
several drug
companies to try and avoid the side effects of NSAIDS. Most currently
commercially
available NSAIDS are nonselective Cox inhibitors and are associated with
peptic
ulceration in the stomach. Nimesulide is a novel NSAID that is one hundred
times more
selective for Cox-2 than for Cox-1.Nimesulide had no significant effect on
Thromboxane B2 which is suppressed by aspirin. Nimesulide suppressed Cox-2
in vivo
with no detectable effect on platelet Cox-1.
Nimesulide has been commercially available throughout most of the rest of
the world
for more than 10 years.
--
Blaine P. Carmichael, PA-C
bpcarmichael@stic.net
C0-Moderator, PRIMARYPA Clinical discussion List
VP Association of Family Practice Physician Assistants
Disease Detection and Prevention National CME Conference
San Antonio, Texas November 4-7, 1999
AFPPA Job Bank: http://www3.ns.sympatico.ca/yngdoc/
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