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Andrew,
Great post on clinical pharmacology.
It reminded me of a search I recently conducted on which analgesic
should be used when taking 81 mg aspiririn (as prophylaxis for heart
attach/stroke). As I recall ibuprofen negated much of aspirin's
benefit. So, which NSAID do you recommend? I think ketoprofen was
OK, but this is out of my area of expertise. Celebrex seemed not to
interfere with 81 mg aspirin. So, I would be grateful to hear your
views, as well as that from others on this bulletin board/listserv.
Thanks. Harold Boxenbaum
Arishel Inc.
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Hi Harold:
Thanks and you ask a good question. There is an excellent review of
analgesics in cardiovascular disease by Steinhubl 2005 (1) who states:
"In the initial landmark study, Catella-Lawson et al demonstrated that
when the nonselective COX inhibitor ibuprofen was taken before
aspirin, aspirin's ability to inhibit serum thromboxane (TX)B2
formation and platelet aggregation was prevented. Acetaminophen,
diclofenac, and rofecoxib did not share this effect." So to answer
your question, it would look to me as though the standards of choice
would be paracetamol (perhaps you call it acetaminophen) and diclofenac.
The mechanism of the interaction featured in a very recent paper by
Hohlfeld, et al 2008 (3) who found that the interaction extends to
dipyrone's active metabolite 4-Methylaminoantipyrine (MAA). It
virtually abolished the inhibition of arachidonic acid-induced
platelet aggregation, thromboxane formation and P-selectin expression
by aspirin through attenuating the effect of aspirin on COX activity
of platelet microsomes, ie: probably competing with aspirin at the
COX-1 enzyme. Other pyrazolinones, as well as the conventional NSAIDs
ibuprofen and naproxen did the same as MAA. They did some docking
studies that revealed that MAA forms a strong hydrogen bond with
serine 530 within the COX-1, thereby preventing enzyme acetylation by
aspirin.
I hope that helps
Andrew
Andrew Sutton, MD(London) FFA,
Consultant in Clinical Pharmacology
References
1.) Steinhubl SR. The use of anti-inflammatory analgesics in the
patient with cardiovascular disease. J Am Coll Cardiol, 2005;
45:1302-1303.
2.) Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase
inhibitors and the antiplatelet effects of aspirin N Engl J Med
2001;345:1809-1817.
3.) Hohlfeld T, et al. January 2008. Pyrazolinone analgesics prevent
the antiplatelet effect of aspirin and preserve human platelet
thromboxane synthesis. Journal of Thrombosis and Haemostasis 6 (1),
166-173.
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