Posted by Larry Hoover on March 2, 2005, at 15:55:06
In reply to Re: Holy Basil » Larry Hoover, posted by Sarah T. on February 17, 2005, at 3:04:01
> Larry, thanks for the information. I read that the reason Vioxx, Bextra and Celebrex cause the increased incidence of strokes and heart attacks is that one of the prostaglandins that is produced by the COX-2 enzyme has some beneficial, protective effects in addition to its inflammatory properties. When the COX-2 enzyme is inhibited by the drugs, the prostaglandin known as prostaglandin I2 is not formed in sufficient amounts. Although prostaglandin I2 can cause inflammation, it also prevents damage to artery walls and prevents blood clots. Apparently all of the COX-2 inhibitors mentioned above inhibit the production of Prostaglandin I2 and, at present, there is no way to stop the inflammation caused by Prostaglandin I-2 without also blocking its protective effects.
The more common name for prostaglandin I2 is prostacyclin. It's a derivative of arichidonic acid (omega-6).
I've done a lot of research into the prostaglandin cascade (there are a number of interlinked and embedded cycles and feedback loops), and the effects of inhibition of COX-2 on prostacyclin and clotting. It is my considered opinion that blocking of COX-2 is only a risk factor when other cardiac risks are already well advanced. Moreover, it seems to be necessary that extremely high doses of the COX-2 inhibitors are required (i.e. near absolute inhibition of that enzyme). Paradoxically, concurrent inhibition of COX-1 abolishes the adverse effect, which is why older nonselective COX inhibitors were not associated with these risks. Taking an enteric-coated 37.5 mg aspirin would probably do the trick, or intermittent use of the COX inhibitor, or not "maxing out" on the dose.
Frankly, I cannot believe the attention this adverse effect is getting. The net effect is really quite small, it is difficult to disentangle the effect from comorbidity, and there are many many far more dangerous drugs in common use. Tylenol kills more people every year than did Vioxx (allegedly) over its entire period of use.