As we read a couple weeks ago in the review articles about the ‘Use of Non Steroidal Anti-inflammatory Drugs’ NSAID’s are very controversial in clinical use as they have shown increase use risk of cardiovascular and cerebrovascular events. This article was very good review article to warn people of the clinical cases that have been reported but there was no lab research done on these drugs. The article “Comparison of the Intestinal Toxicity of Celecoxib, a Selective COX-2 Inhibitor, and Indomethacin in the Experimental Rat” gives a new perspective on NSAID’s and compares two NSAID’s, Celecoxib a selective COX-2 inhibitor and Indomethacin a non-selective COX inhibitor. The claim is that all the problems with NSAID’s are that they cause a ‘topical’ effect and inhibit mucosal constitutive COX-1 enzyme. They used both in vivo and in vitro methods of Celecoxib and Indomethacin to test intestinal permeability and inflammation along with pro inflammatory proteins and production of ulcers. They found that Indomethacin, a non-selective COX inhibitor had a significant damaging effect to the intestinal mucosa, where Celecoxib, a selective COX inhibitor showed less intestinal damage, lower PGF levels and did not show the ‘topical’ effect on the mitochondria.
This article in essence showed a in vivo and in vitro with rat models and found evidence that shows that different NSAID’s may have different effects. Granted that this study was more focused on the digestive system and most of the problems reported have been with the cardiovascular and cerebrovascular systems. It does shed a new light on NSAID’s and maybe the idea to look at research of NSAID’s effect on the heart and brain.
Comparison of the Intestinal Toxicity of Celecoxib, a Selective COX-2 Inhibitor, and Indomethacin in the Experimental Rat
J.A. Tibble, G. Sigthorsson, R. Foster, I Bjarnason
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I wonder if selective Cox-2 inhibitors that don't have an adverse affect within the G.I. system eventually selectively affect the cardiovascular and cerebrovascular receptors in a negative way. Maybe there's some sort of protective role in the G.I. tract that's not present within other vascular systems...Either way, it's an interesting problem that's presented by Cox-2 inhibitors.
I think that Cox-2 inhibitors, which block Cox-2 enzyme, have their positive effects and potentially adverse effects on any system of the body where inflammation may occur. Cox-1 inhibitors, on the other hand, which would selectively block only the Cox-1 enzyme, which is in the GI track and inhibits the production of stomach acids and thereby protects the stomach lining, is not involved in inflammation and its being blocked by non-selective NSAIDS, results in the ulcerative and bleeding problems associated with their use. So, there are two different proteins affected here by NSAIDs and only NSAIDs that differentiate Cox-1 and Cox-2 avoid the potential GI complications associated with their use. Selective Cox-2 inhibitors, like Vioxx and Celebrex, certainly have positive effects for patients of chronic inflammation and associated pain, but, as I suppose is anything, comes at a price and with risk. I never understood fully why my father doesn't tolerate aspirin well - now it makes more sense!
Reference:
http://www.stronghealth.com/services/cancer/research/Cox2enzyme.cfm
I'm wondering what the toxicological effects of these particular NSAIDS on the brain are. Opiates have a devastating effect on the brain and spinal cord if given chronically (still bad short term). Studies in rats show extreme sensitivity to stimuli that normally would not be noxious (hyperalgesia).
I know the mechanism for NSAIDS is different compared to opiates in the brain and spinal cord, but I'm curious of anyone has researched neurological effects of NSAIDS.
Indomethacin does have CNS effects including dizziness, headache and somnolence. NSAIDS are known to cause apectic menigitis as well. These effects are not limited to COX-1 inhibitors but have been seen in COX-2 inhibitors as well.
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