A very good read on NSAID's, ulcers, the cox enzymes. Gives a good grasp of the $10 billion arthritis pain relief market, and the pros and cons of some players in it.
http://elfstrom.com/arthritis/nsaids/
The elucidation of NSAIDS effects on the cox enzymes is fairly new stuff, and the first generation of pain relievers using this new understanding have just popped out of the drug testing pipelines (cox2 inhibitors). These things will be fiddled with for years to come to maximize pain relief while minimizing side effects.
The presentation suggests aspirin in the bloodstream causes the majority of the deleterious effects by shutting down the cox1 prostaglandin mucous production promoting pathway, so the trend would likely be away from aspirin (one of the worst offenders of the NSAID classes) and towards less deleterious NSAIDS combined with some sort of promoter of GI mucous production, perhaps downstream from the cox 1 modulator.
There are two components to NSAID-induced ulceration (Figure 7). First, there is a local acid effect of the dissolved drug. Most NSAIDs are weakly acidic, lipid-soluble compounds. Since the cell membranes on the stomach wall contain lipids for protection against strong acids, they offer little resistance to the lipid-soluble NSAID. The NSAID acts against the cell membrane, increasing its permeability. This results in cell swelling and death (8). The local acid effect of NSAIDs has been reduced by enteric-coating the drug, delaying dissolution until later in the digestive process. However, not all NSAIDs are enteric-coated as it increases cost. In addition, enteric-coating does little more than improve the symptoms of upset stomach. Patients must be informed that enteric-coated NSAIDs are still just as likely to cause stomach ulcers as regular NSAIDs.
The second and much more significant component to NSAID-induced ulceration is the systemic effect after being absorbed into the bloodstream. As described in the How NSAIDs Work, NSAIDs inhibit COX-1, reducing prostaglandin production. Normal COX-1 present in stomach tissue produces prostaglandins which:
increase mucous and bicarbonate production,
inhibit stomach acid secretion,
increase blood flow within the stomach wall.
By acting on COX-1, NSAIDs restrict these self-protection mechanisms, allowing stomach ulcers to develop. It is primarily through this mechanism, not a local acid effect, that NSAIDs cause stomach ulcers. Unfortunately, the general public is not aware of this fact. Despite announcements by the U.S. Food and Drug Administration about the dangers of NSAIDs and calling for increased warnings on NSAID packaging (25,30), patients are still receiving conflicting information. Bayer continues to produce advertising that promotes use of its coated aspirin tablets for people who experience stomach upset (9). Although Bayer’s promotional literature is technically correct, it does not educate consumers about the risks associated with long-term aspirin use. This gives patients a false sense of security, and they are generally unaware that aspirin is one of the more dangerous NSAIDs. Aspirin in particular was recently found to be a more common cause of GI perforation than previously recognized (23). The responsibility for patient education about aspirin use lies with both physicians and pharmacists. |
