Adverse Effects of Non-Steroidal Anti-Inflammatory Drugs on the Gastrointestinal Tract. Part 2

NSAIDs suppress but do not eliminate inflammation completely. NSAID-mediated COX-1 inhibition must be maintained over long durations to achieve clinical remission of inflammation symptoms. It is this lengthy period of NSAID use that is the likely cause of GI side effects. The physiological mechanisms that account for GI side effects produced by COX-1 inhibitors involve alterations in many important GI metabolic events, including, increased gastric acid production, decreased gastric mucin and bicarbonate production as well as suppression of gastric muscosa cell division. NSAIDs also inhibit platelet function by altering the synthesis of prostacyclin and thromboxane(s). Thus, platelet regulation of bleeding in general, and GI bleeding specifically, can be disrupted by NSAIDs so that platelet adhesiveness to gastric muscosa is compromised. Several NSAIDs that target COX-1 such as indomethacin and sodium meclofenamate are metabolized and are then re-circulated after passing through the liver, which potentially increases their GI toxicity.

Estimates by the U.S. FDA as to the percentage of patients using NSAIDs for arthritis who experience adverse GI reactions, which include, ulceration, bleeding and perforation, ranges from one to two percent, after three months of NSAID use, to two to five percent after one year of NSAID use.

While these percentages appear relatively low, GI reactions cause significant co-morbid medical problems in those experiencing these problems. Reluctance to continue NSAID use by these patients often results in an exacerbation of the inflammatory symptoms of arthritis. To allow for continuation of NSAID use by these patients, those experiencing significant GI side effects are often also maintained on additional drugs including, antacids, H2 blockers or muscosa protecting agents such as misoprostol, a synthetic prostaglandin.

If COX-2 inhibitors were developed, in part, to reduce potential GI side effects inherent with the use of conventional NSAIDs, has the clinical data compiled thus far indicated that adverse GI events have been suppressed or eliminated by COX-2 inhibitors? First, patients who have a risk factor for GI side effects concomitant with conventional chronic NSAID use cannot always be predicted ahead of time. In order to avoid potential complications, these patients are generally candidates for acetaminophen therapy. In fact, acetaminophen is prescribed to almost one-half of patients with rheumatoid arthritis, in addition to other anti-rheumatic medications. Patients with osteoarthritis also frequently use acetaminophen or salsalates. Thus, many physicians use acetaminophen to avoid GI complications knowing full well that the inflammatory components of arthritis will be generally unaffected by the use of acetaminophen alone.

Celecoxib (Celebrex) or refecoxib (Vioxx) are members of the COX-2 inhibitor class. The medical management strategy employed suggests that COX-2 inhibitors be considered when patients do not respond to conventional NSAIDs for treatment of rheumatoid arthritis or osteoarthritis, or when adverse GI outcomes occur early from conventional NSAID therapy. Of interest in this regard, the use of low-dose aspirin in combination with conventional NSAIDs such as ibuprofen or diclofenac did not appear to significantly increase the risk for GI toxicity. However, according to Dr. Fred Silverstein and colleagues, publishing in The Journal of the American Medical Association (September 13, 2000), results from the CLASS (Celecoxib Long-term Arthritis Safety Study), clinical trials showed that celecoxib at dosages even greater than those normally employed clinically for the therapy of arthritis was associated with a low rate of GI complications (i.e., ulcers) when compared to conventional NSAID at standard dosages. The reduction in upper GI toxicity was greatest in patients who were not also using aspirin. These results of this study support the view that COX-2 inhibition, which suppresses the inflammation of arthritis, also results in fewer and less severe GI reactions when compared to COX-1 inhibitors. These results have important ramifications in consideration of long-term arthritis therapy with COX-2 inhibitors. The results of follow-up clinical trials will likely influence how COX-2 inhibitors are employed for aggressively treating inflammation during the very early stages of active arthritis.

People do not guess at what time an urgent situation can happen. Thus, doctors and safety officials recommends us to have individual first aid kits in home, office, car, workplace.