Preface [Hot topic: Implications of COX-2 Inhibition in the Gastrointestinal Tract (Executive Editor : Angel Lanas)]

E-ISSN： 1873-4286|9|27|i-ii

ISSN： 1381-6128

Source： Current Pharmaceutical Design, Vol.9, Iss.27, 2003-10, pp. : i-ii

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Abstract

Since the seminal observations made in 1971 where it was proposed that the ability of aspirinlike drugs to suppress inflammation was due their ability to inhibit the production of prostaglandins, much work has been done and many targets have been achieved. More recently, in 1991, it was discovered that COX exists in two different isozymes (COX-1 and COX-2) and that COX-2 was primarily responsible for inflammation but apparently had no role as a housekeeping enzyme for the gastrointestinal mucosal integrity or platelet aggregation. This achievement led to the development of new compounds that are selective inhibitors of this isoenzyme, the so-called coxibs, which retain anti-inflammatory activity but minimize the risk of gastrointestinal toxicity and bleeding. Now, more than ten years of intense research with these compounds have shown that things are more complicated than previously believed. Furthermore, our understanding of the roles or the involvement of COX-1 and COX-2 in both physiology and pathological conditions have been greatly expanded and all these aspects have been well updated and summarized by Dr. Claria [1] in the first chapter of this supplement.This issue of the Current Pharmaceutical Design Journal is focused on the effects of COX-2 inhibition in the gastrointestinal tract and deals with the two most important aspects that have or may have a direct impact on clinical practice, namely the gastrointestinal side effects associated with the use of either non-specific non-steroidal antiinflammatory drugs or selective COX-2 inhibitors and the impact of the use of these drugs on the prevention or treatment of gastrointestinal cancer. All the chapters, written by experts from all over the world, are updated up to March 2003.With a progressively ageing society in many countries, the increase in the incidence of different rheumatic conditions parallels the increase in the use of analgesics and anti-inflammatory agents. One of the major concerns for the clinician who treats this type of patients is the high rate of gastrointestinal side effects associated with the use of non-specific COX-1 and COX-2 inhibitors. The mortality associated with these side effects has been estimated to be higher than many other diseases such AIDS, carcinoma of the cervix, asthma, etc. These aspects are covered “in extenso” in one of the chapters written by Prof. Hawkey, [2] a well known expert in the field, and it is followed by another one written by Prof Scheiman [3] focused on the benefits in the reduction of gastrointestinal side effects with selective COX-2 inhibitors. We now have extensive information on the impact of this new class of drugs on basically all aspects of gastrointestinal side effects including ulcers, complications and dyspepsia. Clinical studies of the COX-2-selective inhibitors have shown that these agents have an efficacy equivalent to that of nonselective NSAIDs but with lower rates of GI toxicity. The results of large outcome studies have confirmed that supratherapeutic doses of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID. However, these studies have also shown that more data are needed to elucidate other aspects regarding the overall safety of the patients, especially in the cardiovascular system. Also, more data are needed to assess the gastrointestinal safety (particularly with regard to ulcer complications) of the use of lowdose aspirin concomitantly with a coxib. COX-2 may also have a positive role in circumstances of pre-existing lesions (e.g. gastric ulcer) where the inhibition of COX-2 may have a detrimental effect. The existing experimental data regarding this interesting area is covered by Dr. Perini and Prof. John Wallace [4].One area of growing concern is the association of NSAIDs with side-effects located beyond the duodenum. For years most studies had been focused in the upper GI tract, but the implication of NSAIDs with lower