rheumatoid arthritis. Some of these compounds are powerful enough to be effective
against the major pain caused by malignancies.
In theory the selective COX-2 inhibitors may offer some advantages. There are at
least two forms of the COX enzyme: COX-1 and COX-2. COX-1 is located in most tissues, including stomach and kidneys. COX-2, on the other hand, is undetectable in most
tissues under physiological conditions. COX-2 is induced at sites of inflammation,
secondary to the effects of cytokines. Accordingly, specific COX-2 inhibitors, such as
celecoxib (8.79) and rofecoxib (8.80), are less likely to cause stomach ulceration and
gastrointestinal bleeding. Nevertheless, they still have the capacity to cause fluid retention and renal damage. More significantly, in 2004 it was recognized that COX-2
inhibitors may pose an increased cardiovascular risk. For example, rofecoxib was suddenly withdrawn from the market when it was noted that there was an increased relative risk for confirmed cardiovascular events, including heart attack and stroke, beginning
after 18 months of treatment, compared to placebo.
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MEDICINAL CHEMISTRY