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 tis-
sues, 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 reten-
tion and renal damage. More significantly, in 2004 it was recognized that COX-2
inhibitors may pose an increased cardiovascular risk. For example, rofecoxib was sud-
denly withdrawn from the market when it was noted that there was an increased rela-
tive risk for confirmed cardiovascular events, including heart attack and stroke, beginning
after 18 months of treatment, compared to placebo.
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