Sulindac gastrointestinal effects

Selectivity for COX-1 versus COX-2 is variable and incomplete for the older NSAIDs, but many selective COX-2 inhibitors have been synthesized. The selective COX-2 inhibitors do not affect platelet function at their usual doses. In testing using human whole blood, aspirin, ibuprofen, indomethacin, piroxicam, and sulindac are somewhat more effective in inhibiting COX-1. The efficacy of -2-selective drugs equals that of the older NSAIDs, while gastrointestinal safety may be improved. On the other hand, selective COX-2 inhibitors may increase the incidence of edema and hypertension. As of December 2008, celecoxib and the less selective meloxicam are the only COX-2 inhibitors marketed in the USA. Rofecoxib and valdecoxib, two previously marketed, selective COX-2 inhibitors, have been withdrawn from the market due to their association with increased cardiovascular thrombotic events. Celecoxib has an FDA-initiated "black box" warning concerning cardiovascular risks. It has been recommended that all NSAID product labels be revised to include cardiovascular risks. 

In addition to its rheumatic disease indications, sulindac suppresses familial intestinal polyposis and it may inhibit the development of colon, breast, and prostate cancer in humans. It appears to inhibit the occurrence of gastrointestinal cancer in rats. The latter effect may be caused by the sulfone rather than the sulfide. 

Sulindac can cause all of the gastrointestinal adverse effects that are associated with indometacin, from... 

In pharmacological studies, sulindac did not signiflcantly alter the anticoagulant effect of warfarin or phenprocoumon. Isolated cases of a modest to marked increase in the anticoagulant effects of warfarin have been reported with sulindac. Note that all NSAIDs increase the risk of gastrointestinal bleeding, and an increased risk is seen when they are combined with anticoagulants. 

NSAIDs, such as aspirin, IND, ketoprofen, ibuprofen, naproxen, sulindac and flurbiprofen, are widely used in treatment of chronic inflammatory diseases. Recent studies have also shown that they have activity in retardation of colonic tumor growth [89-91]. However, oral administration of NSAIDs usually generates gastrointestinal side effects (e.g. gastric ulcers and gastric perforation) [92]. Therefore, colon-specific and controlled release of NSAIDs are important to achieve sustained pharmacologic effects and reduce the side effects. 

---