Aspirin selective toxicity

Thus the effect on clotting might be seen as an unwanted side effect by someone who suffers stomach bleeding after repeat doses of aspirin, but in some circumstances it is desirable. This again illustrates a principle in the use of chemicals that is illustrated by the use of anti-cancer drugs (see below), the principle of selective toxicity, which we shall revisit in Chapter 4 what might be considered an adverse or toxic effect in some circumstances or in some organisms may be beneficial in others. The assessment and appreciation of toxicity sometimes needs to take this into account. 

Thus, NSAIDs tend to be differentiated on the basis of toxicity and cost-effectiveness. For example, the gastrointestinal and renal side effects of ketorolac limit its use. Some surveys suggest that indomethacin or tolmetin are the NSAIDs associated with the greatest toxicity, while salsalate, aspirin, and ibuprofen are least toxic. The selective COX-2 inhibitors were not included in these analyses. 

Celecoxib 1.34 (1.19-1.52) Naproxen 1.35 (0.97-1.88) Ibuprofen 1.51 (0.95-2.41) Acetaminophen 1.29 (1.17-1.42) Naproxen is associated with the highest risk of AMI/GI events in those not taking aspirin. Celecoxib and acetaminophen AMI/GI risk is similar and less than the other NSAIDs (selective and non-selective). Celecoxib and naproxen are the least toxic in comparison to the other NSAIDs in those using aspirin. 

There is little evidence to support clinically important differences with regard to the frequency of ulcers and upper GI complications among most available nonaspirin, nonselective NSAIDs (see Table 33-3) when used in equipotent anti-inflammatory dosages. However, the nonacetylated salicylates (e.g., salsalate) and newer NSAIDs (e.g., etodolac, nabumetone, and meloxicam) may be associated with a decreased incidence of GI toxicity. NSAIDs that selectively inhibit cyclooxygenase-2 (COX-2) decrease the incidence of gastroduodenal ulcers and related GI complications when compared to the nonselective NSAIDs. The use of buffered or enteric-coated aspirin confers no added protection from ulcer or GI complications. ... 

Selective COX-2 inhibitor acts mainly on enzymes of cells involved in inflammation. Used in rheumatoid arthritis and other inflammatory disorders. Tox GI toxicity, but less than that of aspirin and other NSAIDs. Rofecoxib is similar. 

Aspirin and non-selective NSAIDs inhibit the mechanisms that protect the gastrointestinal mucosa and so cause gastrointestinal toxicity. COX-2 selective NSAIDs (coxibs) are less likely to have this effect. 

NSAIDs can be classified on the basis of their COX inhibitory and selective properties. Most NSAIDs inhibit both COX-1 and COX-2 to some extent. Most are mainly COX-1 inhibitory, e.g., aspirin, ibuprofen, diclofenac, naproxen, while some are COX-2 inhibitory, e.g., celecoxib, rofecoxib, and lumiracoxib. Vane et al. established the relative inhibitory potencies of NSAID COX-1 and COX-2 inhibitors. NSAIDs with the highest gastrointestinal toxicity have the highest COX-1 selectivity. 

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