Gastrointestinal tract NSAIDs

The effectiveness of ketoprofen at dosages of 100-300 mg/d is equivalent to that of other NSAIDs. In spite of its dual effect on prostaglandins and leukotrienes, ketoprofen is not superior to other NSAIDs in clinical efficacy. Its major adverse effects are on the gastrointestinal tract and the central nervous system (see common adverse effects above). 

Goldstein JL. Challenges in managing NSAID-associated gastrointestinal tract injury. Digestion. 2004 69(suppl 1) 2 5—3 3. 

Rofecoxib, a furanose derivative, is a potent, selective COX-2 inhibitor (Table 36-1). In the USA, rofecoxib is approved for osteoarthritis and rheumatoid arthritis, and it also appears to be analgesic and antipyretic—in common with other NSAIDs. This drug does not inhibit platelet aggregation and appears to have little effect on gastric mucosal prostaglandins or lower gastrointestinal tract permeability. At high doses it is associated with occasional edema and hypertension. Other toxicities are similar to those of other coxibs. 

Most NSAIDs are well absorbed from the gastrointestinal tract, although there can be substantial inter- and intra-individual variations, e.g. indometacin [1, 24],... 

Indometacin is the best-known and most thoroughly tested indoleacetic acid derivative. It is one of the most effective NSAIDs, and most of its toxic and therapeutic effects appear to be due to marked inhibition of prostaglandin sjmthesis. Because of its potency, its clinical efficacy is comparable, if not superior, to any other NSAID, but for precisely the same reason its adverse effects on the gastrointestinal tract and the nervous system inevitably limit its use. However, patients who tolerate it reasonably well are naturally not anxious to exchange it for any newer drugs with fewer problems but less potency. A meta-analysis of patients preference in 37 crossover comparisons of indometacin with newer NSAIDs did not provide evidence of a trend to replace indometacin with newer NSAIDs (1). 

Data are insufficient to indicate whether the oxicam NSAID lornoxicam is safer for the gastrointestinal tract than other oxicam derivatives (SEDA-16, 113). 

In normal doses, paracetamol, in contradistinction to aspirin and the NSAIDs, is well tolerated by the gastrointestinal tract. 

As in the gastrointestinal tract, the negative effects of NSAIDs on the kidneys are thought to result from inhibition of the production of protective PGs. Several different PG subtypes appear to serve homeostatic functions in the kidney (Dunn 1984, Duim et al 1988, Stillman Schlesinger 1990). For example, PGI2 is the predominant PG produced in the renal cortex, glomeruli, arteries and cortical collecting tubes. In contrast, in the... 

Meclofenamic acid is an anthranilic acid derivative that is typically administered orally to horses. The pharmacokinetics of this NSAID in horses has been well defined. For example, the plasma half-life in horses has been determined in several studies and varies between 0.7 and 1.4 h (Johansson et al 1991, Snow et al 1981). Absorption is variable after oral dosing with estimates of bioavailability ranging from 60 to 90% and peak plasma concentrations occurring 1-3 h after administration (Johansson et al 1991). The effect of ingesta on the absorption of meclofenamic acid from the gastrointestinal tract has not been determined definitively. In one study, the absorption rate of the NSAID was the same in ponies whether they were fasted or fed (Snow et al 1981). However, another study found that absorption of meclofenamic acid was delayed in horses allowed free access to hay (May Lees 1999). In horses, the liver metabolizes meclofenamic acid primarily by oxidation to an active hydroxymethyl metabolite, which may be further oxidized to an inactive carboxyl metabolite (Plumb 1999). 

Wallace. J.L. (1994) Mechanisms of nonsteroidal antiinflammatory drug (NSAID) induced gastrointestinal damage - Potential for development of gastrointestinal tract safe NSAIDs. Can.. Physiol. Pharmacol., 72.1493-1498. 

The most common adverse effects of NSAIDs involve the gastrointestinal tract. Minor complaints (nausea, dyspepsia, anorexia, and abdominal pain) are common (up to 60% of patients). Serious GI complications associated with NSAIDs including perforations, gastric outlet obstruction, and GI bleeding, occur in 1.5% to 4% of patients per year. 

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