NSAIDs definition

Severe, active, classical or definite adult RA (ACR criteria) in selected adults who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full-dose NSAIDs. 

Celecoxib and rofecoxib have also been studied in AD. Randomized double blind, placebo controlled trials failed to demonstrate a therapeutic benefit (Sainetti et al., 2000 Aisen et al., 2003). The rofecoxib trial used naproxen as a control the results were consistent with other studies in which nonselective NSAIDs such as diclofenac, have been ineffective in AD (Scharf et al., 1999). Other NSAIDs including ibuprofen, indomethacin and sulindac sulfide have demonstrated potential efficacy in AD (Rogers et al., 1993 t Veld et al., 2001), but definitive trials have not yet been conducted. 

Observational cohort or case control designs have been used to determine ADR relationships with specific therapeutic classes. " Medical claims data are often used in these studies and caution should be warranted due to lack of definite confirmation of drug exposure and the potential for confounding variables. However, these studies have been beneficial in determining risk of ADRs with specific classes (e.g., NSAIDs and the risk of peptic ulcer disease). 

In conclusion, although these three studies suggest that patients who take naproxen have a lower incidence of myocardial infarction than those who take other NSAIDs or who do not take NSAIDs, the data do not provide definitive evidence that naproxen is cardioprotective. The data therefore raise a cautionary flag about the risk of severe cardiovascular events with COX-2 inhibitors and again call for more studies. 

This study also had two main limitations first, most of the trials were small, which precluded definitive conclusions about the effects of individual NSAIDs or individual antihypertensive drug classes secondly, in most studies, therapy was short term and the patients were relatively young, making generalization of the results difficult, as NSAIDs are most often prescribed long term and for elderly people. 

These conflicting results can probably be explained by important differences in the characteristics of the patients and the study methods. The inclusion criteria in the two studies were mutually exclusive patients with long-term NSAID use and a history of ulceration were excluded in the first study and included in the second. Furthermore, there were differences in the definition of endoscopic ulcers, the eradication regimen, the definition of H. pylori infection, and the length of follow-up. 

All NSAIDs, by definition, inhibit COX enzymes to some degree. This prevents the metabolism of arachidonic acid to the unstable endoperoxide intermediate PGG2 (Ziel Krupp 1975). Currently two isoforms of the COX enzyme, known as COXl and COX2, have been described (Vane Dotting... 

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). 

The efficacy of meclofenamic acid as an antiinflammatory agent in horses has been determined in a number of studies using the recommended doses (Table 14.1) (Galbraith McKellar 1996, Johansson et al 1991, Tobin 1979). It is known for its slow onset of action, requiring 36-96 h of therapy before clinical effects are evident (Boothe 1995). It has also been proposed to be particularly effective in the treatment of acute and chronic laminitis, although its superiority over other NSAIDs in the treatment of these conditions has not been definitively proven (Lees Higgins 1985). In one study, meclofenamic acid was shown to decrease the accumulation of lactate and increase the lactate threshold in an exercise tolerance test carried out in seven standardbred horses (Johansson et al 1991). 

Helicobacter pylori infection is identified as the main causative factor for duodenal ulcer disease, although the process is definitely aggravated by smoking and drugs such as NSAIDs. 

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