Meclofenamate, effect

Meclofenamate and mefenamic acid (Table 36-1) inhibit both COX and phospholipase A2. Meclofenamate appears to have adverse effects similar to those of other NSAIDs, though diarrhea and abdominal pain may be more common it has no advantages over other NSAIDs. This drug enhances the effect of oral anticoagulants. Meclofenamate is contraindicated in pregnancy its efficacy and safety have not been established for young children. 

All NSAIDs, including aspirin, are about equally efficacious with a few exceptions—tolmetin seems not to be effective for gout, and aspirin is less effective than other NSAIDs (eg, indomethacin) for ankylosing spondylitis. 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. Fries et al (1993), using a toxicity index, estimated that indomethacin, tolmetin, and meclofenamate were associated with the greatest toxicity, while salsalate, aspirin, and ibuprofen were least toxic. The selective COX-2 inhibitors were not included in this analysis. 

Mefenamic acid [meh FEN a mick] and meclofenamate [meh KLO fen a mate] have no advantages over the other NSAIDs as antiinflammatory agents. Their side effects, such as diarrhea, can be severe and associated with inflammation of the bowel. Cases of hemolytic anemia have been reported. 

J, Walter PB, Tomer KB, Barrett JC, Mason RP. Biomarkers of oxidative stress study 111. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCI4 poisoning. Free Radic. Biol. Med. 2005 38 711. 

Flufenamic acid and meclofenamic acid are anthranilic acid derivatives similar to mefenamic acid. The withdrawal rate because of adverse effects is 7-31% and is higher in longterm studies. Flufenamic acid and meclofenamic acid are not widely prescribed and so there is little evidence to show whether they have any advantages over other NSAIDs. Both have a high incidence of gastrointestinal adverse effects (30-60% of patients at recommended doses). Diarrhea affects 11 6% of patients (SEDA-4, 68) (SEDA-6, 99) (SEDA-7, 116) (SEDA-14, 95). Thrombocytopenia with positive rechallenge has been described (1). Rashes occur in under 10% of patients. Meclofenamic acid exacerbates psoriasis in psoriatic arthropathy (2). 

There is limited evidence that a few NSAIDs, such as meclofenamic acid and ketoprofen, have some inhibitory effects on lipoxygenase. For example, meclofenamic acid has been shown to inhibit 5-lipoxygenase and 15-lipoxygenase activities in... 

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). 

Fenamic acid (fenemate) derivatives include mefenamic acid and meclofenamic acid. These, too, are very powerful NSAIDs, but their GI side-effects seriously limit their use as antirheumatics. 

NSAIDs probably rednce proteinnria throngh prostaglandin E2 inhibition, resulting in a rednction of intraglomemlar pressure, a decrease in GER, and also restoration of the barrier size-selectivity of the GBM. Indomethacin and meclofenamate are the two NSAIDs that have been evalnated the most. Their antiproteinuric effect is comparable to those attained with ACEIs, and combined treatment with an ACEI results in additional proteinnria rednction. However, adherence to a low-sodinm diet or concnrrent nse of a dinretic is needed to maximize the antiproteinuric effect. Due to their potential for nephrotoxicity, especially in patients with poor renal fnnction, long-term use of an NSAID for renoprotection is not preferred. ... 

The fenamates are a family of NSAIDs first discovered in the 1950s that are derivatives of N-phenylanthranilic acid. They include mefenamic, meclofenamic, and flufenamic acids. They have no clear advantages over several other NSAIDs, and frequently cause GI side effects. 

Mefenamic acid has central and peripheral actions, and meclofenamic acid may antagonize directly certain effects of prostaglandins, although it is not clear that receptor blockade is attained at therapeutic concentrations. 

Probenecid reduces the clearance of dexketoprofen, diflunisal, in-dometacin (toxicity seen), ketoprofen, ketorolac, naproxen, sodium meclofenamate, tenoxicam and tiaprofenic acid and raises their levels. Ketorolac and probenecid are specifically contraindicated. The uricosuric effects of probenecid are not affected by in-dometacin but may be slightly reduced by sulindac. 

In healthy subjects dextropropoxyphene 260 mg daily and sodium meclofenamate 400 mg daily for a week was found to have no effect on the plasma levels of either drug."... 

The uricosuric effects of sulfinpyrazone are not opposed by the concurrent use of flufenamic acid, meclofenamic acid or mefenamic acid. Consider also Aspirin or other Salicylates + Sulfinpyrazone , p.l38). 

Robinson RG, Radcliff FJ. The effect of meclofenamic acid on plasma uric acid levels. MedJ... 

Blasingham, M.C., Shade, R.E., Share, L. and Nasjletti, A. (1980). The effect of meclofenamate on renal blood flow in the unanesthetized dog relation to renal prostaglandins and sodium balance. ]. Pharmacol. Exp. Ther., 214, 1-4... 

DeForrest, J.M., Davis, J.O., Freeman, R.H., Seymour, A.A., Rowe, B.P., Williams, G.M. and Davis, T.P. (1980). Effects of indomethacin and meclofenamate on renin release and renal hemodynamic function during chronic sodium depletion in conscious dogs. Circ. Res., 47, 99-107... 

Levison, S.P. and Levison, M.E. (1976). Effect of indomethacin and sodium meclofenamate on the renal concentrating defect in experimental enterococcal pyelonephritis in rats. ]. Lab. Clin. Med., 88, 958-64... 

Chronic treatment with sodium meclofenamate in normotensive rats was reported to have no effect on blood pressure. Similarly, blood pressure did not change in rabbits receiving indomethacin at 3 or 10 mg kg May for... 

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