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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-inflammatory, analgesic, antipyretic and ulcerogenic activities of etodolac (CAS 41340-25-4), a new nonsteroidal anti-inflammatory agent, were compared with those of indometacin and other anti-inflammatory drugs in experimental animals. Etodolac had a remarkable anti-inflammatory effect in various experimental models: ultraviolet erythema, carrageenin-induced edema and swelling of adjuvant arthritis. In these models, the effective dose of etodolac was several fold that of indometacin. Etodolac inhibited prostaglandin E2 formation in a concentration-dependent manner, and its inhibitory potency was about 1/5 of that of indometacin. Etodolac also caused marked inhibition of granuloma formation and leucocyte functions such as chemotaxis, lysosomal enzyme release and active oxygen generation. These effects of etodolac were observed at similar doses of indometacin. Etodolac suppressed inflammatory pain but not non-inflammatory pain, and had an antipyretic effect but did not lower normal rectal temperature. Etodolac had no effect on delayed hypersensitivity reactions and was much less ulcerogenic than indometacin. These results indicate that etodolac is a low ulcerogenic anti-inflammatory agent with suppressing activities on leucocyte functions to the same extent as indometacin and prostaglandin biosynthesis.
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PMID:Pharmacological properties of the new non-steroidal anti-inflammatory agent etodolac. 165 Oct 85

Etodolac is a new nonsteroidal anti-inflammatory drug (NSAID). Published and unpublished data on etodolac in pain management are reviewed to assess the analgesic effectiveness of this drug. Data are presented from four representative studies that showed the analgesic activity of etodolac in postsurgical pain models. These results suggest that the drug would have analgesic utility in other painful conditions such as gout and musculoskeletal disorders. The efficacy of etodolac in such conditions is confirmed by the results from eight controlled clinical studies in patients with gouty arthritis, tendinitis and bursitis, and acute sports injuries. Etodolac 200 or 300 mg twice a day (b.i.d.) or 200 mg three times a day (t.i.d.) was compared with naproxen 500 mg b.i.d. and diclofenac 50 mg b.i.d. or 50 mg t.i.d. All three NSAIDs provided analgesia, and etodolac was comparable in efficacy to the comparators. The data presented in this review suggest a future role for etodolac as an analgesic as well as an anti-inflammatory agent.
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PMID:Clinical response to etodolac in the management of pain. 169 64

Etodolac, a new nonsteroidal anti-inflammatory drug, was administered orally at doses of 1 and 5 mg/kg to MRL/MpJ-lpr/lpr (MRL/lpr) mice, and its effect on articular lesions was compared with that of indomethacin. Both etodolac and indomethacin significantly reduced swelling of the hind paw. Histopathological examination showed that etodolac significantly reduced cartilage and bone damage, whereas indomethacin treatment did not achieve a statistically significant effect. Rheumatoid factors were not affected by either etodolac or indomethacin. These results indicate that etodolac delays the development of arthritis in MRL/lpr mice, and reduces cartilage and bone damage.
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PMID:Effect of etodolac, a new nonsteroidal anti-inflammatory drug, in MRL/lpr mice with articular lesions. 183 69

To investigate the role of PGE2 in the development of bone and joint pathology in rat adjuvant arthritis, hindlimb paws were evaluated by calcified tissue histologic techniques focusing on histochemical visualization of cartilage and bone lesions. Case studies of hindlimbs from normal, adjuvant arthritic, and etodolac-treated arthritic rats demonstrated the association of disease severity with inflammation, chondromalacia, replacement of adipose bone marrow with a fibroid marrow, osteoclastic bone resorption, synovial cysts, and pannus formation within the joints. Extensive periosteal intramembranous bone formation was temporally associated with joint destruction and medullary tissue pathology. In vivo data were correlated with in vitro effects of inflammatory mediators (IL-1, PGE2) on bone resorption. Etodolac blocked bone explant PGE2 accumulation at concentrations of 10(-7) M and higher, and inhibited bone resorption at concentrations of 10(-5) M and higher. The data indicate that in vitro and in vivo models of bone metabolism are well correlated regarding prostaglandin synthesis; that the inflammatory mediator PGE2 is largely responsible for the involvement of skeletal tissue in the adjuvant arthritis model; and that the effects of etodolac are specifically mediated by its ability to inhibit PGE2 accumulation in vivo.
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PMID:Prostaglandins in inflammatory bone pathology: mechanism and therapeutic benefit of etodolac. 252 14

Etodolac, a new anti-inflammatory analgesic drug found to be effective in treating arthritis in a dose range of 100 to 300 mg bid, has been shown to induce significantly less gastrointestinal microbleeding in normal men than several other NSAIDs. In this study, the effect on gastrointestinal blood loss of high-dose etodolac, 300 and 500 mg bid, versus piroxicam at its normal therapeutic dose of 20 mg qd, was investigated by the 51Cr method in 23 men with osteo- or rheumatoid arthritis. Placebo periods preceded and followed 28 days of active drug treatment. Blood and stool analyses were performed by an analyst not aware of drug assignment or study design. Patients receiving piroxicam, but not those receiving either dose of etodolac, had a significantly higher mean level of fecal blood loss in the active treatment phase compared with the pretreatment placebo level (p less than 0.01). Further, microbleeding was significantly greater for the piroxicam group during treatment than for either of the etodolac groups (p less than 0.01). There were no significant differences in fecal blood loss between the two groups receiving etodolac compared with pretreatment. Even at doses two to three times those found effective in the treatment of arthritis, etodolac produces no increase in fecal blood loss, in contrast to blood loss seen with the recommended dose of piroxicam. Fecal blood loss in osteoarthritic patients, not receiving an NSAID, was similar to normal subjects in previous studies.
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PMID:Gastrointestinal blood loss in arthritic patients receiving chronic dosing with etodolac and piroxicam. 294 24

Etodolac is the first anti-inflammatory drug belonging to the tetrahydropyranoindole class. In contrast to several other common anti-inflammatory drugs, etodolac exhibited an unusually high potency as an inhibitor of established adjuvant arthritis relative to its activity against carrageenan paw edema in the rat. This phenomenon led us to investigate whether the ability of NSAIDs to inhibit prostaglandin biosynthesis differed between cultures of macrophages, which are present in inflammatory exudates, and cultures of synoviocytes and chondrocytes, which contribute to inflammation of the articulating joint. Although other anti-inflammatory drugs were found to be equally active in all three cell types, etodolac was found to be much more effective on the cells of the joint than on the macrophage. This differential activity may be responsible for the striking efficacy of etodolac as an anti-arthritic drug.
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PMID:Inhibition of prostaglandin biosynthesis by etodolac. I. Selective activities in arthritis. 295 97

The pharmacokinetics of etodolac have been evaluated in five patients with arthritis given 200 mg etodolac, twice daily, at 12-hour intervals, for 7 days. Albumin and total protein concentrations were markedly lower in synovial fluid than in serum, and etodolac free fraction was significantly higher. Etodolac readily penetrated into the synovial fluid, and in the postdistributive phase the concentration of free etodolac (i.e., the drug responsible for pharmacologic activity) remained higher than that in serum at all times. No differences in the half-life of etodolac elimination were noted.
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PMID:The pharmacokinetics of etodolac in serum and synovial fluid of patients with arthritis. 296 93

Etodolac, 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid, a clinically effective analgesic and antiinflammatory agent, has been resolved via a chromatographic separation of its diastereoisomeric esters with (-)-borneol. The effects of the enantiomers were studied in vitro on prostaglandin synthetase and on adjuvant-induced arthritis in rats. The biochemical and pharmacological results show that virtually all of the effects of etodolac are due to the (+) enantiomer.
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PMID:Resolution of etodolac and antiinflammatory and prostaglandin synthetase inhibiting properties of the enantiomers. 622 48

The effect of treatment with the new anti-inflammatory drug etodolac on the articular and bone pathology associated with adjuvant arthritis in rats has been compared to the effects produced by aspirin and naproxen. Five measures of drug effect were made (changes in hind paw edema, body weight, normal hind leg function and articular damage as assessed by radiologic and histopathologic techniques). Drug treatment was initiated 16 days after adjuvant injection when arthritis was already established and continued for either 14 or 28 days. Etodolac produced a dose-related inhibition of all arthritic changes. Results from the radiologic study indicated that etodolac not only prevented the further development of articular damage by arthritis but actually caused a regression of these lesions established before drug treatment began. Similar results were obtained from the histopathologic study. Naproxen prevented the further development of arthritic damage but aspirin, although it decreased hind paw edema and increased body weight gains, had no significant effect on the articular damage produced by arthritis.
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PMID:Effect of etodolac on articular and bone pathology associated with adjuvant arthritis in rats: a comparison with aspirin and naproxen. 623 45

The effect of prolonged treatment with etodolac (8 mg/kg) on the articular and bone pathology at the tibiotarsal joint associated with adjuvant arthritis in the rat has been studied and compared to the effects produced by treatment with naproxen (8 mg/kg) and ibuprofen (50 mg/kg). Drug effects were assessed by radiologic and histopathologic examinations. The effects on hindpaw edema, hindleg function, and body weight gain were also evaluated. Treatment was initiated on day 16 after adjuvant injection and continued for 28, 56 or 84 days. The degree of relapse which occurred after a 28 day period without treatment following 28 or 56 days of treatment was also assessed. Etodolac prevented the progression of the disease. Further, it appeared to diminish the incidence and severity of the lesions already present on day 16 before drug treatment began. All the parameters measured were improved and there was good agreement between the radiologic and histopathologic assessments of joint damage. At the doses used, the onset of drug activity was more rapid with etodolac than with either of the other two drugs. By comparison naproxen and ibuprofen inhibited the progression of joint damage, but neither drug consistently decreased the magnitude of the joint damage below that of day 16. With all three drugs there was less resurgence of disease symptoms when treatment was stopped after 56 days rather than 28 days of drug administration.
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PMID:Comparative effects of long term treatment with etodolac, naproxen and ibuprofen on articular and bone changes associated with adjuvant arthritis in rats. 624 Sep 30


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