RESUMEN

The mechanism of action of various types of drugs for treating inflammation and arthritis is reviewed. Three classes of agents, the steroidal, the acidic non-steroidal and the basic therapy drugs, are discussed. The first two types of drugs act rapidly on the symptoms of inflammation, interfering at various points in the inflammatory response. The non-steroidal agents are especially linked to a mechanism involving, at least in part, the prostaglandins. Piroxicam, a potent, structurally unique member of the non-steroidal class, is discussed in some detail. The basic therapy drugs act slowly, generally exhibit more severe side effects and probably affect some immunological aspects of rheumatoid arthritis. The precise mechanisms of action of this latter class of structurally diverse drugs is generally poorly understood at this time.

Asunto(s)

RESUMEN

Piroxicam is a chemically unique, long-acting, potent antiinflammatory/analgesic agent now available for the treatment of arthritis and other inflammatory diseases in over 80 countries around the world. The literature of the last 2 years on preclinical and clinical results with piroxicam has been reviewed. Recent laboratory experiments have given insights into additional actions of piroxicam which may play a role in its broad spectrum of antiinflammatory activity. In various animal models, piroxicam inhibits cell migration into an inflamed site. In vitro, piroxicam inhibits both superoxide anion production and lysosomal enzyme release from human neutrophils and also inhibits IgM-rheumatoid factor production by human lymphocytes. The safety and excellent toleration of piroxicam in animals has been reconfirmed. Extensive clinical trials in over 66,000 patients have demonstrated the high efficacy and excellent toleration of piroxicam in rheumatoid arthritis, osteoarthritis, gout, various musculoskeletal disorders and pain of varied etiology. Patient preference and compliance has consistently been higher for patients on piroxicam therapy. A single 20 mg, daily oral dose produces 24 hour control of symptoms. Piroxicam has been shown to be a useful addition to the physicians armamentarium.

Asunto(s)

RESUMEN

Piroxicam, a potent, long acting non-steroidal anti-inflammatory drug, was tested in several rodent models of arthritis to assess further the possible mechanisms underlying its anti-inflammatory action. Piroxicam inhibited rat adjuvant disease and its associated manifestations, which include erosion of bone and cartilage (as evidenced by X-ray examination), soft tissue swelling and disease-induced weight loss. Piroxicam also inhibited the edema, the total leukocyte infiltration and the mononuclear cell infiltration into the carrageenan-injected pleural cavity of the rat. The possible relationship of these effects to the clinical activity of piroxicam is discussed.

Asunto(s)

RESUMEN

A unique class of immunosuppressive agents has been found be the use of a mouse model of immunity. A number of bensothiopyrano[4,3-c]pyrazol-3-ones are potent inhibitors of both the humoral and cellular immune response developed in mice in response to El4 tumor cells. These compounds exhibit a selectivity for inhibiting the humoral response. Structure-activity relationships and Hansch analyses of data from the mouse model are discussed. One of the most potent compounds, 2-(4'-chlorophenyl)bensothiopyrano[4,3-c]pyrazol-3-one (1, CP-17 193), exhibits ED50 values for inhibiting the humoral and cellular responses in the range of 0.5-2 mg/kg, po, in the mouse model and also inhibits antibody production to several other antigens and prolongs skin graft survival in mice. These compounds are shown in several ways to be distinct from the lymphocytotoxic drugs cyclophosphamide and azathioprine.

Asunto(s)

Asunto(s)

RESUMEN

Four possible pyridine monohydroxylated metabolites of the antiinflammatory agent piroxicam have been synthesized for comparison with a natural pyridine-hydroxylated metabolite of this compound. In addition, another metabolite of piroxicam, derived from dehydration of the parent drug, has been made and characterized. The antiinflammatory activity of these compounds and four other known metabolites of piroxicam has been measured in the carrageenan-induced rat paw edema model and all are found to be less active than piroxicam itself.

Asunto(s)

RESUMEN

Piroxicam is a structurally novel, long-acting anti-inflammatory drug with potent activity following oral administration in animal models of inflammation and in human inflammatory diseases. The present studies, performed in rats, demostrate that topically applied piroxicam is a potent inhibitor of inflammation induced by either carrageenin or complete Freund's adjuvant. Comparable potencies (ED50 approximately 1--5 mg/kg) were obtained for topically and orally administered piroxicam in these models of inflammation. The potency of topical piroxicam exceeds that of topically applied bufexamac or phenylbutazone in the rat adjuvant arthritis model.

Asunto(s)

RESUMEN

Piroxicam is a potent inhibitor of prostaglandin biosynthesis. Experiments utilizing cell culture and microsomes derived from various sources have demonstrated that piroxicam is a selective inhibitor of the cyclooxygenase step of arachidonic acid metabolism. Little blocking activity is observed at the phospholipase, thromboxane or prostacyclin synthetase, and arachidonic acid lipoxygenase steps.

Asunto(s)

RESUMEN

The new non-steroidal antiinflammatory (NSAI)2 agent, piroxicam [4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide], is a highly active inhibitor of prostaglandin (PG) synthesis by methylcholanthrene transformed mouse fibroblasts (MC5-5) and rabbit synovial cells in culture. Comparison of the PG biosynthesis inhibitory activity of piroxicam with other NSAI drugs in these experiments ranks piroxicam as among the most potent agents of this type now known. Some specific modifications of piroxicam's structure result in significant loss in PG synthesis blocking activity.

Asunto(s)

RESUMEN

Piroxicam (CP-16 171) is a potent acidic anti-inflammatory agent structurally distinct from the current agents such as indometacin, phenylbutazone or naproxen. Pharmacokinetic studies indicate a longer plasma half-ife for piroxicam than for these agents. Potency in the range of indometacin is observed when piroxicam is tested in the carrageenan rat paw edema model. This activity is not dependent on an intact adrenocorticoid system. The high potency, long half-life and absence of cardiovascular or cental nervous system effects have encouraged clinical trial of piroxicam.

Asunto(s)

RESUMEN

Fifteen acidic antiinflammatory agents, for which some clinical data have previously been published, have been examined for their potency in the carrageenan-induced rat foot edema test, and for their acidity (pKa) and partition coefficients. Published serum half-life data and daily clinical (anti-arthritic) dose have been tabulated for these drugs and correlations between these various parameters are discussed. The rat foot edema carrageenan test has proved to be a fairly reliable predictor of clinical dose for most acidic antiinflammatory agents of moderate serum half-life.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)