In rheumatoid arthritis

It affects the metabolisms of glucose and proteins used in rheumatoid arthritis, inflammatory conditions, etc. 

Unfortunately steroids merely suppress the inflammation while the underlying cause of the disease remains. Another serious concern about steroids is that of toxicity. The abmpt withdrawal of glucocorticoid steroids results in acute adrenal insufficiency. Long term use may induce osteoporosis, peptidic ulcers, the retention of fluid, or an increased susceptibiUty to infections. Because of these problems, steroids are rarely the first line of treatment for any inflammatory condition, and their use in rheumatoid arthritis begins after more conservative therapies have failed. 

In an approach to opioid receptor ligands,diazabicyclononanones were prepared in a double Petrenko-Kritschenko reaction. Diester 76, in the presence of methylamine and aryl aldehydes, was converted to piperidone 77. This was immediately resubmitted to the reaction conditions however, in this iteration formaldehyde replaced the aryl aldehyde component. The outcome of this reaction produced 78 which was further investigated for its use in rheumatoid arthritis. 

While the obvious value of in vivo animal models is clear, there also are instances—especially in cases of inflammatory arthritis, behavior, and tumor growth—where they have failed to be predictive of useful clinical activity in humans [51], For example, leukotriene (LTB4) antagonists showed activity in animal models of inflammatory arthritis yet failed to be useful in rheumatoid arthritis [52]. Similarly, dopamine D4 antagonists showed activity in animal behavior models previously predictive of dopamine D2 antagonists in schizophrenia. However, testing of dopamine D4 antagonists showed no efficacy in humans [53]. 

The first two selective COX-2 inhibitors to be marketed and subjected to in depth clinical trials were celecoxib and rofecoxib. Both compounds are as effective as standard NSAIDs in rheumatoid arthritis, osteoarthritis and for pain following orthopaedic or dental surgery. Gastrointestinal side effects were far fewer than with comparator diugs and in fact were no... 

Miossec P (2004) An update on the cytokine network in rheumatoid arthritis. Curr Opin Rheumatol 16 218-222... 

Soluble receptor constructs Etanercept This genetically engineered drug consists of the extracellular-part of the TNF-receptor type I and the Fc portion of human IgG. Its application in rheumatoid arthritis mirrors that of infliximab. 

IL-1 receptor antagonist Anakinra A naturally occurring complete antagonist, effective in rheumatoid arthritis. 

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

It is an autoantibody whose autoantigen is the Fc portion of IgG. Rheumatoid factors may be of any immunoglobulin isotype but it is IgM rheumatoid factor that is commonly measured in rheumatoid arthritis. Classification criteria for rheumatoid arthritis include only one serological test, namely rheumatoid factor. However, it is not diagnostic test rather it may be confirmatory when a number of other clinical features are present. 

In rheumatoid arthritis the damage that is found in joints may also be a result of the inactivation of a-1-PI due to the oxidation of an essential methionine(s) residue in this protein. It has been found that a-l-PI purified from the synovial fluid of patients with rheumatoid arthritis contained four Met(O) residues and was not able to form a binary complex with elastase89. It is probable that the presence of the Met(Oj residues in a-l-PI from these patients results from a high level of oxidants produced by neutrophils in the inflammed joint. 

The Structure of the Hyaluronic Acid Component of Synovial Fluid in Rheumatoid Arthritis," S. A. Barker, S. H. I. Bayyuk, J. S. Brimacombe, C. F. Hawkins, and M. Stacey, Clin. Chim. Acta, 9 (1964) 339-343. 

Anakinra/Kineret, an IL-1 receptor antagonist approved for use in rheumatoid arthritis, was recently evaluated in a small phase II trial. When initiated within 6 hours after stroke onset, Anakinra treatment yielded promising preliminary results it was deemed safe with demonstrable biologic activity and likely favorable clinical outcome." ... 

Kofoed, J.A. and Barcelo, A.C. (1978). The synovial fluid hyaluronic acid in rheumatoid arthritis. Experimentia 34, 1545. 

Rowley, A., Gutteridge, J.M.C., Blake, D.R, Farr, M. and Halliwell, B. (1984). Lipid peroxidation in rheumatoid arthritis thiobarbituric acid reactive material and catalytic iron salts in synovial fluid from rheumatoid patients. Clin. Sci. 66, 691-695. 

Honkanen, R.D., Kontinnen, Y.T. and Mussalo-Rauhamaa, H. (1989). Vitamins A and E, retinol binding protein and zinc in rheumatoid arthritis. Clin. Exp. Rheum. 7, 465-469. 

Jason, M.I.V. and Dixon, A. St. J. (1970a). Intra-articular pressures in rheumatoid arthritis of the knee. I. Pressure changes during passive joint distention. Ann. Rheum. Dis. 29, 261-265. 

Marklund, S.L., Bjelle, A. and Elmqvist, L. (1986). Superoxide dismutase enzymes of the synovial fluid in rheumatoid arthritis and in reactive arthritides. Ann. Rheum. Dis. 45, 847-851. 

Pruzanski, W., Keystone, E.C., Sternby, B., Bombardier, C., Snow, K.M. and Vadas, P. (1988). Scrum phospholipase A2 correlates with disease activity in rheumatoid arthritis. J. Rheumatol. 15, 1351-1355. 

Situnayake, R.D., Thurnham, D.I., Kootthep, S., Chirico, S., Lunec, J. Davis, M. and McConkey, B. (1991). Chain breaking antioxidants in rheumatoid arthritis clinical and laboratory correlates. Ann. Rheum. Dis. 50, 81-86. 

Munthe, E., Kass, E. and Jellum, E. (1982). Evidence for enhanced radical scavenging prior to drug response in rheumatoid arthritis. In Advances in Inflammation Research (ed. S. Gorini) pp. 2II-2I8. Raven Press, New York. 

FIGURE 54-1. Patterns of joint involvement in rheumatoid arthritis. (From DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy. 6th ed. New York McGraw-Hill 2005, Figure 89-3, p. 1673, with permission.)... 

Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001 344( 12) 907—916. Cronstein BN. Low-dose methotrexate A mainstay in the treatment of rheumatoid arthritis. Pharmcol Rev 2005 57(2) 163—172. 

Cyclic citrullinated peptide A circular peptide (a ring of amino acids) containing the amino acid citrulline. Autoantibodies directed against cyclic citrullinated peptide provide the basis for a test of importance in rheumatoid arthritis. 

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