Rheumatoid arthritis suppressants

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. 

A glucocorticoid-resistance model has been proposed to provide an explanation for how stress might influence diseases in which excessive inflammation is observed (e.g., allergies, autoimmune diseases, rheumatoid arthritis, and cardiovascular disease). In these cases, chronic stress diminishes the immune system s sensitivity to glucocorticoids that normally terminate the inflammatory response. For example, in a study of a group of 50 parents caring for a child undergoing treatment for pediatric cancer, whole blood of parents of cancer patients exhibited a lesser dexamethasone-dependent suppression of IL-6 production in vitro compared to parents of medically healthy children.94... 

Heavy Metals. Some heavy metals such as gold and platinum are used pharmacologically as immunomodulators to treat rheumatoid arthritis and as antineoplastic drugs, respectively. Most heavy metals inhibit mitogenicity, antibody responses, and host resistance to bacterial or viral challenge, and tumor growth. Platinum has been shown to suppress humoral immunity, lymphocyte proliferation, and macrophage function (Lawrence, 1985). Clinically, mild to moderate myelosuppression may also be evident with transient leukopenia and thrombocytopenia. 

Hydroxychloroquine (Plaquenil), like chloroquine, is a 4-aminoquinoline derivative used for the suppressive and acute treatment of malaria. It also has been used for rheumatoid arthritis and discoid and systemic lupus erythematosus. Hydroxychloroquine has not been proved to be more effective than chloroquine. Adverse reactions associated with its use are similar to those described for chloroquine. The drug should not be used in patients with psoriasis or porphyria, since it may exacerbate these conditions. 

Cyclosporine appears to have promise in the treatment of autoimmune diseases. It has a beneficial effect on the course of rheumatoid arthritis, uveitis, insulin-dependent diabetes, systemic lupus erythematosus, and psoriatic arthropathies in some patients. Toxicity is more of a problem in these conditions than during use in transplantation, since higher doses of cyclosporine are often required to suppress autoimmune disorders. 

A. Glucocorticoid treatment of rheumatoid arthritis does not eradicate all symptoms, nor does it reverse the degenerative process. Suppression of the hypothalamic-pituitary-adrenal axis is an unwanted side effect of glucocorticoid therapy. While development of a sense of well-being may be attributed to the relief of symptoms, it is not the primary basis for employing the potent glucocorticoids. 

Mecfianism of Action Gold compounds that alter cellular mechanisms, collagen biosynthesis, enzyme systems, and immune responses. Therapeutic Effect Suppress synovitis in the active stage of rheumatoid arthritis. 

Contraindications Concomitant medications which cause bone marrow suppression, rheumatoid arthritis, lupus erythematosus, glucose-d-phosphate dehydrogenase (G-6 PD) deficiency, hypersensitivity to primaquine or any of its components... 

As antirheumatic Salicylates are the drug of choice in the treatment of rheumatoid arthritis. In larger dose they suppress the swelling, immobility and redness of the joints involved. They are also useful in the acute rheumatic fever. They produce relief in pain, swell-... 

It is a selective and very potent long acting glucocorticoid. It causes suppression of pituitary adrenal axis. Used in shock due to trauma, allergic emergencies, rheumatoid arthritis, asthma, nephrotic syndrome and suppression of inflammation in eye and skin disorders. 

It is a purine antimetabolite which has marked effect on T-lymphocytes, suppresses cell mediated immunity (CMI). It selectively affects differentiation and functions of T cells and inhibits cytolytic lymphocytes. It is used primarily as immunosuppressant in organ transplantation, progressive rheumatoid arthritis and some other autoimmune diseases. 

The main clinical uses of immunosuppressive drugs are suppression of organ and tissue rejection after transplant surgery and the treatment of diseases with an autoimmune component. Thses include renal diseases, e.g. glomerulonephritis, some nephrotic syndromes, connective tissue diseases, such as systemic lupus erythematosus rheumatoid arthritis, and systemic vasculitis. 

Sulfasalazine is metabolized to sulfapyridine and 5-aminosalicylic acid, and it is thought that the sulfapyridine is probably the active moiety when treating rheumatoid arthritis (unlike inflammatory bowel disease, see Chapter 62). Some authorities believe that the parent compound, sulfasalazine, also has an effect. In treated arthritis patients, IgA and IgM rheumatoid factor production are decreased. Suppression ofT-cell responses to concanavalin and inhibition of in vitro -cell proliferation have also been documented. In vitro studies have shown that sulfasalazine or its metabolites inhibit the release of inflammatory cytokines, including those produced by monocytes or macrophages, eg, interleukins-1, -6, and -12, and TNF-a. These findings suggest a possible mechanism for the clinical efficacy of sulfasalazine in rheumatoid arthritis. 

Modest but significant improvement has been observed in patients with chronic hepatitis C, Crohn s disease, psoriasis and rheumatoid arthritis after subcutaneous administration of IL-10 in human clinical trials. The systemic administration of IL-10 produces general immune suppression, inhibition of macrophage and T-cell infiltration, less secretion of IL-12 and TNF-a by monocytes and suppression of nuclear factor (NF)-kB induction. In patients with acute myelogenous leukemia, IL-10 increases the serum levels of TNF-a and IL-1 (3. The use of IL-10 for human cancer therapy is under investigation and despite its immunosuppressive effects it may serve a role as a facilitator in preconditioning tumors to be recognized by immune effector cells. 

Mechanism of Action. The basis for the antiar-thritic effects of penicillamine is unknown. Reductions in serum immunoglobulin M-rheumatoid factor have been observed with penicillamine, and this drug has been shown to depress T-cell function.53 These and similar findings suggest that penicillamine works by suppressing the immune response in rheumatoid arthritis, but the exact mechanisms remain to be determined. 

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