Rheumatoid inflammations, treatment

Among the most abundant steroids, cholesterol is present in almost all human and animal tissue (Real Life 4-2). Bile acids are produced in the liver as part of a fluid delivered to the duodenum to aid in the emulsification, digestion, and absorption of fats. An example is cholic acid. Cortisone, used extensively in the treatment of rheumatoid inflammations, is one of the adrenocortical hormones produced by the outer part (cortex) of the adrenal glands. These hormones participate in regulating the electrolyte and water balance in the body, as well as in protein and carbohydrate metabolism. 

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. 

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. 

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... 

Tumor necrosis factor-a (TNF-a) is a critical mediator of inflammation in autoimmune diseases like Crohn s disease and rheumatoid arthritis. Infliximab binds TNF-a and prevents its binding to the TNF receptor for treatment of these diseases. 

Etanercept is a recombinant human soluble tumor necrosis factor-alpha (TNFo ) receptor fusion protein that binds to TNFo and decreases its role in disorders involving excess inflammation. It is approved for subcutaneous use in the treatment of patients with moderate to severe active rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing arthritis and plaque psoriasis. To the adverse reactions mentioned for infliximab, rare reports of congestive heart failure should be added. 

Phenylalanine Decreases pain and inflammation in the treatment of rheumatoid arthritis and osteoarthritis... 

Nabumetone is used for the treatment of pain and inflammation associated with osteoarthritis and rheumatoid arthritis. The drug is is administered orally (500-2000 mg/day). 

Clinical use Niflumic acid (Auclair et al., 1989) is a nonsteroidal anti-inflammatory drug used for the treatment of inflammation and pain in musculoskeletal and joint disorders such as rheumatoid arthritis as well as traumatic and postoperative pain. Niflumic acid is used in oral, rectal or topical preparations (up to 750 mg/day). 

---