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pharmacology of DMARD's

methotrexate mechanism of action probably relates to secondary effects of polymorphonuclear chemotaxis secondary to inhibition of aminoimidazolecarboxamide transformylase and thimidylate synthase inhibition
methotrexate decreases the rate of appearance of new erosions in RA, evidence supports its use in juvenile chronic arthritis, polymyositis, wegner's, SLE, and vasculitits
methotrexate side effects: nausea and mucosal ulcers are the most common side effects. progressive dose related hepatoxicity occurs frequently
chlorambucil cross-links DNA, therby preventing cell replication.
chlorambucil most common toxicity is dose realted bone marrow supression. infertility with azoospermia and amenorrhea also occurs. the risk of neoplasia is increased with the relative risk of leukemia increased about 10 fold after more than 3 years of use
cyclophosphamide cross links DNA to prevent cell replication
cyclophosphamide causes significant dose related inferility in men and women as well as bone marrow suppression, alopecia, hemorrhagic cystitis, and rarely bladder carcinoma
cyclosporine regulates gene transcription to inhibit IL1 and IL@ receptor production and secondarily inhibits macrophage T cell interaction and T cell response
cyclosporine grapefruit juice increaes its bioavailability up to 60%
cyclosporine has significant nephrotoxicity, and its toxicity can be increased by drug interactions with diltiazem, K sparing diuretics, and other drugs inhibiting CYP3A
azathioprine suppresses inosinic acid synthesis, B cell and T cell function, immunoglobulin production, and IL-2 secretion by 6-Thioguanine which is the major merabolite
azathioprine toxicity includes bone marrow suppression, gastrointestinal disturbances and some increase in infection risk
mycophenolate mofetil inhibits cytosine monophosphate dehydrogenase and secondarily inhibits T cell lymophocyte proliferation
mycophenolate mofetil effective for the treatment of renal disease due to systemic lupus erythematosus and may be useful in vasculitis and Wegener's granulomatosis
mycophenolate mofetil side effects similar to azathioprine with a possibly decreased incidence of fungal infections
Gold alters the morphology and functional capabilities of macrophages
Gold IM compounds also alter lysosomal enzyme activity, reduce histamine release from mast cells, inactivates the first componant of complement and suppresses the phagocytic activitys of PMN's
Gold tends to concentrate in synovial membranes, liver, kidney, spleen, lymph nodes and bone marrow after IM administration
Gold adverse effects: pruitic skin rash sometimes associated with eosinophilia. stomatitis and a metallic taste in the mouth are common. hematologic abnormalities may occur
sulfasalazine IgA and IgM rheumatoid factor production are decreased
sulfaslazine adverse effects incluse nausea, vomiting headache, and rash. hemolytic anemia and methemoglobinemia also accur but rarely. reversible infertility occurs in men.
adalimumab anti TNF monoclonal antibody; down regulates macrophage and T cell function
adalimumab has a half life of 9-14 days
adalimumab can reactivate latent TB. anti-dsDNA and anti ANA has been documented
inflixamib adverse reactions: URI, nausea, headache, sinusitis, rash, and cough are common. can reactivate latent TB
Created by: swohlers