| A | B |
|---|
| methotrexate at doses used for arthritis, effects probably due to: | inhibition of aminoimidazolecarboxamide ribonucleotide transformylase and thymidylate synthase |
| methotrexate anti-inflammatory actions include : | decrease leukocyte adhesion to endothelial cells |
| may inhibit transmethylation reactions of phospholipids and polyamines altering lymphocyte and neutrophil function/chemotaxis | methotrexate |
| methotrexate at doses used for arthritis, most common adverse effects: | nausea and mucosal ulcers, hepatotoxicity, monitor liver enzymes, after 5 years of use - -liver biopsy |
| alkylating agents/cross link DNA | cyclophosphamide, chloramabucil |
| toxic effects of cyclophosphamide, chloramabucil | bone marrow suppression, infertility, increased risk of infections and neoplasia |
| azathioprine MOA | converted to 6-mercaptopurine, inhibits de novo purine synthesis |
| azathioprine primary targets | T and B cells |
| any rapidly growing cell population
| azathioprine toxicity |
| mycophenolate mofetil MOA | inhibits inosine monophosphate dehydrogenase de novo purine biosynthesis |
| interferes with leukocyte adhesion by inhibition of E- and P-selectin expression | mycophenolate mofetil MOA |
| T and B cell sensitive due to lack of salvage pathway | mycophenolate mofetil MOA |
| sulfasalazine MOA | acts by scavenging free radicals and as COX inhibitor and dihydrofolate reductase inhibitor |
| leflunomide | pro-drug; inhibits de novo ribonucleotide synthesis and triggers p53 translocation to nucleus arresting cells in G1 phase |
| leflunomide adverse effects | diarrhea as adverse effect in about 25% patients some liver toxicity |
| cyclosporine MOA | inhibits calineurin phosphatase activity, decrease transcription of cytokines in T-cells |
| somewhat selective effect on T-cells | cyclosporine indications |
| cyclosporin toxicity | Renal |
| chloroquine and hydroxychloroquine MOA | unclear MOA in arthritis, may decrease T-cell response to mitogens |
| chloroquine and hydroxychloroquine effects | decrease leukocyte chemotaxis, stabilize lysosomal membranes, trap free radicals, general decrease in DNA and RNA synthesis |
| chloroquine and hydroxychloroquine toxicity | fairly well tolerated |
| penicillamine MOA | unclear MOA in arthritis, may decrease DNA, collagen, and mucopolysaccharides synthesis |
| penicillamine | rarely used, toxic - - kidney damage, leukopenia, thrombocytopenia,and aplastic anemia |
| gold compounds toxicity: | lesions of skin and mucous membranes GI effects, renal toxicity, hematologic abnormalities |
| gold compounds indications: | use is in decline, second line drugs, use is in decline, second line drugs, |
| gold compounds MOA: | Unclear MOA, inhibit PMN and T-cell fxn may inhibit release of histamine, prostaglandins, leukotrienes |
| auranofin: | oral administration, lipid soluble |
| aurothiomalate, aurothioglucose | IM, water soluble |
| Anti- TNF-a drugs | Etanercept, Infliximab, Adalimumab |
| Anti- TNF-a drugs therapeutics | agents must given by injection, screen for latent or active tuberculosis |
| Anti- TNF-a drugs adverse effects | increase risk of macrophage dependent infections |
| Etanercept | recombinant fusion protein consisting of two soluble TNF receptor regions linked to Fc portion of human IgG |
| Infliximab | chimeric monoclonal antibody with variable murine region linked to constant human region specific against human TNF |
| Adalimumab | Recombinant human anti-TNF monoclonal antibody |
| Rituximab MOA | monoclonal antibody that targets CD20 (on B-cells) |
| Rituximab main use: | treatment of rheumatoid arthritis refractory to anti-TNF agents |
| Abatacept MOA | inhbt T-cell actvtn: binds CD80 (on APCs) prvnts interaction w/CD28 (on T cells) |
| Immunoadsorption apheresis | may down-regulate B-cell function by release of small amounts of immune complexes consisting of IgG and staph protein A |
| Immunoadsorption apheresis adverse effects: | fever, chills, joint pain and swelling,hypotension from IV, pulmonary emboli and sepsis |
| Immunoadsorption apheresis indications: | generally used in patients who have failed other therapies for rheumatoid arthritis |
| Dietary manipulation of rheumatoid arthritis inflammation : | Increase intake of eicosapentaenoic acid (EPA)(20:5, fish oil) |
| Cyclooxygenase-derived metabolites of EPA… | are much less potent mediators of inflammation than the corresponding metabolites of AA (prostaglandins) |
