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What four drugs act against circulating proinflammatory cytokines?
- Infliximab (monoclonal antibody)
- Adalimumab (monoclonal antibody)
- Etanercept (receptor)
- Anakinra (receptor agonist)
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What three drugs fall under the miscellaneous category? Give a quick synopsis of each.
- Penicillamine:
- Hydroxychloroquine:
- Sulphasalazine:
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What are the four cytotoxic drugs? Give a quick synopsis of each.
- Methotrexate:
- Azathioprine:
- Leflunomide:
- Cyclosporine:
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What is the therapeutic goal of anti-rheumatoid arthritis therapy?
To arrest the progress of the disease (remission) and to regulate the debilitating pain.
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What is the general therapeutic strategy for the three DMARD classes as a whole?
Almost always use anti-cytokines and miscellaneous in conjuction, and more commonly using cytotoxic tx as well. This prevents upregulation of inflammation and kills off rapidly dividing hematopoietic cells.
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What three types of cells produce IL-1 and TNF-α in rheumatoid arthritis?
- Dendritic cells
- Macrophages
- Synovial cells
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What are the 5 major roles of IL-1 in rheumatoid arthritis?
- Stimulates cytokine synthesis (PGE2, NO, metalloproteases)
- Endogenous pyrogen
- Augments T- and B-cell, and macrophage activation
- Stimulates cartilage destruction
- Stimulates integrin and selectin production in endothelium
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What are the 4 major roles of TNF-α in rheumatoid arthritis?
- Pro-inflammatory
- Cytotoxic
- Stimulates all leukocytes (proliferation, Ab production, etc)
- Stimulates cartilage destruction
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Infliximab: Give the structure, RoA, MoA, primary uses, and adverse effects
- Human/mouse chimeric IgG1 MAB
- RoA: IV @ 0, 2, and 6wks, then every 8
- MoA: binds soluble and transmembrane TNF-α
- Uses: Rheumatoid Arthritis, Crohn's, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis
- Adverse: hypersensitivity, infections (TB), hepatosplenic lymphoma (T-cell), heart failure
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