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24 Cards in this Set
- Front
- Back
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Symptoms of an RA patient
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Pain, redness, stiffness (starting in the small joints), heat (acute inflammation), decreased motile junction, bone erosion,
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Immune cells found in the synovium
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Th1, macrophages, b cells
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Infectious causes?
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Mycobacterium, Mycoplasma, Epstein-barr virus. Evidence of their role not conclusive, but could possibly have antigens remaining that lead to a chronic immune response. Mycobacterium similar to collagen in joints.
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Biomarkers
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V. few so hard to diagnose but...Rheumatoid factor, anti-citrullinated protein
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1st line treatment
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NSAIDs - anti-inflam, analgesic and antipyretic
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What COX enzyme should be blocked?
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COX-2 as it promotes PG formation.
COX-1 is a housekeeping enzyme and blocking is associated with gastrointestinal bleeding. |
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When should steroids be used and why?
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During flare ups. Whilst, steroids are effective anti-inflammatory drugs they have serious long term side effects
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List some DMARDs
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MTX, sulfosalazine, Gold,
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TNF-alpha causes..
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It promotes proinflammatory cytokine release (IL-1, IL-6, IL-23, GM-CSF), PGE2 production, macrophage activation, osteoclast activation (bone resorption), chondrocyte activation (MMP production and cartilage destruction), angiogenesis, chemokine release, leukocyte accumulation (induction/maintenance of HLA class II expression), endothelial cell activation (upregulate E-selectin and VCAM) and hepcidin induction
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Anti-TNF-alpha mAbs
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Golimumab, adalimumab, infliximab
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How does Etanercept target TNF?
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soluble TNF receptor
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What activates IL-6
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TNF-alpha and IL-1
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Function of IL-6
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Induces ab production from b cells, activates T cells, macrophages, and osteoclasts; and it is a major activator of the hepatic acute-phase response.
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mAb targeting IL-6?
mAb targeting indirectly? |
Tocilizumab
Enlinomab (Anti-ICAM therefore blocks T cell migration - T cells release IL-6) |
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What endogenous hormone inhibits IL-6?
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Oestrogen
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Why do pregnant women go into remission?
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Increased hormones (DHEA)and possibly the presence of alloantibodies acting against HLA-DRB4 epitopes
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Infliximab type of mab?
Immunogenic? Monitor patient? |
Chimeric
Yes - given with MTX to minimize Yes - for infections |
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Certolizumab type of mAb?
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Humanized - only CDR is murine
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What does ICE do?
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Activate IL-1. ICE aka caspase 1
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What activates IL-1?
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Released from macrophages, can be upregulated by C5a and TNF. Release facilitated by ATP receptor P2X7
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IL-1 effect
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High conc enter blood and cause fever
Increases synthesis of COX-2 and iNOS Increases expression of VCAM and ICAM Increases bone erosion (osteoclasts, RANKL) |
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Golimumab
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Anti-TNF, fully humanized. Only prescribed for rheumatoid arthritis if the arthritis is active, the patient has already tried methotrexate and another DMARD such as sulfasalazine, or if you can’t use these drugs for any reason. Expensive!
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Adalimumab
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Anti-TNF, full humanized mAb.
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What is Anakinra
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IL-Ra - competitively inhibits IL-1 binding
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