Rheumatoid Arthritis
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| Rheumatoid Arthritis | RA is a classic autoimmune disease with abnormalities of cellular and humoral components of immunity.
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| Pannus | Major cell types:
1. Macrophages
2. T Lymphocytes
Minor cell types:
1. Dendritics cells
2. Endothelium
3. Plasma cells
4. Fibroblast
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| Cellular Immunity | relies on thymus to delete self-reactive lymphocytes, forming T-cells.
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| T-cell | - Direct destruction of infected cells.
- orchestration of further immune response.
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| Humoral Immunity | - relies on cellular maturation in the bone marrow resulting in B cell.
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| B-cell | 1. production of antibodies
2. contribute to inflammation
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| COX 1 | 1. constitutive form of COX.
2. poor inducibility.
3. Smaller active site.
4. PG tat regulate normal kidney & stomach function.
5. substract only C20 carboxylic.acd.
6. main source of PGs in CHRONIC inflammation
7. Acetylation of SEr 530 by aspirin.
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| COX 2 | 1. Inducible form of COX.
2. Induced during inflammation.
3. produce PGs inolved in inflammation.
4. larger active site.
5. Substrates C18 & C20 C.A.
6. Main source of PG in ACUTE inflam.
7. Acetylation of ser516.
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| NSAIDs s/e | 1. heartburn
2. dyspepsia
3. abdominal pain
- inhibition of prostaglandin which act as the protective of the GI tract.
4. serious: Bleeding/ ulceration
* PPI should be prescribed with long term NSAIDs.
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| Sulfasalazine | 500mg once daily
nausea/rashes/ bone marrow suppression
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| Methotrexate | 5-25mg once weekly
rashes/nausea/ stomatitis/ hepatitis
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| Sodium aurothiomalate | 10mg test then 50mg weekly
rashes/ stomatitis/ marrow suppression
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| penicillame | 250-750mg once daily on empty stomach
rashes/ nausea/ taste disturbance
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| cyclosporin | 2.5mg/kg/day
renal impairment
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| Leflunomide | 10-20mg daily for maintanence, 100mg for loading dose- 3 days
GI disturbance/hypertension/alopecia(loss of hair)
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| Azathioprine | 1.5-2.5mg/kg/day
nausea/hepatitis/ marrow suppression
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