S8.2 Immunosupression And Rheumatoid Arthritis Flashcards
Define rheumatoid arthritis
Chronic autoimmune condition that results in inflammation of the synovium leading to dissolution of cartilage and bone.
What is the pathogenesis of rheumatoid arthritis?
The chronic synovial inflammation is caused by T-cell activation and production of rheumatic factor which stimulates macrophages.
Macrophages release many cytokines (e.g IL-1, TNF-α) which causes inflammation of the synovium.
What is the mechanism of methotrexate?
Dihydrofolate reductase inhibitor (in malignant disease)
Inhibitor of T-Cell activation (in non-malignant disease e.g RA)
What is the route of administration and ADRs of methotrexate?
Oral, give weekly dosing
ADRs: mucositis, pneumonitis, teratogenic
What is the mechanism of sulfasalazine?
Inhibit T-cell proliferation and IL-2 production.
Effective in RA and IBD
What are the ADRs of sulfasalazine?
Myelosuppression, hepatitis, rash.
What is the mechanism of Rituximab?
Causes B cell apoptosis
What is the mechanism of corticosteroids?
Bind to intracellular cytoplasmic receptors and promotes or inhibits gene transcription.
Prevents T cell activation.
What is the mechanism of Azathioprine?
Used in RA, lupus, vasculitis
It is a prodrug which is metabolised to 6-MP, reducing DNA and RNA synthesis. 6-MP is eliminated by TPMT.
What are the ADRs of Azathioprine?
Bone marrow suppression, increased risk of infection
What is the mechanism of mycophenolate mofetil?
A prodrug that acts to inhibit the enzyme inosine monophosphate dehydrogenase, which is required for guanine synthesis.
The result is impaired B-cell and T-cell proliferation
What are the ADRs of mycophenolate mofetil?
Myelosuppression, vomiting, and diarrhoea
What is the mechanism of cyclophosphamide?
A pro-drug that is metabolised by the CYP450 complex into its active drug form called 4-hydroxycylcophosphamide, which cross-links DNA so it cannot replicate, this supresses T and B cell activity
What are the ADRs of cyclophosphamide?
Bladder cancer, lymphoma,infertility
Describe some biological therapies for RA
Eg adalimubab, infliximab
Recombinant DNA technology produces substances identical to the body’s signalling proteins.
Monoclonal antibodies made specifically to block any substance, or target any cell type.
