Immunosupression Flashcards
What is the pathogenesis of rheumatoid arthritis?
Imbalance of pro-infammatory cells to anti-inflammatory cells
How is Rheumatoid arthritis diagnosed?
Mostly clinical, morning stiffness, at least three joints, symmetrical, rheumatoid nodules. High anti-CCP antibodies
How do corticosteroids work?
prevent interleukin 1 and 6 production by macrophages, inhibit all stages of T-cell activation
Name 3 side-effects of steroids
Weight gain, thrush, glaucoma/cataracts, mood changes, muscle weakness
What is azathioprine used for?
Lupus and vasculitis as maintenance therapy, also IBD
Which enzyme is used to metabolise azathioprine?
TPMT (tested before prescription)
What are the adverse effects of immunosupressants?
bone marrow suppression, increased risk of malignancy, increased risk of infection, hepatitis
What are calcineurin inhibitors used for?
Atopic dermatitis and psoriasis
What is the mechanism of action of calcineurin inhibitors?
Prevents helper T cells producing IL-2
What is mycophenolate mofetil used for?
Transplantation, Lupus and vasculitis maintenance
What is the mechanism of action of Mycophenolate mofetil?
Prodrug derived from penicillium that impairs B and T cell proliferation
How does Cyclophosphamide work?
prodrug alkylating agent that cross-links DNA stopping it replicating, suppresses B and T cell activity
What is Cyclophosphamide used for?
`Lymphoma, leukaemia, solid cancers, Lupus
What is the gold standard treatment for RA?
Methotrexate
What is the mechanism of action of Methotrexate?
Reversibly inhibits DHFR, inhibiting DNA, RNA and protein synthesis (anti-folate action) ONLY WORKS THIS WAY IN MALIGNANCY
How often should Methotrexate be dosed?
Weekly, long half life
What else can methotrexate be used for?
Ectopic pregnancy
When can sulfasalazine not be given?
Aspirin allergy
How does sulfasalazine work?
Inhibits proliferation of T cells and IL-2 production. Reduced chemotaxis and degranulation of neutrophils
Why is sulfasalazine used when it is not as effective as methotrexate?
Very few drug interactions and it is safe in pregnancy
Which drugs block TNF-alpha?
Biologicals
What are the effects of blocking TNF-alpha?
Reduced inflammation, reduced angiogenesis, and reduced joint destruction
What must be screened for before giving Anti-TNF therapy?
Latent TB (reactivation risk)
