Immunomodulators Flashcards
Immunomodulators
Medications used to modify (weaken or stimulate) the activity of the immune system
What conditions require immunosuppression?
Autoimmune (lupus, IMHA, immune mediate thrombocytopenia)
Allergy (cell-mediated- atopic derm and graft rejection)
Chronic inflammation(IBD)
What are the classes of immunosuppressive drugs?
Non-specific agents
Specific agents
Non-specific agents
Reduce response of T and B cells to Ags
Dangerous- intestinal epithelium and hematopoietic stem cells affected
Ex: Radiation, cytotoxic drugs
Specific agents
Selectively eliminate specific immune cell population
Ex: therapy, leflunomide
Glucocorticoids
Stimulate synthesis of IKBa (inhibitor of NF-KB)
Blocked cytokine synthesis and T cell responses
Inhibit enzyme phospholipase
ANTI-INFLAMMATORY
Cyclophosphamide (cytotoxic drugs) method of action
Cytotoxic effect, DNA damage, block cell division
Directly suppresses B cell activity and Ab formation
How is cyclophosphamide used?
Lymphoid tumors, immune mediated skin diseases
Administered orally or parenterally
Need to be activated in liver
Adverse effects of cyclophosphamide?
Bone marrow suppression
Secondary infections, thrombocytopenia, anemia
Sterile hemorrhagic cystitis
Minimized by concurrent use of glucocorticoids or furosemide
How is azathioprine used?
As an alternative to cyclophosphamide
For dermatological and immune mediated diseases and to control allograft rejection
Azathioprine method of action
Prodrug: intracellular enzyme
Metabolites inhibit DNA synthesis
What are the adverse effects of azathioprine
Leukopenia and thrombocytopenia (monitor closely with CBC)
Canine patients develop hepatic toxicity
Long terms effects of demodex infection, recurrent pyoderma and dermatophyte infections
Methotrexate (folic acid antagonist)
Suppresses Ab formation
Used for the testament if rheumatoid arthritis in humans
Cyclosporine
Selective immunosuppressant and calcineurin inhibitor
More specific for T cells
Birds and inhibits calcineurin
What are the results of cyclosporine
Cytokines can’t be produced
Block proliferation of activated T cells and block Th1 responses
Clinical use of cyclosporine
Dermatological conditions
Immune mediated diseases
Cats (organ transplant, eosinophilia granuloma complex)
Ophthalmic products
Adverse effects of cyclosporine
Vomiting and diarrhea
Gingival hyperplasia (33%)
Increased risk of infection
Lymphoma
Tacrolimus (calcineurin inhibitor)
Causes severe intestinal toxicity in dogs
Used for atopic derm, discoid lupus erythrmatosus
More potent than cyclosporine
Target of Rapamycin inhibitors (selective immunosuppressant)
Inhibits serine kinase: mechanistic target if rapamycin
R inhibits B and T cell proliferation and sever intestinal toxicity in dogs
Target of Rapamycin inhibitors is a synergistic to ____________
Calcineurin inhibitors
Monophosphate dehydrogenase inhibitors
Prevents synthesis of DNA
Blocks B and T cell proliferation and Ab formation
Prevents renal allograft rejection between unrelated dogs
What are Monophosphate dehydrogenase inhibitors effective in?
Immune mediated conditions
Well tolerated by dogs
Leflunomide therapy
Anti-inflammatory agent that inhibits pyrimidine synthesis
Used in prevention of allograft rejection in dogs
Intravenous immunoglobulin therapy
Immunosuppressive and anti-inflammatory
Used to inhibit activities of autoantibodies
Used in autoimmune diseases
