Flashcards in Immunosuppressive Medications Deck (25):
what are the 5 main immunosuppressive medications?
-agents which block T cell activation
Corticosteroids bind to GC receptors and NF-kappa-B (TF) in order to:
-upregulate and downregulate genes that result in:
immunosuppression and anti-inflammatory effects (macrophages, B cells, leukocytes)
what are the most common corticosteroids used for immunosuppression?
What are the side effects of corticosteroids?
-infection: aggressive hep B, TB reactivation
-glucose intolerance/ DM
-skin changes: fragility, striae, photosensitivity, acne
-poor wound healing
-accelerated atherosclerotic disease
-risk of adrenal insufficiency with prolonged use (ACTH feedback inhibition)
List common antiproliferative agents (prevents proliferation of lymphocytes involved in autoimmunity/rejection):
-cyclophosphamide: prevent DNA synthesis/cell proliferation
-azathioprine: purine analog
-mycophenolic acid: block purine synthesis
-leflunomide: block pyrimidine synthesis
-methotrexate: block folic acid action
what is the major toxicity of anti-proliferative agents?
Bone marrow suppression (rapidly dividing cells)
what cancer treatment is commonly used for immunosuppresion?
what are the side effects?
cyclophsphamide: leukemia, lymphoma, breast cancer, ovarian cancer
SE: hematuria, neutropenia, ovarian failure, bladder cancer, leukemia
what are SE of antiproliferative agents in general?
-neutropenia (due to suppression of cell proliferation)
-hepatotoxicity, pancreatitis, GI upset
how does sirolumus work?
-mTOR inhibitor: prevents cytokine-dependent cell proliferation (block G1--> S transition)
*also prevents proliferation of some cancers (renal cancer)
What are two major calcineurin inhibitors (CnI)?
How do they work?
block T cell response and decrease cytokine production and lymphocyte proliferation (prevents production of IL-2)
what conditions are CnI good for treating?
-ophthalmic disease (drops)
How are monoclonal antibodies delivered for immunosuppressive therapy?
IV or SC
how does the following mAb work: Basiliximab
-binds IL-2 receptor on T cell (alpha chain of CD25)--> T cell not activated
* prophylactic, not used after rejection
how does the following mAb work: Infliximab
-anti-TNF alpha antibody, prevents TNF-alpha from binding to its receptor --> apoptosis of TNF-alpha expressing T cells
uses: IBS, ankylosing spondylitis , psoriasis
What polyclonal antibody is used for immunosuppression therapy?
How many antigens does it contain Abs against?
How does it work?
(made by injecting human thymus into animal to stimulate Ab production)
-T cell depletion mechanism, some activity against B cells and dendritic cells
What is a main SE of thymoglobulin?
prolonged lymphopenia (CD4/CD8 ratio stays abnormal for many years after transplant)
What is IVIg
(pooled Ig from thousands of donors)
*doesn't increase risk of infx or malignancy!
What is IVIg used to treat?
-chronic demyelinating polyneuropathy
-transplantation (rx rejection)
How does IVIg work?
-inhibits Abs (Abs that inhibits Ab!)
-inhibits B cells
-inhibits adhesion molecules
What are fusion proteins?
They are proteins that join Fc part of Ab with receptor on target molecules--> prevents other molecules from binding to and activating the target molecule
* end in "-cept"
What is Etanercept?
-a fusion protein
-TNF-alpha blocker: TNF receptor and Fc IgG: blocks TNFalpha from binding to WBC receptor
What is abatacept/belatacept?
-fused Fc portion of IgG and extracellular domain of CTLA-4
-prevents costimulation of T cells (binds B7 on APC to prevent B7-CD28 interaction)
What is often the first line rx of IBD?
5-ASA: 5-aminosalicylic acid (sulfa drug)
What immunossupressive drug may cause macular toxicity and was originally an antimalarial drug?