Immunosuppressants and Transplants (Rx) Flashcards
Describe Induction Therapy.
- Group biologic depleting agents and immune modulators.
- Delay the use of Calcineurin inhibitors
- Intensity of initial immunosuppressive therapy in high risk patients
Describe Maintenance Therapy.
- use of multiple drugs to achieve synergistic effects
- calcineurin inhibitor, glucocorticoids, mycophenolate mofetil
- use protocols without steroids
What is the therapy for established rejection.
Agents against T-cell functions
Define the purpose of Calcineurin inhibitors. Provide 2 examples.
-Prevent transplantation rejection for kidney, liver, heart and other organs
-given IV/orally, peak: 1.5-2 hours at maintenance doses
-renal toxicity can occur with unfavorable drug interactions (p450 enzyme drugs)
Ex:) Cyclosporine and Tacrolimus
Define mTOR inhibitors (purpose, admin, toxicity). Provide 2 examples.
-therapeutic uses: autoimmune conditions
-mTOR downstream of IL-2
-1 hour after oral administration
-dose-dependent increase in cholesterol/TG
-anemia/leukopenia
-affects CYP3A4 and enhances renal toxicity
Ex:) Sirolimus and Everolimus
Define Cytotoxic drugs.
Medications that kill/ damage infected cells
Describe Azathioprine.
- Prevents kidney rejection and can be given as a treatment for severe RA. Can also be used as an anti-cancer drug.
- MOA: inhibits DNA synthesis as a purine analogue
- toxicity: increased risk of neoplastic infections
Define Mycophenolate Mofetil (MOA, clinical use and side effect).
- Cytotoxic drug that’s an inhibitor of IMP Dehydrogenase (reduces de novo purine synthesis; crippling to B and T cells that have no salvage pathway)
- approved for oral/IV use with corticosteroids and calcineurin inhibitors
- toxicity: GI disturbances, headaches, HTN and myelosuppression
Define the purpose of immuno-suppressive antibodies. Provide 2 examples.
- Work against lymphocyte receptors
- Reduce lymphocyte/thymocyte activity
- Daclizumab monoclonal AB and Muromonab-CD3
Define Daclizumab (Cx use, MOA, toxicity)
- Binds IL-2 receptor on activated T-cells to antagonize its function.
- used for acute renal transplant rejection
- lowers immunogenecity and immuno-suppressive
Define Muromonab (Cx use, MOA, toxicity)
- Anti-CD3 antibody of T-cell receptor (depleting agent)
- Used for acute graft rejections, kills ONLY T-cells (cell-mediated suppression only)
- side effect: acute hypersensitivity and risk of infections
Describe the purpose of immune checkpoint inhibitors.
- These drugs take the “brakes” off the immune system, which helps it attack cancer cells.
- Anti-PD1 antibodies (i.e. Nivolumab)
Describe the purpose of glucocorticoids as immunosuppressants (MOA, Cx use and adverse effects)
- inhibit expression of cytokine genes (IL-1, IL-2, IL-6, interferon and TNF-alpha), T-cell proliferation and T-dependent immunity
- reduces INFLAMMATION, treats organ transplant rejection, autoimmune disorders, shock, asthma
- prolonged use = Cushingoid features, muscle wasting, increased risk of infections
Describe the function of anti-TNF drugs and their clinical use. Provide an example.
- these are immunosuppressive antibodies that reduce TNF-alpha cytokines
- treats RA
- Ex) Infliximab, Adalimumab (Humira)
If a physician is using immunosuppresants for a recent organ transplant patient, what should he keep in mind when using Calcineurin and mTOR inhibitors?
Space out use of cyclosporine and sirolimus administration to prevent renal toxicity from occuring.
Define Acute Cellular rejection in context of a kidney transplant.
CD8+ T-cells infiltrate the transplanted organ and damage the tubular epithelium of the donor kidney.
Define Chronic Rejection in context of a renal transplant.
Blood vessel thickening occurs after some time from the kidney transplant. This includes interstitial and glomerular fibrosis.
Define Hyperacute rejection in context of a kidney transplant.
This type of rejection occurs within minutes in which fibrinoid necrosis and thrombosis can occur in the transplanted kidney. Pre-formed circulating antibodies result in a DIC reaction that forms fibrin thrombi.
Describe Graft-vs-Host Disease (GVHD). What are the features?
If acute, this involves toxic transplanted CD8 T-cells that attack the recipient’s tissue. This can feature inflammation and fibrosis.
Define the purpose of Infliximab (Remicade).
This is an anti-TNF-alpha drug that can be used as a treatment for rheumatoid arthritis.
