Chapter 24 Immunosuppressive therapy Flashcards
(46 cards)
When does immunosuppressive therapy become necessary?
When immune-mediated tissue damage is life-threatening or causes organ dysfunction.
What are the main risks associated with immunosuppressive therapy?
Clinical side effects and systemic susceptibility to infections, particularly fungal and viral organisms.
What are some inhibitors of gene expression or transcription used in horses?
Corticosteroids.
What drugs inhibit nucleotide synthesis in horses?
Azathioprine and methotrexate.
What are some alkylating agents used for immunosuppression in horses?
Cyclophosphamide, chlorambucil, and vincristine.
What are phosphatase and kinase inhibitors used in equine immunosuppression?
Cyclosporine A, tacrolimus, and rapamycin.
What role do monoclonal antibodies play in immunosuppressive therapy?
They target specific B cell molecules.
What is the general effect of glucocorticoids on the immune system?
They are potent anti-inflammatory and immunosuppressive drugs.
What are commonly used glucocorticoids in horses?
Hydrocortisone, dexamethasone, prednisolone, methylprednisolone, isoflupredone, triamcinolone, beclomethasone, and fluticasone.
What are the common side effects of prolonged glucocorticoid use?
Adrenal suppression, hyperglycemia, polyuria/polydipsia, gastrointestinal ulceration, delayed wound healing, growth suppression, osteoporosis, myopathy, hypertension, and hypokalemia.
What mechanism allows glucocorticoids to suppress immune function?
They bind to cytosolic glucocorticoid receptors, allowing the receptor to translocate into the nucleus and inhibit transcription factors like NF-kappa B.
What are the two main outcomes of glucocorticoid binding to gene promoters?
Transrepression (suppression of other transcription factors) and transactivation (activation of gene transcription).
What is the effect of glucocorticoids on neutrophils?
Decreased diapedesis and migration to the site of infection.
What is the effect of glucocorticoids on antigen-presenting cells?
Decreased expression of inflammatory cytokines IL-1, IL-6, and TNF-alpha, and lower expression of MHC class II and IL-12 cytokines.
What effect do glucocorticoids have on T cells?
They cause profound T cell lymphopenia via inhibition of proliferation, sequestration in the reticuloendothelial system, impaired release from lymphoid tissues, and induction of apoptosis.
What is the role of azathioprine in immunosuppression?
It inhibits the synthesis of DNA and RNA, thus inhibiting lymphocyte activation and proliferation.
What are the adverse effects of azathioprine?
Leukopenia, anemia, thrombocytopenia, alopecia, dermatitis, and hepatotoxicity.
What is the mechanism of action of cyclophosphamide?
It alkylates DNA bases, resulting in mutagenic, cytotoxic, antiproliferative, and chemotherapeutic effects.
What are the adverse effects associated with cyclophosphamide?
Anemia, leukopenia, alopecia, and secondary malignancies.
What is the mechanism of action of vincristine?
It binds to tubulin in the mitotic spindle and prevents purine synthesis, inhibiting cell proliferation.
What are the common uses of cyclosporine in horses?
Intravitreal treatment of recurrent uveitis and immune-mediated keratitis.
What are the potential adverse effects of systemic cyclosporine?
Vasoconstriction, hypertension, nephrotoxicity, hepatotoxicity, diarrhea, hyperlipidemia, hyperglycemia, neurotoxicity, and susceptibility to infections.
What are the uses of tacrolimus and rapamycin in horses?
Tacrolimus has been used topically for hyperkeratosis, and rapamycin’s ocular toxicity and distribution have been studied for potential clinical use.
What is the effect of glucocorticoids on the CD4:CD8 ratio in horses?
Decreases the CD4:CD8 ratio due to a reduction in CD4+ T cells and an increase in CD8+ T cells.
