Chapter 24 Immunosuppressive therapy Flashcards
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.
What is the effect of fluticasone on heaves-affected horses?
Long-term fluticasone treatment had no statistically significant detectable effect on innate and adaptive immune parameters.
What is the role of adrenocortical function in glucocorticoid therapy?
Parenteral, oral, and aerosolized corticoids reversibly suppress adrenocortical function while the response to ACTH stimulation remains intact.
What are the side effects of glucocorticoids on neutrophil phagocytosis?
Variable, depending on the experimental system used, but generally results in decreased diapedesis and migration to the infection site.
What is the effect of glucocorticoids on eosinophils and basophils/mast cells?
Decreased degranulation of these cells.
What is the effect of azathioprine on glucocorticoid dosage?
Allows reduction in glucocorticoid dose when combined in therapy.
What is the effect of cyclophosphamide on B cells?
Promotes its application for the treatment of autoantibody-mediated diseases.
What is the therapeutic effect of vincristine in immune-mediated thrombocytopenia?
It inhibits cell proliferation, resulting in an anti-tumor and immunosuppressive effect.
What are the adverse effects of vincristine in horses?
Mild neurologic adverse effects (proprioceptive deficits) and ileus.
What is the mechanism of action of cyclosporine?
It binds to the cytoplasmic receptor cyclophilin, inhibiting calcineurin and preventing the translocation of transcription factors like NFAT to the nucleus.
What are the effects of tacrolimus compared to cyclosporine?
Tacrolimus is considered to be a more powerful immunosuppressive drug.
What are the common clinical uses of cyclophosphamide and vincristine in horses?
Treatment of lymphosarcoma, immune-mediated thrombocytopenia, and pemphigus foliaceus.
What are the dose-related clinical adverse effects of cyclosporine?
Similar to those promoted by cyclosporine, including vasoconstriction, hypertension, nephrotoxicity, hepatotoxicity, diarrhea, hyperlipidemia, hyperglycemia, and neurotoxicity.
What is the primary use of corticosteroids in horses?
To treat inflammatory, allergic, autoimmune, and neoplastic diseases, and to prevent allograft rejection in transplantation.
What is the main benefit of combining different immunosuppressive drugs?
Increases effectiveness while allowing the use of doses tolerated by the patient.
What is the main goal of immunosuppressive therapy?
To manage immune-mediated tissue damage when it is life-threatening or causes organ dysfunction.
What is the main mechanism by which glucocorticoids exert their effects?
They bind to glucocorticoid receptors, allowing the receptor to translocate into the nucleus and suppress or activate transcription factors.
What are the two main categories of glucocorticoid effects?
Transrepression (suppression of transcription factors) and transactivation (activation of gene transcription).
What are the main adverse effects of prolonged high-dose glucocorticoid treatment?
Adrenal suppression, hyperglycemia, gastrointestinal ulceration, osteoporosis, myopathy, and hypertension.
What is the role of glucocorticoids in acute phase anti-inflammatory action?
They inhibit vasodilation, vascular permeability, chemotaxis, adhesion molecules, and diapedesis.
What is the main therapeutic effect of azathioprine?
Inhibition of DNA and RNA synthesis, thus preventing lymphocyte activation and proliferation.
What is the recommended monitoring for horses on azathioprine?
Periodic complete blood cell counts and blood biochemistry tests to monitor for severe leukopenia and hepatotoxicity.
What is the mechanism of action of tacrolimus and rapamycin?
They bind to the cytoplasmic FK-binding protein (FK-BP), inhibiting calcineurin and preventing the translocation of transcription factors.
