Exam 4: Dr. Thomason Immunosuppressive Therapy Flashcards
What do long term immunosuppressive therapies cause?
Susceptibility to bacterial infections (common)
Overwhelming, unusual infections
What are the common infections that can occur with long term therapies?
Cystitis
Pyoderma
Pneumonia
What are the overwhelming, unusual infections that can occur with long term therapies?
Fungal (aspergiullus)
Protozoal (toxoplasma)
Parasitic (demodex)
What are mechanisms of immunosuppression?
Decrease antibody synthesis by plasma cells
Decrease antibody-cell binding affinity
Impair mononuclear phagocytic system cell destruction of antibody-coated cells
What are glucocorticoids?
Prednisone, prednisolone, dexamethasone
Mainstay of immunosuppressive therapy
What are the mechanisms of corticosteroids?
Once in the nucleus, it binds to specific DNA sequences
- -Enhance/inhibit transcription of genes
- -Induce or inhibit protein translation
What do glucocorticoids do?
Decrease antibody synthesis (days)
Decrease antibody cells binding affinity
Impair MPS (hours)
What do corticosteroids have effects on?
Complement and rapid down -regulation of Fc receptor expression on macrophages leads to the reduction of phagocytosis of opsonised cells
What are the additional immunosuppressive effects?q
Decrease egress of cells from the blood
Suppress macrophages and neutrophil bactericidal functions
Inhibit amplification pathways of the complement cascade
Decrease antigen presentation to Th cells
Anti-inflammatory properties
What are corticosteroids?
Very effective immunosuppressive agent and the mainstay treatment of most immune-mediated diseases
What are the acute side effects of glucocorticoid therapy?
Polyuria/polydipsia
Polyphagia
Panting
+/- GI ulcerations
What are the chronic side effects of glucocorticoid therapy?
Alopecia Thin skin Pot belly Hepatomegaly Muscle weakness
How does standard glucocorticoid therapy work?
Wean down dose
Ultimate goal is to remove all medications
Describe local-acting steroids
Local effect and fewer systemic side effects
Poor systemic absorption metabolized by the liver right after absorption
What is combination immunosuppressive therapy?
Increase immunosuppresion
Dose-sparing effect with side effects
What is an example of immunosupressive agent?
Azathioprine
What does azathioprine interfere with?
Purine synthesis
What does azathioprine lead to?
Production of fraudulent nucleotides
What does azathioprine do?
DNA and RNA syntheses are inhibited, and mitosis and cellular metabolism is disrupted
Reduction in lympocyten proliferation
What are side effects of azathioprine?
Myelosuppression
Acute pancreatitis
Hepatopathy
Gastrointestinal
How can you minimize side effects of prednisone and azathioprine?
Combination therapy of the 2
What does cyclosporine do?
Decreases antibody synthesis
- -Impairs IL-2 production
- -Reduces lymphocyte activation
What does suppressed IL-2 production due to cyclosporine reduce?
T cell, then B cell proliferation
What does cyclophosphamide do?
Cross-links DNA
Preventing DNA separation
Toxic to resting and dividing cells, particularly proliferating lymphocytes
Suppresses CMI and humoral immunity
What are cyclophosphamide side effects?
Myelosuppression
Gastrointestinal disease
Refractory cystitis or bladder neoplasia
What does vincristine do?
Binds to tubulin and disrupts assembly of the mitotic spindle in mitosis
What does vincristine do for IMTP?
Increases platelet counts
What can management of immune-mediated blood disorders?
High dose intravenous immunoglobulins
What does human intravenous immunoglobulin do?
Competitively inhibits the binding of canine IgG to monocytes by saturation of Fc receptors
Prevention of phagocytosis of antibody-coated erythrocytes and platelets
Describe human intravenous immunoglobulins
Minimal toxicity but very expensive
May increased risk of blood clots
Availability is an issue
