Immunosuppressive Therapy and Immunomodulatory Agents Flashcards
Long term immunosuppressive therapy
Susceptibility to bacterial infections (common)
- ex: cystitis, pyoderma, pneumonia
Overwhelming, unusual infections
- fungal, protozoal, parasitic
Mechanisms of immunosuppression
- decrease antibody synthesis by plasma cells (days)
- decrease antibody-cell binding affinity
- impair mononuclear phagocytic system cell destruction of antibody-coated cells (hours)
Common therapies
- glucocorticoids
- azathioprine
- cyclosporine
Additional medications
- mycophenolate
- vincristine
- chlorambucil
- leflunomide
- cyclophosphamide
Glucocorticoids
Prednisone, prednisolone, dexamethasone
- mainstay of immunosuppressive therapy
Every animal requires some small degree of _______
Glucocorticoids
Corticosteroid mechanisms
Once in the nucleus, binds to specific DNA sequences
- enchance/inhibit transcription of genes
- induce or inhibit protein translation
Corticosteroid effects
Effects on complement and rapid down-regulation of Fc receptor expression on macrophages leads to the reduction of phagocytosis of opsonized cells
Additional immunosuppressive effects
- 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
Glucocorticoid therapy: acute side effects
Polyuria/polydipsia - increase urination and water consumption Polyphagia - increase food intake Panting \+/- GI ulcerations
Glucocorticoid therapy: chronic side effects
- alopecia
- thin skin
- pot belly
- hepatomegaly
- muscle weakness
Local acting steroids
Local effect and fewer systemic side effects
- poor systemic absorption
Combination immunosuppressive therapy
Increase immunosuppression
- drugs of different mechanisms of action
- “dose sparing” effect with side effects
Immunosuppressive agents are ______ used in dogs
Commonly
- glucocorticoid side effects common
- immunosuppressive agents often well tolerated
Immunosuppressive agents are _____ used in cats
Rarely
- can tolerate chronic high doses of steroids
- immunosuppressive agents are poorly tolerated
Azathioprine
Interferes with purine synthesis
- does not directly reduce serum antibody production
- indirect reduction in lymphocyte proliferation
- can enter all cells, but only benefits rapidly dividing cells
Azathioprine side effects
- myelosuppression
- acute pancreatitis
- hepatopathy
- GI
Combo therapy with prednisone minimizes side-effects
What part of T cell activation directly correlates with B cell activation?
Th1 (IL-2, IFN-y) —> plasma cells –> antibody secretion
Cyclosporine
Decreases antibody synthesis
- impairs IL-2
- reduces lymphocyte activation
= reduces T cell and then B cell proliferation
Cyclosporine side effect
- myelosuppression
- GI
- refractory cystitis or bladder neoplasia
Vincristine
Disrupts assembly of mitotic spindle in mitosis - IMTP: increases platelet counts = impairs phagocytosis of opsonised platelets by impairing microtubule assembly in macrophages
Vincristine binds to ____ and targets_____
Platelets; macrophages
Management of immune-mediated blood disorders
High dose intravenous immunoglobulins
Human intravenous immunoglobulin
Competitively inhibits binding of canine IgG to monocytes by saturation of Fc receptors
- prevention of phagocytosis of antibody coated RBC and platelets
hIVIG
- minimal toxicity, but expensive
- may increase risk of blood clots
- availability is a major issue
