Immunomodulators Flashcards
Immunomodulator definition
- meds used to weaken/stimulate immune activity
- EX: immunosuppressants; immunostimulants
3 types of condition groups that require immunosuppression
- autoimmune
- allergy
- chronic inflammation
Autoimmune conditions
- lupus
- IMHA
- IMTP ( immune mediated thrombocytopenia)
Allergy conditions that require immunosuppression
- cell mediated: atopic dermatitis & graft rejection
T or F: IBD requires immunosuppression
True
Non specific agents (immunosuppressive drugs)
- reduce T & B cell response to antigens
- Dangerous b/c intestinal epithelium & hematopoetic stem cells can be affected
- EX: radiation, corticosteroids, cytotoxic drugs, alkylating agents, folic acid antagonists, dna synth. inhibitors
Specific agents (immunosuppressive)
- eliminate specific immune cell population
- EX: calcineurin inhibitors target of rapamycin inhib., inosine monophosphate, dehydrogenase inhib., lefunomide, IV Ig therapy
Radiation
- immunosuppressive
- ionizing rays affect DNA, oxidate free radicals in cell, inhibit cell division
Glucocorticoids
- immunosupp.
- stimulate IkBa synthesis (inhibitor of NF-kB)
- block NF-kB mediated processes; i.e. cytokine synthesis & T cell responses
- reduce immunological and inflammatory processes
- anti-inflammatory b/c inhibit phospholipase A2
- EX: drugs that end in -one or -olone
Glucocorticoid effect on neutrophils
- neutrophilia
- reduced chemotaxis, margination, phagocytosis, ADCC, bactericidal activity
- stabilize membranes
- inhibit phospholipase A2
Glucocorticoid effect on macrophages
Decreased: chemotaxis, phagocytosis, bactericidal activity, IL-1 &6 prod., antigen process.
Glucocorticoid effect on lymphocytes
Decreased: prolif., T cell response and cell-mediated cytotoxicity, IL-2 prod., lymphokine prod.
Alkylating agents
-MOA: cytotoxic effect via blocking cell division, causing DNA damage
- Uses: lymphoid tumors, immune mediated skin disease, oral or parenteral, activated in liver
- Adverse effects: bone marrow suppression (secondary infect., thrombocytopenia, anemia, sterile hemorrhagic cystitis
- minimized by use of glucocorticoids or furosemide @ same time
Thiopurine
- azathioprine
- alternative for cyclophosphamide
- Uses: dermalogic diseases, immune mediated diseases, control allograft rejection
- MOA: prodrug (must b activated by intracell. Enzyme: thiopurine methyltr.)
- causes leukopenia & thrombocytopenia
- dogs can develop hepatic toxicity, demodex infection, recurrent pyoderma, dermatophyte infections
Folic acid antagonists
- binds to dihydrofolate reductase, blocks tetrahydrofolate synth.
- inhibit synth. of thymidine and purines
- suppresses antibody formation BIG IDEA
- side effects similar to cyclophosphamide
- treats rheumatoid arthritis in humans
Cyclosporine
- from soil fungus
- binds & inhibits calcineurin, transcription factors not able to enter nucleus
- can’t produce cytokines, blocks prolif of activated t lymphocytes and blocks Th1 reponses
- doesn’t cause significant myelosuppression or suppress non specific immunity
- can cause vomiting/diarrhea, gingival hyperplasia, lymphoma (humans handling drug/animals)
Tacrolimus
- more potent than cyclosporine; inhibits t and b cell responses
- severe intestinal toxicity in dogs
- used for atopic derm., discoid lupus erythematosus in canines
Rapamycin inhibitors
- inhibit serine kinase called mTOR
- inhibits b and t cell proliferation
- synergistic w/ calcineurin inhibitors
- severe intestinal toxicity in dogs
Inosine monophosphate dehydrogenase inhibitors
- MOA: inhibits IMD in activated lymphocytes & prevents DNA synth.
- blocks b/t cell prolif. and antibody formation
- when given w/ cyclosporine, prev. Renal allograft rejection in mongrel dogs
- well tolerated by dogs
Leflunomide and IV Ig therapy
- anti-inflammatory that inhibits pyrimidine synth.
- prev. of allograft rejection in dogs
- inhibits autoantibody activities
