Term
Basic Principles of Therapy
Sub-chronic or Chronic Therapy |
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Definition
-Toxicity is dose-limiting factor
-Disposition-effect variability
-Avoid factors that facilitate infections |
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Term
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Definition
-First line immunosuppressive agents
-multifaceted MOA
-chronic use can results in iatrogenic hyperadrenocorticism |
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Term
Corticoid-Sparing Protocols
Calcineurin inhibitors
Cyclosporine |
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Definition
-Binds to its immunophilin, cyclophylin, and forms a complex
-complex binds and blocks the fxn of calcineurin
-End result is inhibition of early T-cell activation and prevents formation of cytokines (IL-2)
-T-cell cytotoxic activity is reduced |
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Term
Corticoid-Sparing Protocols
Cyclosporine |
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Definition
-Not cytotoxic or myelotoxic
-specific for T-lymphocytes
-Increased chance for infections and neoplasia
-adverse effects: GI, dermatologic effects
-dosing needs are EXTREMELY variable |
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Term
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Definition
-NeoOral - F= 20-40%
-Sandimmune- F= 5%
-Gengrat (human)
-Atopica - vet formulation; indicated for control of atopic dermatitis; food may decrease bioavail |
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Term
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Definition
-wide but variable
-high binding affinity for RBC and lipoproteins
-use whole blood for TDM |
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Term
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Definition
-vary in variability
-liver, SI, kidney
-extensive hepatic metabolism
-Ketoconazole decreases metabolism |
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Term
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Definition
-Tmax after oral admin is 1-2 hrs
-very variable half-life |
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Term
Cyclosporine Dosing Needs
non- life threatening |
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Definition
-Atopic derm, anal furunculosis, mild IBD, pemphigus
-often effective at std, low oral initial dose
-start low, increase as needed
-generics may be possible
-TDM may not be necessary |
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Term
Cyclosporine
Acute and Life Threatening Cond |
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Definition
IMHA, IMT
-generics not appropriate
-no compounds
-higher doses initially
-need to TDM |
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Term
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Definition
-need to individualize therapeutic range
-interpret results:
-type of sample (whole blood)
-assay used (RIA/FPI used but not as accurate as HPLC)
-clinical response of the p
-peak AND trough need to be looked at |
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Term
Cytokine and GF Inhibitors
Leflunomide |
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Definition
-inhibits pyrrdine synthesis
-dog lymphocyte very sensitive
-GI toxic metabolite in dogs
-less tox in cats
-slower metabolism |
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Term
Cytokine and GF Inhibitors
Mycophenolate Mofetil |
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Definition
-prodrug of mycophenolic acid
-inhibits purine synhesis
-acts on T and B-cells
-combine with cyclosporine |
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Term
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Definition
-used when corticosteroids doesn't work
-Affects B and T-cells
-oral and parenteral
-side effects
-myelotoxic, GI, hemorrhagic cystitis (Acrolein metabolite), alopecia |
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Term
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Definition
-similiar mechanism as cyclophosphamide
-less toxic alternative in cats
-pemphigus foliaceous
-feline granuloma complex
-combined with prednisolone |
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Term
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Definition
-(-) feedback on kinases
-admin with glucocorticoid or cyclophosphamide
-more myelotoxic in cats than dogs
-GI effects, bone marrow suppression
-hepatotoxicity
-4-6 wks for peak |
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