Immunomodulators Flashcards
Immunomodulators
Modify or weaken the activity of the immune system
“Immunosuppressants”
Autoimmune conditions requiring immunosuppression
Lupus
Immune mediated hemolytic anemia (IMHA)
Immune mediated thrombocytopenia (ITP)
Allergy conditions requiring immunosupression
Cell-mediated type: atopic dermatitis and graft rejection (organ transplant)
Chronic inflammation requiring immunosuppression
IBD
Classes of immunosuppressive drugs
Alkylating agents
Glucocorticoids
JAK Inhibitor
Antimetabolites purine analog (thiopurine)
Calcineurin inhibitor
Glucocorticoids
Suppresses cell-mediated immunity by inducing apoptosis in normal lymphoid cells
Functions of Glucocorticoids
Inhibits clonal expansion of T and B cells
↓ IgG and complement
Reduce eosins, basos, and monos
Reduce leukocyte accumulation
With Glucocorticoids, immunosuppressive activity is generally seen with ________________ doses
Medium to high
When are Glucocorticoids used
IMHA and AIH
Prednisolone and dexamethasone for induction
Prednisolone for maintenance
Recommeded Glucocorticoids use
Highest doses until CS abate
Therapy discontinued after disease in remission for 2-3 months
Cyclophosphamide (alkylating agent) MOA
Cytotoxic effect (damage DNA)
Suppresses B cell activity and Ab formation
Cyclophosphamide adverse effects
BM suppression
Sterile hemorrhagic cystitis (bleeding with urination, lining of bladder attacked)
Azathiopruine (thiopurine)
Alternative to Cyclophosphamide
Used for dermatologic and immune mediated diseases
Azathioprine MOA
Prodrug: intracellular enzyme
Metabolites inhibit DNA synthesis
Azathioprine adverse effects
Leukopenia and thrombocytopenia
Canines develop hepatic toxicity
Long term effects of azathioprine
Demodex infection
Recurrent pyoderma
Dermatophyte infections
Kinase inhibitor MOA
Phosphorylation (on and off switch for cell functions, growth regulation)
Ligands
Oclactinib (Jak-Stat inhibitor)
Cytokine signaling (IL-31)
Canine: pruritus with atopy, oral
Immunosuppression @ high dose, rapid onset
Cyclosporine (calcineurin inhibitor) clinical use
Dermatologic conditions (atopic derm)
Immune mediated diseases
Ophthalmic products (keratitis sicca)
Cyclosporine in cats
Organ transplantation
Eosinophilia granuloma complex
Cyclosporine MOA
Specific for T cells
Binds and inhibits calcineurin
Results: cytokines no produced, IL-2, block proliferation of activated T cells
What doesnt Cyclosporine do?
No significant myelosuppression
Doesn’t suppress non specific immunity
Cyclosporine drug interactions
Inhibits P-glycoprotein (GI epithelial cells)- ↑ Cyclosporine concentration
Ketoconazole inhibits CYP 450 (↑ half life)
Cyclosporine adverse effects
Vomiting/ diarrhea
Gingival hyperplasia
↑ risk of infection with high doses
Lymphoma (humans handling drug)
Cytopoint
Targets IL-31
For atopic dermatitis in dogs (SC)
May need 2-3 injections before max benefit
Contraindications to cytopoint
Hypersensitivity
Don’t use in < 3 kg
