Non-Steroidal Immunomodulators

Question 1

Consequences of immunosuppressant drugs

Answer 1

Good: inappropriate autoimmune responses are blunted
Bad: normal immune responses are blunted

Question 2

What do immunosuppressant drugs inhibit

Answer 2

T cell activation
B cell activation
either or both

Question 3

NSIM General uses

Answer 3

Systemic diseases: IMHA,immune mediated thrombocytopenia,systemic lupus erythematosus (SLE)
-autoimmune diseases involving multiple organ systems
Dermatological diseases:
Pemphigus, lupus-like syndromes

Question 4

Cyclosporine

Answer 4

Calcineurin inhibitor
Treats broad autoimmune disease
Systemic: IMHA, IBD, immune mediated polyarthritic, atopic dermatitis, perianal fistulas, organ transplants, keratoconjuctivitis sicca

Question 5

Calcineurin

Answer 5

Enzyme that activates T cells.
Inhibitors block T-cell proliferation thru inhibition of key signaling pathways
B cell response normal

Question 6

Tacrolimus

Answer 6

Calcineurin inhibitor
Minimal vet med uses (systemic tox)
Topical admin for dermatoses

Question 7

Oclacitinib (Apoquel) MOA

Answer 7

NSIM immune suppressant
JAK (-STAT) inhibitor
Decrease effects of inflammatory cytokines made by lymphocytes (IL-2, IL-4, IL-6, IL-13)
Decrease IL-31 (itch)

Question 8

Apoquel Uses

Answer 8

Manage chronic itch
Causes bone marrow suppression
Good alternatives for dogs who do not tolerate steroids or cyclosporine

Question 9

Cytopoint

Answer 9

Monoclonal antibody against IL-31 (itch)
Atopic dermatitis
Can lead to resistance

Question 10

Cyclophosphamide

Answer 10

Potent Immunosuppressant
Cytotoxic: T and B cells (systemic blockade) and other rapidly dividing cells
MOA: nitrogen mustard
Uses: anti-neoplastic, immunosuppression: immune mediated thrombocytopenia, SLE, rheumatoid arthritis, pemphigus, IMHA (?)

Question 11

Cyclophosphamide Toxicity

Answer 11

Bone Marrow suppression
V/D, alopecia
STERILE HEMORRHAGIC CYSTITIS
acrolein accum. in urine and damages bladder epithelium (tx: glucocorticoids/diuretics/mesna)

Question 12

Chlorambucil

Answer 12

Cytotoxic to T, B cells, rapidly dividing cells (bone marrow)
MOA: nitrogen mustard
Slower acting than cyclophosphamide
Uses: same as cyclophos. but potentially not as effective, often pemphigus in cats
Does NOT cause sterile hemorrhagic cystitis and less bone marrow suppression

Question 13

Azathioprine

Answer 13

Pro-drug
interferes w/ T and B cell proliferation
May take weeks for immunosuppression
Uses: IBD, immune mediated skin diseases, IMHA etc
mostly dogs
Tox: immunosuppression, bone marrow suppression (esp cats)

Question 14

Mycophenolate mofetil

Answer 14

Pro-drug
Interferes w/ T and B cell proliferation
Alternative to azathioprine but EXPENSIVE
Uses: Cats, IBD (but GI side effects), Organ transplants