Immunomodulators

Question 1

Immunomodulators

Answer 1

Modify or weaken the activity of the immune system
“Immunosuppressants”

Question 2

Autoimmune conditions requiring immunosuppression

Answer 2

Lupus
Immune mediated hemolytic anemia (IMHA)
Immune mediated thrombocytopenia (ITP)

Question 3

Allergy conditions requiring immunosupression

Answer 3

Cell-mediated type: atopic dermatitis and graft rejection (organ transplant)

Question 4

Chronic inflammation requiring immunosuppression

Answer 4

IBD

Question 5

Classes of immunosuppressive drugs

Answer 5

Alkylating agents
Glucocorticoids
JAK Inhibitor
Antimetabolites purine analog (thiopurine)
Calcineurin inhibitor

Question 6

Glucocorticoids

Answer 6

Suppresses cell-mediated immunity by inducing apoptosis in normal lymphoid cells

Question 7

Functions of Glucocorticoids

Answer 7

Inhibits clonal expansion of T and B cells
↓ IgG and complement
Reduce eosins, basos, and monos
Reduce leukocyte accumulation

Question 8

With Glucocorticoids, immunosuppressive activity is generally seen with ________________ doses

Answer 8

Medium to high

Question 9

When are Glucocorticoids used

Answer 9

IMHA and AIH
Prednisolone and dexamethasone for induction
Prednisolone for maintenance

Question 10

Recommeded Glucocorticoids use

Answer 10

Highest doses until CS abate
Therapy discontinued after disease in remission for 2-3 months

Question 11

Cyclophosphamide (alkylating agent) MOA

Answer 11

Cytotoxic effect (damage DNA)
Suppresses B cell activity and Ab formation

Question 12

Cyclophosphamide adverse effects

Answer 12

BM suppression
Sterile hemorrhagic cystitis (bleeding with urination, lining of bladder attacked)

Question 13

Azathiopruine (thiopurine)

Answer 13

Alternative to Cyclophosphamide
Used for dermatologic and immune mediated diseases

Question 14

Azathioprine MOA

Answer 14

Prodrug: intracellular enzyme
Metabolites inhibit DNA synthesis

Question 15

Azathioprine adverse effects

Answer 15

Leukopenia and thrombocytopenia
Canines develop hepatic toxicity

Question 16

Long term effects of azathioprine

Answer 16

Demodex infection
Recurrent pyoderma
Dermatophyte infections

Question 17

Kinase inhibitor MOA

Answer 17

Phosphorylation (on and off switch for cell functions, growth regulation)
Ligands

Question 18

Oclactinib (Jak-Stat inhibitor)

Answer 18

Cytokine signaling (IL-31)
Canine: pruritus with atopy, oral
Immunosuppression @ high dose, rapid onset

Question 19

Cyclosporine (calcineurin inhibitor) clinical use

Answer 19

Dermatologic conditions (atopic derm)
Immune mediated diseases
Ophthalmic products (keratitis sicca)

Question 20

Cyclosporine in cats

Answer 20

Organ transplantation
Eosinophilia granuloma complex

Question 21

Cyclosporine MOA

Answer 21

Specific for T cells
Binds and inhibits calcineurin
Results: cytokines no produced, IL-2, block proliferation of activated T cells

Question 22

What doesnt Cyclosporine do?

Answer 22

No significant myelosuppression
Doesn’t suppress non specific immunity

Question 23

Cyclosporine drug interactions

Answer 23

Inhibits P-glycoprotein (GI epithelial cells)- ↑ Cyclosporine concentration
Ketoconazole inhibits CYP 450 (↑ half life)

Question 24

Cyclosporine adverse effects

Answer 24

Vomiting/ diarrhea
Gingival hyperplasia
↑ risk of infection with high doses
Lymphoma (humans handling drug)

Question 25

Cytopoint

Answer 25

Targets IL-31
For atopic dermatitis in dogs (SC)
May need 2-3 injections before max benefit

Question 26

Contraindications to cytopoint

Answer 26

Hypersensitivity
Don’t use in < 3 kg