Immunomodulators

Question 1

Immunomodulator definition

Answer 1

• meds used to weaken/stimulate immune activity
• EX: immunosuppressants; immunostimulants

Question 2

3 types of condition groups that require immunosuppression

Answer 2

• autoimmune
• allergy
• chronic inflammation

Question 3

Autoimmune conditions

Answer 3

• lupus
• IMHA
• IMTP ( immune mediated thrombocytopenia)

Question 4

Allergy conditions that require immunosuppression

Answer 4

• cell mediated: atopic dermatitis & graft rejection

Question 5

T or F: IBD requires immunosuppression

Answer 5

True

Question 6

Non specific agents (immunosuppressive drugs)

Answer 6

• 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

Question 7

Specific agents (immunosuppressive)

Answer 7

• eliminate specific immune cell population
• EX: calcineurin inhibitors target of rapamycin inhib., inosine monophosphate, dehydrogenase inhib., lefunomide, IV Ig therapy

Question 8

Radiation

Answer 8

• immunosuppressive
• ionizing rays affect DNA, oxidate free radicals in cell, inhibit cell division

Question 9

Glucocorticoids

Answer 9

• 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

Question 10

Glucocorticoid effect on neutrophils

Answer 10

• neutrophilia
• reduced chemotaxis, margination, phagocytosis, ADCC, bactericidal activity
• stabilize membranes
• inhibit phospholipase A2

Question 11

Glucocorticoid effect on macrophages

Answer 11

Decreased: chemotaxis, phagocytosis, bactericidal activity, IL-1 &6 prod., antigen process.

Question 12

Glucocorticoid effect on lymphocytes

Answer 12

Decreased: prolif., T cell response and cell-mediated cytotoxicity, IL-2 prod., lymphokine prod.

Question 13

Alkylating agents

Answer 13

-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

Question 14

Thiopurine

Answer 14

• 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

Question 15

Folic acid antagonists

Answer 15

• 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

Question 16

Cyclosporine

Answer 16

• 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)

Question 17

Tacrolimus

Answer 17

• more potent than cyclosporine; inhibits t and b cell responses
• severe intestinal toxicity in dogs
• used for atopic derm., discoid lupus erythematosus in canines

Question 18

Rapamycin inhibitors

Answer 18

• inhibit serine kinase called mTOR
• inhibits b and t cell proliferation
• synergistic w/ calcineurin inhibitors
• severe intestinal toxicity in dogs

Question 19

Inosine monophosphate dehydrogenase inhibitors

Answer 19

• 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

Question 20

Leflunomide and IV Ig therapy

Answer 20

• anti-inflammatory that inhibits pyrimidine synth.
• prev. of allograft rejection in dogs
• inhibits autoantibody activities