immunosuppressive drugs

Question 1

Cyclophosphamide: MOA and ADE

Answer 1

Alkylates DNA, S phase specific. Produces both T and B cell cytosine and suppresses T cell activity and antibody production.

Side effects: myelosuppresion, GI, alopecia, hemorrhagic cystitis

Question 2

Azathioprine: MOA and ADE

Answer 2

purine analog. Decreased purine biosynthesis

Greater effect on humoral then cell mediated immunity. Not used for IMHA

ADE: bone marrow suppression, leukopenia, anemia and thrombocytopenia. Also hepatotoxicity and pancreatitis. Don’t use in cats bc of myelosuppression

Question 3

Methotrexate: MOA and ADE

Answer 3

inhibits folic acid reductase. Decreased purine and pyrimidine biosynthesis

It’s used for cancer more than immunosuppression

GI toxicity most common ADE

Question 4

Prednisolone MOA

Answer 4

stabilize cell membrane of endothelial cells, inhibit production of local chemotactic factors, thus decreasing infiltration of neutrophils, monocytes, and lymphocytes. Inhibits secretion of destructive proteolytic enzymes like collegians, elastase, and plasminogen activator . GCC also inhibit the release of AA from membrane phospholipids- no synthesis of thromboxanes and leukotrienes. GCC redistribute monocytes and lymphocytes from the peripheral circulation to the lymphatics and bone marrow. This affects T cells- and also activation and cytotoxicity of T cells reduced. Also suppress cytokine activity and alter macrophage function.

Question 5

Cyclosporine

Answer 5

inhibit calcineurin.

Cyclosporine binds cyclophilins. These complexes associate with calcium dependent calcineurin calmodulin complexes to impede calcium dependent signal transduction.

This inhibits early T cell activation and prevents synthesis of lots of cytokines, like IL-2. Without IL-2, further T cell proliferation inhibited, and T cell cytotoxic activity reduced.

Also causes synthesis of TGF-beta. Which is an inhibitor or IL-2 stimulated T cell proliferation.

This medication is SPECIFIC FOR LYMPHOCYTES- IE allows innate immune system to work.

ADE: hepatotoxic in very high doses, and nephrotoxic in cats maybe. Opportunistic infections but also may predispose animals to cancer, like lymphoma. May cause increase in hair growth, or severe gingival hyperplasia, fibropapillomatosis, and severe or fatal pyodermas

Question 6

What’s the difference between Neoral and Sandimmune

Answer 6

Sandimmune: oil base. VERY NOT bioavailable

Neoral is a microemulsion. More bioavailable.

Question 7

Tacrolimus

Answer 7

Same MOA as cyclosporine. Tacrolimus- FKBP complex binds to calcineurin and inhibits its phosphatase activity. This results in decrease T cell activation and decreased pro inflammatory cytokine snthesis

Use for KCS, topical for perianal fistulas. May not be safe PO- anorexia, vasculitis, intussusception, myocardial inflammation and infarction, hepatic failure

Question 8

Mycophenolate MOA and ADE

Answer 8

cytostatic for lymphocytes because of its inhibition of inosine monophosphate dehydrogenase, an enzyme necessary for purine biosynthesis. This is an inhibitor of T and B cell proliferation during S phase of cell cycle.

ADE: GI

Question 9

Leflunomide

Answer 9

inhibits pyrimidine biosynthesis via actions of dihydroorotate dehydrogenase. Inhibits also tyrosine kinases associated with growth factor receptors. In addition to its effects on T and B lymphocytes, it also has an anti proliferative effect on smooth muscle cells and fibroblasts.

Maybe helpful for viral diseases- in humans used for that.