Immunopharmacology

Question 1

Cyclosporine:

Answer 1

• Calcineurin inhibitor.
• Binds to cyclophilin.
• Inhibits dephosphorylation of NFAT, synthesis of IL-2.
• Selective for T cells.
• Uses: prevent rejection, autoimmune disorders.
• Tox: nephrotoxicity, HTN, hepatotoxicity.

Question 2

Tacrolimus:

Answer 2

• Calcineurin inhibitor.
• MOA: binds FKBP. Inhibits dephosphorylation of NFAT, synthesis of IL-2.
• Selective for T cells.
• Uses: prevent rejection, autoimmune disorders.
• Tox: nephrotoxicity, neurotoxicity, HTN, DM.

Question 3

Sirolimus/Everolimus:

Answer 3

• MOA: binds to FKBP. Inhibits mTOR.
• Blocks T cell at the G1–>S transition, blocks T cell expansion.
• Use: stents used to inhibit restenosis of blood vessels, prevent rejection, autoimmune disorders.
• Tox: hyperlipidemia, delay in graft function and delayed wound healing, anemia, leukopenia, thrombocytopenia.

Question 4

Azathioprine:

Answer 4

• Prodrug –> 6-MP.
• MOA: block the de novo pathway of purine synthesis.
• Uses: adjunct for prevention of rejection, RA.
• DI: if allopurinol is given then azathioprine dose reduced.
• Tox: bone marrow suppression, leukopenia, anemia, thrombocytopenia, increased risk of infection.

Question 5

Mycophenolate mofetil:

Answer 5

• Prodrug –> MPA
• MOA: reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH). Inhibits de novo synthesis of guanine.
• Use: prevent transplant rejection.
• DI: antacids decrease absorption.
• Tox: GI effects, leukopenia.

Question 6

Antithymocyte globulin (ATGAM):

Answer 6

• Polyclonal antibody from serum of horses or rabbits.
• MOA: binds to circulating T cells which induces lymphopenia and decreases T cell function.
• Use: prevent rejection.
• Tox: serum sickness, nephritis, chills, fever and rashes.

Question 7

Muromonab-CD3

Answer 7

• Mouse monoclonal antibody against CD3.
• MOA: induces internalization of the TCR complex.
• Use: prevent rejection.
• Tox: cytokine release syndrome, anaphylactic reactions, CNS tox, increased risk for infections and malignancy.

Question 8

Daclizumab/basiliximab:

Answer 8

• MOA: bind the alpha subunit of IL-2R on T cells; inhibits T cell proliferation.
  Use: D - relapsing MS. B - prevent rejection.

Question 9

Alemtuzumab:

Answer 9

• Humanized anti-CD52 antibody.
• MOA: induces cytolysis upon binding CD 52 on the surface of B and T cells, monocytes, macrophages and NK cells.
• Use: relapsing remitting MS, chronic lymphoid leukemia.
• Tox: depletion of normal neutrophils and T cells, serious myelosuppression.

Question 10

Tocilizumab:

Answer 10

• Humanized anti-IL-6 antibody.
• MOA: neutralizes IL-6, suppresses inflammation.
• Use: RA, juvenile RA.

Question 11

Rituximab:

Answer 11

• Chimeric anti-CD20 antibody.
• MOA: induces B cell apoptosis by binding to CD20 on malignant B cells.
• Use: chronic lymphoid leukemia, non-Hodgkin’s lymphoma and RA.

Question 12

Infliximab:

Answer 12

• Chimeric anti-TNFalpha antibody.
• MOA: bind to and neutralize TNFalpha.
• Use: RA, psoriasis, ulcerative colitis, Crohn’s disease.
• Tox: increased risk for infection, lymphomas and other cancers.

Question 13

Certolizumab:

Answer 13

• Humanized PEGylated anti-TNFalpha antibody.
• MOA: bind to and neutralize TNFalpha.
• Use: RA, psoriasis, ulcerative colitis, Crohn’s disease.
• Tox: increased risk for infection, lymphomas and other cancers.

Question 14

Adalimumab:

Answer 14

• Human anti-TNFalpha antibody.
• MOA: bind to and neutralize TNFalpha.
• Use: RA, psoriasis, ulcerative colitis, Crohn’s disease.
• Tox: increased risk for infection, lymphomas and other cancers.

Question 15

Etanercept:

Answer 15

• Decoy TNFalpha receptor.
• MOA: bind to and neutralize TNFalpha.
• Use: RA, psoriasis, ulcerative colitis, Crohn’s disease.
• Tox: increased risk for infection, lymphomas and other cancers.

Question 16

Golimumab:

Answer 16

• Human anti-TNFalpha antibody.
• MOA: bind to and neutralize TNFalpha.
• Use: RA, psoriasis, ulcerative colitis, Crohn’s disease.
• Tox: increased risk for infection, lymphomas and other cancers.

Question 17

Abatacept/Belatacept:

Answer 17

• Fusion proteins CTLA-4 IgG1.
• Belatacept more potent.
• MOA: binds CD80/86 on APCs and prevents their binding with CD28 on T cells, inhibiting co-stimulation.
• Uses: A - juvenile arthritis, RA. B - prevent rejection.

Question 18

Immune globulins:

Answer 18

• From pooled human plasma.
• Provide passive immunity.
• Use: immunodeficiency states, to prevent measles, hep-A and tetanus.

Question 19

Bacillus Calmette-Guerin (BCG) vaccine:

Answer 19

• Viable attenuated strain of mycobacterium bovis.
• Muramyl dipeptide is active component.
• Stimulates NK cells and T cell activity.
• Use: bladder cancer.
• Tox: severe hypersensitivity reactions and shock.

Question 20

Levamisole:

Answer 20

• Inhibits T-suppressor cells.

- Use: anthelminic agent, immunostimulant in colon ca.

Question 21

INF-alpha:

Answer 21

• MOA: activates macrophages, T cells and NK cells.
• Use: cancers and Hep B/C
• Human recombinant INF-alpha used.
• Tox: flue like symptoms, pulmonary hypertension.

Question 22

IL-2:

Answer 22

• MOA: activates cellular immunity.
• Use: metastatic melanoma, renal cell carcinoma and AIDS.
• Tox: severe hypotension, cardiovascular tox.
• Pulmonary edema is dose limiting.
• Natural or recombinant forms.

Question 23

G-CSFs:

Answer 23

• Produced by monocytes, fibroblasts and endothelial cells.
• Stimulate increases in granulocytes and monocytes.
• Use: reduce neutropenia.