Immunosuppressants

Question 1

Cyclosporine

Answer 1

MOA:
Calcineurin inhibitor; binds cyclophilin. Blocks T cell activation by preventing IL-2 transcription*.

Use:
Transplant rejection prophylaxis, psoriasis, rheumatoid arthritis

Toxicity:
Highly nephrotoxicity*, htn, neurotoxicity, gingival hyperplasia, hirsutism

Metabolized by CYP450

Question 2

Tacrolimus

Answer 2

MOA:
Calcineurin inhibitor; binds FK506 binding protein. Blocks T cell activation by preventing IL-2 transcription*

Use:
Transplant rejection prophylaxis

Toxicity:
Similar to cyclosporine*, increased risk of diabetes and neurotoxicity; no ginigival hyperplasia or hirsutism

Question 3

Sirolimus (Rapamycin)

Answer 3

MOA:
mTOR inhibitor; binds FKBP. Blocks T cell activation and B cell differentiation by preventing response to IL-2*

Use:
Kidney transplant rejection prophylaxis*

Toxicity:
Pancytopenia, insulin resistance, hyperlipidemia; not nephrotoxic*

Synergistic w/ cyclosporine

Also used in drug-eluting stents

Question 4

Daclizumab, basiliximab

Answer 4

MOA:
Monoclonal antibodies; Block IL-2R

Use:
Kidney transplant rejection prophylaxis

Toxicity:
Edema, htn, tremor

Question 5

Azathioprine

Answer 5

MOA:
Antimetabolite precursor of 6-mercaptopurine
Inhibits lymphocyte proliferation by blocking nucleotide synthesis.

Use:
Transplant rejection prophylaxis, rheumatoid arthritis, Crohn disease, glomerulonephritis, other autoimmune conditions

Toxicity:
Leukopenia, anemia, thrombocytopenia

6-MP degraded by xanthine oxidase; toxicity increase by allopurinol

Question 6

Mycophenolate mofetil

Answer 6

MOA:
Reversibly inhibits IMP dehydrogenase, preventing purine synthesis of B and T cells

Use:
Transplant rejection prophylaxis, lupus nephritis

Toxicity:
GI upset, pancytopenia, hypertension, hyperglycemia, less nephrotoxic and neurotoxic

Associated with invasive CMV infection

Question 7

Corticosteroids

Answer 7

MOA:
Inhibit NF-kB
Suppress both B and T cell func by decreasing transcription of many cytokines
Induce apoptosis of T lymphocytes

Use:
Transplant rejection prophylaxis, many autoimmune and inflammatory disorders

Toxicity:
Hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, hypertension, cataracts, avascular necrosis (femoral head)

Can cause iatrogenic Cushing syndrome

Question 8

Alemtuzumab

Answer 8

Target: CD52

Use: CLL, MS

Question 9

Bevacizumab

Answer 9

Target: VEGF

Use: Colorectal cancer, renal cell carcinoma

Question 10

Cetuximab

Answer 10

Target: EGFR

Use: Stage IV colorectal cancer, head and neck cancer

Question 11

Rituximab

Answer 11

Target: CD20

Use: B-cell non Hodgkin lymphoma, CLL, rheumatoid arthritis, ITP

Question 12

Trastuzumab

Answer 12

Target: HER2/neu

Use: Breast cancer

Question 13

Adalimumab, certolizumab, infliximab

Answer 13

Target: Soluble TNF-a

Use:
IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis

Question 14

Eculizumab

Answer 14

Target: Complement protein C5

Use: Paroxysmal nocturnal hemoglobinuria

Question 15

Natalizumab

Answer 15

Target: alpha4-integrin

Use: Multiple sclerosis, Crohn disease

alpha4-integrin: WBC adhesion, risk of PML in ptns with JC virus

Question 16

Abciximab

Answer 16

Target: Platelet glycoproteins IIb/IIIa

Use: Antiplatelet agent for prevention of ischemic complications in patients undergoing percutaneous coronary intervention

Question 17

Denosumab

Answer 17

Target: RANKL

Use: Osteoporosis; inhibits osteoclast maturation (mimics osteoprotegerin)

Question 18

Digoxin immune Fab

Answer 18

Target: Digoxin

Use: Antidote for digoxin toxicity

Question 19

Omalizumab

Answer 19

Target: IgE

Use: Allergic asthma; prevents IgE binding to FcERI

Question 20

Palivizumab

Answer 20

Target: RSV F protein

Use: RSV prophylaxis for high risk infants

Question 21

Ranibizumab, Bevacizumab

Answer 21

Target: VEGF

Use: Neovascular age-related macular degeneration