Immuno Pharm from FA

Question 1

Immunosuppressants: generally what do they do?

Consequences of chronic use?

Answer 1

• Block lymphocyte activation and proliferation
• Reduce acute transplant rejection by suppressing cellular immunity
• May be combined -> greated efficacy and decr toxicity.
• Chronic use increases risk of infection and malignancy

Question 2

Cyclosporine

Mech? Use? Toxicity? Notes?

Answer 2

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

Use: Transplant rejection prophy, psoriasis, RA

Tox: Nephrotoxic, HTN, Hyperlipidemia, hyperglycemia, tremor, hirsutism, gingival hyperplasia

Notes: BOTH calcineurin inhibitors are highly nephrotoxic (Cyclosporine & Tacrolimus)

Question 3

Tacrolimus

Mech? Use? Toxicity? Notes?

Answer 3

Mech: Calcineurin inh (binds FK506 binding protein (FKBP). Blocks T cell activation by preventing IL-2 transcription

Use: Transplant rejection prophy

Tox: Nephrotoxic, incr risk of diabetes, NO gingival hyperplasia or hirsutism (compared to Cyclosporine)

Note: “-limus” drugs bind FKBP

Question 4

Sirolimus

Mech? Use? Toxicity? Notes?

Answer 4

Mech: mTOR inhibitor, binds FKBP. Blocks T cell activation and B cell differentation by preventing IL-2 signal transduction

Use: kidney transplant rejection prophy, drug-eluting stents

Tox: Anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipedemia, non-nephrotoxic

Notes: Kidney “sir”vives. Synergistic with cyclosporine.

Question 5

Basiliximab

Mech? Use? Toxicity?

Answer 5

Mech: monoclonal antibody; blocks IL-2R

Use: Kidney transplant rejection prophy

Tox: Edema, HTN, tremor

Question 6

Azathioprine

Mech? Use? Toxicity?

What Rx should you avoid using this with?

Answer 6

Mech: antimetabolite precursor of 6-mercaptopurine (6-MP). Inhibits lymphocyte proliferation by blocking nucleotide synthesis.

Use: Transplant rejection prophy; RA, Crohn’s; glomerulonephritis; other autoimm diseases

Tox: Leukopenia, anemia, thrombocytopenia

Notes: 6-MP degraded by xanthine oxidase; toxicity incr by allopurinol. Think “azathiopurine”

Question 7

Glucocorticoids (aka corticosteroids)

Mech? Use? Toxicity? Notes?

Answer 7

Mech: inhibit NF-kB. Suppress both B and T cell function by decr transcription of many cytokines

Use: Transplant rejection prophy; many autoimm disorders; inflammation

Tox: hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, HTN, cataracts, peptic ulcers

Notes: can cause iatrogenic Cushing’s

Question 8

Clinical use for Epoetin alfa (aka erythropoietin)?

Answer 8

Anemias, esp in renal failure

Question 9

Clinical use for Thrombopoietin?

Answer 9

Thrombocytopenia

Question 10

Clinical use for Oprelvekin (aka IL-11)?

Answer 10

Thrombocytopenia

Question 11

Clinical use for Filgrastim (granulocyte colony-stimulating factor)

Answer 11

Recovery of bone marrow

Question 12

Clinical use for Sargramostim (granulocyte-macrophage colony-stimulating factor)?

Answer 12

Recovery of bone marrow

Question 13

Clinical use for Aldesleukin

Answer 13

(IL-2)

Renal cell carcinoma; metastatic melanoma

Question 14

Clinical use for IFN-alpha?

Answer 14

Chronic Hep B and C

Kaposi sarcoma

hairy cell leukemia

condyloma acuminatum

renal cell carcinoma

malignant melanoma

Question 15

Clinical use for IFN-beta?

Answer 15

Multiple sclerosis

Question 16

Clinical use for IFN-gamma?

Answer 16

Chronic granulomatous disease

Question 17

Alemtuzumab

Target? Use? Notes?

Answer 17

Target: CD52

Use: CLL

Notes: “Alymtuzumab”: chronic lymphocytic leukemia

Question 18

Bevacizumab

Target? Use?

Answer 18

Target: VEGF

Use: colorectal cancer, renal cell carcinoma

Question 19

Cetuximab

Target? Use?

Answer 19

Target: EGFR

Use: Stage IV colorectal cancer; head and neck cancer

Question 20

Rituximab

Target? Use?

Answer 20

Target: CD20

Use: B cell non-Hodgkin lymphoma; Rheum arthritis (with MTX); ITP

Question 21

Trastuzumab

Target? Use?

Answer 21

Target: Her2/neu

Use: Breast cancer, gastric cancer

Note: HER2 - tras2zumab

Question 22

Infliximab, adalimumab

Target? Use?

Answer 22

Target: TNF-alpha

Use: psoriasis, ank spond, IBD, rheumatoid arth

*(similar to HLA-B27 associated diseases: PAIR - Psoriatic arth, Ank spond, arthritis of IBD, Reactive arthritis) *

Note: RA “inflix” pain in “da limbs”

Question 23

Natalizumab

Target? Use?

Answer 23

Target: alpha4-integrin

Use: MS, Crohn’s

Note: alpha4-integrin: leukocyte adhesion.

Risk of PML in patients with JC virus

Question 24

Abciximab

Target? Use?

Answer 24

Target: Glycoprotein IIb/IIIA

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

IIb x IIIa = absiximab

Question 25

Denosumab

Target? Use?

Answer 25

Target: RANKL

Use: Osteoporosis; inhibits osteoclast maturation (mimics osteoprotegrin)

Denosumab affects osteoclasts

Question 26

Digoxin immune Fab

Target? Use?

Answer 26

Target: Digoxin

Use: Antidote for digoxin toxicity

Question 27

Omalizumab

Target? Use?

Answer 27

Target: IgE

Use: Allergic asthma; prevents IgE binding to FceRI

Question 28

Palivizumab

Target? Use?

Answer 28

Target: RSV F protein

Use: RSV prophy for high risk infants

PaliVIzumab = VIrus

Question 29

muromab

MoA

ADR

Answer 29

mAb binds CD3 that blocks T cell signaling

cytokine release storm

Question 30

mycophenolate mofetil

MoA

ADR

Answer 30

blocks guanine nucleotide synthesis, thereby inhibiting lymphocyte proliferation

ADR: myelosuppression, Dramatic diarrhea