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1

Cyclosporine

1. Post-transplant immunosuppression; select autoimmune disorders

2. Binds to cyclophilins. Complex blocks differentiation and activation of Tcells by inhibiting calcineurin--> preventing production of IL-2 and its receptor

3. Nephrotoxicity, hypertension, hyperlipidemia, hyperglycemia, tremor, gingival hyperplasia, hirsutism

4. Think old man with diabetes who wants to look good for his date so he put in dentures and got hair plugs: old (renal failure, HTN, cholesterol), diabetes (hyperglycemia), dentures (gum hyperplasia), hair plugs (hirsutism, and he is taking the drug because of his hair transplant)

1

Tacrolimus (FK-506)

1. Post- organ transplant immunosuppression; POTENT

2. Binds to FK protein->inhibiting calcineurin->preventing IL-2

3. Nephrotoxicity, hypertension, hyperlipidemia, hyperglycemia, tremor
4. Think old with diabetes who is nervous because he is super sick: old (renal failure, HTN, cholesterol), diabetes (hyperglycemia), nervous (tremor), super sick (strong immunosuppressant)

2

Sirolimus (rapamycin)

1. Immunosuppression post-KIDNEY transplant (Give with cyclosporine); used with drug-eluting stents

2. Inhibits mTOR. Decreased cell proliferation in response to IL-2

3. Hyperlipidemia, thrombocytopenia, leukopenia

4. SIROlimus= SERIOUS complications: immunosuppression

3

Azathioprine

1. Immunosuppression post-KIDNEY transplant; autoimmune disorders (including glomerulonephritis and hemolytic anemia)

2. Antimetabolite. precursor of 6-MP-> decreased synthesis of nucleic acids. Toxic to proliferating lymphocytes.

3. Bone marrow suppression.

4. Active metabolite (mercaptopurine) is metabolized by XO so more toxic when given with Allopurinol

4

Muromonab-CD3 (OKT3)

1. Immunosuppression post-KIDNEY transplant

2. Monoclonal antibody to CD3 on T-cells. Blocks interaction with CD3 protein responsible for T-cell signal transduction
3. Cytokine release syndrome, hypersensitivity reaction

4. Antibodies= hypersensitivity, hypersensitivity= cytokine release -nab= monocolonal antibody therapy (usually)

5

Recombinant Cytokines

Aldesleukin (interleukin-2) Epoetin alfa (erythropoietin) Filgrastim (CSF-G) Sargramostim (CSF-GM) Alpha-Interferon Beta-Interferon Gamma-Interferon Oprelvekin (interleukin-11) Thrombopoietin

6

Aldesleukin

1. Renal cell carcinoma Metastatic Melanoma

2. Cytokine: Interleukin-2 MOA: increases helper, cytotoxic, and regulatory T cells

7

Epoetin alfa

1. Anemias (esp in renal failure)

2. Cytokine: Erythropoietin MOA: Stimulates Erythrocyte replication

8

Filgrastim

1. Recovery of bone marrow

2. G-CSF (Granulocyte Colony Stimulating Factor)

9

Sargramostim (CSF-GM)

1. Recovery of bone marrow

2. GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor)

10

Alpha-Interferon

1. Hepatitis B and C, Kaposi's Sarcoma, Leukemia, Malignant Melanoma

2. Inhibit viral protein synthesis and activates NK cells to kill virally infected cells

11

Beta-Interferon

Multiple Sclerosis

12

Gamma-Interferon

1. Chronic Granulomatous disease

2. Activates macrophages and Th1 cells Suppresses Th2 cells.

4. (G)amma = (G)ranulomatous

13

Oprelvekin

1. Thrombocytopenia

2. IL-11

14

Thrombopoietin

Thrombocytopenia

15

Muromonab-CD3 (OKT3)

1. Immunosuppression post-KIDNEY transplant

2. Monoclonal antibody to CD3 on T-cells. Blocks interaction with CD3 responsible for T-cell signal transduction

3. Cytokine release syndrome, hypersensitivity reaction

4. Antibodies= hypersensitivity, hypersensitivity= cytokine release -nab= monocolonal antibody therapy (usually)

16

Digoxin Immune Fab

Target: Digoxin Use: Antidote for Digoxin toxicity

16

Infliximab

Target: TNF-alpha Use: Crohn's Disease, Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis

17

Adalimumab

Target: TNF-alpha Use: Crohn's Disease, Rheumatoid arthritis, psoriatic arthritis

18

Abciximab

Target: Glycoprotien IIb/IIIa Use: Prevent cardiac ischemia in unstable angina and patients treated with percutaneous coronary intervention

MOA: Prevents platelet aggregation by inhibiting the platelet-GIIb/IIIa-fibrinogen bonds

19

Trastuzumab (Herceptin)

Target: HER2 Use: HER2 overexpressing breast cancer

20

Rituximab

Target: CD20 Use: B-cell non-Hodgkin's lymphoma

21

Omalizumab

Target: IgE Use: Additional treatment for severe asthma