Immunosuppressants - Pharm Flashcards
Mechanism: Calcineurin inhibitor; binds cyclophilin. Blocks T-cell activation by preventing IL-2 transcription.
Use: Transplant rejection prophylaxis, psoriasis, rheumatoid arthritis.
Toxicity: Nephrotoxicity, hypertension, hyperlipidemia, hyperglycemia, tremor, hirsutism, gingival hyperplasia.
Cyclosporine
Mechanism: Calcineurin inhibitor; binds FK506 binding protein (FKBP). Blocks T cell activation by preventing IL-2 transcription.
Use: Transplant rejection prophylaxis
Toxicity: Anemia, cyclosporine, increased risk of diabetes and neurotoxicity; no gingival hyperplasia.
Tacrolimus
Mechanism: mTOR inhibitor; binds FKBP. Blocks T cell activation and B cell differentiation by preventing IL-2 signal transduction.
Use: kidney transplant rejection prophylaxis
Toxicity: Anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipidemia, non-nephrotoxic.
Sirolimus (Rapamycin)
Mechanism: Monoclonal antibody; blocks IL-2R.
Use: Kidney transplant rejection prophylaxis.
Toxicity: Edema, hypertension, tremor.
Basiliximab
Mechanism: Antimetabolite precursor of 6-mercaptopurine. Inhibits lymphocyte proliferation by blocking nucleotide synthesis.
Use: transplant rejection prophylaxis, rheumatoid arthritis, Crohn’s disease, glomerulonephritis, other autoimmune conditions.
Toxicity: Leukopenia, anemia, thrombocytopenia.
Notes: 6-MP degraded by xanthine oxidase; toxicity increased by allopurinol.
Azathioprine
Mechanism: Inhibit NF-kB. Suppress both B and T cell function by decreasing transcription of many cytokines.
Use: transplant rejection prophylaxis (immune suppression), many autoimmune disorders, inflammation.
Toxicity:Hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, hypertension, cataracts, peptic ulcers.
Glucocorticoids
Recombinant Cytokines:
Agent: Epoetin alpha (erythropoietin)
Clinical use:?
Clinical uses: Anemias (especially in renal failure).
Recombinant Cytokines:
Agent: Oprelvekin (interleukin-11)
Clinical use:?
Clinical uses: Thrombocytopenia
Recombinant Cytokines:
Agent: Filgrastim (granulocyte colony-stimulating factor).
Clinical uses:?
Clinical uses: Recovery of bone marrow
Recombinant Cytokines:
Agent: Sargramostim (granulocyte-macrophage colony-stimulating factor).
Clinical uses:?
Clinical uses: Recovery of bone marrow
Recombinant Cytokines:
Agent: Aldesleukin (interleukin-2)
Clinical uses:?
Clinical uses: Renal cell carcinoma, metastatic melanoma
Recombinant Cytokines:
Agent: IFN-alpha
Clinical uses:?
Clinical uses: chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma.
Recombinant Cytokines:
Agent: IFN-beta
Clinical uses:?
Clinical use: multiple sclerosis
Recombinant Cytokines:
Agent: IFN-gamma
Clinical uses:?
Clinical uses: chronic granulomatous disease
Therapeutic antibodies:
Target: CD52
Clinical use: CLL
Notes: chronic lymphocytic leukemia
Cancer Therapy:
Alemtuzumab
Therapeutic antibodies:
Target: VEGF (Vascular endothelial growth factor)
Clinical use: Colorectal Cancer, renal cell carcinoma
Cancer Therapy:
Bevacizumab
Therapeutic antibodies:
Target: EGFR (Epidermal growth factor receptor)
Clinical use: Stage IV colorectal cancer, head and neck cancer.
Cancer therapy:
Cetuximab
Therapeutic antibodies:
Target: CD20
Clinical use: B-cell non-Hodgkin lymphoma, rheumatoid arthritis (with MTX), ITP
Notes:
Cancer therapy:
Rituximab
Therapeutic antibodies:
Target: HER2/neu
Clinical use: Breast cancer, gastric cancer
Cancer therapy:
Transtuzumab
Therapeutic antibodies:
Target: TNF-alpha
Clinical use: IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis
Notes: rheumatoid arthritis
Autoimmune disease therapy:
Infliximab, adalimumab
Certolizumab, golimumab
Therapeutic antibodies:
Target: Alpha4-integrin
Clinical use: multiple sclerosis, Crohn disease
Notes: alpha-4-integrin: leukocyte adhesion. Risk of PML in Px with JC Virus.
Autoimmune disease therapy:
Natalizumab
Therapeutic antibodies:
Target: Glycoprotein IIb/IIIa
Clinical use: Anti-platelet agent for prevention of ischemic complications in Px undergoing percutaneous coronary intervention.
Notes: IIb times IIIa equals “xxxxx”
Other:
Abciximab
Therapeutic antibodies:
Target: RANKL
Clinical use: Osteoporosis; inhibits osteoclast maturation (mimics osteoprotegrin)
Other:
Denosumab
Therapeutic antibodies:
Target: Digoxin
Clinical use: Antidote for digoxin toxicity
Other:
Digoxin immune Fab
Therapeutic antibodies:
Target: IgE
Clinical use: Allergic asthma; prevents IgE binding to FcERI
Other:
Omalizumab
Therapeutic antibodies:
Target: RSV F protein
Clinical use: RSV prophylaxis for high-risk infants.
Other:
Palivizumab
What are the SE of Basiliximab??
Edema, hypertension, and tremor
