Immunosuppressants Flashcards
The recombinant cytokine Aldesleukin is an IL-2 used for which 2 clinical conditions?
RCC
metastatic melanoma
The recombinant cytokine Epoetin alfa is erythropoietin used in?
Anemias, especially in renal failure
The recombinant cytokine Filgrastrim is a G-CSF used to?
recover bone marrow
The recombinant cytokine Sargramostim is a GM-CSF used to?
recover bone marrow
The recombinant cytokine IFN-alpha used in?
Chronic hepatitis B and C
Kaposi sarcoma
malignant melanoma
The recombinant cytokine IFN-beta used in?
multiple sclerosis
The recombinant cytokine IFN-gamma used in?
Chronic granulomatous disease (NADPH oxidase deficiency -can’t take care of O2 produced and make HOCL) -more susceptible to catalase + organisms (2H2O2 –> 2H2O + O2)
“Cats Need PLACESS to hide”
Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E. coli, Staphylococci, Serratia
The recombinant cytokines Romiplostim and eltrombopag used to treat?
thrombocytopenia
The recombinant cytokine Oprelvekin is a recombinant IL-11 used to treat?
thrombocytopenia b/c IL-11 can help in maturation of megakaryocytes
List the 3 recombinant cytokines to treat thrombocytopenia
-Romiplostim, eltrombopag, Oprelvekin (IL-11)
List the 2 recombinant cytokines used to recover bone marrow
- Filgastrim (G-CSF)
- Sargramostim (GM-CSF)
Both cyclosporine and tacrolimus are immunosuppressants that inhibit calcinerin (impt in transcription of IL-2 for T cell activation), but they bind different proteins. State them
cyclosporine inhibits calcinerin by binding cyclophilin
tacrolimus inhibits calcineurin by binding FKBP
*Both block T-cell activation by blocking IL-2 transcription
List the 2 immunosuppressants that inhibit calcineurin. They share a very impt side effect, which is?
The 2 immunosuppressants: cyclosporine + tacrolimus are BOTH VERY NEPHROTOXIC
Cyclosporine is an immunosuppressant that inhibits calcineurin impt in transcription of IL-2 for activation of T-cell. No calcineurin = no tx of IL-2 = no activation of T cell. What are the clinical uses and side effects?
Clinical uses: tx rejection ppx, psorasis, rheumatoid arthritis
toxicity: nephrotoxicity, HTN, hyperlipidemia, neurotoxicity, gingival hyperplasia, hirsutism
Tacrolimus is an immunosuppressant that inhibits calcineurin (no calcineurin = no transcription of IL-2 = no activation of T cells). What are clinical uses and side effects?
Clinical uses: tx rejection ppx
toxicity: nephrotoxicity, increase risk of DIABETES, neurotoxicity
Sirolimus aka Rapamycin is an immunosuppressant that works how? What is it used in. toxicity?
Sirolimus (Rapamycin) is a mTOR inhibitor by binding FKBP. FKBP can bind mTOR to cause proliferation of genes. Sirolimus, as a mTOR inhibitor, blocks T cell activation and B cell differentiation by preventing response to IL-2. It is used in kidney tx rejection ppx.
Toxicity: bone marrow suppression, insulin resistance, hyperlipidemia.
T/F: Sirolimus is syngergistic with Cyclosporine
Cyclosporine: calcineurin inhibitor prevents tx of IL-2 = no T cell activation
Sirolimus: mTOR inhibitor prevents T cell activation and B cell differentiation
True
*remember impt side effect of cyclosporine is nephrotoxicity; sirolimus is not nephrotoxic
What are the 2 monoclonal antibodies used as immunosuppressant therapy to block IL-2R used in kidney tx rejection ppx? What are 3 side effects?
- Basiliximab
- Daclizumab
side effects: Edema, HTN, tremor
Azathioprine is an anti-metabolite that is a prodrug to? It can be used as in immunosuppressant b/c? What are some side effects. Also, what drug is contraindicated?
Azathioprine is an antimetabolite that is a prodrug to 6-mercaptopurine that blocks nucleotide synthesis which will then inhibit lymphocyte proliferation.
Side effects are mainly bone marrow suppression. People on azathioprine or 6-mercaptopurine should not be on allopurinol b/c allopurinal is a xanthine oxidase inhibitor preventing uric acid build up but xanthine oxidase is the enzyme responsible for degrading azathioprine/6-MP.
Glucocorticoids can be used as immunosuppressants as transplant rejection ppx because it? What are some side effects of long-term use?
glucocorticoids inhibit NF-kb, a nuclear transcription factor, that is impt in activating immune response genes. No NF-kb = suppression of both B and T cell function due to decrease tx of many cytokines.
side effects: hyperglycemia, osteoporosis, central obestiy, muscle breakdown, psychosis, acne, HTN, cataracts, avascular necrosis ***can cause iatrogenic cushing syndrome.
Therapeutic antibodies: Alemtuzumab targets? used in?
Alemtuzumab targets CD52 used in chronic lymphocytic leukemia
CLL is the most common leukemia overall due to neoplastic proliferation of naive B cells that co-express CD5 and CD20; will see SMUDGE cells on blood smear)
Therapeutic antibodies: Bevacizumab targets? used in? Similuar to which other therapeutic ab in that it also has the same target and uses?
Bevacizumab targets VEGF used in colorectal cancer, RCC.
Ranibizumab is also an antibody that blocks VEGF that can be used for neovascular age-related macular degeneration. In addition to being used in colorectal cancer and RCC, bevacizumab is also used for neovascular age-related macular degeneration.
Therapeutic antibodies: Cetuximab targets? used in?
Cetuximab targets EGFR used in stage IV colorect cancer, head and neck cancer.
Therapeutic antibodies: Rituximab targets? used in?
Rituximab targets CD20 and used in B-cell non-Hodgkin Lymphoma, CLL, rheumatoid arthritis, Immune thrombocytopenic purpura (ITP: autoimmune production of IgG against platelet antigens by plasma cells in the spleen –> MOST COMMON cause of thrombocytopenia in children and adults)
Therapeutic antibodies: Trastuzumab targets? used in?
Trastuzumab is a monoclonal antibody that targets HER2/neu (a tyrosine kinase receptor) to treat breast cancer that overexpresses HER2. (kill cells via Ab-dependent cytotoxicity
Therapeutic antibodies: Adalimumab, Infliximab target? used in?
Adalimuab and Infliximab target soluble TNF-alpha used in inflammatory bowel disease [chrohn’s or ulcerative], rheumatoid arthritis, anklosing spondylitis (bamboo spine, HLA-B27), psoriasis
How is etanercept different from adalimumab and infliximab?
Adalimumab and Infliximab are monoclonal antibodies that target solube TNF-alpha. Etanercept is a DECOY TNF-alpha RECEPTOR and NOT a monoclonal antibody.
Therapeutic antibodies: Eculizumab targets? used for?
Eclizumab targets complement protein C5 used in paroxymal nocturnal hemoglobinuria
PNH is anacquired defect in myeloid stem cells –> ABSENT glycosylphophatidylinosoital (GPI); GPI is impt in preventing cell from getting killed by complement b/c it anchors DAF & MIRL on RBC membranes that inhibit C3 convertase; At night, we breathe shallow (respiratory acidosis) that can activate complement –> intravascular hemolysis at night
***RBCS, WBCS, and PLTS are lysed (pg 49 in pathoma)
Therapeutic antibodies: Natalizumab targets? used for? There’s a risk for what type of side effect?
Natalizumab targets alpha4-integrin used in multiple sclerosis and Chrohn’s.
Alpha4-integrin is impt in cell adhesion bringing WBCs into GI and CNS. If you inhibit alpha-4 integrin and prevent movement of WBCs and inflammatory cells thru CNS can be linked to progressive multifocal leukoencephalopathy in pts with JC virus (DNA virus -polyomavirus).
Therapeutic antibodies: Abciximab targets? used for?
Abciximab targets platelet glycoproteins IIb/IIIa (impt in binding fibrinogen) used as antiplatelet agent for prevention of ischemic complications in patients undergoing percutaneous coronary intervention.
Therapeutic antibodies: Denosumab targets? used for?
Denosumab targets RANKL (on osteoclast) used to treat osteoporosis by inhibiting osteoclast maturation by mimicking osteoprotegerin.
Therapeutic antibodies: Digoxin immune Fab targets? used for?
Digoxin immune Fab targets digoxin and is used as an antidote to digoxin poisoning.
Therapeutic antibodies: Omalizumab targets and used for?
Omalizumab targets IgE and is used in allergic asthma, prevents IgE binding to FceRI.
Therapeutic antibodies: Palivizumab targets and used for?
Palivizumab targets RSV F protein used for RSV ppx in high-risk infants.
RSV = RNA virus in paramyxovirus family along with parainfluenzae, mumps and measles –> ssRNA, nonsegmented negative linear, helical.
