Immunosuppressants Flashcards
general mechanism of immunosuppressants
- agents that block lymphocyte activation and proliferation
how would you reduce acute transplant rejection?
- suppress cellular immunity
why would you combine immunosuppressants?
- immunosuppressants are frequently combined to achieve greater efficacy with decrease toxicity
what may occur with chronic immune suppression?
increased risk of infection and malignancy
what are the 2 calcineurin inhibitors? what kind of toxicity is likely with both?
- cyclosporine
- tacrolimus (FK506)
- highly nephrotoxic
cyclosporine–mechanism
- calcineurin inhibitor
- binds cyclophilin
- blocks T cell activaiton by preventing IL-2 transcription
cyclosporine–use
- transplant rejection prophylaxis
- psoriasis
- rheumatoid arthritis
cyclosporine–toxicity
-
nephrotoxicity
- hypertention
- hyperlipidemia
- neurotoxicity
- gingival hyperplasia
- hirsutism
tacrolimus (FK506)–mechanism
- calcineurin inhibitor
- binds FK506 binding protein (FKBP)
- blocks T cell activation by preventing IL-2 transcription
tacrolimus (FK506)–use
- transplant rejection prophylaxis
tacrolimus (FK506)–toxicity
- similar to cyclosporine
- inc risk of diabetes and neurotoxicity
- no gingival hyperplasia or hirsutism
Sirolimus (Rapamycin)–mechanism
- mTOR inhibitor
- binds FKBP
- blocks T cell activation and B cell differentiation by preventing response to IL-2
Sirolimus (Rapamycin)–use
- kidney tranplant rejection prophylaxis
- drug eluting stents
Sirolimus (Rapamycin)–toxicity
- “PanSirtopenia”–pancytopenia
- insulin resistance
- hyperlipidemia
-
not nephrotoxic
- “kidney sir-vives”
what is sirolimus (rapamycin) synergistic with?
cyclosporine
Daclizumab, basiliximab–mechanism
- monoclonal antibodies
- block IL-2R
Daclizumab, basiliximab–use
- kidney transplant rejection prophylaxis
Daclizumab, basiliximab–toxicity
- edema
- hypertension
- tremor
azathioprine–mechanism
- antimetabolite precursor of 6-mercaptopurine
- “pronounce ‘azathiopurine’“
- inhibits lymphocyte proliferation by blocking nucleotide synthesis
azathioprine–use
- transplant rejection prophylaxis
- rheumatoid arthritis
- Crohn disease
- glomerulonephritis
- other autoimmune conditions
azathioprine–toxicity
- leukopenia
- anemia
- thrombocytopenia
what degrades 6-MP?
xanthine oxidase
what increases the toxicity of azathioprine?
allopurinol
mycophenolate mofetil–mechanism
- reversibly inhibits IMP dehydrogenase
- prevents purine synthesis of B and T cells
mycophenolate mofetil–use
- transplant rejection prophylaxis
- lupus nephritis
mycophenolate mofetil–toxicity
- GI upset
- pancytopenia
- hypertension
- hyperglycemia
- less nephrotoxic and neurotoxic
what is mycophenolate mofetil associated with?
- invasive CMV infection
corticosteroids–mechanism
- inhibit NF-kappaB
- suppress both B and T cell function by decrease transcriptionof many cytokines
- induce apoptosis of T lymphocytes
corticosteroids–use
- transplant rejection prophylaxis
- many autoimmune and inflammatory disorders
corticosteroids–toxicity
- hyperglycemia
- osteoporosis
- central obesity
- muscle breakdown
- psychosis
- acne
- hypertension
- cataracts
- avascular necrosis (femoral head)
what can result due to taking corticosteroids?
iatrogenic Cushing syndrome
what is the clinical use of Aldesleukin (IL-2)?
- renal cell carcinoma
- metastatic melanoma
what is the clinical use of epoetin alfa (erythropoietin)?
- anemias (especially in renal failure)
what is the clinical use of filgrastim (G-CSF)?
- recovery of bone marrow
what is the clinical use of sargramostim (GM-CSF)?
- recovery of bone marrow
what is the clinical use of IFN-alpha?
- chronic hepatitis B and C
- Kaposi sarcoma
- malignant melanoma
what is the clinical use of IFN beta?
- multiple sclerosis
what is the clinical use of IFN gamma?
- chronic granulomatous disease
what is the romiplostim, eltrombopag (thrombopoietin receptor agonists)?
- thrombocytopenia
what is the oprelvekin (IL-11)?
- thrombocytopenia
name the therapeutic antibodies for cancer therapy
- alemtuzumab
- bevacizumab
- cetuximab
- rituximab
- trastuzumab
alemtuzumab–target
- CD52
alemtuzumab–use
- CLL
- “Alymtuzumab”–chronic lymphocytic leukemia
- MS
bevacizumab–target
- VEGF
bevacizumab–use
- colorectal cancer
- renal cell carcinoma
cetuximab–target
- EGFR
cetuximab–use
- stage IV colorectal cancer
- head and neck cancer
rituximab–target
- CD20
rituximab–use
- B cell non Hodgkin lymphoma
- CLL
- rheumatoid arthritis
- ITP
trastuzumab–target
- HER2/neu
- HER2–“tras2zumab”
trastuzumab–use
- breast cancer
name the therapeutic antibodies for autoimmune disease therapy
- adalimumab, certolizumab, infliximab
- eculizumab
- natalizumab
adalimumab, certolizumab, infliximab–target
- soluble TNF alpha
adalimumab, certolizumab, infliximab–use
- IBD
- rheumatoid arthritis
- ankylosing spondylitis
- psoriasis
etanercept–type of drug
- decoy TNF alpha receptor
- not a monoclonal antibody
eculizumab–target
- complement protein C5
eculizumab–use
- paroxysmal nocturnal hemoglobinuria
natalizumab–target
- alpha 4 integrin
- WBC adhesion
natalizumab–use
- multiple sclerosis
- Crohn dz
what are patients with JC virus at risk of if given natalizumab?
- PML
abciximab–target
- platelet glycoprotein IIb/IIIa
- “IIb times IIIa equals ‘absiximab’”
abciximab–use
- antiplatelet agent for prevention of ischemic complication in patients undergoing percutaneous coronary intervention
denosumab–target
- RANKL
- denosumab affects osteoclasts
denosumab–use
- osteoporosis
- inhibits osteoclast maturation
- mimics osteoprotegerin
digoxin immune Fab–target
- digoxin
digoxin immune Fab–use
- antidote for digoxin toxicity
omalizumab–target
- IgE
omalizumab–use
- allergic asthma
- prevents IgE binding to FcERI
palivizumab–target
- RSV F protein
palivizumab–use
- RSV prophylaxis for high risk infants
- “palivizumab–virus”
ranibizumab, bevacizumab–target
- VEGF
ranibizumab, bevacizumab–use
- neovascular age related macular degeneration
