Immunosuppressants Flashcards
Sirolimus is synergistic with ___ and is also used in ___.
Cyclosporine
Drug-eluting stents
Mechanism: Epoetin alfa
Recombinant EPO
Other uses: Corticosteroids
Many autoimmune and inflammatory disorders
Adrenal insufficiency
Asthma
CLL
Non-hodgkin lymphoma
Toxicity: Mycophenolate mofetil
GI upset
Pancytopenia
Hypertension
Hyperglycemia
Less nephrotoxic and neurotoxic
Clinical use: IFN-beta
Multiple sclerosis
6-MP (azathioprine) degraded by ___; increased toxicity by ___
Xanthine oxidase
Allopurinol and febuxostat
Mechanism: Mycophenolate mofetil
Reversibly inhibits IMP dehydrogenase → inhibiting purine synthesis of B and T cells
Other use: Cyclosporine
Psoriasis
RA
Clinical use: Oprelvekin
Thrombocytopenia
Clinical use: IFN-gamma
Chronic granulomatous disease
Clinical use: Aldesleukin
Renal cell carcinoma
Metastatic melanoma
Mechanism: Sirolimus (rapamycin)
Binds FKBP → inhibits mTOR
Blocks T-cell activation and B-cell differentiation by preventing response to IL-2 (blocks G1→S)
Toxicity: Azathioprine
Myelosuppression → pancytopenia
Hepatotoxicity
GI distress
Other uses: Basiliximab
Kidney transplant rejection prophylaxis specifically
Mechanism: Azathioprine
Purine (thiol) analog → decreases de novo purine synthesis
Activated by HGPRT
Metabolized into 6-MP
Mechanism: Eltrombopag
Thrombopoetin receptor agonist
Toxicity: Corticosteroids
Cushing syndrome-like effects:
Osteoporosis
Hyperglycemia
Diabetes
Amenorrhea
Adrenocortical atrophy
Peptic ulcers
Psychosis
Cataracts
Avascular necrosis (femoral head)
Mechanism: Sargramostim
Recombinant GM-CSF
Mechanism: Oprelvekin
Recombinant IL-11
Clinical use: Romiplostim
Thrombocytopenia
Clinical use: IFN-alpha
Chronic hepatitis B and C
Kaposia sarcoma
Malignant melanoma
Hairy cell leukemia
Condyloma acuminata
Renal cell carcinoma
Mechanism: Basiliximab
Monoclonal antibody → blocks IL-2R
Clinical use: Epoetin alfa
Anemias (especially in renal failure)
Mechanism: Tacrolimus
Binds FK506 binding protein (FKBP) → inhibits calcineurin
Blocks T-cell activation by preventing IL-2 transcription
Mechanism: Cyclosporine
Binds cyclophilin → inhibits calcineurin
Blocks T-cell activation by preventing IL-2 transcription
Clinical use: Filgrastim
Recovery of BM and WBC counts by granulocyte stimulation
Clinical use: Eltrombopag
Thrombocytopenia
Mechanism: Corticosteroids
Inhibit NF-kB
Suppress both B- and T-cell function by decreasing transcription of many cytokines
Induce T-cell apoptosis
Toxicity: Basiliximab
Edema
Hypertension
Tremor
Toxicity: Sirolimus
Pancytopenia
Insulin resistance
Hyperlipidemia
NOT nephrotoxic
Use of ___ causes demargination of WBCs, which causes artificial leukocytosis. ___ may develop if drug is stopped abruptly after chronic use.
Corticosteroids
Adrenal insufficiency
Mechanism: Aldesleukin
Recombinant IL-2
Mechanism: Romiplostim
Thrombopoetin analog
Toxicity: Tacrolimus
Similar to cyclosporine, but with increased risk for:
Diabetes (hyperglycemia)
Neurotoxicity
NO:
Gingival hyperplasia
Hirsutism
Other use: Sirolimus
Kidney transplant rejection prophylaxis specifically
Other uses: Azathioprine
RA
Crohn disease
Glomerulonephritis
Other autoimmune conditions
Toxicity: Cyclosporine
Nephrotoxicity
Gingival hyperplasia
Hirsutism
Hypertension
Hyperlipidemia
Neurotoxicity
Mycophenolate mofetil is associated with ___
Invasive CMV infection
Other uses: Mycophenolate mofetil
Lupus nephritis
Mechanism: Filgrastim
Recombinant G-CSF