• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/39

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

39 Cards in this Set

  • Front
  • Back
  • 3rd side (hint)
Site of action of glucocorticoids
Glucocorticoid response elements in DNA (regulate gene transcription)
Site of action of Muromondab-CD3
T-cell receptor comlex (blocks antigen recognition)
Site of action of Cyclosporine
Calcineurin (inhibits phosphatase activity)
Site of action of Tacrolimus
Calcineurin (inhibits phosphatase activity)
Site of Action of Azathioprine
DNA (false nucleotide incorporation)
Site of action of Mycophenolate Mofetil
Inosine monophosphate DH (inhibits activity)
Site of action of Daclizumab and Basiliximab
IL-2 receptor (block IL-2-mediated T-cell activation)
Site of action of Sirolimus
Protein kinase involved in cell-cycle progression (mTOR) (inhibits activity)
Azathioprine, methotrexate, cyclophosphamide, rapamycin, corticosteroids, mycophenolic acid function
interferes with proliferation and differentiation
ATG, OKT3, anti-CD4, cyclosporine and tacrolimus function
interferes with expression of IL-2 and other cytokines, then proliferation and differentiation
Corticosteroids function
interferes with stimulation of IL-1, then expression of IL-2 and other cytokines, then proliferation and differentiation
Rh (D) immune globuline function
interferes with antigen recognition, then stimulation of IL-1, then expression of IL-2 and other cytokines, then proliferation and differentiation
Examples of corticosteroids. Differences.
Prednisone
Methylprednisolone
Dexamethosone
Prednisone carbonyl reduced to (-OH) with added (-CH3). Dexamethasone displaced (-CH3) and added (-F)
MOA of glucocorticoid receptor (GR)
glucocorticoid steroid enter cells and interact with the GR to change the GR conformation, induce GR nuclear translocation, and activate gene transcription. S and GR separate from HSP70 and HSP90 and enter nucleus.
Corticosteroids (effect on lymphocytes) (4)
1. Reduce the number of circulating lymphocytes
2. Suppress proliferation of lymphocytes.
3. Decrease thymic mass.
4. Interfere with cell cycle of lymphocytes.
Corticosteroids (effect on inflammatory response) (4)
1. Reduce the phagocytic and cytotoxic ability of macrophages and neutrophils.
2. Reduce chemotaxis.
3. Reduce macrophage production of IL-1
4. Synthesize lipocortins (annexins) - inhibit PLA2 - PAF, PGs, and LTs
Corticosteroids (other effects) (3)
1. Diminish expression of MHC Class II molecules in APCs
2. Stabilize lysosomal membranes
3. Diminish levels of inducible form of COX-II
Corticosteroids (major adverse effects) (7)
1. Infections
2. Salt and water retention (hypertension, edema, electrolyte disturbances
3. peptic ulcer
4. adrenal suppression
5. hyperglycemia
6. steroid psychosis
7. Long term AEs: (Cushingoid changes, osteoporosis, cataracts, glaucoma)
Cyclosporine (characteristics)
fat soluble cyclic polypeptide of 11 aa's
SandImmune (non-modified)
Neoral and Gengral (modified lipid ME)
Cyclosporine MOA
binds to specific immunophilin (cyclophilin) which interferes with gene transcription of IL-2 and INF-gamma
Cyclosporine (effects) (2)
1. inhibits activation and proliferation of immunocompetent celss, esp. TH1 cells
2. inhibits gene transcription of cytokines (IL-2, IL-3, INF-gamma)
What metabolizes cyclosporine?
CYP3A enzymes
Also CYP3A-metabolized are:
HIV protease inhibitors, anticonvulsants, azole antifungals, macrolides, grapefruit juice, etc...
Cyclosporine (indications) (4)
1. allogeneic transplants (kidney, liver, heart)
2. RA
3. psoriasis
4. "dry eye syndrome" (Restasis)
Unlabeled:
1. autoimmune and graft-vs.-host dz's
2. aplastic anemia
3. resistant leukemia
Cyclosporine (major AE's) (8) (3)
1. infections
2. cancer
3. nephrotoxicity
4. HTN
5. hepatic toxicity
6. anaphylactic rxn's
7. hyperglycemia
8. hyperliidemia
Similar to Corticosteroids:
1. infections
2. hypertension
3. hyperglycemia
Tacrolimus (characteristics)
1. macrolide
2. terminal t 1/2 about 12 hrs in liver transplant pt.'s and 21 hrs for normal pt.
Prograf
Protopic
Tacrolimus (MOA)
binds to a specific immunophilin -> decrease transcription for IL-2 and INF-gamma
FK binding protein-12 (FKBP-12) - immunophilin
What metabolizes Tacrolimus?
CYP3A enzymes
Tacrolimus (indications) (2) (3)
1. rejection prophylaxis of allogenic liver, kidney, and heart transplants
2. atopic dermatitis (Protopic)
unlabeled:
1.autoimmune and graft-vs.-host dz's (GVHD)
2. RA
3. Crohn's dz
Tacrolimus (major AEs) (6) (4)
1. infections
2. cancer
3. nephrotoxicity
4. hyperkalemia
5. hyperglycemia
6. neurotoxicity (tremor, HA, seizures, coma, delirium)
Similarities
1. infections (CCs)
2. cancer (cyclosporine)
3. nephrotoxicity (cyclosporine)
4. hyperglycemia
Pimecrolimus (characterisitics) (4)
1. macrolide immunosuppressant
2. don't use in immunocompromised pt.'s
3. after 6 weeks, reexamine
4. apply thin layer BID
Elidel
Pimecrolimus (MOA)
binds with FKBP-12 and inhibit calcineurin activity
Sirolimus (characteristics)
macrolide immunosuppressant
Rapamune
Pimecrolimus (actions) (2)
1. prevents mast cell degranulation
2. block transcription of IL-2 and IFN-gamma
Sirolimus (MOA) (5)
1. binds to FKBP-12
2. NO effect on calcineurin
3. inhibit mTOR (key regulatory kinase)
4. inhibit G1 to S phase of T-cell proliferation
5. blocks lymphocyte activation and proliferaiton *after* IL-2
Sirolimus (indications) (2) (1)
1. renal transplants (conjunction w/ glucocoritcoids)
2. coronary stents (Cypher)
unlabeled:
1. psoriasis
What metabolizes sirolimus? (1) (2)
CYP3A enzymes
Same as:
1. cyclosporine
2. tacrolimus
Sirolimus (major AEs) (12) (4)
1. infections
2. hepatic artery thrombosis, graft loss, excess mortality (liver)
3. bronchial anastomotic dehiscence (lungs)
4. cancer
5. nephrotoxicity
6. cholesterol and TGs rise
7. anemia
8. leukopenia
9. thrombocytopenia
10. hypokalemia
11. fever
12. diarrhea
Similarities:
1. infections
2. cancer
3. nephrotoxicity
4. hypokalemia
Everolimus (characteristics) (1) (2)
1. macrolide immunosuppressant
1. Novartis (Xience and Afinitor)
2. Macolides:
tacrolimus, pimecrolimus, sirolimus
Everolimus (MOA) (2)
1, binds to FKBP (like tacrolimus)
2. inhibits mTOR (like sirolimus)