DA4 Immunomodulation Part 1 UNFINISHED
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The 3 types of drugs used to modulate the immune response are...
- Tolerance inducers
What class of immunosuppressive drugs works by inhibiting gene expression?
What 3 immunosuppressants are cytotoxic agents?
- MPA (mycophenolic acid)
What 3 agents are specific lymphocyte-signaling inhibitors?
- CsA (cyclosporine A)
- mTOR inhibitors (sirolimus, everolimus)
What 3 classes of agents are immunosuppressive by their cytokine inhibition?
- TNF-alpha inhibitors
- IL-12 inhibitors
- IL-1 inhibitors
T/F Suppression of the immune system after organ transplant is specific and treatment lasts 2-4 weeks, also increases risks of infection and cancer
F is nonspecific, lifelong treatment
GC-receptor complexes increase ______ expression, thereby curtailing activation of ____, which increases apoptosis of
Which is not downregulated by glucocorticoids?
IL-1, IL-2, IL-3, IL-4, IL-6, TNFalpha
Decreased expression of ____ by glucocorticoids results in decreased proliferation and activation of T cells.
glucocorticoids are used to block first-dose _____ ______ caused by treatment with muromonab-CD3
What are some toxicities of glucocorticoids?
- hyperglycemia (diabetogenic)
- risk of infection
- growth retardation
combination of glucocorticoids and ______ allows for reduced doses of steroids
Azathioprine, a purine antimetabolite, is cleaved to _____ after nucleophile exposure, then converted to _____ by HGPRT, which inhibits IMPDH. It may also be converted to ______ which can cause DNA strand breaks
How is azathioprine and 6-MP metabolized
oxidation or methylation in the liver and/or erythrocytes
What are some toxicities associated with azathioprine?
- increased infections
What are the uses for azathioprine
- organ transplant rejection prevention
- severe RA
What is the MOA for methotrexate
- DHFR inhibitor
- Neu adhesion inhibitor
- causes apoptosis of activated CD4 and CD8
Azathiprione dose must be decreased while used concurrently with ______ because of an interaction
What is the MOA of mycophenolate mofetil (MMF)?
hydrolyzed to active drug mycophenolic acid (MPA), inhibits IMPDH (type 2), which inhibits guanosine formation, then inhibiting B and T lymphocyte proliferation
T/F Plasma concentrations of MPA and MPAG are decreased in patients on MMF with renal insufficiency
F -- increased
What is MMFs therapeutic use
prophylaxis of transplant rejection
What are some toxicities associated with MMF
- GI/hematologic toxicities
- increased infections (sepsis from cytomegalovirus)
- Viral infections when combined with tacrolimus (polyoma nephritis)
_____ delays elimination of MMF by impairing the conversion of MPA to MPAG. This may enhance GI toxicity.
These 2 antivirals compete with MPAG for tubular secretion, resulting in increased concentrations of both, especially in those with renal insufficiency
acyclovir and ganciclovir
What is the MOA for cyclosporine A?
binds cyclophilin which blocks calcineurin, which blocks dephosphorylation of NFAT, blocking expression of IL-2 and T-cell growth
What is the MOA for tacrolimus
binds FKBP-12 which blocks calcineurin, which blocks dephosphorylation of NFAT, blocking expression of IL-2 and T-cell growth
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