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Immunosuppresants
n/a
51
Other
Post-Graduate
11/21/2011

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Cards

Term
How does treatment vary with different stages of chemo?
Definition

Induction: high dose combo or therapy

Consolidation: repetition of induction therapy during remission

Intensification: induction therapy at higher doses Maintenance: Long term, lower dose therapy during remission

Term
When are immunosuppressants used?
Definition
During organ transplantation
Diseases where inflammation is underlying cuase
Term
What is phase 1 activation of the mechanism of Immunosuppressants?
Definition
Block T cell surface receptor
Block Transmission of prolif signals from cell surface receptors to nucleus
Block transcription of pro-inflam mediators
Term
What is phase II activation of the mechanism of immunosuppressants?
Definition
Block prolif of already activated T cells
Term
When is Induction regimens of immunosuppressants done?
Definition
At the time of transplantation to prepare for it.
Term
What factors should be considered during induction immuno therapy?
Definition
MHC match
Prep of Organ
Hx of recipient
Term
Why isn't induction immuno therapy sustainable?
Definition
Relatively intense prolong-> toxicities
Term
What does Maintenance Immuno therapy generally consist of?
Definition
triple-drug therapy that work at different levels of the inflammation cascade
Lower does/potency
Term
When is rescue immuno therapy used?
Definition
in response to rejection episodes
Intense, high dose
Term
What drugs block presentation of Ag by APC to TCR and concurrent binding of costimulatory molecules?
Definition
alefacept
muromonab-CD3
Term
What drugs inhibit activation of calcineurin (a phosphatase)?
Definition
cyclosporine
tacrolimus
Term
What drugs block increased transcription of IL-2 gene?
Definition
corticosteroids
Term
What drugs blocks IL-2 binding to CD25 of activated T-cells?
Definition

daclizumab

 

Term
What drug inhibits mTOR activation?
Definition
sirolimus
Term
What drugs block regulation of cell cycle?
Definition

Mycophenolate mofetil

Azathioprine

Cyclophosphamide

Term
What are the immunosuppressant antibodies that bind to surface receptors?
Definition
Alemtuzumab
Muromonab-CD3
Term
Which immunosuppressant is an anti-CD52 Ab?
Definition
Alemtuzumab

(CD52 expressed on mature B and T cells, NK cells, monocytes, macrophages, platelets, and male reproductive tissues)
Term
What Antibody immuno has profound and long lasting lymphopenia that may require prophylaxis to prevent infections?
Definition
Alemtuzumab
Term
Which antibody immunos effects are reversible?
Definition
Muromonab-CD3
Term
Who should not recieve Muromonab-CD3?
Definition
pts who develope human-mouse Ab titers >1:1000 (will be ineffective)
Term
What are the Calcineurin Inhibitors?
Definition
cyclosporine
tacrolimus
Term
What is the mechanism of Calcineurin inhibitors?
(cyclosporine, tacrolimus)
Definition
inhibts phase I activation of T cell

Inhibits calcineurin-> NFAT no dephosphorylated-> NFAT cant translocate to nuleus-> no cytokine production
Term
What Calcineurin inhibitor is more potent in inhibiting T cell prolif?
Definition
Tacrolimus 100x more potent then cyclosporine
Term
What is the major toxicity for the calcineurin inhibitors?
Definition
Renal Toxicity
Term
What is the mechanism of corticosteroids?
Definition
Decrease number of circulation cells and inhibit cytokine production
Term
How do low doses of corticosteroids work in the nucleus?
Definition
decrease transcription of inflammatory mediators
Term
How do high doses of corticosteroids work in the nucleus?
Definition
increase transcription of ANTI-inflammatory gens
Term
What is the CD25 inhibitor?
Definition
daclizumab
Term
What is the mechanism of the CD25 inhibitors?
(declizumab)
Definition
block IL-2R expressed on surface of activated Tcells
Term
What adverse effects do the CD25 inhibitors have?
Definition
GI disorders
Severe Acute hypersensitivity rxns
Term
What is sirolimus?
Definition
mTOR inhbitor
Term
What phase of activation does sirolimus inhibit?
Definition
Second Phase
Binds FkBP12 but inhibits activation of rapamycin
Term
What is sirolimus synergistic with?
Definition
cyclosporine
Term
What is sirolimus effect on B cells?
Definition
prevents B cell differentiation into Ab producing cells
Term
What toxicity of sirolimus can be Fatal with chronic exposure?
Definition
hepatotoxicity
hepatic necrosis
Term
What are the cell cycle Disruptors?
Definition
Mycophenolate mofetil
Azathioprine
Cyclophosphamide
Methotrexate
Term
What cell cycle disruptor inhibits inosine monophosphate DH?
Definition
Mycophenolate mofetil

(->prevents guanosine production form inosine-> decre DNA syn-> stops cell cycle)
Term
What are the advantages of Mycophenolate mofetil?
Definition
Blocks secondary Ab response mediated by memory B cells
Selective effect on lymphocyte prolif
No chromosomal Breaks
Term
What cell cycle disruptor is used as a precursor to 6-MP?
Definition
Azathioprine
Term
If a patient has a variant TPMT genotype what happens when if they take Azathioprine?
Definition
normal dose-> increased toxicity
(not metabolized to less active metabolites)
Term
What drug can increase the toxicity of Azathioprine?
Definition
Allopurinol
Term
What tests need to be done before dosing of Azathioprine?
Definition
TPMT
preg test
CCBC
metabolic panel
Term
Which cell cycle disruptor is metabolically activated?
Definition
Cyclophosphamide
Term
Which cell cycle disruptor has a side effect of hemorrhagic cystitis?
Definition
Cyclophosphamide
Term
What is the dose limiting toxicity of cyclophosphamide?
Definition
Hematologic
Term
What metabolite of cyclophosphamide binds with MESNA?
Definition
acrolein
Term
What cell cycle disruptor inhibits DHFR?
Definition
Methotrexate
Term
At what phase does methotrexate inhibit the cell cycle?
Definition
S phase
Term
What is leucovorin used for after methotrexate treatment?
Definition
to re establish the cell cycle in other cells
Term
What is the Costimulator Blockers?
Definition
Abatacept
Term
What costimulator blockers is used to treat psoriasis?
Definition
Alefacept
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