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142 Cards in this Set
- Front
- Back
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What type of transplant donor has the higher rate of survival?
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Living transplant donors.
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Name the cellular components of the innate immune system.
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NK cells
Dendritic Macrophages Neutrophils |
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Name the molecular component of the innate immune system.
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complement
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Name the cellular components of the adaptive immune system.
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B-cells
CD4+ CD8+ |
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Namr the molecular components of the adaptive immune system,
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antibodies
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Which part of the immune system is "non-specific, and immediate"?
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innate
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Which part of the immune system is "specific, and delayed"?
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adaptive
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What is the purpose of the innate immune system?
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1. identify and engluf pathogens.
2. recruit other immune cells 3. activate the adapative immune system. |
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What is the purpose of the adaptive immune system?
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1. provide targeted response for a specific pathogen.
2. enhance b-cell and macrophage actions. |
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What are the antigen presenting cells?
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b-cells
macrophages dendritic cells |
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T/F
MHC is polymorphic. |
True
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How many MHC classes are there? Which classes are pertinent to transplantation?
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I, II, III
only I and II** |
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What are the alleles for MHC class I?
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A, B, C
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Where can MHC I be found?
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on all nucleated cells....including APC's.
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MHC I is produced from _________ peptides.
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endogenous
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What specific T-cell binds to MHC I?
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CD8+ ( cytotoxic)
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What are the alleles for MHC II?
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DP, DQ, DR
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Where can MHC II be found?
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all APC's
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MHC II are produced from ________ peptides.
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exogenous
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What specic T-cell binds to MHC II?
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CD4+ ( helper)
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Describe the afferent adaptive immune system.
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1. APC engulfs antigen
2. antigen internalized and bound to MHC II. 3. MHC II + Antigen complex expressed on cell surface. |
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Describe the efferent adaptive immune system.
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1. APC binds to T-cell
2. T-cell produces IL-2--- stimulates T-cell activation & proliferation. 3. T-cell secretes cytokines to enhance B-cell and Macrophages response to pathogen. |
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Which cells contribute to Humoral Rejection?
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B-cells
antibodies complement platelets coagulation factors |
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Which cells contribute to Cellular rejection?
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T-cells
APC's cytokines adhesion molecules NK cells |
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__________ rejection is described as having pre-existing antibodies.
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Hyperacute
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_________ rejection occurs when antibodies form against donor organ AFTER transplant.
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Acute
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List 4 things that increase the risk for hyperacute rejection.
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1. blood transfusion
2. previous transplant 3. pregnancy 4. vaccination |
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Time frame of hyperacute rejection.
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within 24 hours
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Hyperacute rejection mechanism..
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1. Humoral ( antibody mediated)
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What are some signs of hyperacute rejection?
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hemmorage
graft enlargement necrosis |
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How can you prevent hyperacute rejection?
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1. blood type matchin
2. cross match |
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Time fram of Acute rejection.
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1- 90 days after transplant
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Is acute rejection reversible? if so, with what?
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yes. with immunosuppression.
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Acute rejection mechanism.
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cellular***
humoral |
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What are the signs of an acute rejection?
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pain
fever swelling decreased organ function increase in SCr > 30% baseline |
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Prevention of acute rejection
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adherance to maintenace suppression.
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Time frame of chronic rejection.
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months- years after transplant.
(slow and insidious) |
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Is chronic rejection reversible? If so, with what?
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No.
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What is the rejection mechanism for chronic rejection?
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cellular and humoral
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what are the signs of chronic rejection?
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slow loss of graft function.
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How can you prevent chronic rejection?
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1. prevent acute rejection
2. prevent comorbidities |
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MOA of _____________.
inhibition of transcription of genes for inflammation. |
Corticosteroids.
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Corticosteroids are produced by ________.
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adrenal cortex
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List 3 physiological functions of corticosteroids.
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1. carb, lipid, protein metabolism.
2. fluid/electrolyte balance 3. preservation of organ function |
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_____________ are gene expression inhibitors.
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corticosteroids.
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_________ are used to BLOCK first-dose cytokine storm.
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corticosteroids,
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T/F
Corticosteroids work instantly. |
F
there is a delay |
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used to limit allergic reactions to other immunosuppressants
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corticosteroids.
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Used to for autoimmune disorders.
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corticosteroids.
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name 2 CNI's.
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Tacrolimus
Cyclosporine |
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Which CNI was isolated from a fungus?
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Cyclopsporine.
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Which CNI is isolated from a bacteria?
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tacrolimus
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T/F
Tacrolimus is more potent than cyclosporine. |
True
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________ binds to cyclophilin to inhibit calcineurin.
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cyclopsporine
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_________ binds to FKBd to inhibit calcineurin.
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tacrolimus
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List 2 Proliferation signal inhibitors.
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1. sirolimus
2. everolimus. |
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Which PSI is isolated from a bacteria?
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sirolimus
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MOA of______________.
binds to FKBP-12 to inactivare mTOR which inhibits cell proliferation. |
PSI's.
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Therapeutic uses for lymphocyte signaling inhibitors.
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1. transplants
2. r. arthritis. 3. psoraisis ( tacrolimus) |
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T/F
An initial does of a lymphocyte siganling inhibitor should be given prior to transplant. |
False.
Nephrotoxicity |
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List common toxicites seen with CNI's and PSI;s.
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nephrotoxicity*****
tremors HTN hiruitism hyperlipidemia gum hyperplasia |
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__________ are effective immunosuppressants but vary in efficacy and toxicity from batch to batch.
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Polyclonal antibody products
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_________ are consistent is efficacy and toxicity from batch to batch, but are limited by specificity.
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Monoclonal antibody products.
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Name 2 sub-classes of lymphocyte depleteing agents
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polyclonal and monoclonal
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this polyclonal antibody is made from rabbits, and is often used in induction therapy.
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rATG
rabbit anti-thymocyte globulin |
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Why is the rATG use limited?
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very broad,targets all t-cells.
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When using__________, you must pre-medicate with APAP, benadryl, and a steroid.
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rATG
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Which drug causes a first-dose cytokine storm>
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rATG
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T/F
there have been no drug interactions reported for rATG. |
True
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Name 2 monoclonal antibody products.
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1. Alemtuzumab
2. Basiliximab |
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MOA of___________.
Binds to CD52 on many cells. |
Alemtuzumab
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___________ is primarily used for cancer. It's off-label use is for immunosuppression.
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Alemtuzumab
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_________ may cause neutropenia, anemia, and thrombocytopenia.
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Alemtuzumab
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MOA of___________.
binds to CD25 on activated T-cells stimulated by MHC antigens. |
basiliximab.
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T/F
Basiliximab had less toxicity than Alemtuzmab. |
True
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Cytotoxic agents can be used as immunosuppresants and __________.
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antineoplastics ( anti-cancer)
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Name 2 classes of cytotoxic agents.
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1. Antimetabolites-- interefere with nautral metabolit paths
2. Alkylating agents-- conjugate alkyl groups to DNA |
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Name 2 commonly used cytotoxic agents.
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1. AZA
2. MPA |
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T/F
AZA is a prodrug. |
True
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Uses of AZA
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1. IBS
2. adjuct for transplant 3. r. arthritis |
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Anti-metabolite form of AZA.
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6-thoiguanine
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T/F
There is a major DDI between AZA and allopurinol. |
true
** if both used, should decrease AZA dose to 25% of orginal dose. |
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MOA for ____________.
inhibits IMPDH. leads to T-cell death. |
MPA
also AZA. |
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T/F
MPA has good oral bioavailbity. |
False.
must be given as prodrug -MMF or salt form MNa+ |
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what is the active form of AZA?
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6-MP
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T/F
You should reduce the dose of febuxostant to 25% of original dose when giving with AZA. |
False.
You should not give both together. Febuxostant in much more potent than allopurinol. AZA AND FEB. NOT TAKE TOGETHER. |
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Too much 6-MP can lead to ________.
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bone marrow suppression
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T/F
MPA is unstable at gastric pH. |
True.
Must use enteric coated salt or prodrug. |
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MPA has a DDI with _______.
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probenacid.
MPA + probenacid = increase of MPA |
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What enzymes convert Cellcept to its active form?
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hepatic esterases
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MPA uses ___________ for renal elimination.
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OAT;s
probenacid is an OAT inhibitor. |
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cyclopsporine bioavalibilty is dependent on what 3 factors?
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1. bile
2. PGP 3. CYP3A4 |
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cyclosporing is dependent on ______for absorption.
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bile secretions
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T/F
cyclosporine is made up of cyclic peptides and nautral amino acids. |
False.
Cyclic peptides - yes but made of UN-natural amino acids which is why there is an increase in GI stability. |
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T/F
cyclopsporine modified is dependent on bile secretions. |
False
it is a microemulsion. |
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cyclosporine can increase the levels of __________ by inhibiting OATs in the liver.
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statins
** increase risk for rhabdomylosis. |
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T/F
tacrolimus is a macrolide |
true
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Ca++, Mg++, and Al++ can form chelates with _________, decreasing absorption.
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Tacrolimus.
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T/F
Tacrolimus is a PGP substrate. |
True
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T/F
tacrolimus absorption is NOT dependent on bile. |
True
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T/F
sirolimus is a macrolide. |
true
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T/F
sirolimus is more potent than everolimus. |
False
Everolimus is more potent. It has better binding capabilities, and more hydrophilic bc of an extra chain, and hydroxyl group. |
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What 3 disease states cause ESRD?
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Diabetes
HTN Glomerolophritis |
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T/F
Native kidneys are usually removed in transplant patients. |
False..
Typically left inside. |
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What are the 3 goals of immunosuppression?
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1. prevent rejection
2. maintain organ function 3. minimize drug toxicity. |
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what 3 drug classes usually make up the "triple therapy' for maintenance ?
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corticosteroids
anti-proliferative cni's +/- mTOR inhibitors |
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T/F
Most renal transplant patients die from renal failure. |
False.
They die from comorbidities. |
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Typical corticosteroid dosing for transplantation.
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High around transplants. taper down.
Do not stop abruptly. |
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What counseling tip should you give to a patient that is taking antiproliferatives and is nauseated?
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take with food
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T/F
you should adjust CNI's doses according to peak levels. |
False.
you should adjust doses according to TROUGH levels. |
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What should be the level of Tacrolimus 1-3 months into transplant?
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8-12 ng/ml
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What should be the level of Tacrolimus 4-12 months into transplant?
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5-10 ng/mL
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Your should never administer CNI's with_________.
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NSAIDS
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T/F
mTOR inhibitors drug levels should be monitored. |
True
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What I.S. drugs affect the CNS?
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CNI's
tremors, headache, insomnia, seizures CCS mood swings insomnia |
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What I.S. drugs cause Nausea and Diarrhea?
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MPA- take with food
CNI's -take with food |
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What I.S. drug causes hirsutism?
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cyclosporine
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What I.S. drug can cause gingivial hyperplasia?
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cyclosporine
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What I.S. drug can cause alopecia?
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Tacrolimus
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What I.S drug can cause skin thinning?
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corticosteroids.
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What I.S. drugs can delay wound healing?
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mTOR inhibitors
Corticosteroids |
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Which I.S. drugs can cause ulcers?
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sirolimus- mouth ulcers
corticosteroids - GI ulcers (give PPI) |
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Which I.S. drug can cause hyperkalemia and hypomagnesemia?
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tacrolimus
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Which I.S. drugs can cause DMII?
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CNI's
CCS |
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Which I.S. drugs can cause HTN?
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CNI's
CCS |
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Which I.S. drugs can cause hyperlipidemia?
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cyclosporine
sirolimus |
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How do CNI's cause nephrotoxicity?
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cause vasospasms in afferent arterioles.
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What 4 3A4 inhibitors can increase CNI levels?
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antifungals
macrolide antibiotics Ca channel blockers grapefruit |
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T/F
CNI's can act as 3A4 inhibitors. |
True
** can increase levels of statins |
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List 5 3A4 inducers that decrease the levels of CNI's.
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rifampin
st johns wart carmazepine phenytoin phenobarbital |
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T/F
With maintenance immunosuppression, infections are found later, more severe, and are more difficult tor treat. |
True
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Time frame for nosocomial infections
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day 0-1 month
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how can you prevent nosocomial infections?
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antimicrobial and antiviral prophylaxsis.
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where do patients aquire nosocomial infections?
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in the hospital---related to surgery typically.
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Describe a "Latent infection"
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time: 1-6 months
infection: typically viral prevention/treat: antibiotics and antivirals. |
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Time fram of a "community aquired infection"
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> 6months after transplant
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What are the RECPIENT risk factors for acute rejection?
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1. African American- metabolize TAC faster
2. PRA > 20% 3. HLA mismatch 4. young age- immune system very active |
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What are the DONOR risk factors for DGF?
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1. increased age
2. expanded criteria donor 3. cadaveric donor |
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rATG advantages
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1. depletes target cells w/i 24 hours
2. delays start of CNI's 3. decrease acute rejection 4. lymphopenia for a year |
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rATG disadvantages
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1. lymphopenia for a year
2. increased risk for infections and malignancies 3. thrombocytopenia 4. cytokine storm |
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if acute rejection is considered " less severe" what drug therapy should you use?
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high-pulse steroids
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if acute rejection is considered " more severe" what drug therapy should you use?
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rATG
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