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40 Cards in this Set

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What is the definition of induction therapy?
high level of immunosuppressive therapy administered perioperatively
What are the classes of induction agents?
1)polyclonal antibodies
2)monoclonal antibodies
MOA of equine antithymocyte globulin (Atgam) and rabbit antithymocyte globulin (thymoglobulin)
1)antibodies directed against T and B cells
2)induce lymphocyte depletion, complement-mediated lysis, and induction of apoptosis
What is the dosing schedule for polyclonal antibodies?
7-14days
Adverse effects of the polyclonal antibodies
1)dose limiting myelosuppression
2)anaphylaxis
3)hypotension
4)tachycardia
5)dyspnea
6)urticaria
7)rash
8)fever
9)serum sickness (rare)
Monitoring for polyclonal antibodies
1)test dose
2)CBC
3)dose adjustments
What are the 3 monoclonal antibodies used for organ transplatation?
1)OKT3 (mAB)
2)daclizumab (humanized mAB)
3)basiliximab (chimeric mAB)
OKT3 MOA
1)binds to cell surface receptors (CD3) of T cells
2)inhibits T cell activation
-> leading to depletion
daclizumab and basiliximab MOA
1)bind to alpha chain on surface of activated T-lymphocytes
2)prevents IL-2 mediated activation and proliferation of T-cells
Which of the monoclonal antibodies for organ transplantation are immunogenic?
OKT3
OKT3 pharmacokinetics
If CD3 lymphocytes levels rise, may signify presence of anti-murine antibodies
daclizumab pharmacokinetics
saturates IL-2 receptors for 90-120days
basiliximab pharmacokinetics
saturates IL-2 receptors for 36days
OKT3 side effects
1)1st dose rxns include CYTOKINE RELEASE SYNDROME (mild flu-like symptoms -> life threatening shock) PREMEDICATE w/ APAP, steroids, diphenhydramine
2)pulmonary edema
3)infections
daclizumab and basiliximab sid effects
well tolerated
What classes of agents are used for maintenance immunosuppression?
1)Calcineurin inhibitors
2)Antiproliferative agents
3)Corticosteroids
4)Sirolimus
What are 2 calcineurin inhibitors?
1)cyclosporine (CSA)
2)tacrolimus (Prograf)
What is calcineurin responsible for?
gene transcription in the DNA and production of key cytokines for T-cell activity (including IL-2)
cyclosporine MOA
1)binds to cyclophilin
2)inhibits action of calcineurin
tacrolimus MOA
1)binds to FKBP-12
2)inhibits calcineurin activity
cyclosporine adverse effects
1)nephrotoxicity
2)neurotoxicity (tremors, SZR)
3)HTN
4)hyperlipidemia
5)GINGIVAL HYPERPLASIA
6)HIRSUTISM
7)impaired glucose tolerance
8)hyperkalemia
9)hypomagnesemia
9)infection
10)malignancy
tacrolimus adverse effects
1)less HTN than CSA
2)less hyperlipidemia than CSA
3)more neurotoxicity than CSA
4)more glucose intolerance
5)ALOPECIA
Drug interactions of calcineurin inhibitors
CYP3A4 inhibitors
1)CCBs
2)Azoles
3)macrolides (not zithromax)
4)amiodarone, ritonavir, grapefruit juice

CYP3A4 inducers
1)rifampin
2)carbamazepine
3)phenytoin
What are 2 antiproliferative agents used in organ transplations?
1)azathioprine (Imuran)
2)mycophenolate
azathioprine MOA
1)metabolized to 6-MP and ultimately 6-TIMP
2)incorporated into cellular DNA
3)inhibits purine synthesis (both de novo and salvage pathways)
4)inhibits lymphocyte proliferation
mycophenolate MOA
1)noncompetitively binds to inosine momophosphate dehydrogenase (key enzyme in de novo purine synthesis)
2)inhibits lymphocyte proliferation
This antiproliferative agent undergoes enterohepatic cycling
mycophenolate
azathioprine adverse effects
1)myelosuppression
2)malignancy
3)infection
4)ANEMIA
5)HEPATOTOXICITY
6)PANCREATITIS
7)ALOPECIA
8)GI adverse effects
mycophenolate adverse effects
1)myelosuppression
2)GASTRITIS/GI HEMORRHAGE
3)N/V/D
4)ABDOMINAL PAIN
5)infection
6)malignancy
Cyclosporin drug interactions
1)allopurinol (decrease dose by up to 75%)
2)bone marrow suppressing agents (ganciclovir and sirolimus)
mycophenolate drug interactions
1)MAGNESIUM AND ALUMINUM PRODUCTS
2)cholestyramine
3)bone marrow suppressing agents (ganiclovir and sirolimus)
Corticosteroids MOA
1)antiinflammatory (inhibit leukotriene and prostaglandin production)
2)immunosuppressive effects (impairment of transcription rate and expression of cytokines including IL-2; inhibit macrophage activity)
Corticosteroid toxicity
1)insomnia
2)steroid psychosis
3)osteoporosis
4)impaired wound healing
5)LEUKOCYTOSIS
6)pancreatitis
7)peptic ulcer
8)HTN
Sirolimus (Rapamune) MOA
1)binds to FKBP-12 and engages regulatory protein called target of rapamycin
2)reduces cytokine dependent cellular proliferation at G1 to S phase of cell division
3)inhibits T cell proliferation by inhibiting the cellular response to IL-2 and progression of cell cycle
sirolimus drug interactions
metabolized by cytochrome p450 3A4 (same as azothiprine and tacrolimus)
sirolimus toxicity
1)dose dependent thrombocytopenia
2)leukopenia
3)hypertriglyceridema
4)hypercholesterolemia
Induction therapy regimen
1)high-dose maintenance immunosuppression
2)administration of an induction agent
Maintenance therapy regimen
Triple-drug immunosuppression
1)calcineurin inhibitor
2)antiproliferative agent
3)corticosteroids
What is a tacrolimus or CSA fre regimen?
1)Rapamune is usually the primary immunosuppression
2)reduced nephrotoxicity
3)higher incidence of acute rejection
Management of acute rejection
1)high dose steroids
2)administration of an induction agent