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;
84 Cards in this Set
- Front
- Back
What are the 6 Rejection Risk Stratifications? |
Donor Source |
|
What is a Panel Reactive Antibody? Who is performed on and what does it measure?
|
Panel Reactive Antibody (PRA) is a blood test that is routinely performed on patients waiting for kidney and and measures anti-human antibodies in the blood.
|
|
What does the PRA represent?
|
The PRA represents the percentage of the U.S. population that the anti-human antibody in your blood reacts with.
|
|
What scores are good PRA?
What scores are bad? |
High PRA not good
Low PRA is good |
|
What are the 3 types of rejections?
|
Hyperacute
Acute Chronic |
|
What kind of onset is the:
Onset? Cause? Prevention? For hyperacute? |
Onset: Instant
Cause: Preformed antibodies Prevention: Blood typing |
|
What kind of onset is the:
Onset? Cause? Prevention? For acute |
Onset: Days or more
Cause: T-Cells; Cytokines Prevention: Immunosuppressive Medication |
|
What kind of onset is the:
Onset? Cause? Prevention? For chronic |
Onset: Months or more
Cause: (?) B-Cells; Endothelium Prevention: (?) Prevent acute rejection |
|
What are the three immunosuppressove strategies?
|
Induction
Maintenance Rejection |
|
2 Calcineurin Inhibitors
|
Tacrolimus
Cyclosporine |
|
2 steroids
|
Methyprednisolone
Prednisone |
|
1 Monoclonal Antibodies
|
Basiliximab
|
|
3 antimetabolites
|
Mycophenolate mofetil
Mycophenolic acid Azathioprine |
|
2 mTOR Inhibitors
|
Sirolimus
Everolimus |
|
What are 6 goals of Immunosuppression in solid organ transplant (SOT)
|
1.To prevent allograft rejection
2.To prolong allograft functional life 3.To optimize allograft function 4.Prolong patient survival 5.Improve patient quality of life 6.To minimize toxicity of IMS agents non-immune toxicities Immunodeficiency complications |
|
What is the MOA of Thymoglobulin?
|
Polyclonal Antibody
Antibody against human T-cells Depletion of peripheral blood lymphocytes |
|
What are the uses for Thymoglobulin?
|
Induction
Treatment of steroid resistant rejection |
|
What is the dosing for Thymoglobulin?
|
1.5mg/kg IV over 4-6 hrs
(2-14 doses) induction vs rejection Central or Peripheral Line Premedicate |
|
What are the AEs of Thymoglobulin?
|
Infusion related reactions
Serum sickness Thrombocytopenia Leukopenia Anaphylaxis Infections/PTLD |
|
What is the brand name of basiliximab?
|
Simulect
|
|
Simulect (basiliximab) MOA?
|
Monoclonal Antibody
Block CD25 (IL-2 receptor) on activated T cell Blocks the normal physiologic cascade of events initiated by IL-2 |
|
What are the uses of Simulect (basiliximab)?
|
Induction
|
|
What is the dosing of Simulect?
|
Simulect: 20mg IV over 30 minutes x2 on POD 0 and POD 4
No premedication |
|
Is Simulect as potent as thymoglobulin?
|
Less potent than Thymoglobulin.
|
|
What 2 drugs are responsible for Induction?
|
Thymoglobulin >> Basiliximab
|
|
When do you use basiliximab?
|
Low/moderate risk kidney recipients
Exposure to rabbits |
|
When is thymo used?
|
Moderate/high risk kidney recipients
|
|
What are brand names of cyclosporine?
|
Neoral, Gengraf, Sandimmune, CSA)
|
|
What are brand names of tacrolimus?
|
(Prograf, FK-506)
|
|
What are brand names and drug class Azathioprine
|
Imuran, AZA)
Antiproliferative Agents |
|
What are brand names and drug class
Mycophenolate Mofetil |
Cellcept, MMF)
Antiproliferative Agents |
|
What are brand names and drug class
Mycophenolic Acid |
Myfortic, MPA)
Antiproliferative Agents |
|
What are brand names and drug class Sirolimus
|
mTOR inhibitors
Rapamune, Rapamycin) |
|
What are brand names and drug class Everolimus
|
mTOR inhibitors
Zortress) |
|
What are brand names and drug class
Prednisone |
Deltasone)
Corticosteroids |
|
What are brand names and drug class
Methylprednisolone |
Solu-Medrol)
Corticosteroids |
|
Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) MOA?
|
Forms a complex with cyclophilin/FKBP
Complex binds/inhibits calcineurin phosphatase (CNP) CNP prevents NFAT from entering nucleus Inhibits IL-2 production Necessary for full T cell activation |
|
Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) Bioavailability?
|
Variable
Decreased by food |
|
What is the dosing for (CSA) Neoral/Sandimmune
What is the dosing for Prograf (tacrolimus, FK 506) |
CSA: generally ~2 to 4 mg/kg/dose BID
target trough 150-300ng/ml FK: generally ~0.05mg/kg/dose PO BID target trough ~5-12ng/ml. |
|
Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) metabolism?
|
Cytochrome P 450 3A4
P-Glycoprotein |
|
do you take Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) with or without food?
|
Without food –get stomach upset—TAKE WITH FOOD since dose based on trough levels.
|
|
What are the dose conversions for cyclosporine and how long do you infuse it for?
|
Cyclosporine PO:IV = ~3:1
Infuse over 2-4 h cyclosporine |
|
What are the dose conversions for tacrolimus and how long do you infuse it for?
|
PO:IV = ~4:1
24 h for tacrolimus |
|
What kind of formulation is Sandimmune?
What is Neoral? |
Sandimmune – Original formulation
Neoral – Microemulsion formulation |
|
What drugs are cyclosporine modified
Which are cyclospirine non-modifed? |
Neoral, Gengraf)
(Sandimmune) |
|
Neoral – Microemulsion formulation
Has decreased __ ___ Better correlation with wihat? LEss __ ___ absorption |
Decreased intra-patient variability
Better correlation with trough and AUC levels Less bile dependent absorption |
|
GenGraf – Generic Cyclosporine (modified) is which drugs bioequivlant?
|
Neoral
|
|
Sandimmune is __ ___ for absorption
|
bile dependent
|
|
What are cyclosporines AEs
|
Nephrotoxicity
Hypertension GI effects (N,V,D) Headache Electrolyte effects Tremors Hyperlipidemia Gingival hypertrophy HIrsutism |
|
What are Tacrolimus AEs
|
Nephrotoxicity
Hypertension GI effects (N,V,D) Headache Electrolyte effects Tremors and seizures Post transplant DM Hair loss |
|
Explain cyclosporins and tarcolimus electrolytes effect
|
Increased potassium and DECREASED Phos and Mg
Ginigival hypertrophy reversible if we switch to different drug. |
|
Grand mal seizures are more prevelant in which drug?
|
more prevalent with tacrolimus
|
|
Out of tacrolimus and cyclosporine which has cardiovascular effects and nephrotoxic effects?
|
more cardiovascular issues with cyclosporine than tacro but more neurotoxicity seen with tacro.
|
|
What drugs increase effects on concentrations with Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) because they inhibit cyp 3a4 metabolism?
|
Macrolides: Azithromycin does not effect
Erythromycin and Calrithromycin effects Azoles: Fluconazole and voriconazole effect them CCB: diltiazem and verapamil effect them Danazol, chloramphenicol, cimetidine and grape fruit juice effect them |
|
What drugs decrease effects in concentration with Neoral/Sandimmune (CSA) and Prograf (tacrolimus, FK 506) because they inhibit cyp 3a4 metabolism?
|
Anticonvulsants: Phenytoin, phenobarbital, carbamazepine
Rifampin Dexamethasone Prednisone St. John's Wort |
|
What does Cellcept (MMF) and Myfortic (MPA) prevent?
Compare there efficacy? MAJOR SIDE EFFECT? HOw many peaks to they get? How many peaks do they get with cyclosprine? |
Both prevent proliferaton of T-Cells
Efficacy and safety same in both Leukopenia major myelosuppressive side effect MMF and MPA secreted in bile, and bile is reabsorped therefore usually has two peaks, when given with cyclosporine may not get the second peak. |
|
What is the moa of Cellcept (MMF) and Myfortic (MPA)
|
MMF is a prodrug of MPA
Both reversiby inhibit inosine monophosphate dehydrogenase (IMPDH) Block de novo purine synthesis |
|
What is the dosing for MMF?
What is the dosing for MPA? |
MMF: 1gm PO BID
MPA: 720mg PO BID Do NOT break or crush |
|
What is a major SE for MMF and MPA?
|
Leukopenia major myelosuppressive side effect
|
|
What drug decreases AUC with MMF and and MPA?
|
Cyclosporine decreases AUC
|
|
What drug needs to be avoided giving with MMF or MPA?
|
Cholestyramine-avoid!
|
|
What OTC should be given seperately during admin when patient is on MMF and MPA?
|
Antacids-separate admin!
|
|
What kind of pts can you not use MMF and MPA?
|
Pregnancy because they are teratogenic
|
|
What is the prodrug of Imuran (azathioprine)?
|
Prodrug of 6-mercaptopurine
|
|
What is the MOA of Imuran?
|
6-MP is incorporated into DNA where it interferes with RNA synthesis
Blocks proliferation of T cells |
|
What is the dosing of Imuran?
|
~2mg/kg once daily
|
|
What are the AEs of Imuran?
|
Myelosuppression
Macrocytic anemia Pancreatitis Hepatotoxicity |
|
What drug interacts with Imuran?
|
Allopurinol
Decrease AZA dose by 1/3 to ½ per PI Contraindicated in practice! |
|
What is the MOA of Rapamune (sirolimus) andZortress (everolimus)?
|
Binds FKBP
Complex interacts with the target of rapamycin (TOR) Disrupts ability of IL-2 to trigger T cell division |
|
What is the dosing for Rapamune (sirolimus) andZortress (everolimus)?
|
Rapamune: 6mg load then 2 mg daily
Target trough~3-15 ng/ml Zortress: No load required, shorter half-life 1.5 to 3mg daily |
|
What kind of Metabolism does Rapamune (sirolimus) andZortress (everolimus) have?
|
cyp 3A4
Meaning anything that inhibits it is a DI |
|
What are Aes of Rapamune (sirolimus) andZortress (everolimus)
|
Impaired wound healing
Hyperlipidemia Myelosuppression GI effects (N,V,D) Mouth ulcers |
|
What is the MOA of High Dose > 100mg of prednisone equivalents
|
Directly toxic to T cells
|
|
What is the MOA of SteroidsMethylprednisolone and Prednisone Low Dose < 100mg of prednisone equivalents
|
Nonspecific immunosuppression: inhibits IL-1, IL-2, IL-3, IL-6, IL-15, TNF-alpha and INF-gamma
|
|
Methylprednisolone and Prednisone
High doses at induction and maintenance usually___ per day. |
5mg
Usually instituion specfic |
|
What are AEs of SteroidsMethylprednisolone and Prednisone
|
Decreased Growth Rate
Infections Osteoporosis Glucose Intolerance Acne Mood Alterations Weight Gain |
|
What is the 1st agent always used?
What is the 2nd agent often used? |
Use of 2 or 3 agents with different MOAs
Agent #1 is always CNI Agent #2 is often antimetabolite |
|
What drug class of drugs are the Back bone regimen?
|
CNI
Backbone of regimen: Tacro >CSA |
|
What drugs are great adjunctive agents?
|
Great adjunctive agents: MMF = MPA >AZA
|
|
When are mTor inhibitors avoided?
If patients can tolerate a statin shoul they been on sirolimus? |
Typically avoided first 3 months to allow wound healing
If pt cannot tolerate a statin, should not be on sirolimus/everolimus |
|
Infectious Prophylaxis for Kidney Tx Recipients at Maine Medical Center
For viral prophylaxis what drugs should be used? High risk? Mod risk? Low risk? |
High risk ( Donor +/Recipient-) Valganciclovir 450mg QD x 6 months
Mod risk (D+/R-) Valganciclovir 450mg Qd x 3 months Low risk (D-/R-) Acyclovir 400mg q8h x 3 months |
|
Infectious Prophylaxis for Kidney Tx Recipients at Maine Medical Center
PCP prophylaxis (i.e. Pneumocystis jiroveci)? |
Bactrim SS daily x 6 months
Alternatives: Pentamidine, Atovaquone |
|
Infectious Prophylaxis for Kidney Tx Recipients at Maine Medical Center
UTI prophylaxis? |
Bactrim SS daily
Alternatives: any FQ except for Avelox |
|
Infectious Prophylaxis for Kidney Tx Recipients at Maine Medical Center
Fungal prophylaxis? |
Clotrimazole troche 1 lozenge tid x 1 month.
|