Exam 4 Flashcards
List 7 learning objectives for Hematopoietic Stem Cell Transplantation (7)
- Describe purposes of stem cell transplant
- Understand myeloablative vs. nonmyeloablative
- characteristics of chemo in conditioning
- explain role of immunosuppressants
- describe appropriate monitoring plan for patient on immunosuppressants
- describe the supportive care measures used in stem cell transplant patients
- create a treatment plan for a patient with acute graft versus host disease
List 1 granulocyte colony stimulating factor (G-CSF) and three (3) side effects
Filgrastim (1) bone pain (2) n/v (3) infusion-related
List 1 granulocyte-macrophage colony stimulating factor (GM-CSF) and seven (7) side effects
Sargramostim (1) n/v (2) diarrhea (3) fever (4) skin reaction (5) infusion-related reaction (6) hypertension (7) edema
List 1 CXCR4 chemokine inhibitor and 3 (3) side effects
Plerixafor (1) nausea (2) diarrhea (3) injection site reaction
List three (3) components of conditioning regimens
(1) chemotherapy; myeloablative or non (2) total body irradiation (3) immunosuppressants
List six (6) chemodrugs used in conditioning regimens
(1) busulfan (2) melphalan (3) thiotepa (4) carmustine (5) cyclophosphamide (6) cytarabine (7) etoposide (8) fludarabine (9)
List four (4) drug interactions and three (3) dose-limiting toxicites with Busulfan
DI through glutathione competition (a) acetaminophen (b) metronidazole (c) azole antifungals (d) phenytoin
TOX (1) mucositis (2) hepatotoxicity (3) seizures
How to manage busulfan hepatotoxicity?
- veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS)
- prophylax with ursodiol 300 mg PO q8hr
- PK monitoring
How to manage busulfan seizure toxicity?
- seizure prophylaxis with (a) phenytoin (b) benzodiazepines (c) levetiracetam
List drug interactions and dose-limiting toxicity with melphalan?
DI: none
TOX: mucositis, manage w/ 60-min cryotherapy
List drug interactions and two (2) dose-limiting toxicity with thiotepa?
DI: CYP2B6 inhibitor, give cyclophosphamide first.
TOX: mucositis, neurotoxicity (supportive care only)
List 1 drug interaction of carmustine and three (3) dose-limiting toxicity
DI: alcohol diluent so avoid dilsulfiram-drugs
TOX: hepatotoxicity, pulmonary toxicity (predisone 1 mg/kg/day), alcohol intoxication.
List three (3) drug interaction of cyclophosphamide and three (3) dose-limiting toxicity
DI: (a) CYP2B6 (b) 2C9 (c) 3A4
TOX: (1) hemorrhagic cystitis (2) cardiotoxicity (3) hepatotoxicity
List drug interactions with cytarabine and dose-limiting toxicity
DI: None
TOX: (1) neurotoxicity, uncommon at low dose.
List two (2) drug interactions with etoposide and two dose-limiting toxicities
DI: (1) CYP3A4 inducers (2) CYP3A4 inhibitors
TOX: (1) mucositis (2) hypotension during infusion
List drug interaction with fludarabine and dose-limiting toxicity
DI: none
TOX: neurotoxicity
List five (5) immunosuppressants used in bone marrow transplant
- methotrexate
- tacrolimus
- cyclosporine
- mycophenolate mofetil
- sirolimus
List three (3) side effects of methotrexate
- mucositis
- myelosuppression
- does NOT require alkalinization or leucovorin
List 1 DI and four TOX of tacrolimus
DI: CYP3A4 inhibitors or inducers (azole antifungals reduce dose by 50%)
tox: (1) hyperkalemia, hypomagnesemia (2) tremor (3) headache (4) renal dysfunction
List 1 DI and five TOX of cyclosporine
DI: CYP3A4 inhibitors or inducers
TOX: (1) hypertension (2) gingival hyperplasia (3) liver dysfunction (4) renal dysfunction (5) neurotoxicity
List 1 DI and 3 TOX of mycophenolate
DI: none
TOX: (1) myelosuppressive (2) nausea (3) diarrhea
List 1 DI and four TOX of sirolimus
DI: none
TOX: (1) GI upset (2) arthralgia (3) headache (4) renal dysfunction
List three (3) immunosuppressants with TDM and their goal trough levels
- cyclosproine (150-350 nanogram/mL)
- tacrolimus (5-15 ng/mL)
- sirolimus (3-18 ng/mL)
List four prevention medications and their purpose
- Cipro or Zosyn or cefepime (prevention of bacterial infection)
- Voriconazole or Fluconazole (prevention of fungal infections)
- Acyclovir or valacyclovir (prevention of HSV infections)
- Bactrim DS (prevention of PCP infections)
List three (3) agents used in induction therapy
- Antithymocyte globulin
- Basiliximab
- Alemtuzumab
List two (2) calcineurin inhibitors
- cyclosporine
2. tacrolimus
List two (2) antiproliferatives
- azathioprine
2. mycophenolate
List two (2) m-TOR inhibitors
- sirolimus
2. everolimus
List two (2) other immunosuppressants used in solid organ transplant
- corticosteroids
2. belatacept
List 3 aspects of thymoglobulin induction management
- premedicate with acetaminophen/diphenhydramine for infusion-related reaction
- monitor leukopenia and thrombocytopenia and dose adjust
- CMV infection possible
List 3 aspects of basiliximab management
- MOA: IL-2 receptor antagonist
- monitor CBC
- very well tolerated, pain at site of administration
- no reported DDIs
List 4 aspects of alemtuzumab management
- MOA: recombinant DNA-derived monoclonal antibody that binds to CD52
- rapid and extensive lymphocyte depletion
- premedication with acetaminophen/diphenhydramine for infusion
- high incidence of adverse events
List 5 aspects of cyclosporine management
- brand names not AB rated (non-modified requiers food, variable absorption; modified has consistent exposure)
- MOA: binds to cyclophilin which inhibits calcineurin phosphatases, reducing t-cell activation
- goal trough 50-400 ng/mL
- metabolized by CYP3A4 and p-Gp inhibitor
- monitor drug levels, CBC, electrolytes, BP, LFTs, pregnancy
List 5 aspects of tacrolimus management
- Brand names (prograf 2 divided doses, advagraf 1 daily)
- MOA: binds to FK-binding protein which inhibits calcineurin phosphatases
- goal trough 5-15 ng/mL
- avoid IV if possible because contains castor oil w/ anaphylaxis and nephrotox risk
- CYP3A4 substrate
- monitor drug levels, CBC, electrolytes, BP, LFTs, pregnancy
List most common dose-limiting tox for tacrolimus and cyclosporin
TAC: alopecia, diabetes, hand tremor, dysesthesias, headache, insomnia
CSA: HTN, hyperlipidemia, gingival hyperplasia, hirsutism
List five (5) aspects of azathioprine management
- MOA: prodrug for 6-mercaptopurine which is antimetabolite
- dose reduction in renal failure
- monitor for signs of myelosuppression, CBC, BBW for lymphoma, pregnancy cat D.
- leukopenia, thrombocyteopenia, hepatotoxicity
- drug interactions: allopurinol & febuxostat; 6-mercaptopurine (avoid or dose decrease; ACE inhibitor (anemia and leukopenia); warfarin (increase warfarin dose)
List four (4) aspects of mycophenolic acid management
- MOA: reversible inhibitor of inosine monophosphatate dehydrogenase, antiproliferative
- monitoring: CBC, especially WBC (reduce if WBC<4), pregnancy cat D, no routine TDM.
- side effects: (1) diarrhea (2) n/v (3) neutropenia (4) anemia (5) hypertension
- interactions: (1) aluminum and Mg containing antacids (separate by 2 hr before and after); PPI (cellcept > myfortic); cholesytramine decreases absorption (separate by 2 hours before and after)
List four (4) aspects of sirolimus management
- MOA: mTOR inhibitor, prevents progression from G1 to S phase)
- can substitute for CNI or substitute for azathioprine/MPA derivative
- metabolism: CYP3A4, PgP, half-life 62 hours
- monitoring: hepatic function (dose adjust by decrease 1/3 in dysfunction), lipid panel, electrolytes, urinalysis, pregnancy cat C.
- side effects: delayed wound healing (do not give within 30-90 days of surgery), leukopenia, thrombocytopenia, hyperlipidemia
List four (4) aspects of everolimus management
- MOA: mTOR inhibitor
- trough concentration 3-8 ng/mL
- same ADR as sirolimus
- monitor CBC, complete liver panel, lipid panel, blood glucose, pregnancy cat C.
List five (5) aspects of belatacept management
- MOA: inhibit signal 2 by antagonizing CD80 and CD86 on antigen presenting cells
- first long term IV maintenance immunosuppressive based on ABW
- contraindicated in EBV seronegative patients (increased risk of lymphoproliferative disorder)
- monitor prengancy cat C, serum creatinine, EBV status
- potential option for stable transplant patients in steroid-sparing or CNI-sparing regimens
- side effects fever, neutropenia, leukopenia, GI, cough, infection
List three categories of complications in post-solid organ transplant
- malignancy (PTLD)
- infection (BK virus, CMV, PCJ)
- Chronic disease (osteoporosis, hypertension, hyperlipidemia, diabetes)
How to manage BK virus in PSOT?
1st line: decrease immunosuppression
2nd line: leflunomide vs cidofavir
How to manage CMV in PSOT?
- Low risk: no prophylaxis.
- Intermediate risk: valgancyclovir 450-900 mg x3 months.
- high risk: valganciclovir 450-900 mg po QD x 6 months
How to manage PCJ in PSOT?
- Prophylaxis x 6 months with Bactrim, Dapsone, pentamidine or Atovaquone
Three (3) aspects of hypertension management in PSOT
- short-acting agents (clonidine, labetalol, hydralazine) to avoid hypotension
- ACE/ARB - additive hyperkalemia with CNIs, increased SCr, decreasesd GFR
- Nondihydropyridine CCBs - inhibit CYP450 resulting in elevated CNI levels
Two (2) aspects of hyperlipidemia in PSOT
- Statin recommended for adult kidney tx patients
- Statin-cyclosporine drug interactions (avoid simvastatin, lovastatin, atorvastatin, pitavastatin), USE 20 mg pravastatin, 20 mg fluvastatin, 5 mg rosuvastatin.
