Final Exam - Arora Transplant Flashcards
Rabbit antithymocyte globulin (Thymoglobulin) works by what MOA
lymphocyte depletion
this reduces the number of circulating T-lymphocytes which can alter T-cell activation by inhibiting CD3
Rabbit antithymocyte globulin (Thymoglobulin) AE
-leukopenia, thrombocytopenia (dose limiting/dose adjust)
-fever, chills (pre-medicate with Benadryl and APAP)
Alemtuzumab (Campath-1H) antibody-dependent cellular cytotoxicity
profound depletion of T cells
-lymphodepleting like thymoglobulin
Alemtuzumab (Campath-1H) AE
infusion related: chills, rigor, fever
-pre-medicate with Benadryl and APAP
Basiliximab (Simulect) is lymphodepleting or no?
not lymphodepleting
-no effect on B and T cells because it is the IL-2alpha receptor antagonist
-inhibits activation of T and B cell lymphocytes at IL-2 receptor
-specifically targets CD25
which of the induction therapies is/are lymphdepleting?
Thymoglobulin and Alemtuzumab
which of the induction therapies are monoclonal?
alemtuzumab and basiliximab
-(mab)
possible induction agent options
-Rabbit antithymocyte globulin (Thymoglobulin)
-Alemtuzumab (Campath-1H)
-Basiliximab (Simulect)
possible maintenance agent options
calcineurin inhibitors
-cyclosporine
-tacrolimus
antimetabolites
-azathioprine
-mycophenolate mofetil
-mycophenolate sodium
mTOR inhibitors (mammalian target of rapamycin)
-sirolimus
-everolimus
corticosteroids
-methyprednisolone
-prednisone
-dexamethasone
T-cell Co-stimulation blocker
-belatacept
best class of maintenance options
calcineurin inhibitors
-‘cornerstone’ of immunosuppression, most widely used in organ transplant
For cyclosporine there is a non-modified form (Sandimmune) and a modified form (Neoral or Gengraf). Can you use these interchagnably? Why or why not?
You cannot because the modified ones have increased bioavailability and AUC
Tacrolimus (FK) forms and benefits for the better one
immediate release: Prograf
extended release: Astagraf XL, Envarsus XR
-potential benefits to ER dosing: lower overall dose. improved adherence, less peak effects = reduced ADE, less swings/variability in trough concentrations
Is conversion from po to IV and SL 1:1 dosing for tacrolimus?
no
-different going from IR to ER to IV to SL
calcineurin inhibitors (CNIs) elimination considerations
cyclosporine has variable t1/2: 10-40 hours
calcineurin inhibitors (CNIs) metabolized by what pathway?
cyclosporine: CYP450 and p-gycoprotein
-3A4 and p-glycoprotein inhibitors = increase conc.
tacrolimus: CYP450
-3A4 inhibitors = increase conc. (preferred agent)
cyclosproine AE
HTN (~50%)
hypercholesterolemia
hypetryglyceridemia
gingival hyperplasia (2-16%)
hirsutism (21-45%)
tacrolimus AE
HA (64%)
insomnia (64%)
tremor (56%)
dizziness (19%)
hyperglycemia, post transplant diabetes mellitus (~20%)
alopecia
AE of both cyclosporine and tacrolimus
nephrotox
HTN
electrolyte changes (increased K and decreased Mg)
neurotox (especially tremors)
do CYP450 inducers like phenytoin, carbamazepine, phenobarbital, and rifampin cause increase or decrease in CNI conc. and does this lead to more or less tox./effectiveness?
cause decrease in conc. of CNIs leading to less effectiveness and less AE
do CYP450 inhibitors like erythromycin, clarithromycin, azoles, diltiazem, verapamil, ritonavir, and grapefruit juice cause increase or decrease in CNI conc. and does this lead to more or less tox./effectiveness?
increase in conc. of CNIs leading to increased AE
Liver dysfunction shows what alterations in CNI PK?
tacrolimus t1/2 is increased
Renal dysfunction shows what alterations in CNI PK?
none
azathioprine (AZA) AE
GI: ab pain, N/V/D, dyspepsia (indigestion)
bone marrow suppression: agranulocytosis, macrocytic anemia, leukopenia, neutropenia, thrombocytopenia
antimetabolites target cells of high turnover, this is where AE are seen
azathioprine major DI
with allopurinol and febuxostat (xanthine oxidase inhibitors)
-reduce dose of aza by 50-75%
