Drugs used in Organ Transplantation Flashcards
Glucocorticoids MOA is…
suppress distribution and reactivity of lymphoid and myloid cells
catabolic actions at GRE
The main use of glucocorticoids is…
acute use when needed or early on, or in emergencies
Antithymocyte Globulin (ATG) and Antilymphocyte Globulin (ALG)
MOA- polyclonal suppression of thymocytes (T) or lymphocytes (T&B, NK cells)
The administration of what drugs allows early temporary withdrawal of all other drugs?
ATG and ALG
Muromonab-CD3 (OKT-3)
Is a MAB against the T- cell receptor
Alemtuzumab
human MAB against Cd52 on lymphocytes, monocytes, macrophages, NK
Prolonged T and B cell depletion
What drug is used in CLL?
Alemtuzumab
Daclizumab and Basiliximab
humanized and chimeric MABs against IL-2 receptor on T-cell
Daclizumab and Basiliximab are used more for…
acute renal rejections
Abatacept and Belatacept
Fusion of Fc of IgG1 and CTLA-4 –> binds to CD80/CD86 –> suppression of T-cell activation
Thalidomide
- stimulates and changes specificity of T-cells
- suppresses B-cells
- stimulates T-cells but in an immunomodulatory fashion
What are two calcineurin inhibitors?
Cyclosporine (CSA)
Tacrolimus (FK-506)
Calcineurin inhibitors…
block signal transduction activating t-cells
What does Cyclosporine bind to?
Cyclophilin
What does tacrolimus bind to?
FK-506BP12
What are the two antiproliferative agents?
Sirolimus (Rapamycin)
Everolimus
Sirolimus and Everolimus…
inhibit mTOR kinase activity –> prevents CDK2 phosphorylation –> blocks cell cycle progression in T-cells
Sirolimus and Everolimus have drug-drug interactions at what enzyme?
CYP450s
What antimetabolites are used for organ transplantation?
Mycophenolate Mofetil
Azathioprine
MMF
is a prodrug
What is MMF converted to in order to become active?
mycophenolic acid
What is the MOA of MMF?
inhibits T and B cell inosine monophosphate dehydrogenase in purine pathway for GMP synthesis
What is the active form of azathioprine?
6-MP
What is the MOA of 6-MP or AZA?
inhibits ATP and GTP synthesis
What recurrent symptom is seen with cyclosporine use?
gum hyperplasia in heart transplant patients
Lip hypertrophy is seen with cyclosporine (CsA) and is reversed with…
Tacrolimus (FK506 inhibitor)
Tacrolimus binds FK506 first and then binds and inhibits…
PP2B- phosphatase activity of calcineurin
What drug is associated with diabetogenesis when combined with glucocorticoids?
Tacrolimus
What is mTOR?
a serine/threonine protein kinase inhibited by sirolimus
What drugs prevent de novo purine synthesis which is important for B- and T- cells?
MMF
When combined with AZA, what drug needs to have a dose reduction due to inhibition of xanthine oxidase?
Allopurinol- used for hyperuricemia and crystalluria associated with cell death/gout therapy
