Immunosuppressants

Question 0

Tacrolimus

Answer 0

Immunosuppressants
-Calcineurin inhibitor
Therapeutic
-human and stem cell transplantation
-prophylaxis rejection solid-organ therapy
-prophylactic agent GVH (graft vs. host)
MOA
-bind to FKBP->inhibit calcineurin, blocks T-cell activation
ADE
-*neurotoxicity
-*hyperglycemia/kalemia
-*GI complaints
-nephrotoxicity, HTN

Question 1

Cyclosporine

Answer 1

Immunosuppressants
-Calcineurin Inhibitor
Therapeutic
-human organ transplantation
-graft-versus-host (GVH)
-auto-immune disorder
MOA
-bind to cyclophilin->inhibit calcineurin, blocks T-cell activation
ADE
-*Neurotoxicity
-*hyperglycemia, kalemia
-**hirsutism
-*seizures
-HTN, liver dysfx, altered mental status

Question 2

Sirolimus

Answer 2

Immunosuppressants
-Proliferation signal inhibitor
Therapeutic
-*prevent rejection of solid organ allografts
-*steroid-refractory acute and chronic *GVH hematopoietic stem cell transplant recipients (pt don't like corticosteroids)
-dermatalogic disorders
MOA
-bind to FK506-P12->inhibit mTOR
-also binds FKBP
ADE
-*myelosuppression
-*diarrhea
-*hypertriglyceridemia (INC fat in blood)
-hepatotoxicity, pneumonitits, HA

Question 3

Mycophenolate Mofetil (MMF)

Answer 3

Immunosuppressants
Therapeutic
-solid organ transplant (refractory rejection)
-first-line prevent/reduce chronic allograft vasculopathy in cardiac trans pts
-prevent/treat GVH in hematopoietic stem cell pts
MOA
-prodrug (mycophenolic acid)
-inhibits de novo synthesis of purines
-inhibits T & B-lymphocyte response
ADE
-*GI disturbances
-*HTN
-*reversible myelosuppression
-HA

Question 4

Azathioprine

Answer 4

Immunosuppression
-Cytotoxic agent
-antimetabolite - prodrug of mercaptopurine
Therapeutic
-renal allografts
-transplantation of other tissues
MOA
-interfere w/ purine nucleic acid metabolism
-destruction of stimulated lymphoid cells proliferation
ADE
-*skin rashes
-*GI effects (V/N/D)
-bone marrow suppression (leukopenia)
-fever

Question 5

Ganciclovir (CGV)

Valganciclovir (VGC)

Answer 5

Immunosuppressant
-antiviral for CMV
-VGC oral more bioavailable than GCV
Therapeutic
-drug of choice for CMV infx and prevention (transplant setting)
-CMV retinitis in AIDS pts
MOA
-inhibit viral DNA polymerase
-(must be tri-phophorylated, must be activated by enzyme)
ADE
-myelosuppression

Question 6

Foscarnet

Answer 6

Immunosuppresant
-antiviral for CMV
Therapeutic
-GCV - resistant CMV in AIDS pts w/ retinitis
-GCV - resistant transplant recipients
-GCV intolerant
-in addition to GCV for CMV retinitis
MOA
-inhibit viral DNA polymerase and RNA polymerase
-*w/out activation (compared to GCV)
ADE
-impaired renal fx
-hypo/hypercalcemia
-hypomagnesemia
-hypo/hyperphosphatemia
-hypokalemia

Question 7

Cidofovir

Answer 7

Immunosuppressant
-antiviral for CMV
-must be used w/ oral probenecid
Therapeutic
-CMV retinitis in pts w/ AIDS
-previous antiviral therapy failures
MOA
-inhibit viral DNA polymerase and DNA synthesis
-diphosphate independent of viral enzymes
-(doesn’t rely on viral kinases to get it to activate diphosphate form)
-(very effective for tx viruses altered in some way)
ADE
-does-dependent tubular nephrotoxicity
-fanconic-type syndrome - proteinuria, glucosuria, bicarb wasting
Contraindications
-proteinurea (2+ or greater)
-*baseline creatinine > 1.5 mg/dL
-caution in pregnant women

Question 8

Brincidofovir

Answer 8

Immunosuppressant

• CDV prodrug
• its lipid-linked derivative is used to treat Ebola