Pharm Final Lecture 8

Front 1

prednisone

Back 1

Glucocorticoid (immunosup-pressive agents) Converted to prednisolone; Interferes with cell cycle of activated lymphoid cells. Inhibits production and chemotaxis of proinflam. mediators (leukotrienes, prostaglandins, histamine, bradykinin) -- -- Prolonged use: adrenal suppression (body decreases normal corticoid production)

Beware of withdrawal (joint pain, fever, malaise, etc.); gradual removal of drug.

Front 2

cyclosporine

Back 2

Fat soluble peptide antibiotic (Immunosup-pressive agents) Binds to cyclophilin and the complex inhibits calcineurin (calcineurin is essential for activation of T cell transcription factor, NF-AT, which helps make IL-2) -- Prevent rejection after transplant. -- Note: the initial binding of cyclophilin blocks protein modification for cell division, maturation of cell surface receptors, transcription factors, etc.
SYNERGISTIC w/SIROLIMUS.

Front 3

tacrolimus

Back 3

Macrolide antibiotic (immunosup-pressive agents) Similar to cyclosporine, but complex is with an immunophilin, FKBP. Same inhibition of calcineurin and
NF-AT. -- Prevent rejection after transplant. Nephrotoxic 100x more potent than cyclosporine.

Front 4

sirolimus

Back 4

An immunosup-ressive agent. Forms a complex with FKBP, inhibits mTOR (so that cell-cycle DOES NOT progress from G1 to S phase. inhibition of lymphocyte PROLIFERATION (limited numbers) -- -- -- SYNERGISTIC with CYCLOSPORINE.

Less nephrotoxic than tacrolimus.

Front 5

interferon a and b

Back 5

An immunosup-pressive agent Inhibit cell proliferation and activate NK cells. -- α and β:
Melanoma
Renal cell carcinoma
CML
α (+ ribovirin):
Hep B
Hep C
β:
Multiple sclerosis

Front 6

azathioprine

Back 6

Antimetabolite (immunosup-pressive agent) Inhibits DE NOVO purine synthesis; so inhibition of nucleic acid production and lymphoid cell proliferation. -- Used for graft survival, but has largely been replaced by mycophenolate mofetil d/t less side effects. Toxic effect: myeloid suppression. Derivative of mercaptopurine.

Front 7

mycophenolate mofetil

Back 7

Immunosuppres-sive agent Hydrolyzed in the GI tract to mycophenolic acid; Take home point: “inhibits purine synthesis” -- Increased efficacy in prolonging graft survival (replacing azathioprine) -- Similar to 6-MP in that it deprives lymphocytes of key parts of nucleic acids.

Used in a combo with prednisone when others aren’t tolerated (cyclosporine, tacrolimus, etc)

Front 8

Rh0 (D) antibody (anti-D ab)

Back 8

Immunosuppres-sive agent -- -- Hemolytic disease of the newborn -- Key: administered to mom w/in 72 hours of delivery of Rh+; mom doesn’t mount a B cell attack, so no memory B cells are formed.

Front 9

trastuzumab

Back 9

Recomb. Human mAb Binds epidermal growth factor receptor, HER-2/neu; leads to downregulation of receptor. -- Breast cancer (with the HER-2/neu receptor)

Front 10

rituximab

Back 10

Murine-human mAb Binds CD20 on normal and malignant B cells; activates complement-mediated lysis, ADCC, and apoptosis. -- Follicular B cell non-Hodgkin’s lymphoma

Front 11

daclizumab

Back 11

Human mAb Binds CD25 (alpha subunit of the IL-2 receptor); fxns as a IL-2 antagonist and suppresses lymphocyte activation. -- Organ transplant (in conjunction w/glucocorticoids and cyclosporine) -- Graft protection is usually a combo therapy.

Front 12

basiliximab

Back 12

Human mAb Binds CD25 (alpha subunit of the IL-2 receptor); fxns as a IL-2 antagonist and suppresses lymphocyte activation. -- Organ transplant (in conjunction w/glucocorticoids and cyclosporine) -- Graft protection is usually a combo therapy.
same as daclizumab but with high affinity

Front 13

palivuzumab

Back 13

mAb Binds the fusion protein of RSV; prevents infection of the cell. -- Neonates at risk for RSV (prophylaxis in suspected exposure)

Front 14

abatacept

Back 14

Immunosuppres-sive agent Selective co-stimulation modulator; binds CD80 and CD86 (on APC) and blocks interaction with CD28 (on T cell); Basically, the T cell can’t see it, so there’s no activation of an immune response. -- Rheumatoid arthritis -- NEW drug