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38 Cards in this Set
- Front
- Back
Which anti-cancer drugs are immunsupressive at low doses?
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Cyclophosphamide
Methotrexate Vincristine |
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Calcineurin Inhibitors
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Cyclosporine
Tacrolimus Pimecrolimus |
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Cyclosporine (Sandimmune) MA
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(-) activation and proliferation of CD4+ and CD8+ cells
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Which intracellular protein does Cyclosporine bind to?
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Cyclophilin
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What is the result of the Cyclosporine-Cyclophilin complex?
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Inhibition of Calcineurin--blocks translocation of transciption factor NF-ATc
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Why do you need NF-ATc?
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To make IL-2
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How do you administer Cyclosporin?
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Vehicle containing EtOH and oil, either i.v. or capsule
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1/2 life of Cyclosporine
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6 hours
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Metabolism of Cyclosporine
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Liver (CYP3A4)
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Because Cyclosporine is CYP3A4 mediated, what drugs will decrease it activity
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Phenytoin (anti-seizure)
Phenobarbital (anti-epilep) Any P-450 inducers |
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What drugs will decrease Cyclosporine excretion
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Erythromycin
Ketoconazole Amphotericin B St. John's Wart |
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Toxicity of Cyclosporine
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Nephro, Neuro, Hypertension, hirsutism, hyperlipidemia, gigival hyperplasia
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Tacrolimus vs. Cyclosporine
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50-100X more potent but LESS nephrotoxicity, shorter half life
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Use Tacrolimus
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Prevention of transplant rejection and atopic dermatitis
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MA of Tacrolimus
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Binds cytoplasmic protein (FKBP-12), complex (-) Calcineurin
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Adminstration of Tacrolimus
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Shorter half-life so 3 day loading of i.v. then orally 2X/day
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Toxicity of Tacrolimus
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Nephrotoxicity, neurotoxicity, GI distress, hyperglycemia, (-) of pancreatic B-cell fxn
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Use of Pimecrolimus and MA
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Atopic dermatitis
Also binds FKBP-12--inhibits calcineurin |
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Sirolimus (Rapamycin)
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Regulates cytokine response used to prevent rejection in renal transplant
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Other use of Sirolimus
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Prevention of neointimal proliferation and restensosis after stent placement in coranary arteries
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MA of Sirolimus
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Binds FKBP-12 BUT complex inhibits PI kinase related protein kinase mTOR
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Why do you need mTOR?
Mammalian Target Of Rapamycin |
Modulate intracellar signaling pathways for genes involved in cell proliferation - no T or B cell proliferation
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Metabolism of Rapamycin
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CYP3A4
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Everolimus
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Sirolimus analogue, more predictable oral absorption
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Toxcities of Sirolimus (Rapamycin)
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Anemia, thrombocytopenia, hyperlipidemia, post-surgical lymphocoele
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Contraindication for Rapamycin
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After liver transplantation
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Mycophenolate mofetil
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Prodrug metabolized to mycophenolic acid (MPA)
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Use of Mycophenolate mofetil
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In combo with cyclosporin or tacrolimus or in those w/calcineurin-inhibitor toxicity
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Metabolism of Mycophenolate mofetil
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Liver esterases
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MA of MPA
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Inhibition of inosine monophosphate dehydrogenase--no de novo purine synthesis
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How does defective de novo purine synthesis impair immunity
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T and B cells rely on de novo syn. for their source of purines rather than HPRT salvage
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HPRT
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hypoxanthine guanine phosphoribosyl transferase
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Use of Mycophenolate mofetil
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After renal or heart transplant
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Don't do this when using Mycophenolate mofetil
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Do admin with antacids with Mg or Al-- decreased absorption.
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Toxicity of of Mycophenolate mofetil
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leukopenia and diarrhea
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Leflunomide
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prodrug-- active metabolite (-) dihydroorotate dehydrogenase-- no pyrimidine biosynthesis
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Thalidomide (no their not kidding) Use
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Treatment of Erythema nodosum leprosum in patients w/ graft-vs.-host dz
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Toxicity of Thalidomide
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Peripheral neuropathy and NEVER GIVE TO PREGNANT WOMEN--IT'S A TERATOGEN
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