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32 Cards in this Set
- Front
- Back
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**What are the 3 major clinical uses of Immunosuppressive drugs?
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1. Organ transplant
2. Autoimmune disorders 3. isoimmune disorders (like HDN) |
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Corticosteroids (nonselective)
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-essential no toxic effect on proliferating myeloid and erythroid stem cells
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Corticosteroids (nonselective)
MOA*** |
-interfere w/ the cell cycle of act lymphoid cells--> lymphocytopenic
-disrupt IC communication btwn leukocytes, chemotax in monos -in monocytes they inhibit IL-1 production thus inhib IL-2 and INF-Y production |
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Corticosteroids (nonselective)
Indications: |
-Allograft rejection, asthma
-inflam conditions (SLE, IBS, acute GN) -autoimmune hemolytic anemia, ITP, Hashimotos thyroiditis |
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Corticosteroids (nonselective)
AEs |
-no toxic effect on prolif myeloid or erythroid cells
-serious viral, bact, fungal infx -hyperglycemia |
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Corticosteroids (nonselective)
***What do they do to Glucose uptake? |
-inhibit glucose uptake --> inc insulin--> inc lipogenesis --> dec lipolysis --> lipid deposits in hands and jts
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Cyclophosphamide (Cytoxan, Neosar)
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-alklyating agent
-causes Hemorrhagic cystitis (blood in urine --> acrolein toxicity) |
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Cyclosporine
MOA*** |
-suppresses CMI (sup 1st phase of T-Cell act that allows T cells to progress from Go to G1 phase)
-inhibs T-cell prolif by binding to CALCINEURIN - phosphatase enzyme that is req for T-cell act AND synth of IL, INF, etc**** |
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Corticosteroids (nonselective)
MOA cont'd*** |
-inhibs early stages of diff of T-cells and gene transcription of IL-2, IL-3, IFNy
Beauveria--> soil fungus? |
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Corticosteroids (nonselective)
Uses |
-successfully as sole immuno - suppressant in organ transplants such as kidney, liver and cardiac allogenic transplants
-GVH and HVG diseases -ureitis |
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Corticosteroids (nonselective)
Kinetics*** |
-orally or IV, not w/ grapefruit juice
-metab by hepatic CYP3A4 -***P-glycoprotein efflux and cytochrome P450 (CYP3A4) metab dec cyclosporin abs significantly |
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Corticosteroids (nonselective)
AEs*** |
-50% develop Dysarthria (difficulty to speak)
-[high] can activate TGF alpha--> tumor development (Kaposi sarcoma) -hyperglycemia, Osteoporosis, Hirsutisim, cholelithiasis -gingival hyperplasia, tremors |
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Tacrolimus (Prograf)
***Selective MOA*** |
-macrolide Abx by streptomyces
-sim mech to cyclosporine, binds to different immunophilin FKBP and inhibits Calcineurin -more potent than cyclosporine |
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Tacrolimus (Prograf)
***Selective Clinical Uses |
SOLE AGENT for preventing liver rejections
-also used in kidney rejections |
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Tacrolimus (Prograf)
***Selective AEs |
-hyperglycemia, GI dysfunction, nephrotoxic, neurotoxic like Cyclosporine
-NO HIRSUTISM and GINGIVAL HYPERPLASIA like cyclosporine |
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Mycophenolate Mofetil (Cellcept)
MOA*** |
-nonselective
-potent, reversible, uncompetitive inhibitor of Inosine Monophosphate DH--> blocking de novo synth of GMP |
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Mycophenolate Mofetil (Cellcept)
Use |
-rescue therapy in kidney/liver transplants (in combo w/ prednisone)
-reduces rejection renal allografts |
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Azathioprine (Imuran)
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-6-mercaptopurine (antineoplastic drug) derivative, cytotox, IMusupp
-kills the prolif of lymphoid cells by suppressing BM synth -specifically destroy stim lymphoids |
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Azathioprine (Imuran)
Uses |
-mantaining renal allografts
-RA, Gout, Chron's, MS |
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Leflunomide (Arava)
MOA |
-another cytotoxic pyrimidine synth inhibitor
-as M1, inhibs DHODH in the mito, which catalyzes a key step in de novo pyrimidine synthesis |
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Leflunomide
Uses and special note |
-for RA and decreases destruction of joints
-de novo: stims T-cells salvage: at rest |
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Heterologous
Anti-thymocyte Globulin (ATG) Anti-lymphocyte globulin (ALG, LIG) MOA*** |
-reduces the number of circulating T-lymphos which alters T-cell act, homing (process that kills organs; adhesion of T-cells to RBCs), and cytotoxic fxn--> all affect CMI AND HUMORAL!!
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Heterologous
Anti-thymocyte Globulin (ATG) Anti-lymphocyte globulin (ALG, LIG) Uses |
-IM or IV (1/2 life 3-9 days)
-prophylaxis -organ transplant -BM transplant |
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Basiliximab (Simulect)
Daclizumab (Zenapax) MOA*** |
-binds to and blocks the IL-2 receptor alpha chain receptor (IL-2Ralpha) AKA CD25 Ag
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Basiliximab (Simulect)
Daclizumab (Zenapax) Uses*** |
-orphan drug for prophylaxis of solid organ transplant rejection
-Admin IV -renal allograft rejection, decreases acute rejections |
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Pimecrolimus (ELIDEL)***
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-inhibs calcineurin
-prevent serious atopic dermatitis flares -long term use can eventually cause skin cancers |
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Glatiramer (Copaxone)
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-similar in structure to myelin basic protein
-if someone developed immunity against myelin, the T-cells will attack the drug instead of myelin -decreases relapse for remitting MS pts |
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***What are Abs against CD3-TCR complex of T-cells, IL-2 receptors, the CD4 molecule and against lymphokines?
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-Etanercept, Infliximab, Efalizumab, Alefacept
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Entanercept (Enbrel)
Infliximab (Remicade) MOA and Uses** |
-monoclonal Ab to cytokine receptors for TNF-alpha
-tx of RA and works by decreasing the effects of TNF -*TX of Crohn's -psoriasis, RA, colitis |
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Efalizumab (RAPTIVA)
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-anti-CD11a monoclonal Ab
-targets T cells and prevents their activation w/out destroying them -management of psoriasis (esp serious forms like plaque psoriasis) |
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Alefacept (Amevive)
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-new drug for psoriasis
-recombinant human leukocyte fxn associated Ag type 3 (LFA-3)/IgG1 fusion protein |
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Rho (D) immune globulin (Rhogam)
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-the anti-Rho[D] abs cointained in Rho [D] immune globulin interact directly w' the Rho[D] Ags--> preventing the interaction btwn As and maternal immune system
-prevent risk of erythroblastosis fetalis |
