Immunosuppressive Therapy by mC7asl

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									Immunosuppressive
    Therapy


    Rebecca Berquist
    October 12th, 2004
    Immunosuppressive Uses In
           Transplant

   promote graft acceptance (induction)
   reverse episodes of acute rejection
   prevent rejection (maintenance)
    Other immunosuppressive
              use

   Common:
    Autoimmune (RA, psoriasis)
   Uncommon:
    Nephrotic syndrome (CsA), UC (AZA)
General Immunosuppressive
          Effects

   Immunosuppression
   Immunodeficiency toxicity (infection,
    lymphomas)
   Non-immune
    toxicity(nephrotoxicity,diabetes,etc)
              Glucocorticoids
           (Prednisone 5-15mgQD)
   Immunosuppressive and anti-inflammatory
   Mech: 1) Inhibition of cytokine transcription
           2) Induction lymphocyte apoptosis
           3) < MHC expression, adhesion mol
           4) modify leukocyte trafficking
   Side Effects: cortical bone loss, Cushing’s,
    HTN, diabetes, dec wound healing, HL,
    obesity, cataract
      AntiProliferative Agents
Azathioprine(Imuran 2.5mg/kgQD)purine analog6-MP
 Mech: Inhibit DNA synth & LC proliferation
  (denovo&salvage)
 Side Efx: Myelosuppression, reversible w/DC, hepatotox,
  skin cancer
 Interax: Myelosuppression w/allopurinol (AZA metab by
  xanthine oxidase, lower dose), hold if WBC <3000 or if
  drops >50% w/bld draw

Mycophenolate mofetil(Cellcept 500mg-1gmBID)
 Mech: Inhibits de novo purine synthesis (IMP dehyd),
  selectively inhibits LC
 Side Efx: GI (N/V/AP), Heme(leuko/thrombopenia)
 Interax: Antacids w/Mg, Al interfere w/absorption, lower
  dose when used w/CsA or FK506
        Calcineurin Inhibitors
 Mech: Bind immunophilllins (cyclophilin/FKBP) block
  NFAT, IL-2, cytokine production and TLC activ,prolif
Cyclosporine A (Neoral, Gengraf 3-5mg/kgQD)
 Side Efx: Nephrotox*(acute rev,chrn irrev), hirsutism,
  tremor, HTN, glucose intol, HLip,HK, TTP(rare)
 Interax: ACE, Vol Dep, Nephrotox potentiate ,P450


Tacrolimus (Prograf 1-4mgBID)
 Side Efx: Nephrotox*, neurotox(>C), diabetogenic(>C),
  pleural effusion, HUricemia
 Notes: Give on empty stomach
 NephrotoxDx: NSAID,AmphoB,Statin, Acyc,Cipro
Sirolimus (Rapamune)
 Mech: inhibits G1S of TC cycle, inhibits
  cytokine & GF induced cell proliferation
 SideEfx: HLip, Thrombocytopenia, Not
  Nephro
 Interax: CsA+Sir2x increase sirol, dose
  4hr apart, Dec dose in hepatic impairment
  p450, synergistic effect w/Prograf
         CsA P450 Effects
Induction of P450decrease CsA
 Rifampin, INH, Barbit,
  Phenytoin,Carbamaz

Inhib P450increase CsA
 Verapamil, diltiazem, nicardapine, azoles,
  erythro, clarithro
  Biologic Agents: Polyclonal
              Ab
Antithymocyte globulin (ATGAM)-horse
  antihuman thymocyte Ab
 Mech: <TLC via complement-med lysis,Ab
  clearance, blocks expression cell surface mol
 Side Efx: 1) F/C/arthralgias 2) myelosupp,
  Serum sickness, anaphylaxis

Thymoglobulin-rabbit anithuman thymocyte Ab
 Mech:similar to ATGAM, more prolonged supp
 SideEfx: similar
Slow infusion (4-6hrs) prevent thrombophlebitis
 Biologic Agents: Monoclonal
             Ab
OKT3 (Muromonab)-murine monoclonal Ab via CD3Ε of
  TCR, delivered as bolus injection
 Mech: Depletes CD3+ TC, mod CD3 expression
 SideEfx: cytokine release synd: (F/C/N/V/D/My
  hypotension, NCpul edema), encephalop, seizures,
  aseptic meningitis, chest pain, wheezing, dyspnea

Anti-IL2 R: daclizumab(human), basiliximab(chimeric)
 Mech: comp inhibit subunit IL2R(CD25), inhibit TC activ
 SideEfx: Fewer side effects
          THE END




References: UpToDate, Washington Manual of
Therapeutics (MdSkolar), Pharmacology Katzung

								
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