questions 3

Immunosuppressive Drugs

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Topic updated on 02/20/17 12:12pm

Overview
  • Immunosuppressive mechanisms act via three main mechanisms  
    • inhibit immune cell proliferation
      • interfere with cytokine signaling
      • anti-metabolite
    • inhibit immune cell function
    • kill immune cells
Classes of drugs
  • Block proliferation
    • cyclosporine  
      • inhibits expression of IL-2 and IL-2 receptors
      • toxicity
        • nephrotoxicity
        • ginival hyperplasia
        • hirsutism
        • infection/malignancy (from immunosuppression)
    • tacrolimus-FK506
      • binds to FK-binding protein, inhibiting calcineurin
        • inhibits secretion of IL-2
      • toxicity
        • nephrotoxic
    • muromonab-CD3 (OKT3)
      • monoclonal antibody that binds to CD3 on the surface of T cells
        • epsilon chain
      • blocks cellular interaction with CD3 protein responsible for T cell signal transduction
      • toxicity
        • cytokine release syndrome aka cytokine storm
          • presents with fever, hypotension, rigors
        • hypersensitivity reaction
    • daclizumab
      • monoclonal antibody with high affinity for the IL-2 receptor (CD25)  on activated T cells
        • toxicity
          • hypersensitivity
          • GI: constipation, nausea, vomiting, diarrhea, abdominal pain, dyspepsia
    • sirolimus (rapamycin)
      • binds to mTOR (mammalian target of rapamycin)
      • inhibits T cell proliferation in response to IL-2
      • specific clinical use
        • immunosuppression after kidney transplantation in combination with cyclosporine and corticosteroids
      • toxicity 
        • hyperlipidemia
        • thrombocytopenia
        • leukopenia
    • azathioprine
      • antimetabolite precursor of 6-mercaptopurine
      • prevents synthesis of nucleic acids
      • specific clinical use
        • kidney transplantation
        • autoimmune disorders
          • includes glomerulonephritis and hemolytic anemia
      • toxicity 
        • bone marrow suppression
        • active metabolite mercaptopurine is metabolized by xanthine oxidase
        • thus, toxic effects may be ↑ by allopurinol
    • mycophenolate Mofetil
      • inhibits de novo guanine synthesis and blocks lymphocyte production
  • Block function
    • corticosteroids
  • Kill T-cells
    • cyclophosphamide


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Qbank (1 Questions)

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(M1.IM.59) A 31-year-old female receives a kidney transplant for autosomal dominant polycystic kidney disease (ADPKD). Three weeks later, the patient experiences acute, T-cell mediated rejection of the allograft and is given sirolimus. Which of the following are side effects of this medication? Topic Review Topic

1. Nephrotoxicity, hypertension
2. Pancreatitis
3. Hyperlipidemia, thrombocytopenia
4. Cytokine release syndrome, hypersensitivity reaction
5. Nephrotoxicity, gingival hyperplasia

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