USMLE

Azathioprine, 6-MP

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Oncology Pharm
  1. Bleomycin
  2. Dactinomycin, Actinomycin D
  3. Doxorubicin, Daunorubicin
  4. Azathioprine, 6-MP
  5. Cladribine
  6. Cytarabine
  7. Busulfan
  8. Cyclophosphamide, Ifosfamide
  9. Nitrosoureas
  10. Paclitaxel
  11. Vincristine, Vinblastine
  12. Cisplatin, Carboplatin, Oxaliplatin
  13. Etoposide, Teniposide
  14. Irinotecan, Topotecan
  15. Bevacizumab
  16. Erlotinib
  17. Cetuximab, Panitumumab
  18. Imatinib, Dasatinib
  19. Rituximab
  20. Bortezomib, Carfilzomib
  21. Trastuzumab
  22. Dabrafenib, Vemurafenib
  23. Raloxifene and Tamoxifen
  24. Hydroxyurea
  25. Procarbazine

Summary

Azathioprine is an antimetabolite drug used as an immunosuppressive to prevent organ rejection after transplant and to treat steroid-refractory inflammatory conditions. Azathioprine is activated to become 6-MP, which is then further metabolized by HGPRT to form purine analogs that can be incorporated into DNA and RNA and terminate synthesis. 6-MP is degraded by xanthine oxidase, and xanthine oxidase is inhibited by the gout drugs allopurinol and febuxostat. Therefore, gout patients taking azathioprine along with one of those medications can have 6-MP buildup to toxic levels. Additionally, patients on azathioprine may develop myelosuppression and GI and liver toxicity. 

Key Points

  • Azathioprine / 6-MP
    • Mechanism
      • Purine analog
        • Activated by HGPRT
          • Azathioprine → 6-MP → [HGPRT] 6-TGNs
        • Degraded by xanthine oxidase
          • 6-MP → [XO] degradation
    • Clinical Use
      • Immunosuppression
        • Can be used to prevent organ rejection
      • Inflammatory conditions such as RA, IBD, SLE
        • Used to take patients off steroids in chronic disease and to treat steroid-refractory chronic disease
    • Adverse effects
      • Allopurinol and febuxostat increase toxicity
        • 6-MP is degraded by xanthine oxidase, which these drugs inhibit
      • Pancreatitis
      • Myelosuppression (obvious / non-specific)
      • GI and liver toxicity (non-specific)