Nitrogen mustards

Cards (14)

  • Nitrogen mustard is an alkylating agent that causes cross-linking between DNA strands, leading to cell death.
  • Cyclophosphamide and Ifosfamide are prodrugs. They must be activated by CYP3A4 and CYP2B6.
  • Examples of nitrogen mustards include mechlorethamine, cyclophosphamide, ifosfamide, chlorambucil, melphalan.
  • Large fluid infusion and MESNA can used to prevent hemorrhagic cystitis.
  • Acrolein is the metabolite of cyclophosphamide and ifosfamide. It has little antitumour activity. The major SE is hemorrhagic cystitis.
  • At standard dose, they have little cardiac toxicity.
    At high dose, will cause severe myocarditis, exudative pericarditis, myocardial depression arrhythmias, and congestive HF.
  • Cyclophosphamide has an additional immunosuppressant property to treat lupus nephritis.
  • The side effects of cyclophosphamide include myelosuppression, hemorrhagic cystitis, syndrome of inappropriate ADH, alopecia, highly emetogenic, cardiotoxicity.
    Major SE includes alopecia and hemorrhagic cystitis.
  • (Cyclophosphamide): Hemorrhagic cystitis more common in renally compromised and poorly hydrated patient.
    S&S includes gross hematuria (blood in urine).
    Management includes increase IVF, MESNA, total bladder irrigation.
  • MESNA can help to decrease the risk of bleeding in patient with hemorrhagic cystitis.
  • Ifosfamide has a higher risk of hemorrhagic cystitis compared to cyclophosphamide.
  • S&S of hemorrhagic cystitis include dysuria, frequently urination
    Treatment of hemorrhagic cystitis include evacuation of clots, continuous bladder irrigation by using 1% alum, prostaglandins, or high dose tranexamic acid.
  • The side effects of ifosfamide include hemorrhagic cystitis, leukopenia, neurotoxicity Fanconi syndrome, N&V, alopecia, hepatic enzyme elevations.
    Symptoms of leukopenia is WBC nadir, occurs between day 8 to 13; recovery usually be completed by day 17-18 of treatment cycle.
    Symptoms of neurotoxicity include encephalopathy (cerebellar ataxia - inability to coordinate muscle movement, mental confusion, complex visual hallucinations)
    Treatment of neurotoxicity is methylene blue / methylthioninium chloride.
  • Fanconi syndrome is the impairment of proximal renal tubule of kidney function. It is irreversible, long lasting, and progressive. Symptoms of Fanconi syndrome include polyuria, metabolic acidosis, renal phosphate wasting.