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Home » , » Nitrosoureas
Nitrosoureas
Sunday, September 18, 2011 Posted by Piscean


Nitrosoureas
Nitrosoureas are alkylating agents that work by halting cancer cell reproduction. They include:
  • carmustine
  • lomustine
  • streptozocin.
Pharmacokinetics
When administered topically to treat mycosis fungoides (a rare skin malignancy), carmustine is 5% to 28% systemically absorbed. After oral administration, lomustine is absorbed adequately, though incompletely.
I.V. is the way
Streptozocin and carmustine are administered I.V. because they’re poorly absorbed orally.
Metabolism and excretion
Nitrosoureas are lipophilic (attracted to fat), distributing to fatty tissues and cerebrospinal fluid. They’re metabolized extensively before urine excretion.
Pharmacodynamics
During a process called bifunctional alkylation, nitrosoureas interfere with amino acids, purines, and DNA needed for cancer cells to divide, thus halting their reproduction.
Pharmacotherapeutics
The nitrosoureas are highly lipid (fat) soluble, which allows them or their metabolites to easily cross the blood-brain barrier. Because of this ability, nitrosoureas are used to treat brain tumors and meningeal leukemias.
Drug interactions
Each of the nitrosoureas has its own interactions with other drugs. Cimetidine may increase carmustine’s bone marrow toxicity. Streptozocin prolongs the elimination half-life of doxorubicin, prolonging the leukopenia and thrombocytopenia. (See Adverse reactions to nitrosoureas.)
Warning!
Adverse reactions to nitrosoureas
All of the nitrosoureas can produce severe nausea and vomiting.
Down to the bone
Carmustine and lomustine produce bone marrow suppression that begins 4 to 6 weeks after treatment and lasts 1 to 2 weeks.
Kidney concerns
Kidney toxicity and kidney failure may also occur with patients taking nitrosoureas. High-dose carmustine may produce reversible liver toxicity.
Pulmonary problems
Carmustine may cause lung toxicity characterized by lung infiltrates or fibrosis (scarring).

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