Nitrogen mustards represent the largest group of alkylatingdrugs. They include:
· mechlorethamine hydrochloride
Mechlorethamine hydrochloride was the first nitrogen mustard in-troduced and is rapid-acting.
The absorption and distribution of nitrogen mustards, as with most alkylating drugs, vary widely.
Nitrogen mustards are metabolized in the liver and excreted by the kidneys. Mechlorethamine undergoes metabolism so rapidly that no active drug remains after a few minutes. Most nitrogen mustards possess more intermediate half-lives than mechloreth-amine.
Nitrogen mustards form covalent bonds with DNA molecules in a chemical reaction known as alkylation. Alkylated DNA can’t repli-cate properly, thereby resulting in cell death. Unfortunately, cellsmay develop resistance to the cytotoxic effects of nitrogen mus-tards. (See How alkylating drugs work.)
Because they produce leukopenia (reduced number of white blood cells [WBCs]), the nitrogen mustards are effective in treat-ing malignant neoplasms, such as Hodgkin’s disease (cancer caus-ing painless enlargement of the lymph nodes, spleen, and lym-phoid tissues) and leukemia (cancer of the blood-forming tissues), that can have an associated elevated WBC count.
Nitrogen mustards also prove effective against malignant lym-phoma (cancer of the lymphoid tissue), multiple myeloma (cancer of the marrow plasma cells), melanoma (malignancy that arisesfrom melanocytes), and cancers of the breast, ovaries, uterus, lung, brain, testes, bladder, prostate, and stomach.
Nitrogen mustards interact with a wide variety of other drugs:
· Calcium-containing drugs and foods, such as antacids and dairy products, reduce absorption of estramustine.
· Cyclophosphamide taken with cardiotoxic drugs produces additive cardiac effects.
· Cyclophosphamide may reduce serum digoxin levels.
· An increased risk of ifosfamide toxicity exists when the
· drug is taken with allopurinol, barbiturates, chloral hydrate, or phenytoin.
· Corticosteroids reduce the effects of ifosfamide.
· The lung toxicity threshold of carmustine may be reduced when taken with melphalan.
· Interferon alpha may reduce serum concentration of mel-phalan. (See Adverse reactions to nitrogen mustards.)