Nursing Pharmacology Chapter 33-34: Anticancer Drugs
Alkylating Agents (Continued)
Classification8
Nitrogen Mustards
Nitrogen mustards are alkylating agents described chemically as bis(β-haloalkyl)amines.22
Bis refers to 2 and "halo" is an abbreviation for halogen.
For nitrogen mustards the halogen is chlorine.
The two chlorine atoms increase the basicity of the amino nitrogen.
Because of this chlorine effect, the un-ionized amine is the predominant species and predisposes formation of the highly reactive aziridinium ion.
This aziridinium ion is the highly reactive species responsible for destruction of DNA structural integrity22 .
A DNA nucleophile mediates breakages the aziridinium ring promoting DNA alkylation.22
The preferred nucleic acid base for this reaction is guanine.
Importantly, the reactivity of the mustard nitrogen is regenerated accompanying aziridinium ring cleavage.
The next steps involve repetition, this time involving the second mustard arm and a second DNA molecule.
The result is cross-linking of the two DNA molecules. Lastly, a "hydrolytic depurination" step occurs but the released DNA is damaged, incapable of replication.22
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An early study involving mechlorethamine, described as "the first clinically useful antitumor substance" and the simplest example in the nitrogen mustard family demonstrated DNA interstrand cross-linking.25
Mechlorethamine is a synthetic agent related to sulfur mustard.28
This drug has both immunosuppressive and antineoplastic characteristics.
Nitrogen mustard, a chemotherapeutic class which also includes chlorambucil and cyclophosphamide, is itself carcinogenic and an irritant.
Nitrogen mustard is metabolized to a very reactive ethylene immonium derivative which in turn alkylates DNA, thus inhibiting DNA replication.
Mechlorethamine also possesses lympholytic properties.28
Mechlorethamine (chlormethine; chlorethazine) administration produces its cytotoxic activity mainly by forming "DNA adducts" as well as through promoting DNA interstrand cross-linking.
These activities are particularly effective in inhibiting cells that are rapidly dividing.
Mechlorethamine hydrochloride is us classified as an anti-neoplastic drug which has been used in the treatment of lymphoma and Hodgkin's disease.28
Presently it is used in topical application for treating CTCL (Cutaneous T-Cell Lymphoma).27
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