Carmustine alkylating agent

Other subgroups of alkylating agents are the nitrosoureas (examples carmustine, BCNU lomustine, CCNXJ) and the triazenes (example dacarbazine, DTIC). Platinum derivatives (cisplatin, carboplatin, oxaliplatin) have an action that is analogous to that of alkylating agents (formation of crosslinks) and therefore are appended to this class, as well. 

Lomustine is an orally available nitrosurea alkylating agent. Lomustine is converted rapidly to the cis- and frans-4-hydroxy metabolites the range of half-lives of these two metabolites is 2 to 4 hours.25 Lomustine has shown clinical activity in the treatment of Hodgkin s lymphoma and melanoma. Side effects are similar to those of carmustine. Patients should receive only enough drug for one cycle at a time to prevent confusion and accidental overdose. 

Carmustine (BCNU) -alkylating agent (cell cycle-independent mechanism) -bone marrow suppression—delayed with a nadir of 3-5 weeks -nausea and vomiting—can be severe and prolonged -facial flushing -interstitial lung disease (dose independent)... 

Alkyl halides, alkyl sulfonates and other alkylating agents have also been subject to scmtiny in spheres other than pharmaceuticals, such as in environmental analysis. Various approaches have included two-step SPE, derivatisation with trifluoroacetic anhydride followed by GC/MS (for cyclophosphamide and its analogues in sewage water) SPE on surface water to isolate the antineoplastic agents carmustine, chlorambucil, cyclophosphamide and melphalan for LC-UV and LC-fluorescence measurements and derivatisation of alkyl halides and epoxides with 4-nitrothiophenol followed by HPLC-UV detection (claimed to be better than NBP derivatisation). A patent exists for a field test kit for mustard gases in military use based on NBP derivatisation. 

Despite the fact that alkylating agents exhibit a common mechanism of action, their clinical use varies depending on differences in pharmacokinetics, metabolism, hpid solubility, ability to penetrate membranes, and toxicity. They can be classified as nitrogen-containing mustard derivatives (mechorethamine, chlorambucil, melfalan, cyclophosphamide, ifos-famide), derivatives of ethylenimine (thiotepa), nitrosoureas (carmustine, lomustine, strep-tozocin), alkylsulfonates (busulfan), and derivatives of platinum (cwplatin, carboplatin). 

The nitrosoureas are alkylating agents that are highly lipid soluble and share similar pharmacological and clinical properties. Carmustine (BCNU), lomustine (CCNU), and semustine (methyl-CCNU) are chemically unstable, forming highly reactive decomposition products. The chemical half-life of these drugs in plasma is only 5 to 15 minutes. Their marked lipid solubility facilitates distribution into the brain and cerebrospinal fluid (CSF). 

CARMUSTINE H2 RECEPTOR BLOCKERS -CIMETIDINE t adverse effects of alkylating agent, e.g. myelosuppression Additive toxicity Monitor more closely monitor FBC regularly... 

The nitrosourea cytostatic drugs are alkylating agents that include carmustine, lomustine, nimustine, and streptozocin (all rINNs). 

Synonyms Carmustine N,N-bis(2-Chloroethyl)-N-nitrosourea BiCNU Carmubris Nitrumon Chemical/Pharmaceutlcal/Other Class Alkylating agent... 

The alkylating agents include nitrogen mustards (chlorambucil, cyclophosphamide, mechlor-ethamine), nitrosoureas (carmustine [BCNU], lomustine [CCNU]), and alkylsuUbnates (busul-fan). Other drugs that act in part as alkylating agents include cisplatin, dacarbazine, and procarbazine. 

Poorly selective though it was, chlormethine pointed the way to the discovery of the following nitrogen-mustard drugs, currently used in cancer therapy cyclophosphamide (perhaps the most selective of them all), chlorambucil, melphalan, and uracil mustard also the closely related thiotepa and busulfan also the related nitrosoureas lomustine, carmustine, semustine, and strepto-zocin (an antibiotic). All of these are alkylating agents, linking two strands of DNA (see Section 13.4 for details). 

Mechlorethamine, the drug in Problem 45 that is in clinical use, is highly reactive so can be administered only by physicians who are experienced in its use. Explain why cyclophosphamide, carmustine, and chloroambucil are less reactive alkylating agents. 

C 0400 Carmustine DNA alkylating/cross-Unking agent effective against glioma and other soUd tumors. 

Carmustine (BNCU), lomustine (CCNU), and semustine (methyl-CCNU) generate alkyl carbonium ions and isocyanate molecules and hence are able to interact with DNA and other macromolecules. These agents, which are lipid soluble, cross the blood-brain barrier and are therefore effective in treating brain tumors. They are bone marrow depressants. 

---