Lomustine 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. 

Lomustine (CCNU) -nitrosourea alkylating agent cell cycle independent -bone marrow suppression (delayed, prolonged, and cumulative) -nausea and vomiting -pulmonary fibrosis Lung Cancer... 

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). 

LOMUSTINE 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). 

A special subgroup of alkylating agents are the nitrosoureas (Table 4-4). A feature of these agents is their considerable lipophilicity when compared with the other alkylating compounds. Lomustine and semustine do not even ionize at physiological pH. This permits them to cross more readily the blood-brain barrier and to pass into the cerebrospinal fluid. Furthermore, the nitrosoureas have a dual mechanism of action alkylation of nucleic acids and carbamoylation of various proteins via the 8-NH2 group of lysine residues. 

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). 

In the present decade, the search for new types of alkylating agents led to the alkyl nitrosoureas, such as CCNU (lomustine) (12.57) which is chemically i-(2-chloroethyl)-3-o ctohexyl-i-nitrosourea. The nitrosoureas, unlike the mustards, can penetrate the blood-brain barrier and are giving good clinical results with brain tumours. Their action has been shown to be partly by alkylation of macromolecules, but to an even greater degree by carbamoylation after intermediate formation of an isocyanate species (Cheng et al.y 1972 Connors and Hare, 1974). 

LomotiP atropine sulphate diphenoxylate, lomustine [ban, inn, usan] (CCNU CEENU ) Is a lipid-soluble nitrosourea that is an alkylating cytotoxic agent. It can be used as an anticancer agent, particularly for Hodgkin s disease and certain solid tumours. 

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. 

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