Dacarbazine alkylating agent

Dacarbazine Alkylating agent Hepatic metabolism constipation Myelosuppression... 

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. 

The antidote of choice for mechlorethamine extravasations is sodium thiosulfate. This agent binds alkylating agents, resulting in neutralization to inactive compounds that are then excreted. Sodium thiosulfate also may be effective for high-concentration cisplatin or dacarbazine extravasations. 

Dacarbazine (DTIC) -atypical alkylating agent, noncell cycle dependent -bone marrow suppression -nausea and vomiting -vesicant if extravasated -flu-like syndrome -fever... 

Temozolomide is an imidazotetrazine derivative of the alkylating agent dacarbazine. It is an oral alkylating agent used for the treatment of refractory anaplastic astrocytoma. Apart from myelosuppression the most common adverse effects are nausea and vomiting. 

Dacarbazine DTIC-Dome) is activated by photodecomposition and by enzymatic A-demethylation. Eventual formation of a methyl carbonium ion results in methylation of DNA and RNA and inhibition of nucleic acid and protein synthesis. As with other alkylating agents, cells in all phases of the cell cycle are susceptible to dacarbazine. 

A variety of other therapeutic compounds have mechanisms that probably involve alkylation. Procarbazine and dacarbazine are the two most successful agents in this group. Dacarbazine is a synthetic compound that functions as an alkylating agent, following metabolic activation by liver microsomal enzymes, to yield diazomethane. It has been used successfully in the treatment of sarcomas. 

All are powerful alkylating agents. The development of Mitozolomide was progressed by May and Baker in Britain. Although it showed clinical activity and a marked advantage over Dacarbazine in crossing the blood-brain barrier, its development was terminated when it was found to cause severe thrombocytopenia (decrease of the blood platelet count). 

Dacarbazine is converted to an active metabolite that is thought to be an alkylating agent. It has been used to treat metastatic melanoma and, in combination regimens, soft-tissue sarcomas and Hodgkin s disease. 

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. 

Monofunctional alkylating agents (dacarbazine and temozolomide) (SEDA-32, 827)... 

Several other compounds have mechanisms of action that involve DNA alkylation as their cytotoxic mechanism of action. These agents include procarbazine, dacarbazine, and bendamustine. Their clinical activity and associated toxicities are listed in Table 54-2. 

Several other cytotoxic agents appear to act as alkylators, although their structures do not include the classic alkylating groups. They are capable of binding covalently to cellular components and include procarbazine, dacarbazine, temozolamide, the heavy metal compounds, and some antitumor antibiotics (see Table 124-14). ... 

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