Anticoagulant rodenticides coumarin

Hunter, K. (1983). Determination of coumarin anticoagulant rodenticide residues in animal tissue by high-performance liquid chromatography. II. Fluorescence detection using ion-pair chromatography. J. Chromatogr. 270 277-83. 

Lau-Cam, C.A., Chu-Fong, 1. (1972). Thin-layer chromatography of coumarin anticoagulant rodenticides. J. Pharm. Sci. 61 1303-6. 

Mundy, D.E., Machin, A.F. (1982). The multi-residue determination of coumarin- based anticoagulant rodenticides in animal materials by HPLC. J. Chromatogr. 234 427-35. 

The first anticoagulant rodenticide was dicoumarin (19). Its anticoagulant effect was first observed on cattle. Coumarin has an odour reminiscent of hay. When mown sweet clover (Melilotus albe) becomes mouldy, dicoumarin is formed from coumarin, and cattle fed with such mouldy, sweet clover hay bleed to deat when injured because of reduced blood coagulation (Campbell and Link, 1941 Stahmann et al., 1941). Dicoumarin, 3,3 -methylene-bis(4-hydroxycoumarin), is obtained by the condensation of 2 moles of 4-hydroxycoumarin (20) and 1 mole of formaldehyde in aqueous solution. 

Warfarin-specific methods were generally inadequate for anticoagulant rodenticides, so a number of other methods were developed. These include thin-layer chromatography (TLC), high-pressure liquid chromatography (HPLC), mass spectroscopy (MS), and antibody-mediated tests. Coumarin anticoagulant rodenticides were initially detected using TLC (Lau-Cam... 

Twenty to 24 million prescriptions of Coumadin were dispensed in the United States during 2003-2005. Coumadin is an anticoagulant that acts by preventing the synthesis of active vitamin K, a necessary cofactor for synthesizing active clotting factors. Thus, preventing the synthesis of active vitamin K indirectly inhibits the formation of active clotting factors, notably factor II (prothrombin), VII, IX, and X in the liver. Ironically, coumarins, of which Coumadin is a member, are also used as rodenticides. 

The coumarin anticoagulants, which include warfarin [WAR far in] and dicumarol [dye KOO ma role] (formerly bishydroxycoumarin) owe their action to their ability to antagonize the cofactor functions of vitamin K. Initially used as a rodenticide, warfarin is now widely employed clinically as an oral anticoagulant. Conflicting opinions exist concerning the usefulness of these agents in clinical situations such as myocardial infarction and hip arthroplasty. The potential... 

Rodenticides are used to control rats and mice in fields, in storage areas, and in household environments. Rodents not only destroy harvested products, but are also vectors for contagious diseases. Most rodenticides belong to the coumarin group and act as anticoagulants. Bromadiolone is an example of a relative selective rodenticide that is highly toxic to rodents, but less toxic to domestic animals such as dogs and cats. 

Due to their potent anticoagulant activity, some of these compounds have been used to control rodent infestation. Particularly, warfarin has been applied as an effective rodenticide for years. The laevorotatory form of this compound is seven times more active than the dextrorotatory isomer [471]. Recently, a resistance to warfarin has been found to develop in some rats [483]. These animals may metabolise the drug more rapidly or the affinity of the receptor sites for vitamin K may be greater in the resistant animals than in the sensitive ones, hence the coumarin is metabolised and eliminated faster. 

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