摘要:

AbstractWarfarin and related substances have been in use as rodenticides for fifty years. They act by binding to the enzyme vitamin K 2,3‐epoxide reductase, thereby interrupting the cellular recycling of vitamin K. Vitamin K in its hydroquinone form is an essential cofactor for the synthesis of functional prothrombin and related blood‐clotting factors. The binding with the reductase is essentially irreversible, indicating these compounds have a prolonged half‐life in target tissues; 7–10 days for warfarin and congeners and over 100 days for the second generation rodenticides or ‘superwarfarins’ such as difenacoum, brodi‐facoum, and flocoumafen. Rat liver contains 1–2 nmole of enzyme per gram tissue which is a 4–5 fold overcapacity for maintaining effective vitamin K recycling. The use of warfarin as a rat poison has resulted in the natural selection of warfarin‐resistant rats. The resistance is inheritable. Two distinct warfarin resistance genotypes, Welsh and Scottish, have been identified, clearly differing in their biochemistry of vitamin K epoxide reductase. In the Welsh strain, resistance arises from an altered enzyme expressing reduced reactivity to warfarin, whereas the reductase from the Scottish strain is as sensitive as the normal enzyme, but the interaction with warfarin is now readily reversible. The altered enzyme leaves the Welsh rat in need of higher dietary vitamin K intake. The superwarfarins cope with the resistance by having their structures firmly bind with the altered enzymes. Reduced sensitivity to warfarin‐based rodenticides may also be pharmacokin‐etically based, arising from increased warfarin biotransformation. This mechanism may be responsible for resistance to some of the superwarfarins such as difenacoum. A third resistance mechanism may arise from an enhanced capacity to synthesize vitamin K from menadione, a commonly used additive in animal foods on farms. The choice of rodenticide in the case of warfarin resistance should be guided by the underlying

ISSN:0031-613X    

DOI:10.1002/ps.2780430112

出版商:John Wiley&Sons, Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe action necessary for resistance management is specified and compared with what has actually been done, with reference to executive, extension and research activities and to the role of rodenticides and rodenticide development. Some obstacles to resistance management are discussed. To account for the fact that no plausible programme to manage resistance has been developed over the last 36 years, the hypothesis is examined that resistance management is injurious to the parties concerned and, hence, that resistance is perceived not as a problem but as an exploitable asset. If correct, this hypothesis yields the prediction that the action necessary for resistance management will be taken when such action is judged to be economically efficient. The establishment of the Rodenticide Resistance Action Committee indicates that this time may be approaching.

ISSN:0031-613X    

DOI:10.1002/ps.2780430113

出版商:John Wiley&Sons, Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractResistance amongst rats to second‐generation anticoagulants, notably difenacoum, has been recognised since the 1970s. Although initially considered to be of practical significance, doubts were subsequently expressed that the degree of resistance was sufficient to explain ineffective rodenticide treatments. Research published elsewhere demonstrated the overriding importance of poor poisoned bait consumption, caused by the influence of certain ecological factors on rat behaviour, in reducing the effectiveness of second‐generation anticoagulant treatments on farms in southern England. In this paper we consider, however, the subtle effects of resistance to anticoagulants on treatment outcome. The prevalence of resistance was increased amongst survivors of treatments and bait consumption by resistant survivors was higher than amongst susceptible survivors. The overall prevalence and degree of resistance to second‐generation anticoagulants does not, however, currently represent a practical problem. Nevertheless, selection favouring increased resistance remains a long‐term threat to the effectiveness of both difenacoum and broma

ISSN:0031-613X    

DOI:10.1002/ps.2780430114

出版商:John Wiley&Sons, Ltd    

年代:1995

数据来源: WILEY

ISSN:0031-613X    

DOI:10.1002/ps.2780430115

出版商:John Wiley&Sons, Ltd    

年代:1995

数据来源: WILEY

ISSN:0031-613X    

DOI:10.1002/ps.2780430101

出版商:John Wiley&Sons, Ltd    

年代:1995

数据来源: WILEY