2nd generation anticoagulants

All anticoagulant rodenticides have the same mode of action, i.e. interference with the synthesis of clotting factors, which results in haemorrhaging and death. In the liver cells, the biologically inactive vitamin K₁-2,3 epoxide is reduced by a microsomal enzyme into biologically active vitamin K, which is essential for the synthesis of prothrombin and other clotting factors. Anticoagulant rodenticides antagonize the enzyme vitamin K₁-epoxide reductase in the liver causing a gradual depletion of the vitamin and consequently of vitamin K-dependent clotting factors. This results in an increase in blood-clotting time until the point where the clotting mechanism fails. The principal use of anticoagulants worldwide has been for control of commensal rodents, primarily Norway rats, ship rats, and house mice. About ten anticoagulant rodenticides have been brought to the market. Some are reviewed below to illustrate their properties. A number have been registered for commensal rodent control.

The second-generation anticoagulants are more acutely toxic than first-generation anticoagulant rodenticides. Their superior potency is related to their greater affinity for vitamin K-epoxide reductase. Bromadiolone and difenacoum were the first compounds of the second generation introduced to the market.The three most potent anticoagulants are Brodifacoum, Flocoumafen and Difethialone.

No practical resistance is known in Norway rats and house mice against the three most potent second generation anticoagulants.

Bromadiolone has chemical and biological effects that are similar to difenacoum. However, it is somewhat less potent than brodifacoum, difethialone and flocoumafen. Like difenacoum it was developed and came to the market in the 1970s. In spite of bromadiolone belonging to the second-generation anticoagulants, resistance problems have been encountered in some rodent populations but the compound is effective against certain rodent strains that have become resistant to other first-generation anticoagulant rodenticides.

Difenacoum was also introduced to overcome the early strains of resistant rodents found in the UK and on continental Europe. It is unusual among anticoagulants because, at the LD50 level, it is more potent to house mice than Norway rats. As was the case with bromadiolone, some resistance to difenacoum is found in certain strains of rats and mice.

Brodifacoum differs from the first-generation anticoagulants and the above second-generation anticoagulants in that it is very potent and only requires a single dose to induce death, if sufficient toxicant is ingested. Second-generation anticoagulants, like brodifacoum, have an important role in controlling rats and mice that have developed resistance to first-generation anticoagulants and to bromadiolone and difenacoum. However in the New World it has become better known for its role in eradication of rodents from island wildlife sanctuaries. The field use of second-generation anticoagulants has resulted in reports of wildlife contamination.

Flocoumafen and brodifacoum are similar in terms of their chemistry, biological activity and potency, persistence, and risk of secondary poisoning. Flocoumafen is a second-generation anticoagulant that was developed in the early 1980s. Flocoumafen has been used against a wide range of rodent pests including the principal commensal species. It is also effective against rodents that have become resistant to other anticoagulant rodenticides.

Difethialone: In contrast to brodifacoum, which contains bromine in its molecule, and flocoumafen containing fluorine, difethialone contains a sulfur atom. The potency of difethialone is very similar to both above compounds.

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