Anticoagulants poisoning with

Because rodent populations world-wide were becoming resistant to the widely used Warfarin-type anticoagulant poisons, a search was initiated to find a rodenticide with a different mode of action one that would be effective against these resistant rodents. This search led to the discovery of the toxic nature of a family of diphenyl amines which act as uncouplers of oxidative phosphorylation. A structure-activity relationship (SAR) study was undertaken to choose a derivative that would be both poisonous to rodents but still readily consumed by them. This approach led to the discovery of bromethalin,... 

Sulfonylureas In acute poisoning with sulfonylureas, the stomach should be washed and treated with activated charcoal, and hypoglycemia must be treated. Sulfonylureas interact with oral contraceptives, thiazide diuretics, corticosteroids, adrenaline, chlorpromazine, ACE inhibitors, some NSAIDs, antihistamines, anticoagulants, MAOIs, antidepressants, and many other drugs. Care must be exercised when treating with sulfonylureas. 

Zupancic-Salek S, Kovacevic-Metelko J, Radman 1. Successful reversal of anticoagulant effect of superwarfarin poisoning with recombinant activated factor Vll. Blood Coagul Fibrinolysis 2005 16(4) 239-44. 

Warfarin [81-81-2] (6) is prepared by the Michael condensation of benzyHdene acetone with 4-hydroxycoumarin (86). It is used as a rodenticide (see Poisons, commercial) and in anticoagulant therapy. 

The only major side-effect of these oral anticoagulants is prolonged bleeding, thus the dosage levels are chosen with care. Dicoumarol was first isolated from spoiled sweet clover hay, as the agent which promoted haemorrhage disease in cattle. Both dicoumarol and warfarin have also been utilized (at high doses) as rat poisons. 

Vitamin K antagonists, such as dicoumarol (8.61, a natural product) and warfarin (8.62), are used as anticoagulants in human therapy (thrombosis, atherosclerosis) and as rat poisons that lead to internal bleeding and death in rodents. Heparin, a polysaccharide consisting of 2-0-sulfonated glucuronic acid and 2-N,6-0-disulfonated glucosamine, is also a widely used anticoagulant, but its effect is connected not with Vitamin K but with enzyme inhibition. 

Warfarin (Fig. 10-22c) is a synthetic compound that inhibits the formation of active prothrombin. It is particularly poisonous to rats, causing death by internal bleeding. Ironically, this potent rodenticide is also an invaluable anticoagulant drug for treating humans at risk for excessive blood clotting, such as surgical patients and those with coronary thrombosis. ... 

On the other hand, drugs may inhibit the metabolism of other drugs. For example, allopurinol (a xanthine oxidase inhibitor that inhibits the synthesis of uric acid) increases the effectiveness of anticoagulants by inhibiting their metabolism. Chloramphenicol (a potent inhibitor of microsomal protein synthesis) and cimetidine (an H2-receptor blocker used in acid-pepsin disease) have similar properties. In addition, drugs may compete with each other in metabolic reactions. In methyl alcohol (methanol) poisoning, ethyl alcohol may be given intravenously to avert methanol-induced blindness and minimize the severe acidosis. Ethyl alcohol competes with methyl alcohol for... 

Serum concentration of dogs with anticoagulant roden-ticide poisoning ranged from less than 10 ng/1 to 851 ng/1 for brodifacoum, difethialone, and difenacoum (Robben et al, 1998). 

Robben, J.H., Kuijpers, E.A., Mout, H.C. (1998). Plasma superwarfarin levels and vitamin K1 treatment in dogs with anticoagulant rodenticide poisoning. Vet. Q. 20(1) 24-7. 

Concerns are also on the increase with another class of pesticides the coumarin anticoagulants. An increasing number of birds of prey are being found to have been secondarily poisoned by the newer single feed anticoagulant pesticides. Also, a very high proportion of asymptomatic birds appear to be carrying liver residues of these compounds, which is cause for concern. 

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