Superwarfarins are compounds closely related to the blood thinner warfarin, but longer acting and more potent. Warfarin was originally developed for use as a rat poison by Dr. Karl Link at the Wisconsin Agricultural Research Foundation and was marketed as a rodenticide in 1948. After first a fast-acting antidote and then a blood test was developed to adjusti the dose, it was used in humans as a potent blood thinner and is still one of the most important medications used today to prevent and treat blood clots in the legs or lungs.
Warfarin is a synthetic compound related to a naturally occurring compound found in sweet clover called coumarin. When hay containing sweet clover becomes moldy, the coumarin in the sweet clover oxidizes, changing it into a compound with significant anticoagulant properties which causes serious and often fatal bleeding in cows. Veterinarians called this bleeding disorder “sweet clover disease” and advised dairymen to avoid feeding moldy hay to their animals. But in the 1920s, times were so tough economically that many farmers could not afford to discard the spoiled hay.
Dr. Link and his colleagues at the Wisconsin Agricultural Research Foundation, also called WARF, successfully determined and isolated the cause of the bleeding, a compound which they named dicumarol. Dicumarol had a delayed effect on blood clotting, with symptoms of bleeding showing up 15 days after cows first ate tainted hay. Dicumarol was odorless and tasteless, important features of any successful rat poison, and Dr. Link believed that if he could find a compound similar in effect to dicumarol but which acted more quickly, he would have developed a good rat poison.
Eventually Dr. Link’s team found a derivative of dicumarol that fit his criteria, and it was named warfarin, after the facility that funded the research. Warfarin was widely used as a rodenticide until it became obvious that some rats were resistant to its effects. Certain rats had a genetic variation that made them “resistant” – these rats needed 10 times the usual dose to get an anticoagulant effect large enough to cause fatal hemorrhage. While the other rats died from internal bleeding, these rats survived and replaced the warfarin-susceptible rats. Drats!
This discouraging development triggered research to find more potent compounds such as brodifacoum, difenacoum, bromadiolone and difethiolone. Called “second generation anticoagulants” or “superwarfarins”, these agents have become the rat poisons of choice. Brodifacoum is the rodenticide used by more than 50% of professional pest controllers in the United States.
The blood thinning effects of these “superwarfarins” last over 12 times as long as warfarin. If a child or animal eats rat poison made with brodificoum, instead of treatment with an antidote for 1 week, more than 12 weeks of antidote administration will be required.
Another important difference between warfarin and newer “superwarfarins” is their relative toxicity to pets and wild animals. Anticoagulants move quickly into the bloodstream and do their work by causing the rat to build defective clotting compounds instead of active ones, eventually causing it to die from uncontrolled bleeding. As a rat becomes weaker from blood loss it also becomes slower and easier to kill. A successful hunter who eats a rat poisoned by anticoagulant also ingests the poison inside it.
Warfarin is quickly detoxified to inactive compounds, leaving less active anticoagulant inside a poisoned rat to be eaten by a hungry predator. A “superwarfarin” isn’t broken down or detoxified quickly, and instead remains completely active while it works. In 2012, following decades of a disturbing trend of finding increasing amounts of “superwarfarins” in the remains of birds of prey, wildcats and dogs, the Environmental Protection Agency (EPA) restricted the use of “superwarfarins” for rodent control.
