Why is coumadin and rat poison

I saw Warfarin was the main ingredient, with a different molecular structure. My mother-in-law takes warfarin and i never thought twice about it. Until today! Nicotine was originally used as a pesticide as well.

It is a transdermal poison that can cause rapid heart rates, increased BP, heart and liver failure in high concentrations. Arsenic is a good rodenticide.

It causes the rats to run to a source of water as the body rapidly dehydrates. If you have no leaky pipes in your walls or under your house, the rat dies before they can get back inside the house.

Is your idea that the rapid heart rate and increased blood pressure will help the rat bleed to death more quickly from the warfarin-like compound in the rat poison? Arsenic is tasteless and odorless, so it would be hard for a rat to detect. Arsenic was widely used in pesticides in the United States from the s to the s and is still used in some insecticides, fungicides and as a rat poison. Despite recommendations not to feed mouldy hay to their cattle, many farmers did not follow the advice, and sweet clover disease remained prevalent a decade later.

In desperation, Ed Carlson, a Wisconsin farmer, drove a dead cow miles to an agricultural experimental station, where he presented biochemist Karl Link with a milk can of unclotted blood. Link and colleagues set about identifying and isolating the active compound that caused the haemorrhagic disease. They adopted a new in vitro clotting assay using plasma from rabbits to guide chemical fractionation of compounds found in the hay. In , Link considered using a coumarin derivative as a rodenticide.

Dicoumarol acted too slowly to be a practical poison. Link and colleagues worked through a list of variations of coumarin, and number 42 was found to be particularly potent.

The compound was named 'warfarin' after the funding agency, and was successfully marketed in as a rodenticide. In , a US Army inductee attempted suicide with multiple doses of warfarin in rodenticide, but fully recovered after being treated with vitamin K in hospital. Studies then began on the use of warfarin as a therapeutic anticoagulant. Clinical anticoagulants were available at this time, but heparin required parenteral administration, and dicoumarol had a long lag period before onset of a therapeutic effect.

The main advantages of warfarin were high oral bioavailability and high water solubility; it was more potent than dicoumarol, but its effect could still be reversed by vitamin K. Therefore, warfarin transitioned into clinical use under the trade name Coumadin, and was approved for use in humans in An early recipient of warfarin was US president Dwight D.

Eisenhower, who was prescribed the drug after a myocardial infarction in Despite its widespread use, the mechanism of action of warfarin was not discovered until , when John W. Suttie and colleagues demonstrated that warfarin disrupts vitamin K metabolism by inhibiting the enzyme epoxide reductase.

Roderick, L. The pathology of sweet clover disease in cattle. Therapy with this agent must be ceased immediately when it becomes clear that the patient is pregnant.

Low-molecular weight heparins are a good alternative, since they do not cross the placenta and have been proven to be safe for mother, embryo, and fetus [ 58 ]. To say that anticoagulant coumarins have only a few side effects is an absolute understatement.

Warfarin is one of the leading drugs with adverse effects requiring hospital admission [ 59 ]. Most of all, there is the constant chance of severe bleeding [ 60 ]. This can include internal hemorrhagic conditions in the head, gastrointestinal tract, female genitalia, the bladder and urethra or skeletal joints and muscles [ 40 , 61 ].

They generally present as severe headache, stomach pain, and black or bloody stool, heavier than normal menstrual bleeding, discoloration of urine, and pain and swelling of the joints or muscles.

Prolonged bleeding from external sharp or blunt wounds is always present [ 61 ]. All these conditions are the result of inability of the affected tissues to initiate and continue the process of hemostasis after damage to the epithelial barrier [ 62 ]. Patients suffering from hypertension, disorders of the liver, bleeding lesions, and the elderly and patients using drugs and substances that affect coagulation are at higher risk to suffer from bleeding when using warfarin [ 63 ].

Hypertension poses mechanical defects in the blood vessels, especially the arteries. Disorders of the liver reduce the ability of the body to eliminate the warfarin and thus make it more biologically available.

In bleeding lesions, warfarin inhibits hemostasis. Among substances that can lead to bleeding when used with warfarin are steroidal and non-steroidal anti-inflammatory drugs, antibiotics, and alcohol. These potentiate the activity, interfere with the protein binding, and reduce the metabolism of warfarin, respectively [ 63 ]. Other side effects include injury to the kidneys with potential nephritis [ 64 , 65 , 66 ], inflammation of the skin [ 67 ] and blood vessels [ 66 ], and potentiation of rhabdomyolysis by simvastatin [ 64 ].

Due to resistance of rodents against warfarin, superwarfarins have been created [ 68 ]. These have a much longer time of activity and hence need only to be consumed once by the rodents, contrary to warfarin. The result however is that their effect persists much longer when deliberately or accidently consumed by humans [ 69 ] and treatment of this intoxication is a more challenging enterprise. The efficacy of the anticoagulant treatment with warfarin highly depends on its bioavailability, since inhibition of the target epoxy reductase enzyme depends on direct binding of the drug to this protein [ 38 ].

In addition, vitamin K from external sources does not rely on recycling through this enzyme [ 38 ]. Hence, the absorption, transport, delivery, and elimination of warfarin as well as the external availability of vitamin K are potential sites of interaction with other drugs and with food and dietary supplements.

Drugs and food that influence the enterohepatic circulation can all affect the absorption of warfarin. Examples of these are the drug cholestyramine [ 37 ] and the avocado fruit [ 70 ], which prevent the reabsorption of warfarin in the intestines Concomitant administration of other protein-bound drugs may lead to greater amounts of circulating warfarin and increased risks of bleeding.

Valproate sodium increases the bioavailability of warfarin through dislocation of its protein-binding sites [ 71 ]. Interference with the metabolism of warfarin is a potential of most drugs that are eliminated by hepatic metabolism. Among these are aspirin [ 72 ], nonsteroidal anti-inflammatory drugs [ 72 ], serotonin reuptake inhibitors [ 49 ], antiplatelet agents and some antibiotics [ 72 ]. It can go both ways with the metabolism. Induction of the cytochromes will increase the elimination, while occupation of the binding sites by the drugs will increase the availability of warfarin.

Since warfarin acts through elimination of available bioactive vitamin K, variations of the net intake of this vitamin will certainly interfere with the drug action. A high intake of the vitamin will keep the coagulant factors at a higher level and thus inhibit the anticoagulant activity. Likewise, a lower intake will potentiate the effect of warfarin. The vitamin occurs in food in the form of phylloquinone and menaquinone. Phylloquinone is the form mostly found in plants and is also the most abundant form in food [ 73 ].

Menaquinones are mainly the product of bacterial production or conversion [ 74 ]. Consequently, simple multivitamin and other supplements, food with high vitamin K content [ 74 ] as well as antibiotics are sources of fluctuation in vitamin K intake since intestinal bacteria significantly contribute to the production of menaquinones [ 75 ]. Recently, another source of interference came into focus.

In addition to the previous mentioned parameters, genetic variation in the expression of cytochrome P seems to play a role in the metabolism of warfarin [ 76 ], thus influencing the availability of the drug [ 77 ]. All these considerations make it clear that close monitoring of the individual coagulation ability is necessary for a successful therapy with this agent. The abovementioned interactions are just a few of the many that are possible.

Table 1 gives examples of a variety of interactions with drugs, food, natural products, and supplements. This is only to underscore the cautious approach patients should practice when taking warfarin. The missing link: The story of Karl Paul link.

Toxicol Sci ; Discovery of anticoagulant drugs: A historical perspective. Curr Drug Discov Technol ; A tale of two anticoagulants: Warfarin and heparin. J Surg Educ ; Year : Volume : 5 Issue : 3 Page : How to cite this article: Ramachandran S, Pitchai S.