Where is warfarin metabolized
|Synonyms:||3-alpha-acetonylbenzyl-4-hydroxycoumarin, 4-hydroxy-3- (3-oxo-1-phenylbutyl) coumarin|
|Trade names:||Athrombine-K, Brumolin, Compound 42, Coumadin, d-CON, Kumadu, Marfrin, Maveran, Ratoxin, Temus W, Warf Compound 42, Warficide|
|CAS no .:||81-81-2|
|RTECS no .:||GN4550000|
|EU no .:||607-056-00-0|
|EINECS no .:||201-377-6|
|UN classification:||UN hazard class: 6.1, UN packing group: I.|
|Occupational exposure limit values:||TLV as TWA: - ppm; 0.1 mg / m3 (ACGIH 1993/94); MAK as total dust: - ppm; 0.5 mg / m3; II, 2 (1997)|
|Melting point:||161 ° C|
|Solubility in water:||Insoluble|
Properties:The colorless to white crystalline powder is flammable and, in finely divided form, can react explosively in the air. The substance reacts with strong oxidizing agents.
Toxicity:The MAK value for warfarin is 0.1 mg fine dust per m³.
Toxic effect:Warfarin is mostly absorbed enterally (only in extreme cases also percutaneously). Elimination in the body is very slow. The binding to the plasma protein is 90 to 99%. Elimination will mainly take place via the faeces. Almost 90% are eliminated within a period of approx. 4 days. Warfarin is subject to an enterohepatic cycle and can thus develop an effect of 1 - 7 days. The effect is brought about by inhibiting the formation of prothrombin by displacing vitamin K. There is a reduced ability of the blood to clot. Warfarin is metabolized in the liver.
Symptoms: Red spots and bleeding develop after ingestion. Even low concentrations can trigger hemorrhages. There is sometimes a latency period. Repeated or chronic ingestion has shown malformations in newborn test animals. Warfarin causes severe fertility problems. In the case of poisoning, there is an increased willingness to bleed in the area of the mucous membranes. This increased tendency to bleed not only affects the mucous membranes, but can also spread to the skin, tissues, joints, brain (can lead to apoplectic insult), respiratory, urogenital and gastrointestinal tracts. In humans, body and back pain, bleeding from the nose and gums can be recognized. Main risk:Profuse, unstoppable bleeding.
Activities: The patients must be rescued from the contaminated environment immediately. Every patient receives mandatory oxygen. The affected skin should be rinsed thoroughly with plenty of water. When ingestion, the mouth should be rinsed thoroughly. The patients receive 1 g of medicinal charcoal per kilogram of body weight. If the eye is affected, it must be anesthetized and carefully rinsed. The patients must be monitored clinically, as the symptoms may take days to show. If possible, vitamin K should be used in the preclinical phase1 be applied. Antidote administration:The gift of Konakion®, also purely prophylactic, makes sense. Vitamin K1 May only be administered orally if medical charcoal has not been used to bind poison beforehand. Dosage:The dosage is equivalent to the intravenous administration of 20 mg Konakion®. A repetition can be carried out after 1 - 2 hours. Continuous control of the Quick value is urgently required and determines the further course of the application of vitamin K.1.
Forecast:The prognosis is very good if the amount consumed is small.
One soldier took 567 mg of warfarin. After a few days there was slight pain in the back and kidney region, vomiting, epistaxis and abdominal pain. The thromboplastin time was slowed. Treatment with fresh blood transfusions and the administration of vitamin K survived the poisoning.
A man, 32 years old, was given a total of about 1 g of warfarin over a period of 10 days with intent to murder. On the 4th day there was bleeding from the nose. Mouth bleeding occurred the following days. The patient complained of aching limbs. 12 days after the first ingestion of the poison, he died of circulatory failure.
Precautions: Avoid spreading dust. Hands and eyes must be protected with suitable means. Heavy respiratory protection must be used. Pregnant women in particular should avoid contact with the substance.
Annotation: Warfarin is usually commercially available as the sodium salt. The information given here applies to pure warfarin. The decomposition temperature, the flash point and the explosion limits are not known from the literature.
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