Vitamin K antagonism

Most oral anticoagulants are coumarin derivatives that act via vitamin K antagonism ([2] Fig. 2). Vitamin K... 

Particular attention is given to the development of new mechanistic biomarker assays and bioassays that can be used as indices of the toxicity of mixtures. These biomarker assays are typically based on toxic mechanisms such as brain acetylcholinesterase inhibition, vitamin K antagonism, thyroxin antagonism, Ah-receptor-mediated toxicity, and interaction with the estrogenic receptor. They can give integrative measures of the toxicity of mixtures of compounds where the components of the mixture share the same mode of action. They can also give evidence of potentiation as well as additive toxicity. 

Altered gut vitamin K synthesis. Vitamin K antagonizes the effects of warfarin. External sources of vitamin K include the diet and intestinal flora, the latter only becoming significant in those with a low dietary intake of the vitamin. Broad-spectrum antibiotics that may reduce intestinal bacteria may alter the effect of warfarin. 

Park, B.K., Leek, J.B. (1982). A comparison of vitamin K antagonism by warfarin, difenacoum and brodifacoum in rabbit. Biochem. Pharmacol. 31 3635-9. 

HPLC, High-performance liquid chromatography RIA. in vitamin K antagonism or absence. 

Goodman SG, Wojdyla DM, Piccini JP, et al Factors associated with major bleeding events insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation). J Am Coll Cardiol 2014 63 891-900. 

The antagonisms that exist between unsaturated fatty acids, and carotene and vitamin E are compHcated and largely undefined. Linoleic acid acts as an antivitamin to i7/-a-tocopherol [59-02-9, 1406-18-9, 10191-41-0] (vitamin E) by reducing availabiHty through direct intestinal destmction. Various Hpoxidases destroy carotenes and vitamin A (73). Dicoumarol [66-76-2] (3,3 -methylenebis(4-hydroxycoumarin)) is a tme antimetaboHte of vitamin K [12001 -79-5] but seems to occur only in clover and related materials that are used primarily as animal feeds (74). 

Vitamin K can antagonize coumarinic acid compounds (warfaria and its congeners) and iadandione derivatives. Vitamin K exists ia several forms including simple water-soluble meaadioae [58-27-5] (9)... 

EN formulas contain vitamin K, which can antagonize the pharmacologic activity of warfarin. The vitamin K content of EN formulas generally has been adjusted down over the past... 

Warfarin and dicoumaroi antagonize the Y-carboxjdation activity of vitamin K atid thus act as anticoagulants. They interfere with the cotranslational modification during synthesis of the precoagulation factors. Once these proteins have been released into the bloodstream, vitamin K is no longer important for their subsequent activation and function. Itdated to this are two... 

Hypoprothrombinemia may occur in malabsorption syndromes and also the use of broad-spectrum antibiotics may produce a hypoprothrombinemia that responds readily to small doses of vitamin K. In premature infants and in infants with hemorrhagic disease of the newborn the use of vitamin K may be indicated. However, the main indication for the use of vitamin K is to antagonize the anticoagulant activity of coumarins. Oral absorption of phytonadione and the menaquinones is by the lymph while menadione and its water-soluble derivatives are absorbed directly. The absorption of phytonadione is energy-dependent and saturable. Intravenous administration of phytonadione has produced flushing, dyspnea, chest pains, and cardiovascular collapse. 

Green tea Antagonism by vitamin K constituent Decreased INR no signs and symptoms of suboptimal anticoagulation ... 

The coumarin anticoagulants, which include warfarin [WAR far in] and dicumarol [dye KOO ma role] (formerly bishydroxycoumarin) owe their action to their ability to antagonize the cofactor functions of vitamin K. Initially used as a rodenticide, warfarin is now widely employed clinically as an oral anticoagulant. Conflicting opinions exist concerning the usefulness of these agents in clinical situations such as myocardial infarction and hip arthroplasty. The potential... 

As has already been mentioned, naphthomycin inhibits grampositive bacteria, although it does not inhibit RNA polymerase. An antagonism between naphthomycin and vitamin K has been observed28), but the underlying mode of action is not known. 

When these patients are discharged from hospital, prophylactic treatment with an oral anticoagulant is recommended to prevent recurrence of the thrombosis. Warfarin sodium, which antagonizes the effects of vitamin K, is used in prophylaxis and treatment of DVT and pulmonary embolism. It is usual to start with an induction dose of 10 mg daily for two days the dose can then be reduced. Patients need to be monitored as there is a risk of haemorrhage with oral anticoagulant drugs. 

Potential tor reduced bioavailability because of complexation of drug with divalent and bivalent cations found in enteral feeding Decreased absorption of warfarin because of enteral feeding therapeutic effect antagonized by vitamin K in enteral formulations... 

Very high intakes may antagonize vitamin K and hence potentiate anticoagulant therapy. This is probably the result of inhibition of the vitamin K quinone reductase, but a-tocopheryl quinone may compete with vitamin K hydroquinone and hence inhibit carboxylation of glutamate in target proteins (Section 5.3.1). 

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