Vitamin K antagonist

Vitamin K antagonists (VKA) are a class of anticoagulants. They reduce blood clotting by inhibiting the recycling of vitamin K epoxide back to the active reduced form of vitamin K. The term Vitamin K antagonists is a misnomer. These drugs do NOT antagonize the action of Vitamin K. See below for the mechanism of action.

They can cause birth defects (teratogens).^[1]

All VKAs can be neutralized in action by administration of vitamin K, although for the second generation "super warfarins" intended to kill warfarin resistant rodents, the time of vitamin K administration may need to be prolonged to months in order to combat the long residence time of the poison.^[2]

Contents 1 Coumarins (4-hydroxycoumarins) 2 Other VKAs 3 See also 4 References

Coumarins (4-hydroxycoumarins)

Coumarins (more accurately 4-hydroxycoumarins) are the most commonly used VKA (they are a subset of VKAs), and sometimes the terms are loosely used synonymously (though this also is not quite accurate).

In medicine, the most commonly used VKA is warfarin.^[3] The primary mechanism of warfarin is the inhibition of vitamin K epoxide reductase. Note that VKAs are not antagonists of Vitamin K. They are inhibitors of the enzymatic conversion of inactive Vitamin K epoxide to its reduced active form.

Certain VKAs are also used as rodenticides. Warfarin was initially used as a rodenticide, but made the transition to pharmaceutical. Eventually some rodents developed resistance to it. The "second generation" VKAs for dedicated use as rodenticides are sometimes called "super warfarins." These VKAs are enhanced to kill warfarin-resistant rodents. The enhancement to the molecule takes the form of a larger lipophilic group to enhance the fat solubility of the poison and greatly increase the time it acts within the animal's body.^[4]

For a more complete list of VKA's used is pharmaceuticals and rodenticides, see the main article above.

Other VKAs

Not all VKAs are coumarins. For example, fluindione is a VKA,^[5] but not a coumarin.

Another example is phenindione.^[6]

Many of the non-coumarin VKAs are 1,3-indandione derivatives.

See also

• Vitamin K deficiency
• 4-hydroxycoumarin
• warfarin

References

Antithrombotics (thrombolytics, anticoagulants and antiplatelet drugs) (B01) Antiplatelet drugs Glycoprotein IIb/IIIa inhibitors Abciximab • Eptifibatide • Tirofiban ADP receptor/P2Y12 inhibitors thienopyridines (Clopidogrel, Prasugrel, Ticlopidine) • nucleotide/nucleoside analogs (Cangrelor, Elinogrel, Ticagrelor) Prostaglandin analogue (PGI2) Beraprost • Prostacyclin • Iloprost • Treprostinil COX inhibitors Acetylsalicylic acid/Aspirin# • Aloxiprin • Carbasalate calcium • Indobufen • Triflusal Thromboxane inhibitors thromboxane synthase inhibitors (Dipyridamole, Picotamide) • receptor antagonist (Terutroban†) Phosphodiesterase inhibitors Cilostazol • Dipyridamole • Triflusal Other Cloricromen • Ditazole Anticoagulants Vitamin K antagonists (inhibit II, VII, IX, X) coumarins: Acenocoumarol • Coumatetralyl • Dicoumarol • Ethyl biscoumacetate • Phenprocoumon • Warfarin# 1,3-Indandiones: Clorindione • Diphenadione • Phenindione other: Tioclomarol Factor Xa inhibitors (with some II inhibition) Heparin group/ glycosaminoglycans/ (bind antithrombin) low-molecular-weight heparin (Bemiparin, Certoparin, Dalteparin, Enoxaparin, Nadroparin, Parnaparin, Reviparin, Tinzaparin) oligosaccharides (Fondaparinux, Idraparinux) heparinoid (Danaparoid, Sulodexide, Dermatan sulfate) Direct Xa inhibitors xabans (Apixaban, Betrixaban, Edoxaban, Otamixaban, Rivaroxaban) Direct thrombin (II) inhibitors bivalent: Hirudin (Bivalirudin, Lepirudin, Desirudin) univalent: Argatroban • Dabigatran • Melagatran‡ • Ximelagatran‡ Other REG1 • Defibrotide • Ramatroban • Antithrombin III • Protein C (Drotrecogin alfa) Thrombolytic drugs/ fibrinolytics plasminogen activators: r-tPA (Alteplase, Reteplase, Tenecteplase) • UPA (Urokinase, Saruplase) • Streptokinase# • Anistreplase • Monteplase other serine endopeptidases: Ancrod • Fibrinolysin Brinase Non-medicinal Citrate • EDTA • Oxalate #WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase III M: MYL cell/phys (coag, heme, immu, gran), csfs rbmg/mogr/tumr/hist, sysi/epon, btst drug (B1/2/3+5+6), btst, trns

Pest control: rodenticides Anticoagulants/ vitamin K antagonists coumarins/4-Hydroxycoumarins: 1st generation (Warfarin, Coumatetralyl) • 2nd generation (Brodifacoum, Difenacoum, Flocoumafen) 1,3-Indandiones: Chlorophacinone • Pindone • Diphacinone other: Difethialone Convulsants Crimidine • Phenylsilatrane • Strychnine • Tetramethylenedisulfotetramine Calciferols Cholecalciferol • Ergocalciferol Inorganic compounds Aluminium phosphide • Arsenic • Barium carbonate • Calcium phosphide • Cyanide • Thallium • Zinc phosphide Organochlorine Chloralose • Endrin Organophosphorus Phosacetim Metabolic poisons Bromethalin • Fluoroacetamide • 1,3-Difluoro-2-propanol (Gliftor) • Sodium fluoroacetate Other α-Naphthylthiourea • Norbormide • Pyrinuron • Scilliroside