Clinical Experiences with 4-Hydroxycoumarin Anticoagulant No. 63 and the Antagonistic Effect of Menadione and Vitamin K ₁

Abstract

The successful use of dicumarol in the prevention of intravascular thrombosis and subsequent embolism has led to the investigation of other coumarin compounds as therapeutic anticoagulants. 4-Hydroxycoumaiin anticoagulant

Anticoagulant Rodenticide Toxicity to Non-target Wildlife Under Controlled Exposure Conditions

“…While it might seem that inclusion of dietary menadione in AR studies is akin to administering antidote with the test compound, this may, or may not, be the case. Specifically, menadione is much less potent than vitamin K 1 in restoring prothrombin time following therapeutic anticoagulant administration in man (Hanson et al 1951) and in treating AR intoxication in dogs (Mount et al 1986), and it does not reverse prolonged clotting time in chickens receiving coumarin-type ARs (Griminger 1965). The provitamin menadione must undergo enzymatic prenylation (rate limited) to form menaquinone-4 (MK-4, member of the K 2 family) prior to VKOR metabolism to the biologically active form (i.e., vitamin K hydroquinone) required for γ-glutamyl vitamin K-dependent carboxylation (Hirota et al 2013).…”

Challenges in the interpretation of anticoagulant rodenticide residues and toxicity in predatory and scavenging birds

“…While it might seem that inclusion of dietary menadione in AR studies is like feeding an AR antidote, it is unlikely the case. The provitamin menadione is much less potent than vitamin K 1 in restoring prothrombin time following therapeutic anticoagulant administration, 77 and it does not reverse coagulopathy in chickens fed warfarin 78 . It must undergo enzymatic prenylation (rate‐limited) to form menaquinone‐4 prior to VKOR metabolism to the biologically active form (i.e.…”

Proceedings of the Physiological Society, 6 June 1970; Oxford Meeting: Communications

“…The time course of the vasoconstriction in response to maintained subatmospheric pressures is of the same order as vascular resistance changes seen in dog limbs in response to altered perfusion pressures (Hanson, 1964;Jones & Berne, 1964).…”