ChEBI: 2-methyl-3-(3,7,11,15-tetramethylhexadec-2-enyl)naphthalene-1,4-dione is a member of 1,4-naphthoquinones.
Both vitamins K3 and K4 may
produce hyperbilirubinemia and kernicterus in neonates as well as hemolysis in neonates and
glucose-6-phosphate–deficient patients. In fact, the only advantage of vitamins K3 and K4 over
vitamin K1 is that whereas absorption of vitamin K1 requires the presence of bile, absorption of
vitamins K3 and K4 does not, because they are absorbed via a passive process directly from the
intestine. This may be a slight advantage for patients with cholestasis or severe pancreatic
dysfunction. Only vitamin K1, however, is appropriate therapy for bleeding associated with warfarin
and superwarfarin anticoagulation. Vitamin K2 is not used therapeutically.
Vitamin K antagonists, such as warfarin, produce their effect on blood coagulation by interfering
with the cyclic interconversion of vitamin K and vitamin K 2,3-epoxide. Vitamin K is
an essential cofactor necessary for the posttranslational carboxylation of the glutamic acid residues
on the N-terminal portions of the specific clotting factors (II, VII, IX, and X) and anticoagulant
proteins, such as protein C. This γ-glutamyl carboxylation results in a new amino acid,
γ-carboxyglutamate, which through chelation of calcium ions causes the proteins to undergo a
conformational change. This change in tertiary structure allows the four vitamin K–dependent
clotting factors to become activated and bind to the negatively charged phospholipid membranes
during clotting cascade activation.
The half-life of vitamin K1 is quite short—only 1.7 hours via the intravenous route and 3–5 hours via
the oral route. When given orally, vitamin K1 is absorbed directly from the proximal small intestine in
an energy-dependent and saturable process that requires the presence of bile salts. These kinetic
features argue for administration in divided doses rather than larger, single daily doses. The typical
starting point for adults with drug-induced hypoprothrombinemia is 2.5 to 10 mg of vitamin K1 orally,
repeating in 12 to 48 hours if needed. In cases of ingestion of long-acting superwarfarin
rodenticides (e.g., brodifacoum), therapy may be 125 mg/day for weeks or months. Practically
speaking, because vitamin K1 is dispensed as 5-mg tablets, superwarfarin-poisoned patients may
require 10 to 30 tablets every 6 hours.
Vitamin K1 (phytonadione, Mephyton) is
the form of vitamin K most often used therapeutically. Vitamin K1 is safe for use in infants, pregnant
women, and patients with glucose-6-phosphate deficiency.
Moderately toxic by
subcutaneous route. An experimental
teratogen. When heated to decomposition it
emits acrid smoke and irritating fumes.
