VIII. PHARMACOLOGY 435 



"It is possible that vitamin K affects factors which govern prothrombin 

 conversion as well as those which control its concentration." 



VIII. Pharmacology 



CHARLES A. OWEN, JR. 



A. VITAMIN K PREPARATIONS 



Phytyl menadione (thylloquinone, vitamin Ki, 2-methyl-3-phytyl-l,4- 

 naphthoquinone) has been synthesized and is commercially available, al- 

 though expensive. Concentrates of natural vitamin K and synthetic 

 menadione (U.S. P.) (menaphthone B.P., 2-methyl-l,4-naphthoquinone) 

 are relatively inexpensive. All these substances are fat-soluble, and when 

 given orally in the absence of intestinal bile they require the administration 

 of bile salts. 



For the simple deficiencies of vitamin K the water-soluble analogs are 

 generally preferred, such as the following: menadione sodium bisulfite; 

 4-amino-2-methyl naphthol HCl; or 2-methyl-l,4-naphthohydroquinone 

 diphosphate tetra sodium (a menadiol derivative). In the uncomplicated 

 vitamin K deficiencies menadione has been found to be the strongest cor- 

 rective analog with approximately two to four times the activity of phytyl 

 menadione.^' ^ Despite an occasional objection,^ the weight of evidence is 

 that vitamin Ki is more effective than menadione in counteracting the 

 effects of the anticoagulant dicoumarins. 



B. DOSAGES 



For the vitamin K deficiency of obstructive jaundice, biliary fistula, or 

 hemorrhagic disease of the newborn, daily doses of 1 to 5 mg. of any of the 

 vitamin K analogs are usually adequate. One milligram is stated to be 

 sufficient to prevent the clotting changes produced by 1 g. of sodium acetyl- 

 salicylate.'* Ten to twenty milligrams has been recommended for adminis- 

 tration to the mother during the last few hours of labor to prevent hemor- 

 rhagic disease of the infant. These doses are so much greater than minimal 

 effective ones that the slight differences of potency of the various vitamin 



1 H. J. Almquist and A. A. Klose, Proc. Soc. Exptl. Biol. Med. 45, 55 (1940). 



2 S. A. Thayer, R. W. McKee, S. B. Binkley, and E. A. Doisy, Proc. Soc. Exptl. Biol. 

 Med. 44, 585 (1940) ; S. A. Thayer, R. W. McKee, S. B. Binkley, D. W. MacCorquo- 

 dale, and E. A. Doisy, ibid, 41, 194 (1939); H. J. Almquist and A. A. Klose, /. 

 Biol. Chem. 130, 787 (1939). 



3 S. Shapiro, M. Weiner, and G. Simson, New Engl. J. Med. 243, 775 (1950). 

 * S. Shapiro, J. Am. Med. Assoc. 125, 546 (1944). 



I 



