Bishydroxycoumarin

There is thus obtained bishydroxycoumarin (3). Subsequent pharmacologic and clinical work revealed this compound to be an effective anticoagulant drug in humans. It is of note that none of the synthetic anticoagulants shows in vitro activity. Rather, these compounds owe their effect to inhibition of synthesis by the liver of one of the co-factors necessary for coagulation. 

Bile acids, steroids from, 188 Biperidin, 47 Birch, Arthur J., 163 Birch reduction, 163, 167, 170 Bishydroxycoumarin, 331 Bismethylenedioxy group, 193 Blocking agents, of B-sympathet-ic receptors, 65, 117... 

Nl. Nagashima, R., Levy, G., and Nelson, E., Comparative pharmacokinetics of coumarin anticoagulants. I. Unusual interaction of bishydroxycoumarin with plasma proteins—development of a new assay. J. Pharm. Sci. 57, 58-67 (1968). 

This drug is used for preventing and treating thrombosis, thrombophlebitis, thromboe-molium, and for preventing thrombo-formation in post-operational periods. Synonyms of this drug are bishydroxycoumarin, dicumol, cromolyn, and others. 

Bishydroxycoumarin (dicoumarol) is a natural occurring anticoagulant found in sweet clover. A number of coumarin derivatives have been synthesized as anticoagulants, warfarin, phenprocoumon and acenocoumarol being most frequently used. The nonpolar carbon substituent at the 3 position required for activity is asymmetrical. The enantiomers differ in both pharmacokinetic and pharmacodynamic properties. The coumarins are marketed as racemic mixtures. 

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... 

Drug potentiation Transient potentiation of the hypoglycemic effect of tolbutamide (see p. 260) or the anticoagulant effect of warfarin or of bishydroxycoumarin (see p. 199) results from their displacement from binding sites on serum albumin. Free methotrexate (see p. 378) levels may also rise through displacement. 

BISHYDROXYCOUMARIN see BJZOOO BIS(4-HYDROXY-3-COUMARIN) ACETIC ACID ETHYL ESTER see BKAOOO... 

Particle size may play a major role in drug absorption. Dissolution rate of solid particles is proportional to surface area, and hence to particle fineness. Particle size reduction has been used to increase the absorption of a large number of poorly soluble drugs, such as bishydroxycoumarin, digoxin, griseofulvin, nitrofurantoin, and tolbutamide. 

Bishydroxycoumarin Phenytoin Risk of phenytoin toxicity Inhibition of phenytoin metabolism... 

The coumarins were first discovered in Wisconsin, when bleeding in cattle was found to be due to the consumption of bruised sweet clover in the 1920s (1). The causative agent, dicoumarol, was isolated in 1940, and a range of related compounds was then synthesized, the most popnlar of which proved to be warfarin (named after the Wisconsin Alumni Research Foundation). Other conmarins that have been used are acenocoumarol (nicoumalone), bishydroxycoumarin, dicoumarol, ethyl biscoumacetate, and phenproconmon. 

Rgure 10.10 Plasma levels of bishydroxycoumarin (BHC), also known as dicoumarol, in 6 subjects after a 300 mg oral dose with water (solid line), magnesium hydroxide (dotted line) or aluminium hydroxide (dashed line). Closed data points represent a significant difference from control. 

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