Anticoagulant activity

Protein C is a vitamin K-dependent natural anticoagulant activated by thrombin to form APC in the presence of the endothelial receptor, TM. APC proteolyzes factors Va and Villa, thus downregulating thrombin generation. APC may also have anti-inflammatory... 

Sulfinpyrazone may increase die anticoagulant activity of oral anticoagulants. There is an increased risk of hypoglycemia when sulfinpyrazone is administered with tolbutamide. Concurrent administration of sulfinpyrazone widi verapamil may decrease die effectiveness of verapamil. 

The relationship between structure and anticoagulant activity of heparin was a conundrum that puzzled Stacey. He did not solve the problem, but demonstrated that certain structural features of heparin (for example, extensive release of amino groups) alone were not responsible for the biological activity. 

Table VI lists several drugs Inducing hepatic microsomal enzymes (5). These enzymes can metabolize the drug as well as other substrates. Barbiturates, grlseofulvln, and glutethlmlde Induce enzymes which metabolize coumarln and phenlndlone derivatives and thus reduce their anticoagulant activity. Dlphenylhydantoln and phenylbutazone stimulate cortisol hydroxylase activity and Increase the urinary excretion of B-hydroxy cortisol and decrease the concentration of cortisol In the plasma.

Heparin was discovered in 1916 by a medical student at Johns Hopkins University. While attempting to extract thromboplastic substances from various tissues he discovered a substance with powerful anticoagulant activity. This was named heparin because it was first extracted from the fiver. 

FIGURE 7.2 LMWH inhibits factor Xa and minimally affects factor Ha thus, activated partial thromboplastin time is not used to measure its anticoagulant activity. (Reprinted from the American Family Physician published by the American Academy of Family Physicians, February 15th, 1999, in an article entitled Low-molecular-weight heparin in outpatient treatment of DVT. )... 

Desirudin is a SC administered DTI approved for VTE prevention after hip replacement surgery but is not yet commercially available in the United States. Desirudin has an elimination half-life of 2 to 3 hours and is typically dosed every 12 hours. It is primarily eliminated through the kidneys, so dose reduction is needed in patients with renal impairment. The aPTT should be used to measure desirudin s anticoagulant activity.29,38,41... 

The final yield and purity of a heparin preparation depend largely on the use of appropriate, analytical methods at different stages of extraction and purification. Heparin in tissue extracts is still most commonly determined biologically, by such assays as the U.S.P. assay for anticoagulant activity. It is now recognized10 that the anticoagulant activity does not measure the actual concentration of heparin (see also Sections XII and XIII). 

Prepa- ration1 Mean mol. wt. Ratio8 of sulfate to carbox-ylate Ratio8 of N-acetyl to carbox-ylate wr (degrees) Anti- lipemic activity (Luy Anticoagulant activity ... 

Because of interplay of the foregoing interactions with those mediated by antithrombin,509 the antithrombotic effect in vivo does not necessarily reflect the in vitro anticoagulant activities, as measured either by wholeclotting502 or anti-Xa assays.510... 

Table L Intensity of Labelling versus Heparin Anticoagulant Activity...

It is of interest to note that the crystalline barium heparinate, which is an acid salt, tends to lose its anticoagulant powers very readily and that the authors consider that sulfur content gives no indication of heparin activity.93 Some polysaccharide sulfuric esters from marine algae possess anticoagulant activity. 

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