Mode of Action and Characteristics of Some Coagulation-Active Drugs and Their Dosage

Abstract

Proprietary names: Aspirin, Colfarit, Godamed, Monobeltin. The acetyl-group of acetylsalicylic acid is transferred to a series of plasma proteins (albumin, globulin, hemoglobulin, platelet proteins). The functional limitation of the thrombocytes depends on inhibition of their cyclooxygenase by acetylation of this enzyme. The transformation of arachidonic acid into the prostaglandin peroxides PGG₂ and PGH₂ is inhibited, so no thromboxane A₂ is formed. The formation of further prostaglandin derivatives, such as PGF_2α, PGD₂ and PGE₂ also does not occur. The two latter substances have an antiaggregatory effect. Moreover, through inhibition of the cyclooxygenase of the endothelium of the vessel wall, no prostacyclin is synthesized. For inhibition of the vessel wall cyclooxygenase higher doses are necessary than for inhibition of the platelet cyclooxygenase. After a single dose of acetylsalicylic acid the activity of the cyclooxygenase in the vessel wall is again demonstrable after a shorter time than in the platelets. Because in animal research after high doses of acetylsalicyclic acid a transitory thrombotic tendency occurred, and some workers showed a shortening of the bleeding time in man, the opinion arose that a better antithrombotic protection was guaranteed by daily low doses or intermittent administration. The research results mentioned could not be verified by other workers, so that next the therapeutic dose remained to be administered at 1–1.5 g/day. Studies with daily doses of 50–100 mg are in progress.