Anticoagulant action, mechanism

The year of 1961, when Vincent Gott11 observed the inhibition of thrombus formation by immobilized heparin for the first time, was marked as the second birth date of heparin, since it was for the first time isolated from liver tissue. Its anticoagulant action was detected in 1892. Although more than 20 years have passed since Gott s publication, there is still much confusion concerning the views on the mechanism of enhanced thromboresistance of heparin-modified polymers, which greatly hinders the introduction of HCP into clinical practice. 

D. Thrombin-Like Enzymes. Ancrod (arvin), a very specific snake venom component, has been investigated extensively for its anticoagulant action. Ancrod is a very specific protease whose action has some similarity to that of thrombin and occurs in the terminal sequence of a complex blood coagulation mechanism. Ancrod hydrolyzes only the Aa chain of fibrinogen and produces a polymer of the type (a Bp y)n rather than the (aPy)n type normal fibrin clot. The microclot produced by ancrod from fibrinogen is readily hydrolyzed by plasmin that was activated from tissue plasminogen. This results in a defibrination effect. This property is extensively used in the treatment of a patient who has suffered from myocardial infarction. 

Hirsh J, Dalen JE, Anderson DR et al (2001) Oral anticoagulants mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 119 (Suppl.) 8S-21S... 

Compare and contrast the mechanisms of action of drugs used for ventricular rate control, conversion to sinus rhythm and maintenance of sinus rhythm in patients with AF, and explain the importance of anticoagulation for patients with AF. 

Walker, C. and Royston, D. 2002. Thrombin generation and its inhibition a review of the scientific basis and mechanism of action of anticoagulant therapies. British Journal of anaesthesia 88(6), 848-863. 

Mechanism of Action A direct thrombin inhibitor that reversibly binds to thrombin-active sites. Inhibits thrombin-catalyzed or thrombin-induced reactions, including fibrin formation, activation of coagulant factors V, VIII, and XIII also inhibits protein C formation, and platelet aggregation. Therapeutic Effect Produces anticoagulation. Pharmacokinetics Following IV administration, distributed primarily in extracellular fluid. Protein binding 54%. Metabolized in the liver. Primarily excreted in the feces, presumably through biliary secretion. Half-life 39-51 min. 

Mechanism of Action An anticoagulant that specifically and reversibly inhibits thrombin by binding to its receptor sites. Therapeutic Effect Decreases acute ischemic complications in patients with unstable angina pectoris. 

Mechanism of Action An antithrombin that inhibits factor Xa and thrombin in the presence of low-molecular-weight heparin. Only slightly influences platelet aggregation, PT, and aPTT. Therapeutic Effect Produces anticoagulation. 

Mechanism of Action An anticoagulant that binds specifically and directly to thrombin, inhibiting free circulating and clot-bound ihmmhinT herapeuticEffect Prolongs the clotting time of human plasma. 

Mechanism of Action An anticoagulant that inhibits thrombogenic action of thrombin (independent of anf ithrombin II and nof inhibif ed by platelet factor 4). One molecule of lepirudin binds to one molecule of fhrombin. Therapeutic Effect Produces dose-dependent increases in aPTT. 

Mechanism of Action A protein that complexes with heparin to form a stable salt. Therapeutic Effect Reduces anticoagulant activity of heparin. 

Mechanism of Action A low-molecular-weight heparinthat inhibits factor Xa. Causes less inactivation of thrombin, inhibition of platelets, and bleedingthan standard heparin. Does not significantlyinfluence bleeding time, PT, aPTT. Therapeutic Effect Produces anticoagulation. 

Mayer, A. M. S., Rodriguez, A. D., Berlinck, R. G. S., and Hamann, M. T. (2009). Marine pharmacology in 2005-6 Marine compounds with anthelmintic, antibacterial, anticoagulant, antifungal, antiinflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities affecting the cardiovascular, immune and nervous systems, and other miscellaneous mechanisms of action. Biochim. Biophys. Acta 5, 283-308. 

Mayer AMS, Hamann MT (2004) Marine Pharmacology in 2000 Marine Compounds with Antibacterial, Anticoagulant, Antifungal, Anti-Inflammatory, Antimalarial, Antiplatelet, Antituberculosis, and Antiviral Activities Affecting the Cardiovascular, Immune, and Nervous Systems and Other Miscellaneous Mechanisms of Action. Mar Biotechnol 6 37... 

In the same way, the mechanism of action of drugs and coagulant and anticoagulant medication takes place through the variation of surface charge in the blood vessels. 

Ariens [432] was the first to describe drug action through indirect mechanisms. Later on, Nagashima et al. [433] introduced the indirect response concept to pharmacokinetic-dynamic modeling with their work on the kinetics of the anticoagulant effect of warfarin, which is controlled by the change in the prothrombin complex synthesis rate. Today, indirect-response modeling finds extensive... 

---