Antithrombotic agents actions

Mechanism of Action An antiplatelet and antithrombotic agent that binds to platelet receptorglycoproteinllb/Illa, preventing binding of fibrinogen. Therapeutic Effect inhibits platelet aggregation and thrombus formation. 

Garlic is used for a variety of reasons, and some of the attributes associated with it, e.g. for cancer prevention, or to reduce heart attacks, may not be substantiated. Other properties such as antimicrobial activity, effects on lipid metabolism, and platelet aggregation inhibitory action have been demonstrated. Ajoene has been shown to be a potent antithrombotic agent through inhibition of platelet aggregation. 

De ite differmces in their mechanisms of action and in vitro activities, pentasaccharide, DX-9065a and TAP have been shown to be effective antithrombotic agents in experimental models of venous thrombosis, coronary artery occlusion, arterial thrombolysis and acute reocclusion, restenosis after angioplasty, dialysis, and DIG. Pentasaccharide has also demonstrated measurable antithrombotic effects in human trials. Both TAP and DX-9065a produce measurable in vitro anticoagulant effects. In contrast, pentasaccharide does not produce an anticoagulant effect by the typical clot based assays. Thus, with fector Xa inhibitors there is not necessarily a correlation between current lab assays and antithrombotic efficacy as there is with heparin. 

Aspirin has emerged as a very nsefnl antithrombotic agent because of its action against platelet cyclooxygenase activity. 

The value of abciximab as an antithrombotic agent has been evaluated in a wide variety of animal models in several species. The object of these studies was to determine antithrombotic efficacy, bleeding risk, and duration of action, and to provide a comparison with conventional antithrombotic agents and combination therapy. 

There are a number of additional targets that may lead to effective antithrombotic therapy in ACS. In terms of anticoagulants, the concepts of agents that have dual inhibitor sites such as the one we find in heparin but that lack in some of its undesirable qualities could be very useful. The same concept may apply to drugs that have both anticoagulant and antiplatelet properties, It is quite probable that inhibitors of tissue factor as well as of the platelet ADP receptor when combined with aspirin might be very effective. An ability to block the feedback action of the polyphosphates released from platelets upon activation is also an attractive aim (Fig. 3),... 

Pyrazolo[2,3-a]imidazole possesses sedative and antipyretic action. Imidazo[2,l-fc]-[l,3,4]thiadiazoles are antithrombotic and thrombolytic agents. Furo[3,2-c]isoxazol-5-ones and their enantiomeric or racemic mixtures are used in the production of antitumor agents obtained from methyl-L-acosaminide and -daunosaminide. 

Antiplatelet therapy reduces the risk of recurrent vascular events after TIA and ischemic stroke, although few trials have distinguished between different etiological subtypes (Antithrombotic Trialists Collaboration 2002). Most trial data concern aspirin, but other antiplatelet agents such as clopidogrel (CAPRIE Steering Committee 1996) or extended-release dipyridamole (Sivenius et al. 1991) have also been shown to be effective although mechanisms of action may differ (Table 24.2). 

Figure 3. A diagrammatic illustration of the molecular heterogeneity in unfracdonated heparin and a rdated depolymerized agent Beside compoational variation, hq>arin and low molecular wdght heparins exhibit finctional heterogeneity in terms of its interaction with endogenous proteins and cdls The antithrombotic and anticoagulant effects of heparin are based on its polypharmacologic actions.

Chemical modification of the unfiactionated heparin, such as desul tion, deamination and coupling with various agents have resulted in products of non-anticoagulant nature with selective actions on enzymes and cellular receptors. Thioxyloside derivatives have also been reported to produce oral antithrombotic actions in animal models. However, relatively larger dosages are needed to produce these effects. These heparin derivatives are currently tested for such indications as sepsis, viral infections and the treatment of proliferative disorders. 

A synthetic hypersulfeted lactobionic acid amide (Aprosulate) has been developed for prophylactic antithrombotic use. This agent produces its action via heparin cofactor II and by inhibiting protease generation. The bioavailability of this agent is better than that of dermatan and heparan sulfetes. However, this product exhibits heparin-induced ftirombocytopenic effects and some teratogenetic potential. Thus, its use in clinical trials has been stopped. 

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