Antifibrinolytic

H2N(CH2)jCOOH, C H,3N02. Prepared from -benzoylaminocapronitrile or from l-hydroxycyclohexylhydroperoxide, m.p. 205 0. Aminocaproic acid is an antifibrinolytic agent, used to treat thrombosis in the deep veins. amiDoethyl alcohol. See ethanolamines. 

The plasminogen molecule contains several sites that specifically bind a number of antifibrinolytic amino acids, such as lysine [56-87-1] and S-aminocaproic acid [60-32-2] (EACA). These sites are known as lysine binding sites (LBS), and are localized mainly to the A or heavy chain of the molecule. One is located in K4 and at least one more is in K1 through K3. One LBS, which is beheved to reside in Kl, has a stronger affinity for EACA, whereas the others have a weaker affinity. The LBS are important for the interaction of plasminogen with several components of the endogenous fibrinolytic system. 

E. Ogston, Antifibrinolytic Drugs Chemistry, Pharmacology and Clinical Usage, ]ohn Wiley Sons, Inc., Chichester, UK, 1984, p. 1. 

Prophylactic treatment of Cl INH deficiency consists of Cl INH replacement infusions, androgens (danazol, stanozolol, oxymethalone) or antifibrinolytic agents. Acute treatment employs Cl INH replacement (where available), fresh-frozen plasma, and placement of an airway when significant airway obstruction is evident. Abdominal attacks require IV fluid, analgesics, and watchful waiting . 

The inflammatory process in sepsis is linked to the coagulation system. Pro-inflammatory mediators maybe procoagulant and antifibrinolytic, whereas anti-inflammatory mediators may be fibrinolytic. A key factor in the inflammation of sepsis is activated protein C, which enhances fibrinolysis and inhibits inflammation. Protein C levels are decreased in septic patients. 

Proinflammatory mechanisms in sepsis are also procoagulant and antifibrinolytic. Levels of activated protein C, a fibrinolytic and antiinflammatory substance, are decreased in sepsis. 

Tranexamic acid (Cyklokapron, Transamin) is a synthetic derivative of the amino acid lysine. It exerts its antifibrinolytic effect through the reversible blockade of lysine binding sites on plasminogen molecules. 

Mecfianism of Action A systemic hemostatic that acts as an antifibrinolytic and an-tihemorrhagicby inhibitingthe activation of plasminogen activator substances. Therapeutic Effect Prevents formation of fibrin dots. 

Tranexamic acid produces an antifibrinolytic effect by blocking the lysine binding site on plasminogen which is essential for binding to fibrin and thereby prevents the activation of plasminogen on the surface of fibrin. 

Oral anti-coagulants Thrombolytic (fibrinolytic) drugs Antifibrinolytic agents Antiplatelet drugs CLOTTING CASCADE... 

Figure 17.4 Antifibrinolytic action of the lysine analogues. Normally, plasminogen binds to fibrin at a lysine-binding site and is converted in the presence of tissue plasminogen activator (tPA) to piasmin. The lysine analogues block the lysine-bIndIng site and prevent access of plasminogen to tfie fibrin molecule. Reproduced from Dunn O, Goa KL. Drugs 1999 57 1005-32, with permission.)...

Tranexamic acid Solubility enhancer Antifibrinolytic agent, hemophilia... 

A third underlying mechanism seems to involve a reduction in concentrations of free protein S, again more pronounced with third-generation products. When protein S falls, the antifibrinolytic effect of the so-called thrombin-activated fibrinolysis inhibitor is increased in other words, fibrinolysis is impeded, with an increased risk of clotting problems (104). Again, however, these are recent methods, which were not available when the third-generation products were launched. 

Most of the reported thromboembolic complications occurred in elderly patients and desmopressin should not be used in patients with documented arterial disease or even in elderly patients, in whom some degree of latent arterial disease may be assumed to be present (34). Concomitant use of antifibrinolytic agents, such as tra-nexamic acid, should also be avoided. 

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