ATC Group: B01A Antithrombotic agents

Abciximab is the Fab fragment of the chimeric monoclonal antibody 7E3. It is directed against the glycoprotein (GP) IIb/IIIa (α_IIbβ₃) receptor located on the surface of human platelets. Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets.

Acenocoumarol is a derivative of coumarin used as anticoagulant because acts as an antagonist of vitamin K. Vitamin K antagonists produce their anticoagulant effect by inhibition of the vitamin K-epoxide-reductase with a subsequent reduction of the gammacarboxylation of certain glutamic acid molecules which are located at several sites near the terminal end both of coagulation factors II (prothrombin), VII, IX, and X and of protein C or its cofactor protein S.

Acetylsalicylic acid combines significant advantages such as strong anti-pyretic, analgesic and anti-inflammatory action, that is the measure of comparison with all the newer NSAIDs.

Alteplase is a recombinant human tissue-type plasminogen activator, a glycoprotein, which activates plasminogen directly to plasmin. Once bound to fibrin, it is activated, inducing the conversion of plasminogen to plasmin leading to the dissolution of the fibrin clot.

Anistreplase is a thrombolytic drug, also known as anisoylated plasminogen streptokinase activator complex (APSAC). Eminase is a lyophilized formulation of anistreplase, the p-anisoyl derivative of the primary Lys-plasminogen-streptokinase activator complex (a complex of Lys-plasminogen and streptokinase). It is used in the emergency treatment of myocardial infarction and pulmonary emboli.

Antithrombin III is a small glycoprotein anticoagulant that inactivates several enzymes of the coagulation system and accounts for most of the antithrombin activity in plasma. It is a member of the serpin superfamily.

Apixaban is a potent, oral, reversible, direct and highly selective active site inhibitor of factor Xa. It does not require antithrombin III for antithrombotic activity. Apixaban inhibits free and clot-bound factor Xa, and prothrombinase activity. By inhibiting factor Xa, apixaban prevents thrombin generation and thrombus development.

Argatroban, a synthetic L-arginine derivative, is a direct thrombin inhibitor (molecular weight 526.65) that binds reversibly to thrombin. Argatroban exerts its anticoagulant effect independently of antithrombin III and inhibits fibrin formation; activation of coagulation factors V, VIII and XIII; activation of protein C; and platelet aggregation.

Bemiparin is a LMWH obtained by depolymerization of heparin from porcine intestinal mucosa. Bemiparin has confirmed its antithrombotic activity and, at the recommended doses, it does not significantly prolong global clotting tests.

Bivalirudin is a direct and specific thrombin inhibitor that binds both to the catalytic site and the anion-binding exosite of fluid-phase and clot-bound thrombin.

Cangrelor is a direct P2Y12 platelet receptor antagonist that blocks adenosine diphosphate (ADP)-induced platelet activation and aggregation in vitro and ex vivo. Cangrelor binds selectively and reversibly to the P2Y12 receptor to prevent further signalling and platelet activation.

Caplacizumab is a humanised bivalent Nanobody that consists of two identical humanised building blocks (PMP12A2hum1), genetically linked by a three-alanine linker, targeting the A1-domain of von Willebrand factor and inhibiting the interaction between von Willebrand factor and platelets. As such, caplacizumab prevents the ultralarge von Willebrand factor-mediated platelet adhesion, which is characteristic of aTTP. It also affects the disposition of von Willebrand factor, leading to transient reductions of total von Willebrand factor antigen levels and to concomitant reduction of factor VIII:C levels during treatment.

Carbasalate calcium is a complex of calcium acetyl salicylic acid and urea. It is a thrombocyte aggregation inhibitor. The antithrombotic effect is due to the irreversible acetylating of the enzyme cyclo-oxygenase in the thrombocyte, through which the formation of the prostaglandin thromboxane A₂ is inhibited.

Cilostazol and several of its metabolites are phosphodiesterase III inhibitors which suppress cyclic AMP degradation, resulting in increased cAMP in a variety of tissues including platelets and blood vessels. Studies in animals and in man (in vivo and ex vivo) have shown that cilostazol causes reversible inhibition of platelet aggregation.

Clopidogrel is a prodrug, one of whose metabolites is an inhibitor of platelet aggregation. Clopidogrel must be metabolised by CYP450 enzymes to produce the active metabolite that inhibits platelet aggregation.

Dabigatran etexilate is a small molecule prodrug which does not exhibit any pharmacological activity. After oral administration, dabigatran etexilate is rapidly absorbed and converted to dabigatran by esterase-catalysed hydrolysis in plasma and in the liver. Dabigatran is a potent, competitive, reversible direct thrombin inhibitor and is the main active principle in plasma.

Dalteparin is an antithrombotic agent, which acts mainly through its ability to potentiate the inhibition of Factor Xa and thrombin by antithrombin. It has a relatively higher ability to potentiate Factor Xa inhibition than to prolong plasma clotting time (APTT).

Danaparoid has been shown both in animal models and in human studies to be an effective antithrombotic substance. At therapeutic doses danaparoid has no or only a minor effect on haemostatic plug formation, platelet function and platelet aggregability with no significant effect on bleeding time at the recommended doses.

Defibrotide is an oligonucleotide mixture with demonstrated antithrombotic, fibrinolytic, anti-adhesive and anti-inflammatory actions. The mechanism of action is multifactorial. It primarily acts through reducing excessive endothelial cell (EC) activation (endothelial dysfunction), modulating endothelial homeostasis as well as restoring thrombo-fibrinolytic balance.

Desirudin is a highly potent and selective inhibitor of free circulating and clot-bound thrombin. The anticoagulant properties of desirudin are demonstrated by its ability to prolong the clotting time of human or rat plasma whether induced directly (thrombin time) or via the intrinsic (aPTT) or extrinsic (PT) pathways.

Dipyridamole is an antithrombotic agent with antiplatelet activity. Dipyridamole has an antithrombotic action based on its ability to modify various aspects of platelet function, such as platelet aggregation, adhesion and survival, which are factors associated with the initiation of thrombus formation.

Drotrecogin alfa is a recombinant version of the natural plasma-derived activated Protein C, from which it differs only by unique oligosaccharides in the carbohydrate portion of the molecule. Activated Protein C is a crucial coagulation regulator. Furthermore, Activated Protein C is an important modulator of the systemic response to infection and has antithrombotic and profibrinolytic properties. Drotrecogin alfa has similar properties to those of endogenous human Activated Protein C.

Edoxaban is a highly selective, direct and reversible inhibitor of factor Xa, the serine protease located in the final common pathway of the coagulation cascade. Edoxaban inhibits free factor Xa, and prothrombinase activity. Inhibition of factor Xa in the coagulation cascade reduces thrombin generation, prolongs clotting time and reduces the risk of thrombus formation.

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is the sodium salt and has a high anti-Xa activity.

Epoprostenol sodium, the monosodium salt of epoprostenol, a naturally occurring prostaglandin produced by the intima of blood vessels. Epoprostenol is the most potent inhibitor of platelet aggregation known. It is also a potent vasodilator.

Eptifibatide is an inhibitor of platelet aggregation and belongs to the class of RGD (arginine-glycine-aspartate)-mimetics. Eptifibatide reversibly inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor and other adhesive ligands to the glycoprotein (GP) IIb/IIIa receptors.

Fondaparinux is a synthetic and selective inhibitor of activated Factor X (Xa). The antithrombotic activity of fondaparinux is the result of antithrombin III (ATIII) mediated selective inhibition of Factor Xa.

Heparin is an anticoagulant and acts by inhibiting thrombin and by potentiating the naturally occurring inhibitors of activated Factor X (Xa).

Iloprost is a synthetic prostacyclin analogue. After inhalation of iloprost direct vasodilatation of the pulmonary arterial bed occur with consecutive significant improvement of pulmonary artery pressure, pulmonary vascular resistance and cardiac output as well as mixed venous oxygen saturation.

Lepirudin is a recombinant hirudin derived from yeast cells. Lepirudin is a highly specific direct inhibitor of thrombin. Its mode of action is independent of antithrombin III.

Nadroparin is a low-molecular weight heparin. Nadroparin inhibits Factor Xa in particular and thrombin to a lesser extent. Inhibition is partially mediated via the plasma protease inhibitor antithrombin III. Nadroparin has less effect on platelet function and aggregation and only has a minor effect on primary haemostasis compared to heparin.

Phenindione is a synthetic anticoagulant which acts by interfering with the formation of certain clotting factors.

Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets. Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function can result in the reduction of the rate of cardiovascular events such as death, myocardial infarction, or stroke.

Protein C is a serine protease with potent anticoagulant effects, especially in the presence of its cofactor protein S. Protein C exerts its effect by the inactivation of the activated forms of factors V and VIII which leads to a decrease in thrombin formation. Protein C has also been shown to have profibrinolytic effects.

Reteplase is a recombinant plasminogen activator that catalyzes the cleavage of endogenous plasminogen to generate plasmin. This plasminogenolysis occurs preferentially in the presence of fibrin. Plasmin in turn degrades fibrin, which is the main component of the matrix of thrombi, thereby exerting its thrombolytic action.

Reviparin is a low molecular weight heparin and in clinical terms its action on blood coagulation is the most important biological effect. Reviparin is involved in different phases of blood coagulation. Because of its marked inhibitory action on factor Xa and comparatively low level of anti IIa activity, low molecular weight heparin is at its most active during the preliminary stages of coagulation.

Rivaroxaban is a highly selective direct factor Xa inhibitor with oral bioavailability. Inhibition of factor Xa interrupts the intrinsic and extrinsic pathway of the blood coagulation cascade, inhibiting both thrombin formation and development of thrombi. Rivaroxaban does not inhibit thrombin (activated factor II) and no effects on platelets have been demonstrated.

Selexipag is a selective IP receptor agonist distinct from prostacyclin and its analogues. Selexipag is hydrolysed by carboxylesterases to yield its active metabolite, which is approximately 37-fold more potent than selexipag. Stimulation of the IP receptor by selexipag and the active metabolite leads to vasodilatory as well as anti-proliferative and anti-fibrotic effects.

Biofactor streptokinase is a highly purified streptokinase derived from β haemolytic streptococci of Lancefield group C. The activation of the endogenous fibrinolytic system is initiated by the formation of a streptokinase-plasminogen complex. This complex possesses activator properties and converts plasminogen into the proteolytic and fibrinolytic active plasmin.

Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA.

Ticagrelor is an oral, direct acting, selective and reversibly binding P2Y₁₂ receptor antagonist that prevents ADP-mediated P2Y₁₂ dependent platelet activation and aggregation. Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function has been shown to reduce the risk of CV events such as death, MI or stroke.

Tinzaparin is an antithrombotic agent. It potentiates the inhibition of several activated coagulation factors, especially Factor Xa, its activity being mediated via antithrombin III.

Tirofiban is a non-peptidal antagonist of the GP IIb/IIIa receptor, an important platelet surface receptor involved in platelet aggregation. Tirofiban prevents fibrinogen from binding to the GP IIb/IIIa receptor, thus blocking platelet aggregation.

Treprostinil is a vasodilator that is used for the treatment of pulmonary arterial hypertension. Treprostinil is a potent oral antiplatelet agent. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. Other studies have shown that treprostinil causes a dose-related negative inotropic and lusitropic effect. Treprostinil had high affinity for the Prostaglandin D2 receptor (DP1), Prostaglandin E2 receptor EP2 subtype (EP2) and Prostaglandin D2 receptor (IP) receptors (Ki 4.4, 3.6 and 32 nM, respectively), low affinity for EP1 and EP4 receptors and even lower affinity for EP3, Prostaglandin F (FP) and thromboxane (TP) receptors. Treprostinil has demonstrated a unique effect on PPAR gamma, a transcription factor important in vascular pathogenesis as a mediator of proliferation, inflammation and apoptosis.

Triflusal reduces thromboxan biosynthesis through irreversible inhibition of platelet cyclooxygenase, sparing prostacyclin biosynthesis because its effect on vascular cyclooxygenase at therapeutic doses is negligible.

Urokinase is a highly purified form of naturally occurring human urokinase extracted from urine. It is a thrombolytic agent which converts plasminogen into plasmin (fibrinolysin) a proteolytic enzyme that breaks down fibrin as well a fibrinogen and other plasma proteins.

Vorapaxar is a selective and reversible inhibitor of the PAR-1 receptors on platelets that are activated by thrombin.

Warfarin is a synthetic 4-Hydroxycoumarin derivative which acts by preventing the formation of active procoagulation factors II, VII, IX and X in the liver by inhibiting the vitamin K – mediated gammacarboxylation of precursor proteins. Full therapeutic activity is not achieved until circulating coagulation factors have been removed by normal catabolism. This occurs at different rates for each factor, with factor VII having the shortest half-life. Warfarin has no direct thrombolytic effect, though it may limit the extension of existing thrombi.