Pharmacology of Heparin and Related Drugs

The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy

“…The activity of thrombin or factor Xa (fXa, the enzyme responsible for converting prothrombin to thrombin) can be inhibited directly with drugs targeting the enzyme active sites (argatroban, dabigatran, and bivalirudin for thrombin; rivaroxaban, epixaban, and edoxaban for fXa), 2 or indirectly with heparin-related compounds (heparin, low molecular weight, fondaparinux) that enhance the activity of the plasma inhibitor antithrombin. 3 Alternatively, synthesis of prothrombin and factor X (fX), the precursors of thrombin and fXa, can be reduced with vitamin K antagonists such as warfarin. 4 Use of these effective antithrombotic strategies comes with a well recognized cost.…”

“…Use of heparin is associated with major bleeding rates of up to 3%, and with warfarin 2-13%. 3-5 Newer oral thrombin and fXa inhibitors appear to cause less bleeding than the older drugs, and are easier to use. 2,6 However, because of their mechanisms of action, there are limits on the types of patients who are eligible to receive them, the clinical settings in which they can be used, and the intensity of anticoagulation that can be applied.…”

Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: Insights into the physiological role of endogenous heparin

“…In this respect, heparin has been suggested to be primarily important for the storage of histamine and certain pro-inflammatory granule proteins within the mast cell (9,10). However, it would seem unlikely that a potent anticoagulant molecule having a broad range of biological activities (11) should be biosynthesized solely for this purpose, and indeed solely within a cell type found outside the vasculature. The localization of mast cells close to vessels of the microcirculation though, as well as their more recent description in pathological tissue sites including tumors and atheromatous plaques (12,13), suggests that endogenous heparin may be important in regulation of pathophysiological responses, as well as in normal physiology.…”

Legislação Brasileira Aplicada À Produção Do Insumo Farmacêutico Ativo Heparina

“…Sua estrutura química (Figura 1) foi elucidada em 1936 e foi descrita como um éster polissulfúrico de um polissacarídeo composto por glucosamina e ácido urônico (MULLOY et al, 2016). É utilizada há mais de 50 anos na terapêutica como agente anticoagulante e antitrombótico e está presente em uma grande variedade de tecidos animais, sendo obtida principalmente destas fontes, fazendo parte da lista de medicamentos essenciais da Organização Mundial da Saúde (MELLO et al, 2008;BARROWCLIFFE, 2012).…”

“…Para exercer a sua função anticoagulante, a mesma requer um co-fator plasmático, a antitrombina III. A heparina fixa-se à antitrombina III, induzindo uma modificação conformacional dessa molécula, que expõe o sítio ativo acessível à trombina e às outras proteases resultantes da ativação dos fatores da coagulação (DELUCIA et al, 2007;MELLO et al, 2008;MASUKO;LINHARDT, 2012;MULLOY et al, 2016).…”