Current Pharmaceutical Design - Volume 11, Issue 30, 2005

Heparins and vitamin K antagonists are the landmarks of antithrombotic treatment. Both of them were discovered by serendipity; they are multi-targeted drugs and share several limitations. New molecules have been designed in order to be both more selective concerning their biological target and more homogeneous in their biochemical structure aiming at an improved benefit/risk ratio in the treatment of thrombotic dis Read More

Direct thrombin inhibitors represent a new class of anticoagulants that bind directly to thrombin and block the enzyme's interactions with its substrates. These agents have been developed, at least in part, to overcome the limitations of heparin and vitamin K antagonists. This paper (a) reviews why thrombin is an ideal target for new anticoagulants, (b) describes the pharmacological profiles of the various direct thrombin Read More

Unfractionated heparin, low-molecular-weight heparins and vitamin K antagonists are established antithrombotic agents, but all have a number of limitations. Unfractionated heparin requires parenteral administration, has a short half-life and variable dose-response relationship. Low molecular weight heparins are more effective than low-fixed-dose unfractionated heparin in the prevention of postoperative venous thromboembo Read More

Background. Ximelagatran has been approved in Europe for VTE prophylaxis in orthopedic surgery at fixed doses and without laboratory monitoring. Aim of the study was to evaluate safety and efficacy of ximelagatran in a metaanalysis of prophylaxis and/or treatment randomized controlled trials. Methods. Absolute risk of events for ximelagatran and OR for its comparison with LMWH and coumarins were calculate Read More

As acute coronary syndromes are principally sustained by plaque complication and subsequent thrombus formation, anticoagulant therapy plays a central role in avoiding ischemic events; its main targets are thrombin activity and generation. Despite its limitations, such as its scarce ability to activate bound thrombin and its unpredictable pharmacological response, heparin is the most widely uzed drug for this purpose. Direct t Read More

Thrombin is a central enzyme in hemostasis, exerting potent procoagulant effects and activating platelets. Recently, several small molecule direct thrombin inhibitors (DTI's) with important clinical applications have been developed. Both lepirudin and argatroban are effective in treatment of heparin-induced thrombocytopenia resulting in rapid normalization of platelet counts and a reduction in thrombotic events. Because of Read More

Pulmonary fibrosis is characterized by lung inflammation and abnormal tissue repair, resulting in the replacement of normal functional tissue with an abnormal accumulation of fibroblasts and deposition of collagen in the lung. This process involves cellular interactions via a complex cytokine-signaling mechanism and heightened collagen gene expression, ultimately resulting in its abnormal collagen deposition in the lung. Our Read More

Complications from atherosclerosis cause most deaths in western countries, and their incidence appears to be markedly increasing in developing countries, thus suggesting a correlation that is directly proportional to social progress. In recent years, the different branches of medical research, from studies on vascular disease to those on lipid and glucose metabolism, and also clinical research on coronary, carotid and periphera Read More