Drugs of today
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In the nearly 130 years since Trousseau first described migratory thrombophlebitis in cancer patients, thromboembolism has become a well-established presenting sign and complication of cancer. The coagulation system is activated in cancer and is further amplified by treatment with chemotherapy, radiation or surgery. Hypercoagulation is documented in virtually all cancer types, albeit at different rates, and is the second leading cause of death in cancer patients. ⋯ By binding rapidly and strongly to antithrombin, its sole physiologic target in plasma, fondaparinux catalyzes specifically the inhibition of factor Xa, which results in effective and linear dose-dependent inhibition of thrombin generation. Additionally, efficient inhibition of factor Xa activity impairs the activation of tissue factor/factor VIIa complex leading to downregulation of procoagulant state, pro-angiogenesis, and proinflammatory factors induced by tissue factor/factor VIIa. Furthermore, a number of orally active direct antithrombin and anti-factor Xa are in advanced clinical development for various thromboembolic disorders.
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Current treatment options for patients with Alzheimer's disease are limited to providing symptomatic relief, with no effects on the underlying pathophysiology. However, a greater understanding of the importance of beta-amyloid peptides (Abeta) in the pathogenesis of this disease has led to the investigation of a number of potential antiamyloid therapies, of which tramiprosate (Neurochem Inc.) is in the most advanced stage of development. Tramiprosate is a glycosaminoglycan (GAG) mimetic designed to interfere with the actions of Abeta early in the cascade of amyloidogenic events. ⋯ Promising findings for the efficacy of tramiprosate, indicated by improvement or stabilization of cognitive function, have been shown in phase II clinical trials and open-label extensions of these studies. Furthermore, tramiprosate appears to be well tolerated with no reports of safety concerns. This article reviews the unique mode of action of tramiprosate and summarizes the available clinical information on the effects of tramiprosate in patients with Alzheimer's disease.