Article

Beyond Unfractionated Heparin and Warfarin Current and Future Advances

McMaster University, Hamilton, Ontario, Canada
Circulation (Impact Factor: 14.95). 08/2007; 116(5):552-60. DOI: 10.1161/CIRCULATIONAHA.106.685974
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Available from: Jack Hirsh, Aug 02, 2015
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    • "Furthermore, inflammation has also been linked with most chronic illnesses including diabetes and cardiovascular diseases (Aggarwal et al., 2006). Anticoagulants and anti-inflammatory compounds are thus, important in the management of thromboembolic disorders (Hirsh et al., 2007). The reported (Khanapure et *Corresponding author. "
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    ABSTRACT: This work evaluated the anticoagulant and anti-inflammatory activity of a lanosteryl triterpene (3β-hydroxylanosta-9,24-dien-21-oic acid) isolated from Protorhus longifolia stem bark. Tail bleeding time assay was used to investigate the ex vivo anticoagulant activity. The effect of the triterpene on the thermally induced aggregation of malate dehydrogenase (MDH) and citrate synthase (CS) was studied. The anti-inflammatory activity of the triterpene was investigated using the cotton pellet-induced granuloma model in rats. Granuloma formation was measured following 7 days of oral administration of the experimental rats (two groups) with the triterpene at 50 and 250 mg/kg body weight (b.w). The compound (50 mg/kg) significantly (p < 0.05) increased bleeding time in rats by up to 7 min as compared to 2.5 min observed in the normal control group. It also improved the activity of Hsp70 on MDH and CS aggregation suppression. The reduction of the granuloma formation by up to 40.3% was observed. It is apparent that the triterpene has potential to inhibit the aggregation of proteins.
    Journal of medicinal plant research 05/2015; 9:613-619. DOI:10.5897/JMPR2015.5740 · 0.88 Impact Factor
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    • "The efficacy of traditional anticoagulants in preventing VTE in patients undergoing major orthopedic surgery and in hospitalized acutely ill medical patients is well established [5, 8–11]. However, these agents have several limitations that may limit optimal patient care, such as their parenteral administration, need for laboratory monitoring, and ongoing dose adjustment (Table 1) [12] [13] [14] [15] [16]. Newer oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban), have been developed to overcome these drawbacks , and thereby improve patient care. "
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    ABSTRACT: Traditional anticoagulants, such as warfarin and enoxaparin, have several limitations, including parenteral administration, need for laboratory monitoring, and ongoing dose adjustment, which may limit optimal patient care. Newer oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban), have been developed to overcome these drawbacks, and thereby improve patient care. Several of these agents have been approved for use in the prevention and treatment of venous and/or systemic thromboembolism. The objective of this paper is to provide an overview of the available clinical trial data for these new oral anticoagulants in the prevention and treatment of venous thromboembolism and a practical update for clinicians.
    02/2013; 2013:183616. DOI:10.1155/2013/183616
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    • "Our improved knowledge of pharmacology and coagulation pathways has allowed us to develop newer anticoagulants which have shown significant promise. Beginning in the 1980s the low molecular weight heparins, enoxaparin and dalteparin being the principal agents, and then selective indirect factor Xa inhibitors like fondaparinux have been introduced [9]. These agents are parenteral and have their own limitations but nonetheless are seen as increasingly viable options to heparin. "
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    ABSTRACT: After a gap of almost 60 years following the development of warfarin, 2 new categories of oral anticoagulant agents have been approved for clinical use - the direct thrombin inhibitors and factor Xa inhibitors. These agents promise to be more convenient to administer with fixed dosing but still have equivalent efficacy and improved bleeding risk compared to warfarin. The clinical community is looking forward to the widespread usage of these agents but there is also some apprehension regarding bleeding risks, non-availability of specific reversal strategies and lack of specific monitoring parameters. This review article will attempt to educate the reader about three representative drugs from these classes: Dabigatran, Rivaroxaban and Apixaban. We will discuss the historical perspective to the development of these drugs, available research data and pharmacology of these agents. The best strategies for monitoring and reversal of these drugs in special situations will also be touched upon.
    Current Cardiology Reviews 06/2012; 8(2):158-65. DOI:10.2174/157340312801784934
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