Anticoagulants natural

Dennis MS, et al. Peptide exosite inhibitors of factor Vila as anticoagulants. Nature 2000 404 465-470. 

Chemical modification of the unfiactionated heparin, such as desul tion, deamination and coupling with various agents have resulted in products of non-anticoagulant nature with selective actions on enzymes and cellular receptors. Thioxyloside derivatives have also been reported to produce oral antithrombotic actions in animal models. However, relatively larger dosages are needed to produce these effects. These heparin derivatives are currently tested for such indications as sepsis, viral infections and the treatment of proliferative disorders. 

Weiner M. Effect of centrally active drugs on the action of eoumarin anticoagulants. Nature... 

Factor XII activators pLOOD, COAGULANTS AND ANTICOAGULANTS] (Vol 4) -inhibitors in foods pOOD TOXICANTS, NATURALLY OCCURRING] (Volll)... 

Plasma Inhibitors, In Vivo Anticoagulants. Fourteen naturally occurring compounds that normally exert an inhibiting effect on the activity of coagulation, platelet function, and fibrinolytic activity and complement systems have been identified within the circulating blood. 

Protein C is a vitamin K-dependent natural anticoagulant activated by thrombin to form APC in the presence of the endothelial receptor, TM. APC proteolyzes factors Va and Villa, thus downregulating thrombin generation. APC may also have anti-inflammatory... 

Anticoagulant Any substance that inhibits, suppresses, or delays the formation of blood clots. These substances occur naturally and regulate the clotting cascade. Several anticoagulants have been identified in a variety of animal tissues and have been commercially developed for therapeutic use. 

The analysis of human plasma for acetaminophen, the active ingredient in some pain relievers, involves a unique extraction procedure. Small-volume samples (approximately 200 fiL) of heparinized plasma, which is plasma that is treated with heparin, a natural anticoagulant found in biological tissue, are first placed in centrifuge tubes and treated with 1 N HC1 to adjust the pH. Ethyl acetate is then added to extract the acetaminophen from the samples. The tubes are vortexed, and after allowed to separate, the ethyl acetate layer containing the analyte is decanted. The resulting solutions are evaporated to dryness and then reconstituted with an 18% methanol solution, which is the final sample preparation step before HPLC analysis. The procedure is a challenge because the initial sample size is so small. 

Jones D. Anticoagulants, the clot thickens, Nature Reviews Drug Discovery 2 251 (2003). 

The anticoagulant fondaparinux, a synthetic analogue of the terminal fragment of heparin, is synthesized using multiple protection/deprotection steps that result in a route of up to 50 steps. There is, as yet, no enzymatic system that approaches the capability to make such a molecule." As this modified pentasaccharide is a natural product, it should, in theory, be accessible through a series of biotransformations, but we currently lack the biocatalytic tools to achieve more than a few steps and would stiU need to use some protection steps to avoid multiple products. Enzymatic synthesis in vivo depends largely on the levels and selectivities of glycosylating enzymes to achieve multistep reactions, a situation that has been mimicked in vitro for simpler systems." ... 

Because rodent populations world-wide were becoming resistant to the widely used Warfarin-type anticoagulant poisons, a search was initiated to find a rodenticide with a different mode of action one that would be effective against these resistant rodents. This search led to the discovery of the toxic nature of a family of diphenyl amines which act as uncouplers of oxidative phosphorylation. A structure-activity relationship (SAR) study was undertaken to choose a derivative that would be both poisonous to rodents but still readily consumed by them. This approach led to the discovery of bromethalin,... 

As reviewed by Ujvary some of the earliest natural product-based pesticides were those for the elimination of vertebrate pests. For example, strychnine (Fig. 19), obtained from seeds of Strychnos nux-vomica, is a rodenticide that is an antagonist to the neurotransmitter glycine and is used against a few mammal species, as well as pest birds and fish. The first generation of anticoagulant rodenticides were based on dicoumarin. 

Uses AML, ALL, CML Action Purine-based antimetabolite (substitutes for natural purines interfering w/ nucleotide synth) Dose 2-3 mg/kg/d X in severe renal/hepatic impair Caution [D, -] Contra Resistance to mercaptopurine Disp Tabs SE X BM (leucopenia/thrombocytopenia), NA /D, anorexia, stomatitis, rash, hyperuricemia, rare hepatotox Interactions t Bleeding W/ anticoagulants, NSAIDs, salicylates, thrombolytics EMS t Effects of anticoagulants/salicylates/ NSAIDs T risk of Infxn OD May cause NA, hypotension, and diaphoresis symptomatic and supportive... 

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