Effect on platelets

The daily dose of sulfinpyrazone is 200-400 mg. The side effects of sulfinpyrazone are comparable with those of probenecid. A potential therapeutic advantage of sulfinpyrazone in patients with coronary heart disease and thromboembolic diseases is its inhibitory effect on platelet aggregation. 

Celia G, Scattolo N, Luzzato G, Stevanato E, Vio C, Girolami A. Effects on platelets and on the clotting system of four glycosaminoglycans extracted from hog mucosa and one extracted from aortic intima of the calf, J Med 1986 17 331-346. 

Several studies have demonstrated that treatment of diabetic patients with the sulphonylurea, gliclazide, is associated with a fall in lipid peroxidation, protein fluorescence and beneficial effects on platelet function (Florkowski et al., 1988 Jennings et al., 1992). These changes were seen to be independent of changes in giycaemic control. 

Ginseng Rg2 has shown inhibitory effects on platelet aggregation similar to aspirin, and R0 reportedly inhibits the conversion of fibrinogen to fibrin [27]. The amount of ginseng administered may also influence the effect(s) produced. In rats and mice, small doses of ginseng extract result in increased spontaneous motor activity, whereas larger doses produce an inhibitory effect on the central nervous system [28]. 

The plasma proteinase, thrombin, a procoagulant enzyme with effects on platelets, endothelial cells and smooth muscle, has been shown to stimulate bone-marrow-derived murine mast cells to release histamine and jS-hexos-aminidase [135]. This secretory response is rapid, reaching a maximum in 1-2 min, and dose-dependent, beginning at about 0.1 U of thrombin and plateauing at 0.5 U thrombin. 

Many studies have shown that ginseng has a protective effect on the development of atherosclerosis that may lead to myocardial infarction and other cardiovascular diseases. The preventive effects on cardiovascular diseases of ginseng include its potential antihypertensive and antiatherosclerotic effects. Ginsenosides are likely to be responsible for some of these effects as they have been shown to have inhibitory effects on platelet aggregation and to suppress thrombin formation as well as an effect on blood vessel contraction. 

M) and human ISN (8.3 /platelet thromboxane production below 200 //M [152], Oral activity in GPB (20 mg/kg PO) was seen as well. A series of very similar compounds, where the carboxyl group of (51) was replaced by a wide variety of substituents at various positions of the ring, was disclosed in a patent from Otsuka [153]. In agreement with other SAR reports, replacement of the t-butyl groups by methyls enhanced 5-LO inhibition, but decreased oral activity in CPE. 

The ability of feverfew extract to inhibit 5HT-secretion in platelets was used to identify compounds responsible for the inhibitory effects on platelets [44], A crude feverfew extract was separated by chromatography and fractions were screened for antisecretory activity induced by adrenaline. In five active fractions compounds were identified as the sesquiterpene lactones parthenolide (1), canin (19), artecanin (20), secotanapartholide A (24) and 3 8-hydroxyparthenolide (2). The ability of parthenolide to affect platelet activity induced by other agents was confirmed in a study of direct comparison of crude feverfew extract with parthenolide [43], Parthenolide in the micromolar concentration range inhibited platelet 5HT-secretion. 

Fondaparinux does not inactivate thrombin (activated Factor II) and has no known effect on platelet function, fibrinolytic activity, or bleeding time. 

Acetaminophen is similar to salicylates in that it is a useful analgesic for mild to moderate pain, with equal efficacy to aspirin, and like aspirin, it is antipyretic. However, acetaminophen exerts little if any effects on platelet aggregation and is not antiinflammatory. Thus, it is not useful for patients with arthritis or other inflammatory diseases. It is also not useful as an antithrombotic agent in the prevention of myocardial infarction or transient ischemic attacks. Acetaminophen does not produce the gastric ulceration that can occur with aspirin and is useful in patients who are salicylate sensitive or who have a history of ulcers or other gastric ulcerations. 

Rimbach, G., Weinberg, P.D., Pascual-Teresa, S., Alonso, M.G., Ewins, B.A., Turner, R., Minihane, A.M., Botting, N., Fairley, B., and Matsugo, S., Sulfation of genistein alters its antioxidant properties and its effect on platelet aggregation and monocyte and endothelial function, Biochim. Biophys. Acta — Gen. Subjects, 1670, 229, 2004. 

Micromedex, lepirudin directly inhibits all actions of thrombin. It inhibits free and clot-bound thrombin without requiring endogenous cofactors. Lepirudin is not inhibited by platelet factor 4 and acts independently of antithrombin III and heparin cofactor II. It has no direct effect on platelet function, except inhibition of thrombin-induced platelet activation. No physiological inhibitor of lepirudin is known. 

A remarkably potent compound, its effects on platelets are observed at concentrations of 10 11 to 10 10 M. Both lyso-PAF and the glycero-1- phosphocho-line enantiomer are inactive. Specific receptors for this factor are evidently present on platelet surfaces.6-8... 

The protective role of dietary flavonoids against cardiovascular diseases in the above mentioned studies has been attributed to their inhibitory effects on LDL oxidation, their inhibitory effects on platelet aggregation. 

C) Inhibition of cyclic nucleotide PDEs. Elevation in cellular cyclic nucleotides induces vascular smooth muscle relaxation [132]. The cellular accumulation of cAMP and cGMP depends upon the rate of their synthesis and their breakdown. The latter is achieved by cyclic nucleotide PDEs that have been classified into seven families [133]. Some flavonoids (apigenin, kaempferol, fisetin and quercetin) produce an inhibitory action on cyclic nucleotide PDEs [134,135] which may collaborate in the inhibitory effect on platelet aggregation [93] and vascular smooth muscle relaxation... 

The effects of wine and its polyphenol constituents on early indicators of coronary heart disease such as elevated levels of plasma lipids, platelets and serum antioxidant activity were discussed in a review by Cooper et al. (2004). This review also addressed whether the polyphenols or alcohol are responsible for the beneficial effects of wine on cardio-vascular health. The authors conclude that red wine polyphenols have little effect on plasma lipid concentrations, but that wine consumption reduces the susceptibility of low-density lipoprotein (LDL) cholesterol to oxidation and increase serum antioxidant capacity. These effects, however, do depend on the amount of wine that is consumed and the period of supplementation. It was suggested that specific polyphenols appear to have endothelium-dependent vaso-relaxing abilities. Red wine phenolics also have an inhibitory effect on platelet aggregation. Evidence suggests that alcohol has a positive synergistic effect with wine polyphenols on some atherosclerosis risk factors. Thus, evidence that wine drinking is beneficial for cardiac health appears positive. 

Resveratrol has also been reported to offer protection against cardiovascular disease, such as coronary heart disease. The effects of resveratrol on factors implicated in the development of coronary heart disease - human platelet aggregation and the synthesis of eicosanoids (lipids) from arachidonate by platelets - were investigated and compared with the actions of other wine phenolics - catechin (1.39), epicatechin (7.18a), and quercetin (1.43) - and the antioxidants a-tocopherol (7.10a), hydroquinone and butylated hydroxytoluene. Resveratrol and quercetin demonstrated a dose-dependent inhibition of platelet aggregation, whereas the other compounds tested were inactive. Resveratrol also inhibited the synthesis of the eicosanoids in a dose-dependent manner, whereas the other phenolics were less effective of not effective at all. Removal of the alcohol from the wine did not diminish the effect on platelet aggregation (Pace-Asciak et al., 1995 Goldberg et al., 1995). 

Pignatelli P, Di Santo S, Buchetti B, Sanguigni V, Brunelli A, Violi F. 2006. Polyphenols enhance platelet nitric oxide by inhibiting protein kinase C-dependent NADPH oxidase activation Effect on platelet recruitment. FASEB J 20 1082-1089. 

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