Thrombocytes aggregation

Ketanserin is an antagonist at 5-HT2A receptors and produces antihypertensive effects, as well as inhibition of thrombocyte aggregation. Whether 5-HT antagonism accounts for its antihypertensive effect remains questionable, because ketanserin also blocks a-adren-oceptors. 

Hormone-controlled lipases Thrombocyte aggregation Pain production Inflammatory response... 

Sulfinpyrazone is used in medicine as a nonsteroid anti-inflammatory, fever-reducing analgesic however, it is believed, that it inhibits cyclooxygenase of thrombocytes. In addition, it is also possible that its action is also linked with the action on membrane of thrombocytes and reduced quantities of secreted adenosine diphosphate and serotonin, which facilitate thrombocyte aggregation. Unlike aspirin, it has no effect on those who do not have irregular aggregation systems. 

Isosorbide is a diuretic the dinitrate is a vasodilator. Hexahydrofuro[3,2-6 ]pyrrole derivatives are useful as bronchodilators and thrombocyte aggregation inhibitors. 3-Amino-4//-pyrrolo[3,4-c]isoxazoles produce hypotension. 3,4,5,6-Tetrahydro-2H-cycIopen-tathiazol-2-one is an effective analgesic. 

In certain therapeutic situations, rapid presystemic elimination may be desirable. An important example is the use of glucocorticoids in the treatment of asthma. Because a significant portion of inhaled drug is swallowed, glucocorticoids with complete presystemic elimination entail only a minimal systemic load for the organism (p.340). The use of acetylsalicylic acid for inhibition of thrombocyte aggregation (see p.155) provides an example of a desirable presystemic conversion. 

Cox-1 is constitutively expressed and responsible for most of the housekeeping functions of eicosanoids, including processes such as calcium metabolism in the bone, and stomach mucous membrane maintenance. It is also responsible for synthesis of thromboxanes in thrombocytes and of prostacyclin (PGI) in endothelial cells, which have antagonistic function in thrombocyte aggregation and activation (see later). 

The covalent, irreversible mode of action of acetylsalicylic acid is important in its use for inhibiting thrombocyte aggregation in patients with cardiovascular disease (more specifically, atherosclerosis). This is a practically very im-... 

Figure 12.10. Role of eicosanoids in thrombocyte (platelet) aggregation, and rationale of low-dose acetylsalicylic acid treatment. a Thrombocyte aggregation is suppressed by the intact vascular endothelium by a constant secretion of PGE and PGI. b Inhibition subsides at lesions. This sets off aggregation, which is sustained and amplified by the secretion of thromboxanes by the platelets themselves. Aggregation will also promote plasmatic coagulation (i.e., fibrin clot formation), b Effects of low dose application of acetylsalicylic acid. Endothelial cells are nucleated covalently inactivated cyclooxygenase molecules will be replaced by newly synthesized ones, so that the activity is not substantially diminished. In contrast, thrombocytes lack protein synthesis, so that the effect of repeated doses will be cumulative.

Now, does this work There are some intriguing statistics to support this While in western countries 40% of all deaths are due to atherosclerosis (in which both inflammation and thrombocyte aggregation are important), this number stands at 7% among Greenland eskimos and at 12% in Japan both countries have more fish and less meat in their diets. However, it should go without saying that we cannot precisely gauge the contribution of EPA and related fatty acids to this remarkable statistics. 

Avian thrombocytes aggregate poorly in response to ADP, collagen, arachidonic acid, and thrombin. 

Hypertrophic osteoarthropathy (hour-glass nails, clubbed fingers) (s. fig. 4.18), which has been known since 1884, is not caused by hypoxia, as has been assumed up to now. (18) The cause is to be found in the intrapulmonary arteriovenous shunts from the venous limb of the pulmonary vessels, megakaryocytes and thrombocyte aggregates pass directly through the shunts into the arterial limb and hence (unfiltered, uncatabolized or not... 

Thrombocyte dysfunction frequently emerges in the course of liver diseases and their complications, especially in the case of coagulation disorders and elevated fibrinolysis. Thus a decrease in both thrombocyte aggregation and the release of platelet factor 3 may occasionally be witnessed in cirrhosis. In most cases, this is... 

One of the hypotheses for the development of vascular occlusion that precedes proliferative diabetic retinopathy is that disturbances in the thrombocyte aggregation lead to leukostasis and formation of microthrombosis in the retinal capillaries. Consequently, attention has been focused at treating diabetic retinopathy with inhibitors of thrombocyte aggregation. However, a prospective study has shown that acetyl salicylic acid does not reduce the development of diabetic retinopathy. Additionally, this treatment does not increase the risk of developing complications such as vitreous hemorrhage. This is important evidence since inhibitors of thrombocyte aggregation are often used to reduce the risk of the development of the macrovascular complications of the disease [12]. 

In patients with stage II peripheral arterial occlusive disease, 800 mg garlic daily for 12 weeks was found to reduce spontaneous thrombocyte aggregation and plasma viscosity (Kiesewetter et al. 1993b). 

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