Platelet Pharmacology

Screening for drugs that prevent platelet activation 

To some extent, platelet interaction on surfaces is mediated by shear force. Therefore it is essential to screen antiplatelet dmgs under flow conditions. Two different techniques are used to monitor platelet interaction on surfaces. The classical Baumgartner technique employs denuded rabbit aorta to evaluate platelet interaction with basement membrane components (89). The flat chamber technique uses a chamber in which cover slips coated with various test materials can be exposed to flowing blood (90). One can get a layer of cell matrix components for testing, by growing endothelial cells on cover slips and stripping them off the glass surface after they reach confluency. 

Once the drugs are screened using appropriate methods, promising new compounds need to be tested in animal models for their safety, dose and efficacy. It is very important to remeniber that platelets of different species vary widely in their responses to agonists (91, also discussed in other chapters). For instance, majority of dogs have platelets that do not respond to AA with aggregation (50). However, when these AA refiactory platelets are 

Acetyl salicylic acid (aspirin). Nonsteroidal antiinflammatory dmp (NSADD), Phenylbutazone, Mdomethacin, Ibuprofen, Fenoprofen, Fluriboprofen, Neproxen, Sulfinpyrazone, antioxidants (Butylated Hydroxytoluene, BHT Butylated Hydroxyanisole, BHA Dipheylamine, DPA). 

Benzydamine, Imidazole congeners, 9, ll-azo-13 oxa-15 hydroxy prostanoic acid, 9, ll-azoprosta-5-13 dienoic acid (U-51605), 9, ll(epoxmethano) prostanoic acid, l(isopropyl-2-indloy (l)-3 pyridyl-3-ketone (L-8027). 

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For the past two decades Dr. Shivendra D. Shukla s major interest has been phosphoinositide turnover, platelet activating fector receptor signaling and platelet pharmacology. He has made original contributions in this field. His research has been supported by American Heart Association, National Institute of Health and NIH Research Career Development Award. 

Anti platelet Drugs. Table 1 Pharmacological properties of GP llb/llla inhibitors... 

Due to the pivotal role of platelets in thrombus formation, especially in the arterial system, inhibition of platelet function has become a central pharmacological approach. Antiplatelet drugs are given in order to prevent and treat thromboembolic diseases such as coronary heart disease, peripheral and cerebrovascular disease. They have also revolutionized the procedures of invasive coronary interventions as they reduce the risk of restenosis and thrombosis. 

Pharmacologic Therapy Treatments used to decrease bleeding time in patients with uremic bleeding include cryoprecipitate, which contains various components important in platelet aggregation and clotting, such as von Willebrand factor and fibrinogen. Cryoprecipitate decreases bleeding time within 1 hour in 50% of patients. However, cost and the risk of infection have limited the use of cryoprecipitate. 

The treatment of ITP is determined by the symptom severity (Table 64-9). In some cases, no therapy is needed. The initial treatment of children with ITP is controversial because more than 70% of cases resolve spontaneously irrespective of pharmacologic intervention. Currently, therapy is indicated in children with platelet counts less than 10,000 to 20,000/mm3 (10-20 x 103/ j,L or 10-20 x 109/L) because most intracranial hemorrhages occur when platelets are in this range.32... 

Campbell, W.B. and Halushka, P. V., Lipid-derived autacoids eicosanoids and platelet-activating factor, in Goodman and Gilman s The Pharmacological Basis of Therapeutics, 9th ed., Hardman, J.G. and Limbird, L.E., Eds., McGraw-Hill,... 

Radomski, A. et al. (2005) Nanopartide-induced platelet aggregation and vascular thrombosis. British Jornal of Pharmacology, 146 (6), 882-893. 

Subsequent clinical studies provided additional evidence that GTN exerts antiplatelet activity in vivo and offered insight into the nature of GTN s anti-aggregatory pharmacology. A dose-effect relationship between intravenous GTN and inhibition of platelet aggregation was uncovered in healthy male subjects, in whom plasma... 

Antagonists of Platelet-Activating Factor Chemistry, Pharmacology and Clinical Applications... 

Chapter 7 outlines the basic mechanism and treatment of emesis, and in particular, that induced by chemotherapy of cancer. Finally, the chemistry, pharmacology and clinical applications of antagonists of the platelet-activating factor (PAF), an important mediator of many physiological and pathological conditions, are reviewed in Chapter 8. 

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