Platelet aggregation, effects

Bastida, E., Ordinas, A., Giardina, S. and Jamieson, G. A. (1982). Differentiation of platelet aggregating effects on human tumor cell lines based on inhibition studies with apyase, hirudin and phospholypase. Cancer Res. 42, 4348-4352. 

Platelet activating factor (PAF) was first identified by its ability (at low levels) to cause platelet aggregation and dilation of blood vessels, but it is now known to be a potent mediator in inflammation, allergic responses, and shock. PAF effects are observed at tissue concentrations as low as 10 M. PAF causes a dramatic inflammation of air passages and induces asthma-like symptoms in laboratory animals. Toxic-shock syndrome occurs when fragments of destroyed bacteria act as toxins and induce the synthesis of PAF. This results in a drop in blood pressure and a reduced... 

ACE inhibitors inhibit the degradation of bradykinin and potentiate the effects of bradykinin by about 50-100-fold. The prevention of bradykinin degradation by ACE inhibitors is particularly protective for the heart. Increased bradykinin levels prevent postischemic reperfusion arrhythmia, delays manifestations of cardiac ischemia, prevents platelet aggregation, and probably also reduces the degree of arteriosclerosis and the development of cardiac hypertrophy. The role of bradykinin and bradykinin-induced NO release for the improvement of cardiac functions by converting enzyme inhibitors has been demonstrated convincingly with use of a specific bradykinin receptor antagonist and inhibitors of NO-synthase. 

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. 

Dipyridamole exerts its effect by inhibition of platelet phosphodiesterase E5, increasing cyclic guanosine monophosphate and cyclic adenosine monophosphate (cAMP). By inhibiting its uptake and metabolism by erythrocytes, dipyridamole also increases the availability of adenosine within blood vessels, promoting inhibition of platelet aggregation and local vasodilatation. " Dipyridamole may also inhibit cAMP phosphodiesterase in platelets, which further increases cAMP levels and may enhance endothelial nitric oxide production, contributing to its antithrombotic effect. Existing trials of dipyridamole in stroke have focused on secondary prevention and will be discussed briefly. 

Inhibition of platelet aggregation (Rong et al., 1997). Inhibition of aortic streaks (Seetharamaiah and Chandrasekhara 1990 Rong et al., 1997). Hypolipidemic effect (Yoshino et al., 199,9, Seetharamiah and Chandrasekhara, 1990 Nicolosi eta/.,1993 Rukmini and Raghuram, 1991). 

---