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Anti-platelet therapy in acute coronary syndrome
Published in K Sarat Chandra, AJ Swamy, Acute Coronary Syndromes, 2020
Kunal Mahajan, Yashasvi Rajeev, K Sarat Chandra
Adenosine diphosphate (ADP), an important platelet agonist, has P2Y1 and P2Y12 receptors on the platelet plasma membrane through which it exerts its effects. Out of these two, it is the P2Y12 pathway that plays a major contribution in sustaining and stabilising the aggregation of platelets [10]. P2Y12 receptor antagonists are therefore recommended to prevent ischaemic events both in the acute and long-term treatment of ACS. The thienopyridine, ticlopidine, which was the first P2Y12 receptor inhibitor, is seldom prescribed now following the reports of serious adverse reactions with its use, particularly neutropenia and thrombotic thrombocytopenic purpura [11]. Three oral ADP P2Y12 receptors inhibiting drugs that are currently approved for clinical use include clopidogrel, prasugrel (irreversible inhibition), and ticagrelor (reversible inhibition) (Table 11.1).
Pharmacotherapy of Neurochemical Imbalances
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Rupali Patil, Aman Upaganlawar, Suvarna Ingale
ATP has now also established its role as a transmitter through its widespread receptor-mediated actions in the body. ATP binds with two types of receptors, P2X and P2Y receptors. P2X receptors are ligand-gated ion channel receptors subdivided into seven subtypes (P2X1 to P2X7). P2X receptors are widely distributed all over the body. P2X1 and P2X2 receptors are found in the dorsal horn, and hence play an important role in sensory transmission. P2Y receptors are GPCRs and there are eight subtypes of P2Y receptors such as P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14 (Rang et al., 2011; Edward and Gibb, 1993; Barrett et al., 2009; Webster, 2001).
Antiplatelet therapy in interventional cardiology
Published in John Edward Boland, David W. M. Muller, Interventional Cardiology and Cardiac Catheterisation, 2019
The pace of change in antiplatelet and anticoagulant therapies in the last decade has been rapid, with several factors influencing future improvements. Significantly, the endpoints of stent thrombosis and cardiovascular morbidity have become low. Thus, any new drug therapy is likely to need randomised trials involving large numbers of patients to demonstrate an improvement in efficacy over standard therapy.111 However, there are multiple agents currently under development: PZ-128, targeting intracellular signalling on PAR-1; BMS-986141, a PAR-4 antagonist; MRS2179 a P2Y1 antagonist as well as a combined P2Y1 and P2 Y12 antagonist.112–115 In addition, numerous questions remain unanswered about the optimal type, use and duration of antiplatelet therapy during and after PCI. Although unlikely to occur a randomised, multicentre direct comparison between prasugrel, ticagrelor and clopidogrel to evaluate their relative efficacy and safety is desirable, as this evolving field aims to continue to discover the best treatment for patients.
Human Platelets and Influenza Virus: Internalization and Platelet Activation
Published in Platelets, 2022
Josiah Bote, Heather A. Corkrey, Milka Koupenova
As cells become virally infected or stimulated, ATP and ADP are released into the circulation either locally or systemically. ATP can be actively secreted from cells that have been stimulated during infection, while both ATP and ADP can be passively released from dying cells, [33] and are increased post-influenza infection[34]. Once released, ATP can also be converted to ADP by Ecto-ATPase 1 (CD39) located on endothelial cells and elevate local levels of ADP in the circulation[35]. The effect of ATP and ADP on platelet activity is well established, and we and others have discussed it previously in great detail [35–37]. For the purpose of this review, ATP, also serving as a danger associated molecular pattern (DAMP) molecule[33], through P2X1 can lead to platelet spreading and activation although by itself does not lead to platelet aggregation unless in combination with ADP. ADP, on the other hand, is a well-known platelet agonist leading to platelet aggregation through the platelet receptors P2Y12 and P2Y1 (Figure 4). Both ATP and ADP can be actively secreted from platelet granules during activation further amplifying the prothrombotic response.
The molecular basis of platelet biogenesis, activation, aggregation and implications in neurological disorders
Published in International Journal of Neuroscience, 2020
Abhilash Ludhiadch, Abhishek Muralidharan, Renuka Balyan, Anjana Munshi
ADP activates platelets through 3 purinergic receptors, namely P2Y1, P2Y12 and P2X1 which are responsible for platelet shape change, the release of thromboxane A2 and procoagulant activity. [54]. It also results in the intracellular mobilization of calcium. ADP also results in the binding of platelets to vitronectin and osteopontin which helps in the anchoring of platelets to disrupted plaques or injured vessel walls. It also plays an important role in inhibiting stimulated adenylate cyclase, activating phospholipase C and phospholipase A2 [55]. The exposure to sub-endothelial components results in the binding of specific platelet surface receptors to the platelets like the binding of collagen-specific surface glycoprotein Ia/IIa to collagen. von Willebrand factor (vWF) helps in the cross-bridging of platelets to one another or to the endothelial vessel walls via binding sites for extracellular matrix proteins and to platelet glycoprotein receptors GPIb and GPIIb-IIIa. They help in hemostasis by slowing down the platelets in circulation by crosslinking them with collagen or other ECM components. vWf is also important to hold or tether the platelets at the site of the injury even during high shear stress. The interaction of GPIba with vWf is very important for the tethering of platelets, at higher shear rates in arteries [56]. Fibrinogen has been proposed to play a significant role in the interaction of platelets with the walls of vessels especially at reduced shear rates, which is a characteristic of the circulation in veins [57].
Comparison of factors affecting platelet reactivity in various platelet function tests
Published in Platelets, 2019
The VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) is a whole-blood, cartridge-based, optical detection system designed to measure platelet aggregation (22). The ADP P2Y12 receptor is measured in a cartridge channel of the VerifyNow P2Y12 assay containing ADP as a platelet agonist, and prostaglandin E1 (PGE1) as a suppressor of intracellular free calcium levels that reduces the nonspecific contribution of ADP binding to P2Y1 receptors. The VerifyNow P2Y12 assay results are expressed in P2Y12 reaction units (PRU). An electronic quality-control test and positive and negative control tests were performed on each instrument every day prior to analyzing any patient samples. The internal electronic quality-control device and kits with negative and positive control tests were provided by the assay manufacturer.