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P2Y12

P2Y purinoceptor 12 is a protein that in humans is encoded by the P2RY14 gene.

P2Y12 belongs to the family of G-protein coupled receptors, with receptor subtypes with different pharmacological selectivity for various adenosine and uridine nucleotides.

P2Y purinergic receptor for UDP-glucose and other UDP-sugars coupled to G-proteins.

P2Y receptors are a family of seven transmembrane spanning G protein-coupled receptors that are activated by nucleotides and nucleotide-sugars.

The P2Y12R is activated by nucleotide sugars.

The thienopyridine antithrombotic drugs Clopidogrel, ticagrelor, and Prasugrel require enzymatic pre-activation in vivo and react irreversibly with the P2Y12 receptor.

The P2y12 pathway is a therapeutic target for the inhibition of platelet activation with clopidogral treatment.

Any of the above agents are usually combined with low dose of aspirin as dual antiplatelet therapy in patients with acute coronary syndromes or who have undergone coronary stent implantation to decrease the risk of platelet-mediated thrombotic cardiovascular events.

Current guidelines for dual antiplatelet therapy consisted of aspirin and the more potent platelet inhibitors ticagrelor and prasurgrel over clopidogrel because these drugs are more effective for the prevention of thrombotic events, but have a higher risk of bleeding.

Genetic variants of CYP2C19 gene that encodes the CYP2C19 liver enzyme responsible for metabolizing clopidogrel to its active form, and these variants can reduce clopidogrel’s activity resulting in diminished activity activation and reduced antiplatelet efficacy.
Newer P2Y12 inhibitors prasurgrel and ticagrelor do not require a metabolic conversion and are therefore not influenced by CYP2C19 variants.
These new drugs provide faster, more potent and more consistent platelet innovation and are more effective than clopidogrel reducing ischemic events among patients with acute coronary syndrome undergoing PCI.: the studies also revealed higher bleeding risks.

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