[Clopidogrel resistance--risk factor in patients with acute coronary syndromes].
Clopidogrel is an ADP receptor antagonist, an inhibitor of platelet activation and aggregation. The effect is due to its selective and irreversible blockade of the P2Y12 receptor. The concept of clopidogrel resistance emerged since several years ago. This biological finding has a very important impact especially in patients with acute coronary syndromes, explaining by this their worse evolution. Mechanisms of this resistance are very complex including: differences in intestinal absorption, hepatic conversion to the active metabolite through cytochrome 3A4 (CYP3A4) activity, drug interactions, individual variations in the activity of hepatic cytochrome P450 izoenzymes, platelet receptor polymorphisms and also clinical factors. According to this resistance patients are divided in two groups : "low or non-responders" (with a high risk of thrombosis) and "high--responders" (with a high risk of bleeding). Carriers of CYP2C19*2 or *3 alleles have been shown to respond poorly to standard doses of clopidogrel due to reduced metabolic activation of the drug. So, they are likely to develop subsequent thrombotic events. Starting from these, a lot of studies have been performed in order to elucidate the mechanisms of this resistance offering new perspectives regarding a proper administration of antiplatelet therapy in patients with acute coronary syndromes.
Universitatea de Medicină şi Farmacie "Grigore T. Popa" Iaşi.
Irina luliana
Il
Costache
Cristina
C
Rusu
I
I
Ivanov
Roxana
R
Popescu
A
A
Petriş
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013988:Ticlopidine