Inhibitors of ADP-dependent platelet aggregation

Aleksandar Knezevic
2014 Cardiologia Croatica  
Radna skupina za kliniËku kardiovaskularnu farmakologiju, Hrvatsko kardioloπko druπtvo, Hrvatska Working Group on Clinical Cardiovascular Pharmacology, Croatian Cardiac Society, Croatia SAAEETAK: Trombociti imaju srediπnju ulogu u patogenezi aterotromboze. Trombocitni ADP (adenozindifosfatazni) receptori (P2Y12) imaju kljuËnu ulogu u agregaciji potencirajuÊi uËinak brojnih drugih faktora koji pri njoj sudjeluju. Inhibitori ADP ovisne agregacije trombocita (tiklopidin, klopidogrel, prasugrel,
more » ... grel, prasugrel, tikagrelor) su skupina lijekova koja poveÊava antiagregacijski uËinak, poglavito u inicijalnoj fazi aktivacije trombocita te time daju znaËajan doprinos u lijeËenju aterotrombotskih bolesti, posebice ACS (akutnog koronarnog sindroma). Tiklopidin je prvi uveden u kliniËku praksu, no hematoloπke nuspojave i spor poËetak uËinka brzo su ograniËile kliniËku primjenu. Klopidogrel uz acetilsalicilatnu kiselinu brzo postaje zlatni standard u antiagregacijskoj terapiji nakon PCI (perkutane koronarne intervencije) i u ACS. No, njegova farmakokinetska i farmakodinamska ograniËenja dovode do razvoja novih lijekova. Prasugrel ima jaËi i braei antiagregacijski uËinak, ali uz cijenu viπe krvarenja. Tikagrelor je zadnji iz ove skupine lijekova s prednoπÊu snaaene, efikasne, brze i reverzibilne blokade P2Y12 receptora u odnosu na klopidogrel. Time je prema vaaeeÊim smjernicama preferirani lijek za PCI u ACS, ali njegov status na Listi lijekova Hrvatskog zavoda za zdravstveno osiguranje za sada ograniËava njegovu πiru primjenu u Hrvatskoj. KLJU»NE RIJE»I: antiagregacijska terapija, tiklopidin, klopidogrel, prasugrel, tikagrelor. SUMMARY: Platelets play a central role in the pathogenesis of atherothrombosis. Platelet adenosine diphosphate (ADP) receptors (P2Y12) have a key role in the aggregation potentiating the effect of many other factors involved in it. Inhibitors of ADP-dependent platelet aggregation (ticlopidine, clopidogrel, prasugrel, ticagrelor) are a group of drugs that increase antiaggregation effect, especially in the initial phase of platelet activation and thereby make a significant contribution to the treatment of atherothrombotic disease, especially ACS (acute coronary syndrome). Ticlopidine was the first that was introduced into clinical practice, but hematologic side-effects and the slow start of effects have quickly limited the clinical application. Clopidogrel with acetylsalicylic acid is fast becoming the gold standard in antiaggregation therapy after PCI (percutaneous coronary intervention) even in ACS. But its pharmacokinetic and pharmacodynamic limitations lead to the development of new drugs. Prasugrel has a more potent and faster antiaggregation effect, but at the expense of more extensive bleeding. Ticagrelor is the last from this group of drugs with the advantage of a potent, efficient, rapid and reversible P2Y12 receptor antagonist over clopidogrel. According to the applicable guidelines, it is a preferred drug for PCI in ACS and its status in the List of the Croatian Health Insurance Fund limits its wider use in Croatia at the moment.
doi:10.15836/ccar.2014.48 fatcat:6jph6zgr6bdbnfs54llweivebe