Yeung Jennifer, Holinstat Michael
Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
J Blood Med. 2012;3:33-42. doi: 10.2147/JBM.S25421. Epub 2012 Jun 25.
Antiplatelet therapy remains the mainstay in preventing aberrant platelet activation in pathophysiological conditions such as myocardial infarction, ischemia, and stroke. Although there has been significant advancement in antiplatelet therapeutic approaches, aspirin still remains the gold standard treatment in the clinical setting. Limitations in safety, efficacy, and tolerability have precluded many of the antiplatelet inhibitors from use in patients. Unforeseen incidences of increased bleeding risk and recurrent arterial thrombosis observed in patients have hampered the development of superior next generation antiplatelet therapies. The pharmacokinetic and pharmacodynamic profiles have also limited the effectiveness of a number of antiplatelet inhibitors currently in use due to variability in metabolism, time to onset, and reversibility. A focused effort in the development of newer antiplatelet therapies to address some of these shortcomings has resulted in a significant number of potential antiplatelet drugs which target enzymes (phosphodiesterase, cyclooxygenase), receptors (purinergic, prostaglandins, protease-activated receptors, thromboxane), and glycoproteins (αIIbβ3, GPVI, vWF, GPIb) in the platelet. The validation and search for newer antiplatelet therapeutic approaches proven to be superior to aspirin is still ongoing and should yield a better pharmacodynamic profile with fewer untoward side-effects to what is currently in use today.
抗血小板治疗仍然是预防诸如心肌梗死、缺血和中风等病理生理状况下异常血小板活化的主要手段。尽管抗血小板治疗方法有了显著进展,但阿司匹林在临床环境中仍然是金标准治疗药物。安全性、有效性和耐受性方面的局限性使得许多抗血小板抑制剂无法用于患者。在患者中观察到的出血风险增加和复发性动脉血栓形成等意外情况阻碍了新一代更优抗血小板疗法的开发。药代动力学和药效学特征也限制了目前使用的一些抗血小板抑制剂的有效性,这是由于代谢、起效时间和可逆性的变异性所致。为解决其中一些缺点而致力于开发更新的抗血小板疗法,已产生了大量潜在的抗血小板药物,这些药物靶向血小板中的酶(磷酸二酯酶、环氧化酶)、受体(嘌呤能、前列腺素、蛋白酶激活受体、血栓素)和糖蛋白(αIIbβ3、GPVI、vWF、GPIb)。验证和寻找被证明优于阿司匹林的更新抗血小板治疗方法的工作仍在进行中,并且应该会产生一种药效学特征更好、副作用比目前使用的药物更少的药物。