RESUMO
Patients with or at risk of heparin-induced thrombocytopenia (HIT) who are undergoing percutaneous coronary intervention (PCI) are at particular risk of thrombosis due to the prothrombotic nature of HIT and the endovascular disruption from PCI. Patients require aggressive anticoagulation during PCI, and alternative, nonheparin anticoagulation is recommended over heparin in patients with acute or previous HIT. Argatroban, bivalirudin, and lepirudin are nonheparin, fast-acting, parenteral direct thrombin inhibitors (DTIs). Multicenter, prospective studies have demonstrated that argatroban and lepirudin each reduce thrombosis in HIT and that argatroban and bivalirudin each provide adequate anticoagulation during PCI in patients with or at risk of HIT. We review current therapeutic practices with direct thrombin inhibitors in patients with or at risk of HIT during PCI, including individuals requiring periprocedural anticoagulation, and the factors influencing the choice of DTI in this setting.
Assuntos
Angioplastia Coronária com Balão , Antitrombinas/uso terapêutico , Fibrinolíticos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Trombocitopenia/tratamento farmacológico , Trombose/prevenção & controle , Arginina/análogos & derivados , Interações Medicamentosas , Farmacoeconomia , Fibrinolíticos/efeitos adversos , Fibrinolíticos/economia , Hemorragia/etiologia , Heparina/efeitos adversos , Hirudinas/administração & dosagem , Hirudinas/economia , Hirudinas/farmacologia , Humanos , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/economia , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/uso terapêutico , Ácidos Pipecólicos/economia , Ácidos Pipecólicos/farmacologia , Ácidos Pipecólicos/uso terapêutico , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/farmacologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/economia , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Sulfonamidas , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/fisiopatologiaAssuntos
Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária/métodos , Antagonistas da Serotonina/farmacologia , Succinatos/farmacologia , Arginina/análogos & derivados , Epinefrina/farmacologia , Humanos , Técnicas In Vitro , Ácidos Pipecólicos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Serotonina/farmacologia , Antagonistas do Receptor 5-HT2 de Serotonina , SulfonamidasRESUMO
This study investigated the effects of argatroban, a thrombin inhibitor, on brain edema and inflammation in a rat intracerebral hemorrhage (ICH) model. ICH was induced by injecting collagenase IV into the right caudate nucleus. Argatroban was administered intraperitoneally. Argatroban reduced brain edema from 44.6 to 14.3 microl at 72 h. Infiltration of polymorphonuclear leukocytes at 24 h and monocyte/macrophage at 24 and 72 h was significantly suppressed by argatroban. Argatroban did not increase the volume of hematoma. Systemic administration of argatroban reduced secondary brain damage including edema and inflammation in a rat ICH model.
Assuntos
Anticoagulantes/farmacologia , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/patologia , Ácidos Pipecólicos/farmacologia , Animais , Arginina/análogos & derivados , Astrócitos/patologia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/patologia , Hematoma/tratamento farmacológico , Hematoma/patologia , Masculino , Neutrófilos/patologia , Ratos , Ratos Wistar , SulfonamidasAssuntos
Anticoagulantes/efeitos adversos , Antitrombinas/uso terapêutico , Heparina/efeitos adversos , Hirudinas/análogos & derivados , Ácidos Pipecólicos/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Antitrombinas/economia , Antitrombinas/farmacologia , Arginina/análogos & derivados , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Sulfatos de Condroitina/economia , Sulfatos de Condroitina/farmacologia , Sulfatos de Condroitina/uso terapêutico , Cuidados Críticos/métodos , Dermatan Sulfato/economia , Dermatan Sulfato/farmacologia , Dermatan Sulfato/uso terapêutico , Combinação de Medicamentos , Custos de Medicamentos , Monitoramento de Medicamentos/métodos , Heparitina Sulfato/economia , Heparitina Sulfato/farmacologia , Heparitina Sulfato/uso terapêutico , Hirudinas/economia , Hirudinas/farmacologia , Humanos , Ácidos Pipecólicos/economia , Ácidos Pipecólicos/farmacologia , Proteínas Recombinantes/economia , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Sulfonamidas , Trombocitopenia/classificaçãoRESUMO
Argatroban, a direct thrombin inhibitor derived from arginine, is an effective anticoagulant indicated for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT). Argatroban has been used as an alternative anticoagulant in patients with HIT in various clinical conditions including interventional cardiovascular procedures that require anticoagulation. Satisfactory clinical outcomes with acceptable complications have been reported in these patients. Whether argatroban offers additional clinical advantage over conventional heparin therapy in patients without HIT remains unclear. Argatroban has been evaluated as an alternative anticoagulant to replace heparin in various clinical studies, especially in patients with coronary artery disease or cerebral vascular disease. To date, it remains unclear if argatroban is more effective than heparin, although the agent seems to cause less bleeding complications. This article reviews the pharmacology of argatroban and its clinical application beyond the management of HIT, with particular emphasis on interventional cardiology procedure, acute myocardial infarction, unstable angina pectoris, cerebral thrombosis or ischemic stroke, peripheral obstructive arterial disease, and extracorporeal circulation.
Assuntos
Antitrombinas/farmacologia , Antitrombinas/uso terapêutico , Ácidos Pipecólicos/farmacologia , Ácidos Pipecólicos/uso terapêutico , Angioplastia Coronária com Balão , Anticoagulantes/efeitos adversos , Antitrombinas/economia , Arginina/análogos & derivados , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/terapia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/terapia , Honorários Farmacêuticos , Heparina/efeitos adversos , Humanos , Ácidos Pipecólicos/economia , Sulfonamidas , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Argatroban, a direct thrombin inhibitor, is metabolized in vitro by CYP3A4/5 and therefore may be susceptible to clinically relevant CYP3A drug interactions. The effect of erythromycin, a potent CYP3A4/5 inhibitor, on the pharmacokinetics and pharmacodynamics of argatroban was evaluated in 14 healthy male volunteers in an open-label, crossover study with a 5-day washout between regimens. Argatroban 1 microgram/kg/min was infused alone for 5 hours (regimen A) and again on day 6 of a 7-day oral regimen of 500 mg erythromycin four times daily (regimen B). Serial blood samples for the determination of activated partial thromboplastin time (aPTT) and argatroban concentrations were collected for up to 48 hours following infusion. Mean values for argatroban area under the concentration-time curves (AUC0-inf), maximum concentration (Cmax), and half-life (t1/2) were similar between regimens. Mean aPTT values were not affected significantly by the concomitant administration of argatroban and erythromycin compared to argatroban alone. No serious adverse events or bleeding episodes occurred during the study. These results suggest that oxidative metabolism by CYP3A4/5 is unlikely to be an important in vivo elimination pathway for argatroban. Therefore, coadministration of CYP3A4/5 inhibitors should not require a modification in the dosage of argatroban.