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口服抗凝剂。老年人使用中的药理学问题。

Oral anticoagulants. Pharmacologic issues for use in the elderly.

作者信息

Hylek E M

机构信息

Department of Medicine, Division of General Internal Medicine, Clinical Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Clin Geriatr Med. 2001 Feb;17(1):1-13. doi: 10.1016/s0749-0690(05)70102-6.

Abstract

There has been a marked expansion of the indications for oral anticoagulant therapy, particularly among the elderly. Despite the documented benefits, the use of warfarin remains strikingly low among patients 80 years of age and older. Elderly patients often exhibit an enhanced dose response to warfarin. On average, steady-state warfarin doses decrease by 11% per decade of age. Pharmacokinetic changes in the elderly are negligible. Pharmacodynamic differences have not been well characterized. Initiating warfarin dosing in the elderly should be done cautiously, with doses of 5 mg or less. Doses should be adjusted downward in the presence of congestive heart failure, advanced obstructive lung disease, liver disease, malignancy, protracted diarrhea, enteral feedings, or concurrent potentiating medications. Numerous medications interfere with the anticoagulant response of warfarin. The most powerful potentiating drugs are those that interfere with the metabolism of (S)-warfarin. Examples include amiodarone, trimethoprim-sulfamethoxazole, and metronidazole. These drugs should be prescribed with caution in the elderly and mandate frequent INR monitoring during the induction period. An extensive assessment of patient-specific factors that might increase the hazards related to warfarin therapy needs to be conducted and documented before initiating oral anticoagulant therapy. Patients and their caregivers need to understand the risks and benefits, and to recognize signs of abnormal bleeding and the need for frequent monitoring. Patients should be encouraged to maintain consistency in their vitamin K intake and should strive to meet the recommended dietary allowance for vitamin K. To improve anticoagulation control, physicians and other health care providers need to be aware of the many warfarin drug interactions and be cognizant of the increased dose response of warfarin seen in the elderly. Concurrent prescription of multiple drugs known to affect warfarin's anticoagulant response should be minimized and use of nonselective nonsteroidal anti-inflammatory drugs should be limited given their deleterious effects on the gastric mucosa. Transitions from inpatient care to subacute care and back to outpatient care are particularly vulnerable periods for patients' anticoagulation control. Enhanced provider communication and more seamless transitions help to ensure optimal INR follow-up and timely warfarin dose adjustment if indicated.

摘要

口服抗凝治疗的适应证已显著扩大,尤其是在老年人中。尽管有已记录的益处,但华法林在80岁及以上患者中的使用仍然极低。老年患者对华法林的剂量反应往往增强。平均而言,稳态华法林剂量每增加十岁就降低11%。老年人的药代动力学变化可忽略不计。药效学差异尚未得到很好的描述。在老年人中开始使用华法林时应谨慎,剂量为5毫克或更低。在存在充血性心力衰竭、晚期阻塞性肺病、肝病、恶性肿瘤、长期腹泻、肠内营养或同时使用增效药物的情况下,剂量应下调。许多药物会干扰华法林的抗凝反应。最有效的增效药物是那些干扰(S)-华法林代谢的药物。例子包括胺碘酮、甲氧苄啶-磺胺甲恶唑和甲硝唑。这些药物在老年人中应谨慎开具,并在诱导期要求频繁监测国际标准化比值(INR)。在开始口服抗凝治疗之前,需要对可能增加与华法林治疗相关风险的患者特定因素进行广泛评估并记录。患者及其护理人员需要了解风险和益处,并认识到异常出血的迹象以及频繁监测的必要性。应鼓励患者保持维生素K摄入量的一致性,并应努力达到维生素K的推荐膳食摄入量。为了改善抗凝控制,医生和其他医疗保健提供者需要了解许多华法林药物相互作用,并认识到老年人中华法林剂量反应的增加。应尽量减少同时开具已知会影响华法林抗凝反应的多种药物,并鉴于其对胃黏膜的有害影响,应限制使用非选择性非甾体抗炎药。从住院治疗过渡到亚急性护理再回到门诊护理的阶段,对于患者的抗凝控制来说是特别脆弱的时期。加强医护人员之间的沟通以及更无缝的过渡有助于确保最佳的INR随访,并在必要时及时调整华法林剂量。

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