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年龄相关的药效学变化:重点关注作用于中枢神经系统和心血管系统的药物。

Age-related changes in pharmacodynamics: focus on drugs acting on central nervous and cardiovascular systems.

机构信息

Department of Medical Informatics, Erasmus University Medical Center Dr Molewaterplein 50, 3000 DR, Rotterdam, the Netherlands.

出版信息

Curr Drug Metab. 2011 Sep;12(7):611-20. doi: 10.2174/138920011796504473.

Abstract

Aging is characterized by progressive impairment of functional capacities of all system organs, reduction in homeostatic mechanisms, and altered response to receptor stimulation. These age-related physiologic changes influence both pharmacokinetics and pharmacodynamics of drugs in elderly patients. Pharmacokinetic and pharmacodynamics changes as well as polypharmacy and comorbidities may alter significantly the effect of pharmacological treatment with advancing age. With the same drug concentration at the site of action, significant differences in the response to several drugs have been observed in older patients as compared to younger patients. Elderly patients are particularly suceptibles to the effects of frequently prescribed drugs acting on central nervous system, such as benzodiazepines, antidepressants, antipsychotics and lithium, with high potential for adverse drug reactions. Moreover, in older patients increased sensitivity to warfarin resulting in increased risk of bleeding has been previously documented. On the other hand, reduced effectiveness of conventional doses of cardiovascular drugs, such as diuretics and β-blockers, has been observed. Due to pharmacodynamic changes, therefore, dose adjustment of the above mentioned cardiovascular and psychotropic drugs is recommended in elderly. Clinicians should be aware of the age-related physiologic changes affecting several organ systems and their implications on the effect of drugs that are commonly prescribed to elderly patients.

摘要

衰老是所有系统器官功能逐渐受损、内稳态机制减少以及对受体刺激反应改变的特征。这些与年龄相关的生理变化会影响老年患者的药物药代动力学和药效学。药代动力学和药效学变化以及多种药物的使用和合并症可能会随着年龄的增长而显著改变药物治疗的效果。在作用部位有相同药物浓度的情况下,与年轻患者相比,老年患者对几种药物的反应存在显著差异。老年患者特别容易受到经常开处方的作用于中枢神经系统的药物的影响,如苯二氮䓬类、抗抑郁药、抗精神病药和锂,这些药物有发生不良反应的高风险。此外,先前有记录表明,华法林的敏感性增加导致出血风险增加。另一方面,观察到常规剂量的心血管药物(如利尿剂和β受体阻滞剂)的效果降低。因此,建议调整上述心血管和精神类药物在老年人中的剂量。临床医生应意识到影响多个器官系统的与年龄相关的生理变化及其对经常开给老年患者的药物的影响。

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