ElDesoky Ehab S
Pharmacology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
Am J Ther. 2007 Sep-Oct;14(5):488-98. doi: 10.1097/01.mjt.0000183719.84390.4d.
Aging is characterized by a progressive loss of functional capacities of most if not all organs, a reduction in homeostatic mechanisms, and a response to receptor stimulation. Also, loss of water content and an increase of fat content in the body are reported. Therefore, understanding the influence of age-dependent changes in composition and function of the body on the pharmacokinetics and pharmacodynamics of drugs is important before prescribing drugs to elderly patients. In this study, a Medline search for articles published in the period between 1975 and June 2006 was conducted with use of the key words aging, pharmacokinetics, and pharmacodynamics to review data related to alteration in pharmacokinetics and pharmacodynamics in elderly patients. Analysis of data revealed that the most important pharmacokinetic changes in old age include a decrease in the excretory capacity of the kidney more than the decline in the rate of hepatic drug metabolism. On the other hand, pharmacodynamic changes in the elderly are frequent and commonly ascribed to alteration in the sensitivity to drugs, irrespective of changes in drug disposition. For instance, the sensitivity of the cardiovascular system to beta-adrenergic agonists and antagonists decreases in old age, and the incidence of orthostatic episodes in response to drugs that lower blood pressure increases. However, the central nervous system becomes vulnerable in the elderly to agents that affect brain function (eg, opioids, benzodiazepines, and psychotropic drugs). Therefore, these drugs must be used very cautiously in this age group. In conclusion, the complexity of the interactions between polypharmacy, comorbidity, altered pharmacodynamic sensitivity, and even modest changes in pharmacokinetics in elderly necessitate the medical approach "start low and go slow" for aged subjects, especially if drug therapy is considered beneficial or absolutely necessary for them.
衰老的特征是多数（即便不是所有）器官的功能能力逐渐丧失、体内稳态机制减弱以及对受体刺激的反应变化。此外，据报道人体水分含量减少而脂肪含量增加。因此，在给老年患者开药之前，了解身体组成和功能的年龄依赖性变化对药物药代动力学和药效学的影响非常重要。在本研究中，利用关键词衰老、药代动力学和药效学对1975年至2006年6月期间发表在医学文献数据库（Medline）上的文章进行检索，以回顾与老年患者药代动力学和药效学改变相关的数据。数据分析显示，老年最重要的药代动力学变化包括肾脏排泄能力的下降超过肝脏药物代谢速率的降低。另一方面，老年人的药效学变化很常见，通常归因于对药物敏感性的改变，而与药物处置的变化无关。例如，老年人心血管系统对β-肾上腺素能激动剂和拮抗剂的敏感性降低，对降压药物产生体位性低血压发作的发生率增加。然而，老年人的中枢神经系统对影响脑功能的药物（如阿片类药物、苯二氮䓬类药物和精神药物）变得更加敏感。因此，在这个年龄组使用这些药物时必须非常谨慎。总之，老年患者多重用药、合并症、药效学敏感性改变以及药代动力学即使是适度变化之间相互作用的复杂性，使得针对老年受试者的医疗方法必须是“从小剂量开始，缓慢增加剂量”，特别是如果认为药物治疗对他们有益或绝对必要时。
