IV ANESTHETIC DISPOSITION IN THE AGED HEMODYNAMIC STATE

人类的衰老改变了生理功能和药物反应。 静脉注射催眠药和阿片类药物 麻醉、药物进入组织的速度和程度控制 麻醉作用的起效和消退。我们之前的研究已经 研究表明，随着人类年龄的增长，催眠药物(硫喷妥， 依托咪酯)，但阿片类药物(芬太尼、阿芬太尼)不变。中的更改 分布反过来又会影响患者的麻醉剂量需求。 年龄对某些麻醉剂分布的选择性影响 药物可能是由年龄相关的心脏改变引起的。 输出量、区域血流量、组织成分和药物溶解度 纸巾。我们的研究将确定与年龄相关的身体变化 灌注量、组织大小和成分影响组织的再分布 硫喷妥钠、芬太尼和阿芬太尼在F1杂交大鼠中的应用。这些 选择麻醉药是因为它们的临床相关性，而且因为它们 组织分布的速度和程度，脂类的溶解度，以及 在人类和大鼠身上，消除作用明显不同。每种药物有四种类型 将在幼年和老年大鼠身上进行一系列研究。研究1将确定 剂量要求、血浆药代动力学和脑电效应。在研究2中， 长时间输液将评估稳定状态的血液：组织分割 (溶解度)。研究3将量化药物引起的心脏改变 输出量和区域血流量。研究4将测量药物的洗脱率 从不同的组织随着时间的推移。三种药物在人体内的药代动力学 各种组织将被评估并与药物诱导的 局部血流的变化。所得到的药代动力学数据 个体组织将被重新组装，以创造出完整的动物，因此 详细的计算机模拟然后可以估计类型和程度 心输出量的变化是改变局部血流所必需的 麻醉剂量要求、血浆药代动力学和脑电反应。我们 会在年轻女性身上造成这种程度的心血管改变 并前瞻性地评估其药理学后果。我们的 数据将为确定合适的剂量提供科学依据 对于其提供SC药理作用的药物，其终止方式为 随着年龄相关心血管功能的改变而发生再分配。 这项研究将确定血液动力学的程度和程度 与衰老相关的变化改变了麻醉剂药物的重新分配。

Human aging alters both physiologic function and pharmacologic response. For intravenously-administered hypnotic and opioid drugs used in anesthesia, the rate and extent of drug distribution into tissues control the onset and dissipation of anesthetic effect. our previous research has shown that, as humans age, the distribution of hypnotic drugs (thiopental, etomidate) but not opioids (fentanyl, alfentanil) change. Changes in distribution, in turn, affect the patient's anesthetic dose requirement. This selective influence of age on the distribution of some anesthetic drugs may be caused by a combination of age-related changes in cardiac output, regional blood flow, tissue composition, and drug-solubility in tissues. Our research will determine how age-related changes in body perfusion and tissue size and composition affect the redistribution of thiopental, fentanyl, and alfentanil in the Fl Hybrid rat. These anesthetics were chosen for their clinical relevance, and because their rate and extent of tissue distribution, lipid solubility, and rate of elimination differ markedly in humans and rats. For each drug, four types of studies will be performed in young and old rats. Study 1 will determine dose requirements, plasma pharmacokinetics, and EEG effects. In Study 2, prolonged infusions will estimate steady-state blood:tissue partitioning (solubility). Study 3 will quantitate drug-induced changes in cardiac output and regional blood flow. Study 4 will measure the washout of drug from various tissues over time. The pharmacokinetics of the three drugs in various tissues will be estimated and integrated with the drug-induced changes in regional blood flow. The resulting pharmacokinetic data for individual tissues will be "reassembled" to create the intact animal, so that detailed computer simulations can then estimate the type and degree of change in cardiac output a regional blood flow necessary to alter anesthetic dose requirement, plasma pharmacokinetics, and EEG response. We will then create this degree of cardiovascular alteration in young Fl Hybrid rats and prospectively estimate the pharmacologic consequences. Our data will provide a scientific basis for determining the appropriate dosage for drugs whose provide a sC pharmacologic effects are terminated by redistribution as age-related changes in cardiovascular function occur. This research will define the degree and extent to which hemodynamic changes associated with aging alter the redistribution of anesthetic drugs.