Preskorn Sheldon H
PRESKORN: Kansas University School of Medicine-Wichita, Wichita, KS.
J Psychiatr Pract. 2019 Jan;25(1):34-40. doi: 10.1097/PRA.0000000000000362.
This column is the third in a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. The first column in this series discussed why patients being treated with psychiatric medications are at increased risk for taking multiple medications and thus experiencing DDIs and how to recognize such DDIs, and strategies for avoiding them. The second column in the series further discussed strategies for avoiding and/or minimizing adverse outcomes from DDIs. This third column deals with pharmacokinetic considerations concerning DDIs in psychiatric practice. Specifically, this column discusses the 2 major types of pharmacokinetically mediated DDIs: those mediated by cytochrome P450 (CYP) enzymes and those mediated by transport proteins. The role of each of these regulatory proteins in the pharmacokinetics of drugs is reviewed as well as how genetically determined variation in the functional activity of these regulatory proteins can alter the accumulation of a drug in the body (ie, via CYP enzymes) and in specific compartments of the body (ie, via transport proteins), either increasing or decreasing their accumulation leading to either reduced efficacy or increased toxicity. This column further explains how coprescribed drugs can also affect the functional integrity of these regulatory proteins and lead to differences from usual in the accumulation of drugs dependent on the activity of these CYP enzymes and drug transporters. This phenomenon is known as phenoconversion in which a patient can functionally change from his or her genetic status, for example, having extensive or normal metabolism, to having poor or slow metabolism and hence greater accumulation than would be expected based on the patient's genotype.
本专栏是探讨药物相互作用（DDIs）系列文章的第三篇，特别关注精神科药物。本系列的第一篇专栏文章讨论了接受精神科药物治疗的患者为何服用多种药物的风险增加，从而遭遇药物相互作用，以及如何识别此类药物相互作用，还有避免它们的策略。该系列的第二篇专栏文章进一步讨论了避免和/或最小化药物相互作用不良后果的策略。这第三篇专栏文章涉及精神科实践中药物相互作用的药代动力学考量。具体而言，本专栏讨论了药代动力学介导的两种主要类型的药物相互作用：由细胞色素P450（CYP）酶介导的和由转运蛋白介导的。本文回顾了每种调节蛋白在药物药代动力学中的作用，以及这些调节蛋白功能活性的基因决定变异如何改变药物在体内（即通过CYP酶）和身体特定隔室（即通过转运蛋白）的蓄积，要么增加要么减少其蓄积，从而导致疗效降低或毒性增加。本专栏进一步解释了联合处方药物如何也能影响这些调节蛋白的功能完整性，并导致依赖这些CYP酶和药物转运体活性的药物蓄积与通常情况不同。这种现象被称为表型转换，即患者在功能上可以从其遗传状态转变，例如，从具有广泛或正常代谢转变为具有不良或缓慢代谢，因此蓄积量比基于患者基因型预期的更大。
