The Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
Neurology and Toxicology Service and Unit, Shaare Zedek Medical Center, Jerusalem, Israel.
Pharmacogenomics J. 2019 Aug;19(4):337-346. doi: 10.1038/s41397-018-0062-0. Epub 2018 Nov 5.
It is well known that a myriad of medications and substances can induce side effects that are related to blood pressure (BP) regulation. This study aims to investigate why certain drugs tend to cause iatrogenic hypertension (HTN) and focus on drug targets that are implicated in these conditions.Databases and resources such as SIDER, DrugBank, and Genomatix were utilized in order to bioinformatically investigate HTN-associated drug target-genes for which HTN is a side effect. A tree-like map was created, representing interactions between 198 human genes that relate to the blood pressure system. 72 HTN indicated drugs and 160 HTN-inducing drugs were investigated. HTN-associated genes affected by these drugs were identified. HTN indicated drugs, which target nearly all branches of the interaction tree, were shown to exert an effect on most functional sub-systems of the BP regulatory system; and specifically, for the adrenergic and dopaminergic receptor pathways. High prevalence (25 genes) of shared targets between the HTN indicated and HTN-inducing drug categories was demonstrated. We focus on six drug families which are not indicated for HTN treatment, yet are reported as a major cause for blood pressure side effects. We show the molecular mechanisms that may lead to this iatrogenic effect. Such an analysis may have clinical implications that could allow for the development of tailored medicine with fewer side effects.
众所周知,许多药物和物质会引起与血压(BP)调节相关的副作用。本研究旨在探讨为什么某些药物容易引起医源性高血压(HTN),并关注与这些情况相关的药物靶点。我们利用了 SIDER、DrugBank 和 Genomatix 等数据库和资源,从生物信息学角度研究了与 HTN 相关的药物靶点基因,这些基因是 HTN 的副作用。创建了一个树状图,代表了与血压系统相关的 198 个人类基因之间的相互作用。研究了 72 种 HTN 指示药物和 160 种 HTN 诱导药物。确定了受这些药物影响的与 HTN 相关的基因。HTN 指示药物几乎靶向相互作用树的所有分支,对血压调节系统的大多数功能子系统都有影响;特别是对肾上腺素能和多巴胺能受体途径。HTN 指示药物和 HTN 诱导药物类别之间存在 25 个共享靶点,这表明存在高度的共同靶点。我们关注六个并非专门用于 HTN 治疗的药物家族,但据报道它们是血压副作用的主要原因。我们展示了可能导致这种医源性效应的分子机制。这种分析可能具有临床意义,可以开发出副作用更少的定制药物。