Pharmacogenomics and circadian rhythms as mediators of cardiovascular drug-drug interactions.
Pharmacogenomics and circadian rhythms as mediators of cardiovascular drug-drug interactions.
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DOI：
10.1016/j.crphar.2021.100025
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发表时间：
2021
影响因子：
--
通讯作者：
Smolensky MH
中科院分区：
文献类型：
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作者：
Geng YJ;Madonna R;Hermida RC;Smolensky MH
本文总结了目前的文献，并记录了有关药物相互作用（DDI）的新证据，这些药物相互作用来自用于治疗常见心血管疾病（CVD）（如动脉粥样硬化和高血压）的药物基因组学和昼夜节律决定因素。CVD患者通常具有一种以上的病理生理状况，即代谢综合征、高血压、高脂血症和高血糖症等，这些需要多种治疗或多种药物管理。药物、药物和食物/食品补充剂之间的相互作用，或药物和遗传/表观遗传因素之间的相互作用，可能对心血管和身体的其他系统产生不利影响。心血管DDI的潜在机制可能涉及复杂药物相互作用组的形成，包括药物的吸收、分布、代谢和消除，这会影响其各自的生物利用度、疗效和/或有害代谢物。心血管药物的药物相互作用组可能是通过生物钟基因控制的内源性节律来运作的。基础和临床研究已经提高了对心血管药物基因组学和药物相互作用组学的认识和理解，此外，它们还提出了新的证据，即根据药物的给药时间，在觉醒与就寝时，不仅可以不同地影响它们的药代动力学和药效学，而且还介导激动/协同或拮抗DDI。为了正确管理CVD患者并避免DDI，重要的是临床医生对其多种风险因素有足够的了解，即，年龄、性别和生活方式因素（如饮食、吸烟、心理压力和饮酒），以及合并症（如糖尿病、高血压、血脂异常和抑郁症），以及其处方治疗的遗传或表观遗传背景之间的潜在相互作用。心血管药物基因组学和药物相互作用组学。细胞色素P450和心血管药物相互作用的昼夜节律。抗高血压和降胆固醇药物的昼夜节律。心血管药物与昼夜节律相互作用的临床研究。
This article summarizes the current literature and documents new evidence concerning drug-drug interactions (DDI) stemming from pharmacogenomic and circadian rhythm determinants of therapies used to treat common cardiovascular diseases (CVD), such as atherosclerosis and hypertension. Patients with CVD often have more than one pathophysiologic condition, namely metabolic syndromes, hypertension, hyperlipidemia, and hyperglycemia, among others, which necessitate polytherapeutic or polypharmaceutic management. Interactions between drugs, drugs and food/food supplements, or drugs and genetic/epigenetic factors may have adverse impacts on the cardiovascular and other systems of the body. The mechanisms underlying cardiovascular DDI may involve the formation of a complex pharmacointeractome, including the absorption, distribution, metabolism, and elimination of drugs, which affect their respective bioavailability, efficacy, and/or harmful metabolites. The pharmacointeractome of cardiovascular drugs is likely operated with endogenous rhythms controlled by circadian clock genes. Basic and clinical investigations have improved the knowledge and understanding of cardiovascular pharmacogenomics and pharmacointeractomes, and additionally they have presented new evidence that the staging of deterministic circadian rhythms, according to the dosing time of drugs, e.g., upon awakening vs. at bedtime, cannot only differentially impact their pharmacokinetics and pharmacodynamics but also mediate agonistic/synergetic or antagonistic DDI. To properly manage CVD patients and avoid DDI, it is important that clinicians have sufficient knowledge of their multiple risk factors, i.e., age, gender, and life style elements (like diet, smoking, psychological stress, and alcohol consumption), and comorbidities, such as diabetes, hypertension, dyslipidemia, and depression, and the potential interactions between genetic or epigenetic background of their prescribed therapeutics. Cardiovascular pharmacogenomics and pharmacointeractomes. Cytochrome P450 and circadian rhythms of cardiovascular drug interactions. Circadian rhythms of antihypertension and cholesterol-lowering medicines. Clinical aspects of cardiovascular drug interactions with circadian rhythms.