非典型抗精神病药物相关的药物相互作用

［摘要］非典型抗精神病药物的代谢主要经细胞色素P450酶（CYP）系统代谢，影响药物代谢酶活性的各种因素均可能导致非典型抗精神病药物代谢的改变，从而升高或降低血药浓度，使药理作用和毒性作用发生改变。而精神病患者往往接受多种药物治疗，且治疗过程漫长，因此联合用药的情况较多见。综述经CYP酶代谢的新型非典型抗精神病药物之间或与其他药物之间的相互作用，旨在为临床用药提供参考，促进合理用药。     

抗抑郁药的药物相互作用

目的:抗抑郁药物的种类繁多,临床合并用药的几率较大,现将该类药物与其他药物之间的相互作用进行综述,以期为临床合理用药提供依据.方法:检索Medline、中国期刊全文数据库(CNKI)及中文科技期刊数据库相关内容.结果:抗抑郁药的代谢主要由细胞色素P450催化,故影响药物代谢酶活性的各种因素均可能导致典型抗精神病药物代谢的改变,从而升高或降低血药浓度,导致药物药理作用和毒副作用的改变.结论:多数抗抑郁药与其他药物合用时存在药物相互作用,有些相互作用会产生严重的不良反应,在临床治疗过程中应避免类似药物的联合使用.     

抗新型冠状病毒肺炎（COVID-19）药物潜在相互作用研究进展

自2019年12月以来,国内外暴发了新型冠状病毒肺炎(COVID-19)。在COVID-19的患者中,除了抗病毒治疗外,还要治疗并发症,临床需要采取联合用药的方式进行治疗。虽然在近期发布的指南中多次强调注意抗COVID-19药物间的相互作用,但却无相应的详述。主要对治疗COVID-19药物的潜在相互作用进行综述,以期为COVID-19的临床安全、合理用药提供参考。     

抑郁症610例临床药物应用分析

目的 分析我院抗抑郁药物临床应用情况,为临床合理用药提供参考。方法 回顾性分析我院2019年1～10月接受抗抑郁药物治疗的610例患者临床资料,分类别对我院抗抑郁药物临床应用的销售金额、DDDs、DDC进行统计分析。结果 我院抗抑郁药物使用金额总体呈增长趋势,其中SSRIs、SNRIs使用金额占总金额的80%左右,用药频率较高的是帕罗西汀、西酞普兰、舍曲林。结论 抗抑郁药物临床应用日益增长,SSRIs、SNRIs类新型抗抑郁药物已经成为临床治疗抑郁症的一线用药。     

中药注射剂对细胞色素P450的调控与药物相互作用预测

近年来中药注射剂在临床上应用广泛,与其他药物联合应用极为普遍,联合用药是否会产生细胞色素P450（CYP）酶介导的代谢性药物相互作用,从而影响疗效和用药安全,已越来越受到关注.本文就近年来中药注射剂对CYP酶影响的国内外研究进行了综述,按各亚型酶进行归类,归纳了中药注射剂对CYP各亚型酶的作用（诱导、抑制）,以预测中药注射剂及与哪些药物联合应用时可能会产生潜在的代谢性药物相互作用,与哪些药物可安全联用,从而为临床安全合理用药及相关研究提供参考,保障患者用药安全有效,规避用药风险.     

基于细胞色素P450酶的药物相互作用机制探讨

细胞色素P450酶是药物体内代谢的关键酶,药物合用时可能因与同一种代谢酶的相互作用,导致药物在体内的处置过程发生改变.本文旨在探讨常见的细胞色素P450酶相关药物相互作用类型和其机制,为临床联合用药的合理、安全、有效提供依据.     

精神科住院患者医嘱中CYP450介导的药物相互作用风险分析

目的 调查河北医科大学第一医院精神科住院患者存在细胞色素P450酶（CYP450）介导的药物相互作用的住院医嘱，分析潜在具有临床意义的药物相互作用，为临床用药提供参考。方法 对河北医科大学第一医院2018年7月1日-12月31日精神科住院患者所有运行病历的用药情况进行统计分析，筛选联用≥ 2种药物的医嘱，记录联合用药中含有CYP450酶底物、抑制剂或诱导剂的情况。以代谢酶学理论为指导，以药品说明书、相关文献报道为基础，评价医嘱中潜在的代谢性药物相互作用，并统计临床发生实际药物相互作用的病例。结果 共查阅1 658份病历，其中存在代谢性药物相互作用的病历227份，占13.7%，涉及的CYP酶的亚型主要有CYP2D6（n=176，77.5%）、CYP3A4（n=105，46.3%）、CYP2C19（n=24，10.6%）和CYP2C9（n=5，2.2%）。临床发生实际药物相互作用的病历6份，占2.6%。结论 河北医科大学第一医院精神科住院患者病历中存在潜在的代谢性药物相互作用较多。为提高用药的疗效与安全，临床上应尽量避免联用已有文献报道的存在不良相互作用的药物，选择没有相互作用或相互作用较少的同类药物。     

肝脏药物代谢功能与临床个体化用药

目的 通过对细胞色素P450酶的了解,尤其是它的多态性在药物不良反应中的作用及与药物的相互作用、对药物代谢的影响,为指导临床合理用药、避免药物不良反应、实施个体化用药提供参考.方法 Taqman探针技术测定P450酶单核苷酸的多态性.结果与结论 P450酶基因多态性造成个体用药差异,根据患者P450酶的基因型可以了解个体某类药物的代谢情况,从而利于临床医生合理选择适宜的药物和剂量,或联合用药时进行合理配伍.     

磺脲类降糖药的潜在药物相互作用研究进展

目的：了解磺脲类降糖药物的潜在药物相互作用,为临床安全、合理用药提供信息。方法：从细胞色素P450酶介导的代谢性药物相互作用和转运体介导的转运相互作用方面进行文献查阅、归纳和综述。结果：部分磺脲类降糖药与多种临床常用药物合用时存在潜在的药物相互作用,其发生机制与相应酶活性的变化及调控酶基因的多态性有关。结论：全面了解磺脲类降糖药物相互作用方面的知识,有助于提高临床安全、合理用药,提高临床治疗水平。     

中草药与抗艾滋病病毒化学药物相互作用的研究进展

目的 HIV感染者由于免疫力低下导致各种机会性感染,中草药和化学药物联合用药的现象十分普遍。但是中草药成分复杂,可能影响抗病毒化学药物的有效性、安全性,引起HIV耐药等问题。本研究综述中草药与抗艾滋病病毒化学药物相互作用的研究进展。方法 从百度(www.baidu.com)和Pubmed (http://www.ncbi.nlm.nih.gov/pubmed/)中搜索有关“中草药(herb)、抗艾滋病病毒药物(anti-HIV drugs)、药物与药物相互作用(drug-drug interaction)”的文献,然后进行归纳整理。结果 综述了中草药与化学药物联合用药现状,中草药对抗病毒化学药物的药动学影响以及对CYP450代谢酶的作用。结论 系统地综述了中草药与抗艾滋病病毒化学药物的相互作用,为临床合理用药提供参考。     

Clinically significant drug interactions with newer antidepressants

After the introduction of selective serotonin reuptake inhibitors (SSRIs), other newer antidepressants with different mechanisms of action have been introduced in clinical practice. Because antidepressants are commonly prescribed in combination with other medications used to treat co-morbid psychiatric or somatic disorders, they are likely to be involved in clinically significant drug interactions. This review examines the drug interaction profiles of the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine, duloxetine, milnacipran, mirtazapine, reboxetine, bupropion, agomelatine and vilazodone. In general, by virtue of a more selective mechanism of action and receptor profile, newer antidepressants carry a relatively low risk for pharmacodynamic drug interactions, at least as compared with first-generation antidepressants, i.e. monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). On the other hand, they are susceptible to pharmacokinetic drug interactions. All new antidepressants are extensively metabolized in the liver by cytochrome P450 (CYP) isoenzymes, and therefore may be the target of metabolically based drug interactions. Concomitant administration of inhibitors or inducers of the CYP isoenzymes involved in the biotransformation of specific antidepressants may cause changes in their plasma concentrations. However, due to their relatively wide margin of safety, the consequences of such kinetic modifications are usually not clinically relevant. Conversely, some newer antidepressants may cause pharmacokinetic interactions through their ability to inhibit specific CYPs. With regard to this, duloxetine and bupropion are moderate inhibitors of CYP2D6. Therefore, potentially harmful drug interactions may occur when they are coadministered with substrates of these isoforms, especially compounds with a narrow therapeutic index. The other new antidepressants are only weak inhibitors or are not inhibitors of CYP isoforms at usual therapeutic concentrations and are not expected to affect the disposition of concomitantly administered medications. Although drug interactions with newer antidepressants are potentially, but rarely, clinically significant, the use of antidepressants with a more favourable drug interaction profile is advisable. Knowledge of the interaction potential of individual antidepressants is essential for safe prescribing and may help clinicians to predict and eventually avoid certain drug combinations.     

氟西汀与抗精神病药相互作用

氟西汀是抗抑郁药的一线药,可与典型抗精神病药物、非典型抗精神病药物发生药物相互作用.氟西汀通过抑制细胞色素P450酶CYP2D6、CYP2C9、CYP3A4、CYP2C19、CYP1A2等,使其血药浓度升高,增加抗精神病药物的不良反应.临床应重视氟西汀与抗精神病药物的相互作用.     

CYP2D6基因与药物代谢

细胞色素P 45 0 (CYP)中的CYP2D6酶在抗抑郁药、安定药及某些抗心律失常药的代谢中起重要作用 ,CYP2D6基因位于 2 2号常染色体上为隐性遗传 ,CYP2D6基因呈多态性约有 70余种等位基因变异型 ,也存在特异人群差别 ,因而导致所编码的酶活性不同 ,这些数据有助于理解药物代谢的个体差异、有助于预测药物之间的相互作用。     

Mirtazapine and paroxetine: a drug-drug interaction study in healthy subjects

Paroxetine inhibits cytochrome P(450) 2D6, which is involved in the metabolism of mirtazapine. The possible drug-drug interaction between two pharmacologically distinct antidepressants, mirtazapine and paroxetine, has been investigated in a randomized, three-way crossover study in 24 healthy male and female subjects. After a titration phase of 3 days, each subject received single daily doses of 30 mg mirtazapine, 40 mg paroxetine or the combination for 6 days. Assessments included serial blood sampling for pharmacokinetics at steady state, cognitive testing using the test battery of CDR Ltd, a visual analogue mood rating scale (Bond and Lader) and the Leeds Sleep Evaluation Questionnaire. Paroxetine inhibits the metabolism of mirtazapine, as shown by increases of approximately 17% and 25% of the 24 h AUC's of mirtazapine and its demethyl metabolite, respectively. Mirtazapine did not alter the pharmacokinetics of paroxetine. The combined administration of mirtazapine and paroxetine probably does not alter cognitive functioning or result in major changes on the visual analogue mood rating scale and Sleep Evaluation Questionnaire, compared with the administration of either drug alone. The incidence of adverse events was lower during combined administration of mirtazapine and paroxetine than during administration of either drug alone. Fatigue, dizziness, headache, nausea, anxiety and somnolence were the most common adverse events during combined administration. These data suggest that the combination of mirtazapine and paroxetine is unlikely to lead to clinically relevant drug-drug interactions and can be used without dose adjustment of either drug. The combination may even be better tolerated than either drug alone. Copyright 2001 John Wiley & Sons, Ltd.     

CYP450与药物相互作用

目的 探讨细胞色素P450（CYP450）与药物相互作用的关系.方法 检索国内外数据库中与药物相互作用的相关文献,并查阅相关书籍,总结CYP450酶与药物相互作用的关系.结果 CYP450与药物相互作用关系最密切的是酶系统,凡参与代谢的酶都与药物相互作用有关,其中最主要的是CYP1 A2,2C9,2C19,2D6,3A4.结论 充分了解药物的药理及药代动力学特点,当与可能发生相互作用的药物合用时,应密切监测患者的情况,必要时进行药物剂量调整或换用其他药物.     

植物药与化学药相互作用研究现状及发展趋势

植物药即由植物提取精制而得的天然药物,多来源于俗称本草的中药。近年来,植物药与化学药联合应用日益增多,引起诸多药物相互作用和不良反应。与其攸关重要的环节是人体内细胞色素P450和ABC转运体家族参与的药物四大转运过程,因此研究其作用机制对降低相互作用发生率及指导,临床安全合理用药具有十分重要的意义。本文就临床常见植物药与化学药相互作用及其研究现状作一综述,旨在为同行研究提供参考。     

Clinically significant drug interactions with antidepressants in the elderly

Pharmacological treatment of depression in old age is associated with an increased risk of adverse pharmacokinetic and pharmacodynamic drug interactions. Elderly patients may have multiple disease states and, therefore, may require a variety of other drugs. In addition to polypharmacy, other factors such as age-related physiological changes, diseases, genetic constitution and diet may alter drug response and, therefore, predispose elderly patients to adverse effects and drug interactions. Antidepressant drugs currently available differ in their potential for drug interactions. In general, older compounds, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), have a higher potential for interactions than newer compounds, such as selective serotonin reuptake inhibitors (SSRIs) and other relatively novel agents with a more specific mechanism of action. In particular, TCAs and MAOIs are associated with clinically significant pharmacodynamic interactions with many medications frequently prescribed to elderly patients. Moreover, TCAs may be susceptible to pharmacokinetic interactions when given in combination with inhibitors or inducers of the cytochrome P450 (CYP) isoenzymes involved in their metabolism. Because of a more selective mechanism of action, newer antidepressants have a low potential for pharmacodynamic drug interactions. However, the possibility of the serotonin syndrome should be taken into account when drugs affecting serotonergic transmission, such as SSRIs, venlafaxine or nefazodone, are coadministered with other serotonergic agents. Newer agents have a differential potential for pharmacokinetic interactions because of their selective effects on CYP isoenzymes. Within the group of SSRIs, fluoxetine and paroxetine are potent inhibitors of CYP2D6, while fluvoxamine predominantly affects CYP1A2 and CYP2C19 activity. Therefore, these agents should be closely monitored or avoided in elderly patients treated with substrates of these isoforms, especially those with a narrow therapeutic index. On the other hand, citalopram and sertraline have a low inhibitory activity on different drug metabolising enzymes and appear particularly suitable in an elderly population. Among other newer antidepressants, nefazodone is a potent inhibitor of CYP3A4 and its combination with substrates of this isoform should be avoided.     

Drug interactions with cholinesterase inhibitors

Cholinesterase inhibitors are used for the symptomatic treatment of patients with Alzheimer's disease. This population often has numerous comorbidities and receives treatment with multiple medications. The astute clinician should remain mindful of possible drug interactions, both pharmacokinetic and pharmacodynamic, that may occur with concomitant treatment. Although pharmacokinetic interactions have been reported, pharmacodynamic interactions play a far greater role in the significance of drug interactions, with anticholinergic medications being most concerning. Commonly prescribed medications, such as antihistamines and tricyclic antidepressants, often have anticholinergic properties that alone or in combination with one another can antagonise the effects of cholinesterase inhibitors. Other medication classes such as antipsychotics and cholinergic agents may also result in pharmacodynamic interactions. However, for the most part, cholinesterase inhibitors can be used safely in combination with other medications.     

Anticonvulsants - antidepressants pharmacokinetic drug interactions: the role of the CYP450 system in psychopharmacology

The combined treatment with anticonvulsant and antidepressant drugs is reported in both neurologic and psychiatric practice; it is, therefore, evident that the issue of managing such type of polytherapy is frequently encountered by clinicians. To review current literature on pharmacokinetic interactions between anticonvulsant and antidepressant drugs. A search of MEDLINE and EMBASE was conducted for original papers and review articles published in English between January 1970 and July 2008. Among antidepressants, older compounds, such as tricyclics and monoaminoxidase inhibitors, have higher potential for interactions than newer ones. In almost all cases, drug dosages need to be adjusted when prescribed in combination with inducers such as carbamazepine, barbiturates and phenytoin. Data concerning new antiepileptic drugs are still limited; however, in several cases, new generation compounds are characterized by a favorable pharmacokinetic profile, thus, limiting the risk of interactions. In fact, gabapentin, topiramate, lamotrigine and levetiracetam are expected to be safely used in association with antidepressants, although it should be considered that topiramate may have interactions at doses higher than 200 mg. Although new generation antidepressants are not equivalent in their potential for interactions, their use seems to be safe in combination with anticonvulsant drugs. When prescribed with well-known inducers, the drug dose needs to be adjusted in relationship with the clinical response.