依赖苯二氮卓类药物和其他GABA-A受体调节剂的患者的药代动力学驱动的个体化解毒程序。

IF 2.8 3区 医学 Q2 PSYCHIATRY
Anna R Basińska-Szafrańska
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引用次数: 0

摘要

导论:尽管患者间苯二氮卓类药物(BZD)代谢率存在极大差异,但依赖BZD或其他GABA-A受体调节剂的患者在治疗时无需实验室对照。提出的解毒方法是第一个采用浓度反馈来防止常规无法识别的问题:长效BZD替代品的过度积累,停药后的高浓度(模仿患者对“戒断”的适应),在治疗结束后很长时间内持续消除,导致延迟的低浓度危机和药物摄入复发。方法:一种新的方法,虽然是从典型的逐渐减少剂量的方法发展而来的,但它不是由剂量表驱动的,而是由个体BZD浓度演变驱动的。这定义了四个治疗阶段:替代、抗积累范式、消除和重新适应(SAER)。S期,通过滴定替代(使用地西泮或氯硝西酸酯,免疫测定可以很好地识别)以达到满足状态和建立个体临床状态和浓度基线结束。在A阶段,为了尽量减少进一步(不必要的)积累,在浓度反馈的驱动下,每天积极减少剂量,直到积累停止(准平台期)。进一步逐渐减少会开启E期(实际解毒),因此会减慢,这取决于患者的病情和排毒速度,并且以较低的频率(每3-7天)跟踪浓度,包括停药后。只有在完全消除(R期)后,患者才适应真正的禁欲。结论:SAER入路可最大限度地减少与过积累相关的误差。使用血清- bzd反馈抑制最初的过度积累。强制浓度平台为消除过程建立了优化的初始条件。通过减少不必要的高浓度治疗阶段,SAER提供了更多的时间来小心地护送低浓度危机,特别是在停药后几周内完成消除的危机。在不延长常规治疗时间的情况下,该方法旨在提高解毒过程的可靠性和治疗完成率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacokinetics-driven individualized detoxification procedure in patients dependent on benzodiazepines and other GABA-A receptor modulators.

Introduction: Despite extreme inter-patient differences in the benzodiazepine (BZD) metabolism rate, patients dependent on BZDs or other GABA-A receptor modulators are treated without laboratory control. The proposed detoxification method is the first to employ concentration feedback to prevent routinely unrecognized problems: overaccumulation of a long-acting BZD substitute, high concentration upon discontinuation (mimicking patients' adaptation to "abstinence"), elimination continuing long after treatment conclusion, resulting in delayed low-concentration crises and relapses of drug intake.

Methods: A new method, although evolved from a typical gradual dose reduction approach, is driven not by a dosage schedule but by an individual BZD concentration evolution. This defines four treatment stages: Substitution, Anti-accumulation paradigm, Elimination, and Readaptation (SAER). The S stage, substitution by titration (using diazepam or clorazepate, well read by immunoassays) ends with achieving a satiation state and establishing individual clinical-state and concentration baselines. During the A stage, to minimize further (unneeded) accumulation, doses are aggressively reduced daily, driven by concentration feedback, until accumulation ceases (a quasi-plateau). Further tapering opens the E stage (actual detoxification), hence slows, depending on the patient's condition and elimination rate, and concentration is tracked with lower frequency (every 3-7 days), including after drug discontinuation. Only after complete elimination (R stage) patients adapt to true abstinence.

Conclusions: The SAER approach can minimize overaccumulation-related errors. The use of serum-BZD feedback curbs the initial overaccumulation. A forced concentration plateau establishes optimized initial conditions for the elimination process. By minimizing a superfluous high-concentration treatment phase, SAER provides more time for a careful escorting of the low-concentration crises, especially the one coinciding with elimination completion, weeks after drug discontinuation. Without extending the usual treatment time, the method aspires to improve both the reliability of the detoxification process and the treatment completion rate.

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来源期刊
European Addiction Research
European Addiction Research SUBSTANCE ABUSE-PSYCHIATRY
CiteScore
6.80
自引率
5.10%
发文量
32
审稿时长
>12 weeks
期刊介绍: ''European Addiction Research'' is a unique international scientific journal for the rapid publication of innovative research covering all aspects of addiction and related disorders. Representing an interdisciplinary forum for the exchange of recent data and expert opinion, it reflects the importance of a comprehensive approach to resolve the problems of substance abuse and addiction in Europe. Coverage ranges from clinical and research advances in the fields of psychiatry, biology, pharmacology and epidemiology to social, and legal implications of policy decisions. The goal is to facilitate open discussion among those interested in the scientific and clinical aspects of prevention, diagnosis and therapy as well as dealing with legal issues. An excellent range of original papers makes ‘European Addiction Research’ the forum of choice for all.
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