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老年人使用苯二氮䓬类药物的问题与陷阱。

Problems and pitfalls in the use of benzodiazepines in the elderly.

作者信息

Kruse W H

机构信息

Medizinisch-Geriatrische Klinik, Krankenhaus Bethanien, Heidelberg, Federal Republic of Germany.

出版信息

Drug Saf. 1990 Sep-Oct;5(5):328-44. doi: 10.2165/00002018-199005050-00003.

Abstract

Benzodiazepines are frequently prescribed for elderly patients living in the community and for those in hospitals and institutions. Their use is more prevalent in women. Prolonged use of benzodiazepines is particularly likely in old age for the treatment not only of insomnia and anxiety, but also of a wide range of nonspecific symptoms. Long term users are likely to have multiple concomitant physical and psychological health problems. The distinction between benzodiazepine anxiolytics and hypnotics is difficult and somewhat arbitrary, since the differences between the compounds are less than their similarities, especially in respect of adverse reactions. Despite their wide therapeutic range, elderly patients are particularly prone to adverse reactions to benzodiazepines. The incidence of unwanted effects, predominantly manifestations of central nervous system depression, has been found to be significantly increased in hospitalised elderly patients, particularly in the frail elderly. Studies on unwanted effects during long term use are scarce, but there is some evidence of tolerance to side effects. However, benzodiazepines have been found to be frequently implicated in drug-associated hospital admissions. There is suggestive evidence that benzodiazepines, especially compounds with long half-lives, may contribute to the falls which are a major health problem in old age. The incidence of benzodiazepine dependence in elderly patients is unknown. The features of benzodiazepine withdrawal in the elderly may differ from those seen in young patients; withdrawal symptoms include confusion and disorientation which often does not precipitate milder reactions such as anxiety, insomnia and perceptual changes. Problems due to both adverse reactions and to benzodiazepine withdrawal may easily be overlooked in multimorbid elderly patients, particularly in those suffering from disorders of the central nervous system. There are numerous studies on benzodiazepine pharmacokinetics indicating that alterations, especially in distribution and elimination of certain compounds, occur in old age. Benzodiazepines with oxidative metabolic pathways and longer half-lives are likely to accumulate with regular administration. However, changes in pharmacodynamics may be more important to explain altered responses to benzodiazepines in the elderly. Although information on pharmacodynamics is still limited, there is convincing evidence of increased pharmacodynamic response in the elderly which may be further accentuated by disease factors. Since the variability of pharmacological response increases with age and is not always predictable, there is good reason at least to start therapy at lower doses and to titrate dosages individually. This may also be appropriate for the newer benzodiazepines, irrespective of advantageous pharmacokinetics.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

苯二氮䓬类药物常用于社区老年患者以及医院和机构中的老年患者。其在女性中的使用更为普遍。老年人尤其可能长期使用苯二氮䓬类药物,不仅用于治疗失眠和焦虑,还用于治疗多种非特异性症状。长期使用者可能同时存在多种身体和心理健康问题。区分苯二氮䓬类抗焦虑药和催眠药很困难且有点随意,因为这些化合物之间的差异小于它们的相似性,尤其是在不良反应方面。尽管其治疗范围广泛,但老年患者特别容易对苯二氮䓬类药物产生不良反应。在住院老年患者中,尤其是体弱的老年人,不良影响(主要是中枢神经系统抑制的表现)的发生率已显著增加。关于长期使用期间不良影响的研究很少,但有一些证据表明对副作用存在耐受性。然而,已发现苯二氮䓬类药物经常与药物相关的住院治疗有关。有提示性证据表明,苯二氮䓬类药物,尤其是半衰期长的化合物,可能导致跌倒,而跌倒是老年期的一个主要健康问题。老年患者中苯二氮䓬类药物依赖的发生率尚不清楚。老年人苯二氮䓬类药物戒断的特征可能与年轻患者不同;戒断症状包括意识模糊和定向障碍,通常不会引发焦虑、失眠和感知变化等较轻的反应。在患有多种疾病的老年患者中,尤其是患有中枢神经系统疾病的患者中,不良反应和苯二氮䓬类药物戒断引起的问题很容易被忽视。有许多关于苯二氮䓬类药物药代动力学的研究表明,老年时会发生改变,尤其是某些化合物的分布和消除方面。具有氧化代谢途径和较长半衰期的苯二氮䓬类药物在常规给药时可能会蓄积。然而,药效学的变化可能对解释老年人对苯二氮䓬类药物反应的改变更为重要。尽管关于药效学的信息仍然有限,但有令人信服的证据表明老年人的药效学反应增加,疾病因素可能会进一步加剧这种情况。由于药理反应的变异性随年龄增加且并非总是可预测的,至少有充分的理由以较低剂量开始治疗并个体化调整剂量。这对于较新的苯二氮䓬类药物可能也适用,无论其有利的药代动力学如何。(摘要截取自400字)

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