Ramaekers J G
Department of Biological Psychology, Maastricht University, The Netherlands.
Drug Saf. 1998 Mar;18(3):189-208. doi: 10.2165/00002018-199818030-00004.
Behavioural toxicity is relatively common among medicinal drug users and evidence shows that drugs frequently produce adverse effects that prevent their users from performing everyday operations in a normal manner. Epidemiological research generally indicates that the use of sedative drugs is associated with an increased risk of becoming involved in injurious accidents. Empirical studies have also demonstrated adverse effects of sedative drugs on the performance of healthy volunteers and patients in laboratory tests designed to measure psychomotor and cognitive function, and in real life-tests measuring on-the-road driving performance. Empirical studies also indicate that behavioural toxicity can vary widely between individual drugs depending on differences in dose, dosing regimen, duration of treatment, pharmacokinetics or mechanisms of actions. Besides sedation, other CNS adverse effects such as aggression, paranoia, social withdrawal or lack of motivation may disrupt or prevent the initiation of normal performance, thus imposing a burden on the ability of the patients to function in a normal manner. Emotional disturbances are rare as indicated by the small number of case reports that mention their existence. Yet theses disturbances sometimes involve severe reactions that are more debilitating than sedation. Behavioural toxicity can be minimised by avoidance of pharmacodynamic and pharmacokinetic drug interactions, adjustment of dosage regimens to a patient's individual response to a drug, nocturnal administration of drugs that are expected to produce sedation and patient education on the potential risks of the drugs they receive. Much of this information can be gained from experimental literature comparing the effect of individual drugs on performance. Unfortunately this is presently incomplete, since most research on behavioural toxicity has been confined to psychiatric drugs. Yet, in the interest of the patient, it should be the responsibility of drug manufacturers and regulators to always identify problematic drugs.
行为毒性在药物使用者中相对常见，证据表明药物经常产生不良反应，使使用者无法正常进行日常活动。流行病学研究普遍表明，使用镇静药物会增加发生伤害事故的风险。实证研究还表明，在旨在测量精神运动和认知功能的实验室测试以及测量道路驾驶性能的实际生活测试中，镇静药物对健康志愿者和患者的表现有不良影响。实证研究还表明，由于剂量、给药方案、治疗持续时间、药代动力学或作用机制的差异，不同药物之间的行为毒性可能有很大差异。除了镇静作用外，其他中枢神经系统不良反应，如攻击性、偏执狂、社交退缩或缺乏动力，可能会干扰或阻止正常行为的启动，从而给患者的正常功能能力带来负担。如少数提及情绪障碍存在的病例报告所示，情绪障碍很少见。然而，这些障碍有时会涉及比镇静更使人衰弱的严重反应。通过避免药效学和药代动力学药物相互作用、根据患者对药物的个体反应调整给药方案、对预期会产生镇静作用的药物进行夜间给药以及对患者进行所服用药物潜在风险的教育，可以将行为毒性降至最低。这些信息大多可以从比较个别药物对行为表现影响的实验文献中获得。不幸的是，目前这方面并不完整，因为大多数关于行为毒性的研究都局限于精神药物。然而，为了患者的利益，药物制造商和监管机构有责任始终识别有问题的药物。
