George C F, Robertson D
Clinical Pharmacology Department, University of Southampton.
Med Toxicol Adverse Drug Exp. 1987 Sep-Oct;2(5):367-82. doi: 10.1007/BF03259954.
Syndromes due to the abrupt withdrawal of drug treatment occur mainly with adrenal corticosteroids and agents with an action on either the cardiovascular system or central nervous system. The abrupt withdrawal of antihypertensive therapy typically results in symptoms of overactivity in the sympathetic nervous system. Clonidine and beta-adrenoceptor antagonists are clinically the most important of these agents, but numerous other drugs have been implicated. Overall, the problem is small when viewed in the context of the huge scale of prescribing of antihypertensive medicines. A more serious problem is the occurrence of crescendo angina following the abrupt withdrawal of beta-adrenoceptor antagonists. Although other factors may be involved, adaptive up-regulation of beta-adrenoceptor density is the most likely cause of crescendo angina, and renders the patient more susceptible to sympathetic nervous stimulation following withdrawal of treatment. Besides leading to a recrudescence of the disease being treated, the withdrawal of corticosteroids can cause a variety of syndromes. In particular, problems can arise as a result of treatment-induced suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Another steroid withdrawal syndrome of unknown aetiology, without significant abnormalities of the HPA axis occurring, has been described. Benign intracranial hypertension may rarely follow steroid withdrawal in children. The syndromes associated with withdrawal of drugs which have an action on the CNS are poorly understood. Withdrawal of neuroleptic drugs can be followed by symptoms that resemble those described following withdrawal of anticholinergic drugs, and those agents with the greatest muscarinic-receptor-blocking properties are those which are most frequently implicated. However, the less common withdrawal dyskinesias are thought to reflect up-regulation of dopaminergic receptors during long term treatment. Gastrointestinal symptoms predominate following the abrupt withdrawal of antidepressants but hypomania and an 'akathisia-like' syndrome have been reported. Barbiturates are no longer recommended as hypnotics because of severe effects of withdrawal and the existence of safer alternatives. Short acting barbiturates can be withdrawn by replacement with either phenobarbitone (phenobarbitol) or diazepam and subsequent gradual reduction in dose. The recognition of dependency on benzodiazepines has been slow because of the similarity of mild withdrawal symptoms to the original problem which led to treatment being offered.(ABSTRACT TRUNCATED AT 400 WORDS)
药物治疗突然停药所致综合征主要发生于肾上腺皮质激素以及作用于心血管系统或中枢神经系统的药物。突然停用抗高血压治疗通常会导致交感神经系统活动过度的症状。可乐定和β肾上腺素能受体拮抗剂是这类药物中临床上最重要的，但许多其他药物也与之有关。总体而言，从抗高血压药物的巨大处方规模来看，这个问题较小。一个更严重的问题是突然停用β肾上腺素能受体拮抗剂后出现进行性心绞痛。尽管可能涉及其他因素，但β肾上腺素能受体密度的适应性上调是进行性心绞痛最可能的原因，并且使患者在停药后更容易受到交感神经刺激。除了导致正在治疗的疾病复发外，停用皮质类固醇还可引起多种综合征。特别是，治疗引起的下丘脑 - 垂体 - 肾上腺（HPA）轴抑制可能会引发问题。另一种病因不明的类固醇戒断综合征也已被描述，且未出现HPA轴的明显异常。儿童停用类固醇后可能很少发生良性颅内高压。与停用作用于中枢神经系统的药物相关的综合征了解甚少。停用抗精神病药物后可能出现类似于停用抗胆碱能药物后所描述的症状，而那些具有最强毒蕈碱受体阻断特性的药物最常涉及。然而，较少见的戒断运动障碍被认为反映了长期治疗期间多巴胺能受体的上调。突然停用抗抑郁药后胃肠道症状占主导，但也有报告出现轻躁狂和“静坐不能样”综合征。由于戒断的严重影响以及存在更安全的替代品，巴比妥类药物不再被推荐用作催眠药。短效巴比妥类药物可通过用苯巴比妥（鲁米那）或地西泮替代并随后逐渐减少剂量来停药。由于轻度戒断症状与导致提供治疗的原始问题相似，对苯二氮䓬类药物依赖性的认识一直很缓慢。
