Maccari S, Giglioli W, Semrov E, Fornaciari G
III Divisione di Medicina Interna, Azienda Ospedaliera di Reggio Emilia.
Ann Ital Med Int. 1996 Oct-Dec;11(4):279-83.
Disulfiram is used in alcohol rehabilitation because it inhibits aldehyde dehydrogenase and consequently causes the disulfiram-ethanol reaction (vomiting, vertigo, anxiety, cardiovascular effects) after ingestion of alcoholic beverages. However, adverse effects on the central nervous system (for the most part psychotic reactions, acute organic brain syndrome, catatonia) may appear as a direct result of the drug itself. Disulfiram and its metabolite carbon disulfide inhibit dopamine beta-hydroxylase, increasing the levels of dopamine and reducing those of norepinephrine in the central nervous system. We observed direct disulfiram-induced toxicity on the central nervous system in 8 abstinent patients in whom a disulfiram-ethanol reaction had been excluded. Risk is increased when 1) excessive amounts of the drug are ingested; 2) the patient is already suffering from a major psychiatric illness; 3) the patient has anatomical brain lesions. In all cases observed, the toxic effects appeared in the first weeks and were reversed after suspension of the drug (except in one patient who died from severe bronchopulmonary infection). We thus suggest the following protocol: 1) physical examination and interview 3-4 weeks after initiation of treatment; 2) as a general rule, in abstinent patients, the lowest possible maintenance dosage should be administered. This strategy, despite the risk of underdosage, meets the goals inherent in an integrated medical and psychosocial approach to the treatment of alcoholism with which these patients seem better able to comply.
双硫仑用于酒精戒断治疗，因为它能抑制乙醛脱氢酶，从而在摄入酒精饮料后引发双硫仑-乙醇反应（呕吐、眩晕、焦虑、心血管反应）。然而，对中枢神经系统的不良反应（大多为精神反应、急性器质性脑综合征、紧张症）可能直接由药物本身导致。双硫仑及其代谢产物二硫化碳抑制多巴胺β-羟化酶，增加中枢神经系统中多巴胺的水平并降低去甲肾上腺素的水平。我们在8名已排除双硫仑-乙醇反应的戒酒患者中观察到了双硫仑对中枢神经系统的直接毒性作用。当出现以下情况时风险会增加：1）摄入过量药物；2）患者已患有严重精神疾病；3）患者存在脑部解剖学病变。在所有观察到的病例中，毒性作用在最初几周出现，停药后得以逆转（除了一名死于严重支气管肺部感染的患者）。因此，我们建议如下方案：1）治疗开始3 - 4周后进行体格检查和问诊；2）一般来说，对于戒酒患者，应给予尽可能低的维持剂量。尽管存在剂量不足的风险，但这种策略符合酒精中毒综合医学和心理社会治疗方法的固有目标，这些患者似乎更能遵守该方法。
