Naranjo C A, Bremner K E
Clinical Pharmacology and Pharmacotherapy Research Unit, Addiction Research Foundation, Toronto, Canada.
Addiction. 1993 Jan;88(1):25-35.
Alcohol is used in most cultures despite knowledge of the physical, psychological and social problems associated with its abuse. Behavioural impairment is a function of several factors, including blood alcohol concentration (BAC) and the rate of alcohol metabolism by alcohol dehydrogenase and the microsomal ethanol-oxidizing system. Their availability and activity depend upon alcohol use history, ethnicity, other drug use and gender. Adverse social consequences related to alcohol intoxication include impaired driving, acts of aggression and violence towards self and others, and various types of accidents. About 40% of all fatal traffic accidents in Canada and the US in 1986-1987 were alcohol-related. Similar statistics have been reported in the UK and Europe (e.g. Sweden). The risk of a fatal car accident increases exponentially with a driver's BAC, prompting recommendations to lower the legal BAC limit for driving and piloting aircraft. Risks of falls, drownings, and fires and burns may also be increased by alcohol intoxication. At least 22% of work-related accidents may have involved alcohol use. These data are probably conservative estimates as under-reporting of alcohol use is likely. Alcohol facilitates aggressive behaviours, but it is difficult to separate the pharmacological effect from psychosocial effects or some other common factor (e.g. low CSF levels of the serotonin metabolite 5-H1AA have been reported in alcoholics, suicide attempters, violent offenders). In addition, alcohol interacts with other drugs to increase or decrease their behavioural and therapeutic effects. An acutely high BAC inhibits the metabolism of other CNS depressants (e.g. benzodiazepines), but long-term alcohol use increases the metabolism of most drugs. A potential amethystic agent, to block or reverse alcohol's effects, has been identified in preclinical studies (Ro15-4513, an imidazobenzodiazepine). Some clinical studies indicated that naloxone, lithium, ibuprofen, zimeldine and catecholamine agonists may reduce ethanol-induced behavioural or cognitive effects but the results have not been consistently replicated. More research is needed to determine the potential clinical use of amethystic agents and other pharmacotherapies in the prevention and treatment of problem behaviours associated with alcohol abuse and intoxication.
尽管人们知道酒精滥用会带来身体、心理和社会问题，但在大多数文化中都存在饮酒现象。行为损害是多种因素作用的结果，包括血液酒精浓度（BAC）以及酒精脱氢酶和微粒体乙醇氧化系统对酒精的代谢速率。它们的可用性和活性取决于饮酒史、种族、其他药物使用情况和性别。与酒精中毒相关的不良社会后果包括驾驶能力受损、对自己和他人的攻击及暴力行为，以及各类事故。在1986 - 1987年，加拿大和美国所有致命交通事故中约40%与酒精有关。英国和欧洲（如瑞典）也报告了类似的统计数据。致命车祸的风险会随着驾驶员血液酒精浓度呈指数级上升，这促使人们建议降低驾驶和驾驶飞机的法定血液酒精浓度限制。酒精中毒还可能增加跌倒、溺水以及火灾和烧伤的风险。至少22%的工作相关事故可能与饮酒有关。这些数据可能是保守估计，因为饮酒情况可能存在报告不足的问题。酒精会助长攻击性行为，但很难将其药理作用与心理社会作用或其他一些共同因素区分开来（例如，据报道，酗酒者、自杀未遂者、暴力罪犯的脑脊液中血清素代谢物5 - H1AA水平较低）。此外，酒精与其他药物相互作用，会增强或减弱它们的行为和治疗效果。急性高血液酒精浓度会抑制其他中枢神经系统抑制剂（如苯二氮䓬类药物）的代谢，但长期饮酒会增加大多数药物的代谢。在临床前研究中已确定一种潜在的抗酒剂（Ro15 - 4513，一种咪唑并苯二氮䓬类药物），可阻断或逆转酒精的作用。一些临床研究表明，纳洛酮、锂、布洛芬、齐美利定和儿茶酚胺激动剂可能会减轻乙醇引起的行为或认知影响，但结果并未得到一致重复。需要更多研究来确定抗酒剂和其他药物疗法在预防和治疗与酒精滥用及中毒相关的问题行为方面的潜在临床应用。
