双硫仑化学式
但是双硫仑可以有效地加快橡胶的硫化过程，于是，让Grodzki没想到的是，二十几年后，随着橡胶工业飞速发展，双硫仑得到了广泛的应用。而橡胶工业从此也有了一个谜一样的巧合——橡胶工业的工人都不能沾酒，稍一接触酒精就会满面通红，心跳加速，甚至会神志模糊。
1937年，一个名叫E. E. Williams的驻厂医生指出，可能就是橡胶厂里大量使用的双硫仑引起了这些症状。Williams医生认为，双硫仑或许可以用来帮人戒酒 [2]。然而很遗憾的是，Williams医生也没有太大名气，他的文章也没有引起太多关注。
但这都没有阻止双硫仑的逆袭。在Williams医生的研究之后几年，哥本哈根大学的Erik Jacobsen在研究双硫仑时，再一次发现了双硫仑与酒精对人体的影响。他发现，双硫仑抑制了在酒精代谢过程中极为重要的乙醛脱氢酶，导致酒精代谢产生的乙醛在人体内大量积累，于是出现类似酒精中毒的反应。在Jacobsen的努力下，双硫仑被开发成了一款戒酒药物，取名“安塔布司”，取“戒除滥用（酒精）”之意。
1950年代时的Erik Jacobsen（右）与他当时的合作者Hald（左）。图片来源： quitalcohol.com
History[edit source]
The synthesis of disulfiram, originally known as tetraethylthiuram disulfide, was first reported in 1881.
By around 1900, it was introduced to the industrial process of Sulfur vulcanization of rubber and became widely used.
In 1937 a rubber factory doctor in the US published a paper noting that workers exposed to disulfiram had negative reactions to alcohol and could be used as a drug for alcoholism; the effects were also noticed in workers at Swedish rubber boot factory.[16]
In the early 1940s it had been tested as a treatment for scabies, a parasitic skin infection, as well as intestinal worms.[16]
Around that time, during the German occupation of Denmark, Erik Jacobsen and Jens Hald at the Danish drug company Medicinalco picked up on that research and began exploring the use of disulfiram to treat intestinal parasites. The company had a group of enthusiastic self-experimenters that called itself the "Death Battalion", and in the course of testing the drug on themselves, accidentally discovered that drinking alcohol while the drug was still in their bodies made them mildly sick.[16][17]:98–105
They made that discovery in 1945, and did nothing with it
until two years later, when Jacobsen gave an impromptu talk and mentioned that work, which was discussed afterwards in newspapers at the time, leading them to further explore the use of the drug for that purpose.[16][17]:98–105
That work included small clinical trials with Oluf Martensen-Larsen, a doctor who worked with alcoholics.[16] They published their work starting in 1948.[16][18]
The chemists at Medicinalco discovered a new form of disulfiram while trying to purify a batch that had been contaminated with copper. This form turned out to have better pharmacological properties, and the company patented it and used that form for the product that was introduced as Antabus (later anglicized to Antabuse).[16]
This work led to renewed study of the human metabolism of ethanol. It was already known that ethanol was mostly metabolized in the liver, with it being converted first acetaldehyde and then acetaldehyde to acetic acid and carbon dioxide, but the enzymes involved were not known. By 1950 the work led to the knowledge that ethanol is oxidized to acetaldehyde by alcohol dehydrogenase and acetaldehyde is oxidized to acetic acid by aldehyde dehydrogenase(ALDH), and that disulfiram works by inhibiting ALDH, leading to a buildup of acetaldehyde, which is what causes the negative effects in the body.[16]
The drug was first marketed in Denmark and as of 2008 Denmark was the country where it was most widely prescribed.
It was approved by the FDA in 1951.[16][19] The FDA later approved other drugs that cause negative reactions to recreational drugs, namely naltrexone in 1994 and acamprosate in 2004.[16]
https://en.wikipedia.org/wiki/Disulfiram?
一九四八年时，Erik Jacobsen，Jens Hald以及Keneth Ferguson意外的在丹麦的药品公司Medicinalco [18] 中，发现二硫龙的作用。本来二硫龙的存在是打算提供解决寄生虫感染的困扰。然而，测试者将酒精饮入后，竟发现严重的症状。 如今，二硫龙以戒酒硫知名贩售，由Odyssey Pharmaceuticals制造而成。
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引起双硫仑样反应的常见药物
头孢类抗生素
如头孢哌酮、头孢匹胺、头孢哌酮舒巴坦钠、头孢盂多、拉氧头孢、头孢美唑、头孢米诺、头孢甲肟、头孢尼西、头孢替安、头孢噻肟、头孢他啶、头孢磺啶、头孢唑肟、头孢唑啉、头孢克肟等。
头孢哌酮分子结构中母核7氨基头孢烷酸（7A-CA）环的3位上存在与双硫仑分子结构类似的甲硫四氢唑（硫代甲基四唑）活性基，可引起双硫仑样反应。头孢曲松等不具有甲硫氢唑侧链，但有甲硫三嗪侧链也可引起此类反应。化学结构中没有甲硫四氢唑侧链的头孢菌素则无此作用。
硝咪唑类
如甲硝唑、替硝唑，不论是口服或静脉给药，不论是何种酒，也不论是饮酒量多少，都会直接与吸收入血的乙醇发生反应，而出现双硫仑样症状。饮酒后要使用甲硝唑，必须禁酒5d，在使用甲硝唑时也应提醒患者应禁酒7d以上，以免引起双硫仑样反应。此类药物化学结构中含有甲硫四氮唑基团。
其他药物和食物
呋喃类如呋喃唑酮（痢特灵）、氯霉素、酮康唑、灰黄霉素、磺脲类降糖药如氯磺丙脲、达美康、甲苯磺丁脲（D860）、优降糖、苯乙双呱、华法林、三氟拉嗪、妥拉苏林、胰岛素等。
使用上述药物后7d内饮酒（如白酒、红酒、黄酒、啤酒）、服用含有乙醇的药物如糖浆类（棕色合剂、藿香正气水、氢化可的松等）或酊剂、食用某些食物（如酒心巧克力、乳酪、动物肝脏、沙丁鱼等富含酪胺、苯丙胺酸、色胺酸的食物和含乙醇的饮料）、乙醇外用（如乙醇擦浴、消毒）和做光量子治疗等可引起双硫仑样反应。
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the BAC, Blood Alcohol Content.
One standard drink raises the average person’s blood alcohol content (BAC) to 0.015%
IN CONCLUSION
How long does alcohol stay in your system? If you’re looking for the easy answer, it takes about an hour for the body to fully process one drink. From tipping the glass to stomach absorption, the time is quick, maybe five minutes. From the blood to the brain to the kidneys takes most of the time. Metabolism in the liver is relatively quick, maybe the last ten minutes of the beer’s journey. Then, either through liver metabolism, urination, sweating, or breathing ‘alcohol breath’, the beer’s journey is over. In less than 60 minutes, the body is clear of beer.
Remember, though, that having two drinks in one hour’s time does not mean one hour is needed to clear the system. Each drink takes its own hour. Remember this next time you have to drive home or remain sober for other reasons. Food or coffee will not save your sobriety, only time.
https://www.quitalcohol.com/information/how-long-does-alcohol-stay-in-your-system.html
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how long does alcohol stay in your system is one hour per one ounce of alcohol consumed. The liver processes one ounce of pure alcohol in sixty minutes, on average, and a standard drink contains 0.6 ounces of alcohol.
Standard drinks include 12 oz. of beer, 8 oz. of malt liquor, 5 oz. of wine, or 1.5 oz. of liquor.
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双硫仑样反应，又称戒酒硫样反应，是由于应用药物（头孢类）后饮用含有酒精的饮品（或接触酒精）导致的体内“乙醛蓄积”的中毒反应。酒精进入体内后，首先在肝细胞内经过“乙醇脱氢酶”的作用氧化为“乙醛”，乙醛在肝细胞线粒体内经过“乙醛脱氢酶”的作用氧化为“乙酸和乙醛酶A”，乙酸进一步代谢为二氧化碳和水排出体外。由于某些化学结构中含有“甲硫四氮唑侧链”，抑制了肝细胞线粒体内乙醛脱氢酶的活性，使乙醛产生后不能进一步氧化代谢，从而导致体内乙醛聚集，出现双硫仑样反应。
双硫仑（disulfiram）是一种戒酒药物，服用该药后即使饮用少量的酒，身体也会产生严重不适，而达到戒酒的目的。
1948年哥本哈根的Jacobsen等人发现，作为橡胶的硫化催化剂双硫仑被人体微量吸收后，能引起面部潮红、头痛、腹痛、出汗、心悸、呼吸困难等症状，尤其是在饮酒后症状会更加明显。人们把这种在接触双硫仑后饮酒出现的症状称为双硫仑样反应。
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药物
引起双硫仑样反应的药物有头孢类和咪唑衍生物。头孢菌素类药物中的头孢哌酮、头孢哌酮舒巴坦、头孢曲松、头孢唑林（先锋Ⅴ号）、头孢拉啶（先锋Ⅵ号）、头孢美唑、头孢米诺、拉氧头孢、头孢甲肟、头孢孟多、头孢氨苄（先锋Ⅳ号）、头孢克洛等，其中以头孢哌酮致双硫仑样反应的报告最多、最敏感，如有患者在使用后吃酒心巧克力、服用藿香正气水，甚至仅用酒精处理皮肤也会发生双硫仑样反应。头孢噻肟、头孢他啶、头孢磺啶、头孢唑肟、头孢克肟，因不含甲硫四氮唑基团，在应用期间饮酒不会引起双硫仑样反应。
另外甲硝唑（甲硝唑可抑制酒精的代谢，服药后饮酒可能出现腹痛、呕吐、头痛等症状）、替硝唑、酮康唑、呋喃唑酮、氯霉素、甲苯磺丁脲、格列本脲、苯乙双胍等均可引起双硫仑样反应。
https://jiu.ifeng.com/a/20170324/44560918_0.shtml
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防止戒酒硫：一、使用头孢菌素类、呋喃唑酮等戒酒硫前述药物时，应了解患者是否饮酒，用药期间及用药后1周内避免饮酒，或使用含有酒精的注射剂、酏剂、糖浆剂和强壮剂，避免使用酪胺食物和含有酒精的食品如调味汁、发酵的食醋等。
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除双硫仑外，甲硝唑、呋喃唑酮、甲苯磺丁脲、氯磺丙脲及一些具有甲硫四氮唑侧链的头孢菌素（如头孢美唑、头孢孟多、头孢哌酮、头孢甲肟、头孢替安、拉氧头孢等）均可引起本反应。应告诫患者用药期间禁酒和禁用含乙醇的药剂。
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