A 27-year-old young male was seen at 2:00 am on July 20, 2021. His main symptoms were headache, chest pain, shortness of breath, and weakness. He complained that he had taken a friend’s cold medicine the afternoon before when his friends met to play mahjong, and after the mahjong game, he ate hot pot with his friends and inevitably drank several bottles of beer during the hot pot. At that time I considered that the cold medicine may contain cephalosporin antibiotics inside, producing a disulfiram-like reaction, when he carefully asked his friends the name of the cold medicine does contain cephalosporin, then immediately recommended hospitalization, because the patient can not be reimbursed by medical insurance and other reasons of their own, strongly refused to hospitalization so emergency with methylprednisolone, naloxone, vitamin C and other drugs after the symptoms significantly relieved. The auxiliary examination prescribed an electrocardiogram suggesting sinus rhythm, cardiac enzymes, blood routine, liver and kidney function, and electrolytes were all in normal range. The patient improved and left the hospital on his own.
With the prevalence of alcohol culture in China and the increasing abuse of antibiotics, disulfiram-like reactions are becoming more common. What is disulfiram-like reaction and what do people mean by “cephalosporin with wine, just go away”.
First of all, let’s understand what is disulfiram, it is a derivative of Chelam, a drug clinically used for alcoholism or alcohol withdrawal treatment, the use of disulfiram or drugs with the same structure as disulfiram after drinking alcohol will appear a series of uncomfortable symptoms, such as: facial flushing, fever, headache, nausea, vomiting, chest pain, weakness of the limbs, etc., part of the patients will have a violent reaction, and even life-threatening. Patients who take disulfiram orally will experience appeal symptoms, which can cause aversion in drinkers, so it is used to treat alcohol dependence.
Mechanism of disulfiram-like reaction (also known as DSF-like reaction): First of all, let’s understand the metabolism of ethanol in our body. Ethanol is metabolized in the liver by ethanol dehydrogenase to acetaldehyde, acetaldehyde is metabolized by acetaldehyde dehydrogenase to acetic acid and acetate A, and acetic acid is metabolized in the body to carbon dioxide and water and eliminated from the body. However, disulfiram or its drugs of the same structure inhibit the activity of acetaldehyde dehydrogenase in the body, and the metabolism of ethanol into acetaldehyde cannot be further metabolized, making the concentration of acetaldehyde in the body increase, and acetaldehyde binds covalently to some proteins, nucleic acids, phospholipids, etc. in the body, destroying these substances and making them inactive, and the body will produce a series of uncomfortable symptoms. The metabolite of disulfiram itself, diethylenedithiocarbamate, can inhibit dopamine β-hydroxylase activity, which reduces dopamine metabolism, thus increasing the concentration of dopamine in the brain and accumulating it in the body, causing dilation of small arteries, small veins and capillaries throughout the body, extravasation of plasma, increased vascular permeability, excitation of sympathetic nerves, prompting nerve endings to release large amounts of 5-hydroxytryptamine, epinephrine, norepinephrine and other mono This can cause serious results and even sudden death, especially in elderly people with combined cardiovascular and cerebrovascular diseases.
There is no definite diagnostic criteria for disulfiram-like reactions, but we can make clinical diagnosis by the following points:
1. recent use of drugs that cause disulfiram-like reactions.
2. drinking alcohol or taking food and drugs containing ethanol during the use of drugs that cause disulfiram-like reactions.
3.headache, dizziness, nausea, vomiting, facial flushing, sweating, shortness of breath, chest pain, decreased blood pressure, electrocardiogram suggestive of ST-T changes, shock and myocardial ischemia. 4. rapid relief of symptoms after symptomatic treatment.
Those drugs taken after drinking alcohol may lead to disulfiram-like reactions：
1, cephalosporins: a part of cephalosporins have a common point in the chemical structure, the parent nucleus 7-amino cephalosporanic acid ring has an identical side chain at the 3 position, which is methyl tetrazolium, in 5%, 10% glucose solution or saline methyl tetrazolium will be hydrolyzed into methyl tetrazolium thiol, and disulfiram structure like, inhibit the metabolism of acetaldehyde, so appear disulfiram reaction.
2, nitroimidazoles: such as metronidazole, ornidazole, tinidazole and Secnidazole, which has a better inhibitory effect on anaerobic bacteria. Metronidazole contains similar to disulfiram methiotetrazole side connection, can inhibit the activity of acetaldehyde dehydrogenase in liver mitochondria, resulting in acetaldehyde accumulation.
3, quinolones: such as levofloxacin, moxifloxacin, etc., the mechanism of its cause disulfiram reaction is not clear. In addition, there are also erythromycin, sulfonylurea hypoglycemic agents (phenelzine, chlorosulfonylurea, insulin, tolarsulfonylurea, glibenclamide, glipizide, gliclazide), ketoconazole, chloramphenicol, allopurinol, ashwagandha, isoniazid, warfarin, etc.
Treatment: General treatment: Once disulfiram reaction occurs, immediately stop drinking alcohol or discontinue the drugs that may cause it. Symptoms will be gradually relieved after rest in mild cases, and in severe cases, patients should immediately keep the airway open to prevent asphyxia, administer oxygen, ‘V’ position to increase the amount of blood return, and establish intravenous access. Drug therapy: glucocorticoids can choose dexamethasone 5-10mg intravenous push, also can choose methylprednisolone, but not hydrocortisone (hydrocortisone poor water solubility, made into injection solution in order to increase its solubility, ethanol as a solubilizing agent, so hydrocortisone refractive solution contains 50% ethanol, some literature reported that hydrocortisone may lead to increased disulfiram reaction). Naloxone can play an important role in the relief and arousal, and is generally given as 0.4-0.8 mg intravenously. When dexamethasone is used in combination with naloxone, it can effectively shorten the duration of symptoms in patients with disulfiram reactions. Water-soluble vitamin B or C can accelerate the oxidation and decomposition of ethanol in the body, reducing the concentration of ethanol in the blood and thus reducing the symptoms of disulfiram-like reactions. In addition, some Chinese herbal medicines such as geranium, raw vein injection and brain awakening jing can be used.
There is no agreed conclusion on how many days you can drink alcohol after taking medication, but the incidence of disulfiram reaction after drinking alcohol within 3 days after medication is as high as 62.5%, and most literature reports that alcohol is prohibited within 7 days after taking medication. To avoid tragedy, be sure to prohibit alcohol or alcohol-containing foods or medications 3 days before, during, and 7 days after taking the medication to ensure that disulfiram-like reactions are avoided.