Disulfiram (disulfiram) is the common name of the alcoholic sulphur drugs, also known as alcoholic sulphur, disulfiram sobriety, is a drug for the treatment of chronic ethanol intoxication and ethanol toxic psychosis, as a drug for alcohol withdrawal has been used in many countries. Application of this drug after drinking alcohol will be nausea, vomiting, fear and other serious reactions, and the alcoholic fear of drinking alcohol, so as to play a role in alcohol withdrawal. However, the chemical structure or mechanism of action of certain drugs currently used in clinical practice is similar to disulfiram, which can produce disulfiram-like reactions, also known as antabuse reactions.
1, disulfiram-like reaction characteristics
1.1 Clinical characteristics of disulfiram-like reactions
Drinking alcohol within a week after using drugs that can cause disulfiram-like reactions, facial and general skin flushing, conjunctival redness, fever, dry mouth, dizziness, headache, dizziness, panic, chest tightness, shortness of breath, nausea and vomiting, confused speech, talkative, blurred vision, unsteady gait, frenzy, delirium, impaired consciousness, syncope, abdominal pain, diarrhea, tingling in the throat, tremulous feeling, mouth with The patient may also experience tachycardia, decreased blood pressure, irritability, panic and fear, near-death feeling, some may experience confusion, numbness of limbs, incontinence, and in severe cases, shock, convulsions, acute heart failure, acute liver damage, angina pectoris, myocardial infarction, or even death. This performance is related to the inhibition of acetaldehyde dehydrogenase and dopamine β-aldolase in the body by disulfiram, and the performance of this group of clinical syndrome is called disulfiram-like reactions.
1.2 Temporal characteristics of disulfiram-like reactions
Drinking alcohol after using drugs with disulfiram-like reactions can cause symptoms as early as 5 min, generally within 30 min, a few within lh, and rarely after 1 h. Disulfiram-like reactions can occur in children. After the application of drugs that can cause disulfiram-like reactions in pediatric patients, alcohol or food containing ethanol should be avoided for 2 to 3 weeks after the drug is discontinued, because the function of the liver in metabolizing ethanol in pediatric patients is poor, and such reactions can occur even at low concentrations of ethanol. There is individual variability in disulfiram-like reactions. Xie Fang reported that disulfiram-like reactions may occur in children with a history of alcohol consumption 3 d before drug administration. Chen Ling reported that a disulfiram-like reaction occurred in a 2-year-old child 0.5 h after taking 10 mL of Huoxiang Zhengqi water.
1.3 Characteristics of disulfiram-like reactions and the type and amount of alcohol consumed
Disulfiram-like reactions are proportional to the dose of the drug used, the interval after stopping the drug and the amount of alcohol consumed, and the relationship with the type of alcohol consumed is not clear. There are reports of disulfiram-like reactions after drinking 50mL of beer. White wine, red wine, yellow wine, beer and beverages containing ethanol can all cause disulfiram-like reactions. When a disulfiram-like reaction occurs, it often lasts for about 2h and can be gradually relieved, and in severe cases it can last for 24h or several days before it is completely relieved.
2, cause disulfiram-like reaction of common drugs
2.1 Cephalosporin antibiotics
Such as cefoperazone, cefpiramide, cefoperazone sulbactam sodium, cefugenoid, cephalexin, cefmetazole, cefminoxime, cefmenoxime, cefonic acid, cefotiam, cefotaxime, ceftazidime, cefsulodin, cefazoxime, cefazolin, cefixime, etc.
Cefoperazone molecular structure of the parent nucleus 7 amino cephalosporanic acid (7A-CA) ring in the 3 position of the presence of the molecular structure similar to the disulfiram molecular structure of methyl tetrahydrozole (thiomethyl tetrazole) reactive group, can cause disulfiram-like reaction. Ceftriaxone and others do not have a methylthiotetrahydroazole side chain, but have a methylthiotriazine side chain that can also cause such reactions. Cephalosporins without methylthiotetrahydrozole side chain in the chemical structure do not have this effect.
2.2 Nitroimidazoles
Such as metronidazole, tinidazole, regardless of oral or intravenous administration, regardless of what kind of alcohol, and regardless of the amount of alcohol consumed, will react directly with the ethanol absorbed into the blood, and disulfiram-like symptoms will occur. To use metronidazole after drinking alcohol, one must abstain from alcohol for 5 d. Patients should also be reminded that they should abstain from alcohol for more than 7 d when using metronidazole to avoid disulfiram-like reactions. The chemical structure of such drugs contains methylthiotetrazole group.
2.3 Other drugs and foods
Furans such as furazolidone (dysentery), chloramphenicol, ketoconazole, ashwagandha, sulfonylurea hypoglycemic agents such as chlorosulfonylurea, damacell, toluenesulfonylurea (D860), eugenol, phenibut, warfarin, trifluoperazine, tolazurin, insulin, etc.
Drinking alcohol (such as white wine, red wine, yellow wine, beer), taking drugs containing ethanol such as syrups (brown mix, patchouli, hydrocortisone, etc.) or tinctures, consuming certain foods (such as alcoholic chocolate, cheese, animal liver, sardines and other foods rich in tyramine, amphetamine acid, tryptamine acid and drinks containing ethanol), topical application of ethanol (such as ethanol baths, disinfection) and doing Light quantum treatment can cause disulfiram-like reactions.
3. Mechanism of disulfiram-like reactions
3.1 Metabolic pathway of ethanol
When ethanol enters the body, 90% of it is first converted into acetaldehyde in the liver by the action of ethanol dehydrogenase, and then acetaldehyde is converted into acetyl coenzyme A and acetic acid by the action of acetaldehyde dehydrogenase (also called aldose aminopyridyl reductase or acetaldehyde dehydrogenase) in the mitochondria of hepatocytes, and finally converted into water and carbon dioxide and discharged. Disulfiram can inhibit acetaldehyde dehydrogenase and dopamine β hydroxylase, so that acetaldehyde can not be converted into acetic acid, resulting in an increase in acetaldehyde concentration in the body, resulting in discomfort, and can also reduce the body catecholamines, causing a drop in blood pressure, dry mouth, sweating.
3.2 The process of drinking alcohol after the use of disulfiram-like drugs
After the use of these drugs, acetaldehyde dehydrogenase is inhibited in the body. When alcohol is consumed within 7 d after the use of these drugs, ethanol cannot be metabolized to acetic acid normally, and the concentration of the intermediate product acetaldehyde increases sharply, resulting in the accumulation of disulfiram-like reactions in the body, which can inhibit acetaldehyde dehydrogenase and cause the “acetaldehyde accumulation syndrome”.
3.3 Reflex effects
Acetaldehyde accumulation in the body can cause small arteries, small veins and capillaries to dilate and increase vascular permeability, which can also reflexively cause sympathetic excitation and cause peripheral nerves to release large amounts of epinephrine, norepinephrine, dopamine and pentazocine, resulting in vasomotor and neuropsychiatric manifestations.
3.4 Once acetaldehyde deoxygenase is inhibited, it often takes 4d-5d to recover, and 1 week-2 weeks in children, so the reaction can still occur within this time after stopping the drug.
4.Diagnostic criteria, classification and differential diagnosis
4.1 Diagnostic criteria
There is a clear history of using drugs that can cause disulfiram-like reactions; ethanol and its products were used 0d-7d after the drug was administered, or drugs that can cause disulfiram-like reactions were used after drinking alcohol; ethanol drugs and drugs that can cause disulfiram-like reactions were applied at the same time; there are typical clinical manifestations of disulfiram-like reactions; the amount or degree of alcohol consumed is significantly smaller or lower than the usual amount or degree of alcohol consumed, but it is significantly different from the usual amount or degree of alcohol consumed. There is no history of allergy to ethanol and the use of such drugs: in the case of disulfiram-like reactions, if there are no related diseases, the blood routine, blood sugar, renal function, electrolytes, cardiac enzyme spectrum and chest X-ray are mostly abnormal.
4.2 Classification of disulfiram-like reactions
Mild: flushing of the skin on the face or body. Mild dizziness, panic, no nausea, vomiting, fever, headache, etc.; moderate: dizziness, headache, panic, nausea, vomiting, fever, but no chest pain, dyspnea, shock: severe: chest pain, dyspnea, shock, even impaired consciousness, urinary and fecal incontinence.
4.3 Differential diagnosis
4.3.1 Differentiation from ethanol intoxication
There are similarities between disulfiram-like reaction and ethanol intoxication, and it is very easy to misdiagnose. The points of differentiation are: the total amount of ethanol ingested mostly does not reach the average amount of ethanol intoxication of 75g, but only 1/2 or 1/10 of the usual amount of alcohol consumed; the symptoms appear quickly and heavily, different from the usual ethanol intoxication; the appearance of symptoms is not related to the amount of alcohol consumed and the type of alcohol.
4.3.2 Differentiation from ethanol allergy
Bisulfiram-like reaction usually has no history of ethanol allergy with general flushing, while ethanol allergy is mostly local skin flushing; bisulfiram-like reaction has no or little rash, while ethanol allergy can have rash; bisulfiram-like reaction has no itchiness, while ethanol allergy has itchiness; symptoms disappear quickly after treatment of bisulfiram-like reaction, while ethanol allergy symptoms disappear slowly.
4.4 Misdiagnosis
Misdiagnosis rate of disulfiram-like reaction is 75%, about 30% misdiagnosed as coronary heart disease, 7% misdiagnosed as cardiomyopathy, 15% misdiagnosed as ethanol poisoning, 8% misdiagnosed as drug allergy, 3.3% misdiagnosed as hypoglycemia, 3.3% misdiagnosed as arrhythmia, 5% misdiagnosed as asthma, also misdiagnosed as cerebrovascular disease, food poisoning, etc.
5. Treatment of disulfiram-like reactions
Disulfiram-like reactions are pharmacogenic emergencies and need to be treated actively.
5.1 In situ treatment
Immediately stop drinking, induce vomiting, and gastric lavage when available. Keep the airway open and remove oral and nasal vomitus and secretions. Keep the head to the side to prevent asphyxia caused by blockage of the respiratory tract by vomit.
5.2 General treatment
Administer oxygen, rest in bed, observe vital signs, measure blood pressure, pulse and respiration. Check electrocardiogram or electrocardiographic monitoring and observe pulse oximetry, and perform necessary auxiliary examinations.
5.3 Drug treatment
Establish intravenous access, give intravenous drip of 5%-10% glucose 500mL-1000mL, add vitamin C2g-4g, vitamin B6 0.2g-0.4g, dexamethasone 5mg-10mg, which can accelerate the oxidation of ethanol. Intravenous injection and drip injection of naloxone 0.4mg-0.8mg can antagonize the effect of ethanol. H2 receptor blockers and antihistamines can improve the symptoms.
5.4 Symptomatic treatment
Those with chest tightness and angina should apply nitrates; those in shock should supplement fluids or use dobutamine and other antihypertensive drugs; blood-activating drugs should be used; those with vomiting can use gastric renformation. In case of serious complications, active and effective resuscitation should be given to prevent more serious consequences of disulfiram-like reactions.
5.5 Nursing care
①Psychological care: while actively resuscitating the patient, the corresponding psychological care work should be proud according to the patient’s clinical performance, first of all, do a good job of explaining the characteristics of the disulfiram-like reaction produced by drinking alcohol after the drug, the prognosis is good and does not leave sequelae, so that their fear of symptoms can be promptly relieved, and the care and consideration of the medical staff, so that their psychological comfort; ② avoid blaming and reprimanding, so as not to increase the psychological burden; ③ pay attention to keep warm (3) pay attention to warmth, do a good job of life care, to prevent vomiting caused by asphyxiation; (4) patients with disulfiram-like reactions, their relatives can not blame the medical staff with the wrong drugs, the wrong injection, individual family members even shouting, then the patient’s relatives should be comforted, remain calm, good explanation, told to cooperate with treatment; (5) closely observe the condition, strengthen the observation of vital signs.
6.Preventive measures for disulfiram-like reactions
When using drugs with disulfiram-like reactions, attention should be paid to the following aspects.
6.1 Obligations of the manufacturer
All drugs that can cause disulfiram-like reactions, the manufacturer should indicate in the instructions, in a prominent position in the bottle or box or with a colorful sign, that during the use of drugs and within a week after discontinuation of drugs can not drink alcohol or use of drugs or food containing ethanol, so that medical personnel timely grasp and inform patients.
6.2 Precautions after using this type of drugs
Do not use drugs shedding ethanol for skin disinfection or ethanol wipe bath to cool down, or the filter bottle for oxygen absorption should not be added with ethanol.
6.3 Avoid the use of drugs containing ethanol
For example, hydrocortisone injection contains ethanol, which can interact with drugs with disulfiram-like reactions and produce disulfiram-like symptoms after intravenous infusion.
6.4 Ask for medical history
Before using the above drugs, ask if you have consumed alcohol, and avoid using drugs that may cause disulfiram-like reactions if you have consumed alcohol in the past 3 days.
6.5 Forewarning responsibility of medical personnel
Patients should be informed in advance of the use of such drugs that they should not drink alcohol or ethanol-containing beverages during the use of the drugs and within one week after stopping the drugs, and that they should not use ethanol for disinfection or topical rubbing.
6.6 Publicity and education
Health care workers should first familiarize themselves with which drugs can cause disulfiram-like reactions and educate patients that they should not drink alcohol or rub the skin with ethanol during the use of such drugs and for one week after stopping them, and that disulfiram-like reactions can occur even with a very small amount of alcohol.