I. Disulfiram
Disulfiram (disulfiram) is a drug for alcohol withdrawal. After taking the drug, even if a small amount of alcohol is consumed or an alcoholic beverage is taken, the body will produce severe discomfort, and the purpose of alcohol withdrawal is achieved.
Mechanism of action of disulfiram: Disulfiram can inhibit acetaldehyde dehydrogenase in the liver when used in combination with ethanol, so that after the oxidation of ethanol to acetaldehyde in the body, it cannot continue to decompose and oxidize, resulting in a series of reactions due to the accumulation of acetaldehyde in the body. (After entering the body, ethanol is first converted into acetaldehyde by the action of ethanol dehydrogenase in the liver, then acetaldehyde is converted into acetic acid by the action of acetaldehyde dehydrogenase, and acetic acid enters the raffinate cycle, and finally is converted into water and carbon dioxide and discharged. (And disulfiram can inhibit acetaldehyde dehydrogenase, so that acetaldehyde can not be oxidized to acetic acid, resulting in the accumulation of acetaldehyde in the body).
B. Disulfiram-like reaction
(A) disulfiram-like reaction and its clinical manifestations
Disulfiram-like reaction: a toxic reaction caused by the accumulation of acetaldehyde in the body due to the consumption of alcohol or alcoholic beverages during or shortly after the use of antibacterial drugs with similar effects as disulfiram.
Clinical manifestations: facial flushing, conjunctival congestion, blurred vision, severe pulsation of the blood vessels in the head and neck or pulsating headache, dizziness, nausea, vomiting, sweating, dry mouth, chest pain, myocardial infarction, acute heart failure, respiratory distress, acute liver injury, convulsions and death, etc. On examination, there may be a drop in blood pressure, accelerated heart rate (up to 120 beats/min) and normal or partially altered electrocardiogram (such as ST -T changes). The severity of the reaction is proportional to the dose of the drug and the amount of alcohol consumed, and is more serious in the elderly, children, cardiovascular and cerebrovascular disease and those sensitive to ethanol.
(B) drugs that can lead to disulfiram-like reactions
1.Cefoperazone, cefoperazone sulbactam, ceftriaxone, cefazolin (Pioneer V), cefradil (Pioneer VI), cefmetazole, cefminox, cephalexin, cefamandole, cefadroxil (Pioneer IV), cefaclor, etc. Among them, cefoperazone causes the most reports of disulfiram-like reactions and is the most sensitive, such as patients eating wine heart after using Chocolate, taking patchouli, or even just treating the skin with alcohol can also cause disulfiram-like reactions.
The common feature of these cephalosporins in chemical structure is the presence of methylthiotetrazole (thiomethyltetrazole) substituent at the 3-position of its parent 7-amino cephalosporanic acid (7-ACA) ring, which competes with coenzyme I for the active center of acetaldehyde dehydrogenase and can prevent the continued oxidation of acetaldehyde, leading to the accumulation of acetaldehyde and thus causing a withdrawal sulfur-like reaction. The appearance of precordial pain with ECG ST-T changes is due to the increased sympathetic excitability caused by the methylthiotetrazolium substituent, resulting in faster heart rate and increased myocardial oxygen consumption, which shortens myocardial diastole and decreases coronary perfusion pressure, leading to reduced perfusion flow.
Cefotaxime, ceftazidime, cefsulodin, cefazoxime, cefixime, and cefixime, because they do not contain methanetetrazole group, drinking alcohol during application will not cause disulfiram-like reaction.
2, nitromidazole drugs such as metronidazole (methotrexate), tinidazole, ornidazole, Secnidazole.
3, other antibacterial drugs such as furazolidone (dysentery), chloramphenicol, ketoconazole, sulfonylurea hypoglycemic drugs, warfarin, trifluoperazine, tolazurin, insulin, phenelzine, ashwagandha, etc.
(C) First aid and care of disulfiram-like reaction
Once the disulfiram-like reaction occurs, the drug and ethanol-containing products should be discontinued promptly.
The treatment can be gastric lavage to eliminate ethanol from the stomach, reduce ethanol absorption, dexamethasone injection or naloxone injection, and other symptomatic treatment, intravenous infusion of glucose solution, vitamin C and other liver protection treatment to promote ethanol metabolism and excretion. Patients with angina need to improve coronary circulation, and those with decreased blood pressure can apply antihypertensive drugs, which can be relieved within a few hours.
1.After the patient is seen, take medical history while resuscitating, immediately put the patient in a flat position, administer oxygen, measure vital signs and record.
2.For patients in shock, establish intravenous access quickly, replenish crystalloids quickly, give dopamine and other antihypertensive drugs if necessary, and treat actively to shorten the period of hypotension.
3.Give cardiac monitoring to patients with pre-existing cardiovascular diseases, and closely observe the changes of heart rate and rhythm.
4. Patients diagnosed with disulfiram-like reaction should also have electrocardiogram, blood routine and electrolyte examination to exclude the coexistence of multiple diseases and delayed treatment.
5. Because of the sudden onset and obvious symptoms, patients and family members are nervous and fearful. The nurse should comfort the patient, console the family, explain the cause of the disease, introduce successful cases, and do a good job of psychological guidance, so that they can actively cooperate with treatment and care.
6. Treatment is fast-acting and short-course, with symptoms gradually relieved from 4h to 12h.
(D) Prevention of disulfiram-like reactions
It is necessary for medical and nursing staff to have sufficient awareness and attention to the disulfiram-like reactions in the process of applying antibacterial drugs.
1, in the treatment process, must carefully ask the patient’s medication history and allergy history, ask the drinking habits, while strictly grasp the indications for the use of drugs, rational selection of drugs, to prevent abuse tendencies, reasonable combination with the combination, can not be used at the same time containing ethanol drugs. When using drugs that can cause disulfiram-like reactions, the nurse should not start the drip too fast, and closely observe, have a sense of rescue, once the allergic reaction occurs, immediately stop the drug rescue.
2. For patients using drugs that can cause disulfiram-like reactions, patients should be informed to avoid drinking or eating ethanol-containing products (including beverages, food and drugs), such as white wine, yellow wine, beer, wine core chocolate, patchouli, hydrocortisone injection, skin disinfection or scrubbing with alcohol to cool down during the use of the above antimicrobial drugs and within 14 days after discontinuation, especially for the elderly and patients with cardiovascular diseases More attention should be paid.
3. Once the disulfiram-like reaction occurs, the drug should be discontinued and ethanol-related products should be stopped in time.