I. What are disulfiram and disulfiram-like reactions?
Disulfiram (disulfiram) is an abstinence drug, after taking the drug even if drinking a small amount of alcohol, the body will produce serious discomfort, and to achieve the purpose of abstinence from alcohol.
In 1948, Jacobsen et al. in Copenhagen found that disulfiram, a vulcanization catalyst for rubber, when absorbed in small amounts by the body, could cause facial flushing, headache, abdominal pain, sweating, heart palpitations, difficulty breathing, and other symptoms, especially after drinking alcohol. The symptoms that occur after drinking alcohol after exposure to disulfiram are called disulfiram-like reactions.
The mechanism of action of disulfiram is – disulfiram in combination with ethanol can inhibit acetaldehyde dehydrogenase in the liver, so that after the oxidation of ethanol to acetaldehyde in the body, it cannot continue to decompose and oxidize, resulting in the accumulation of acetaldehyde in the body and a series of reactions. (After entering the body, ethanol is first converted to acetaldehyde in the liver by the action of ethanol dehydrogenase, and then acetaldehyde is converted to acetic acid by the action of acetaldehyde dehydrogenase. (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, acetaldehyde is toxic substances, when the body acetaldehyde concentration increases, can be covalently bonded with some proteins, phospholipids, nucleic acids and other substances in the body to destroy these substances inactivation, thus causing a variety of discomfort in the body, showing the symptoms of disulfiram-like reactions.)
Many antibacterial drugs have effects similar to disulfiram. If alcohol is consumed after medication, 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 may occur. On examination, there may be a decrease in blood pressure, an increase in heart rate (up to 120 beats/min) and normal or partial changes in ECG (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.
Second, which drugs can lead to disulfiram-like reactions?
Cefoperazone, cefoperazone sulbactam, ceftriaxone, cefazolin (Pioneer V), cefradil (Pioneer VI), cefmetazole, cefmetazole, cefminox, cephalexin, cefmetime, 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 after using Disulfiram-like reactions can also occur after eating chocolate with alcohol, taking patchouli, or even treating the skin with alcohol alone.
The common feature of these cephalosporins in chemical structure is the presence of methylthiotetrazole (thiomethyltetrazole) substituent at the 3-position of the 7-amino cephalosporanic acid (7-ACA) ring of the parent nucleus, which competes with coenzyme I for the active center of acetaldehyde dehydrogenase and prevents 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 methylthiotetrazole 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, ceftizoxime, cefixime, and cefixime, because they do not contain the methanetetrazole group, alcohol consumption during application does not cause disulfiram-like reactions.)
②Nitroimidazole drugs such as metronidazole (methotrexate), tinidazole, ornidazole, Secnidazole.
③ Other antibacterial drugs such as furazolidone (dysentery), chloramphenicol, ketoconazole, ashwagandha, etc.
First aid and care
Once the disulfiram-like reaction occurs, the drug and ethanol-containing products should be discontinued promptly, the milder cases can be relieved by themselves, the more serious cases need oxygen and symptomatic treatment. 4h~12h symptoms are gradually relieved.
①Take medical history while resuscitating the patient after consultation. Immediately put the patient in a flat position. Keep the airway unobstructed and administer 3-4L/min of oxygen to improve tissue hypoxia. Take vital signs and record them.
②Establish intravenous access, give dexamethasone 5~10mg in glucose solution as prescribed by the doctor, rehydrate and diuretic, and give vasoactive drugs according to the condition.
③Symptomatic treatment. If nausea, vomiting can be given gastroflucan 10mg intramuscularly; if drowsiness, unconsciousness can be given naloxone antagonistic treatment. For patients in shock, quickly replenish crystalloids and give dopamine and other antihypertensive drugs if necessary to shorten the period of hypotension. Patients with angina need to improve coronary circulation.
④ Have all emergency equipment and drugs available at the bedside, such as defibrillators, aspirators, tracheotomy and phlebotomy kits, respiratory stimulants, diuretics and other resuscitation drugs.
⑤ Closely observe the patient’s consciousness, body temperature, pulse, respiration, heart rate, heart rhythm, blood pressure, urine output and other clinical changes, and make nursing records of the dynamics of the condition.
(6) Patients diagnosed with disulfiram-like reactions should also have electrocardiogram, routine blood count and electrolyte examination to rule out the coexistence of multiple diseases and delayed treatment.
(7) Because of the sudden onset and obvious symptoms, patients and family members are nervous and fearful. The nurse should do a good job of psychological care, explaining to the patient and family the reasons for the sudden discomfort, introducing successful cases and eliminating the panic psychology. So that they can actively cooperate with the treatment and care.
IV. Prevention
It is necessary for medical and nursing staff to have sufficient awareness of and pay attention to the withdrawal sulfur-like reaction during the application of antimicrobial drugs.
① During the treatment process, patients must be carefully asked about their medication history and allergy history, ask about their drinking habits, and at the same time, strictly grasp the indications for medication, reasonably select medications, prevent the tendency of abuse, reasonably combine and match, and not use drugs containing ethanol at the same time. For those who have a history of alcohol consumption within 12 hours, it is appropriate to suspend the use.
②Nurses in the use of drugs that can cause disulfiram-like reactions, the speed of the start of the drip should not be too fast, and close observation, awareness of resuscitation, once the allergic reaction immediately stop the drug resuscitation.
③For 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 antibacterial drugs and for 14 days after discontinuation, especially cardiovascular disease, abnormal liver function (including fatty liver including fatty liver), renal insufficiency, old and frail patients should pay more attention.
Once disulfiram-like reactions occur, discontinue the drug and ethanol-related products in a timely manner.