Recently, some netizens posted that their best friend was in the hospital ICU due to liver failure due to eating two cold medicines at the same time, while reminding everyone that "cold medicine can not be taken casually."
Source: Douban
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This post quickly appeared on Weibo hot search, many people did not expect that two common cold medicines to eat together, there are such serious consequences.
In fact, there are not many similar tragedies in life. Some patients always feel that taking only one cold medicine "works too slowly" and "has no effect", and they have to eat a bunch of pills to be at ease.
As everyone knows, the composition of these compound cold medicines is similar, and several of the big-name cold medicines that we are familiar with all contain the same ingredient - acetaminophen, commonly known as "paracetamol".
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It is a classic and commonly used antipyretic and analgesic ingredient. Antipyretic, that is, can help us reduce fever; analgesia, the role of colds is to relieve sore throat, headaches and other symptoms.
As early as the 1970s and 1980s, the US Food and Drug Administration (FDA) proposed a safe adult dose of paracetamol taken every 4 to 6 hours, up to 1000 mg each time, according to a series of studies, with a daily dosage of no more than 4 g and a continuous dose of no more than 10 days [1].
The World Health Organization also recommends that the standard therapeutic dose for adults is 0.5 to 1 g every 4 to 6 hours, and the total daily dose for children should be 20 to 30 mg/kg (as determined by the doctor based on the child's age and weight) [2].
It turns out that taking 1 g of acetaminophen is indeed a therapeutic dose that is effective and safe [3]. However, once acetaminophen is excessive, it is easy to cause liver damage and liver poisoning [4].
Read more medical codes: cold or flu hit, how to relieve fever and analgesia, did you do it right?
We know that the liver is the largest detoxification organ in the body. In the liver, drugs are generally processed into toxic metabolites by liver drug enzymes, and then eliminated by glutathione, an important "antidote" in the liver.
Now let's look at why the liver is "poisoned" with acetaminophen.
When acetaminophen reaches the liver, 85 to 90% of acetaminophen is inactivated by enzyme-binding metabolism and is excreted directly from the urine;
The remaining about 5 to 9% of paracetamol is metabolized by enzymes to hepatotoxic N-acetyl-p-benzoquinone imine (NAPQ1). This toxic guy is bound, "wrapped" in reduced glutathione, and excreted from the urine [5].
Metabolic processes of acetaminophen in the liver[5]
When acetaminophen is taken in therapeutic doses, it produces a small amount of NAPQ1, glutathione is enough to clear it without hepatotoxicity;
However, when acetaminophen is excessive, it will deplete the intracellular glutathione, and acetaminophen directly attacks the macromolecular proteins of liver cells through covalent bond binding, resulting in hepatocyte necrosis and poisoning.
Therefore, the US FDA stipulates that the maximum daily dosage of acetaminophen should not exceed 4g. Once overdose, it is possible to exceed the limits of liver glutathione, increasing the risk of toxic metabolites damaging the liver [6].
For example, a kind of cold medicine, each tablet contains acetaminophen 500mg, someone eats according to the maximum dosage of the instructions, eats 2 tablets each time, takes it every 4 hours (6 times a day), and eats a total of 6g in 24 hours, which has exceeded 4g!
After all, many people only understand what doctors say, "a few tablets at a time, several times a day." How many people will calculate the total dose to ensure that it does not exceed 4 g?
To this end, the US FDA issued a safety bulletin in 2011, limiting the unit dose of acetaminophen in prescription drugs to no more than 325 mg, and adding a black box warning that "severe liver damage may occur" on the label [7].
Compared with the previous unit dose of 500mg, the advantage of this is that even if the patient takes the maximum dosage according to the instructions, it will not exceed the amount, because the maximum amount can only be 650mg each time, 6 times a day, so that the maximum daily eating is 3.9g, just less than 4g.
However, limiting the dosage of prescription drugs is only one aspect. In the actual medication process, there are still some "minefields" that are inevitable.
Going back to the case at the beginning, the landlord who posted said "My friend took both Tylenol and Finbide at the same time".
We only know that Tylenol contains 325 mg of acetaminophen per tablet. But the landlord did not explain which kind of medicine "Fenbide" was.
Because the trade name abbreviated as "Fenbide" is actually two kinds of drugs, one is called "Fenbide (ibuprofen sustained-release capsules)", the active ingredient is only ibuprofen; the other is called "Fenbide (phenol coffee tablets)", each tablet contains 500mg of acetaminophen.
Assuming that fenbide (ibuprofen sustained-release capsules), many netizens are worried about whether the combination of ibuprofen and acetaminophen is safe.
However, researchers have conducted a summary analysis [8], and adult patients taking a fixed dose of acetaminophen and ibuprofen combination (1000 mg/300 mg each time) did not have serious adverse reactions associated with the combination of the two drugs, most of which were nausea and vomiting, gastrointestinal bleeding and other minor adverse reactions.
In this way, it is more likely that it is fenbid (phenolic coffee tablets).
1. Eat Tylenol and Fenbide (phenol curry tablets):
They are taken according to the highest therapeutic dose on the instructions: Tylenol 2 tablets at a time, 4 times a day, equivalent to acetaminophen 2600mg; phenol curry tablets once, 4 times a day, that is, 2000mg. But the two add up to 4.6 g, exceeding the maximum limit of acetaminophen by 4 g/day.
2. Eat tylenol and fenpide (ibuprofen tablets):
They are taken according to the prescribed therapeutic dose, and generally there will be no serious adverse reactions, but the patient may have also taken other compound cold medicines containing acetaminophen, but there is no explanation;
3. Tylenol overdose, or there is an overdose of both drugs.
In either case, there is a central problem: failure to pay attention to or understand the safe dose of acetaminophen leads to repeated medications.
In liver poisoning, nausea, vomiting, epigastric pain, and general weakness occur, which are similar to the symptoms of gastrointestinal colds.
However, patients often think that "the cold is not controlled", continue to take the drug, the more serious the result is to take the medicine, the more serious the disease, there may be jaundice symptoms of yellowing of the skin and whites of the eyes (sclera), and when it is severe, there will be bleeding gums and skin bruises!
When adults use more than 4g of acetaminophen per day, and children use more than 60mg/kg of body weight per day, and when nausea, vomiting, and abdominal pain occur, paracetamol poisoning should be considered, and they should immediately go to the hospital to hang up the emergency department.
Once acetaminophen poisoning is suspected, liver function should be checked as early as possible, and the examination will usually find elevated alanine transaminases (more than 3 times above normal) or elevated alkaline phosphatase (more than 2 times above normal);
Some severely ill patients also experience disproportionately high levels of bilirubin, which is the preferred detoxification for N-acetylcysteine, which can scavenge a variety of free radicals in the liver, and the earlier clinical use, the better [9].
In addition, if the patient takes the drug for no more than 6 hours, the absorption of the drug into the blood can be reduced by inducing vomiting, gastric lavage, and diarrhea.
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1. Have a history of cirrhosis and viral hepatitis.
These patients have insufficient liver glutathione reserves and poor detoxification capacity.
2. People who have just drunk alcohol and have been drinking alcohol for a long time.
Ethanol is also an inducer of liver drug enzymes, and if alcohol is drunk during taking the drug, it will lead to an increase in the hepatotoxic metabolite of acetaminophen, increasing hepatotoxicity.
Acetaminophen (no more than 14 days) is relatively safe for people with long-term alcohol abuse, but acetaminophen is not recommended if people with severe alcohol dependence tend to be malnourished and glutathione utilization is low [10].
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3. Patients who are using anti-epileptic and anti-tuberculosis drugs.
Phenytoin, carbamazepine antiepileptic drugs, as well as isoniazid and rifampicin antituber drugs are all hepatic drug enzyme inducers, which increase the hepatotoxicity of acetaminophen.
Finally, I also remind everyone that when choosing a cold medicine, you must clearly read the ingredient list and dosage on the instructions. Many of the cold medicines sold on the market are compound preparations, including the proprietary Chinese medicine vitamin C silver warp tablets, which contain acetaminophen.
If you have already bought a compound cold medicine, don't stack the medicines with other compound ingredients, otherwise it is likely to lead to drug overdose poisoning.
I hope that the landlord's friend will treat smoothly, and I hope that this case can arouse everyone's vigilance and strengthen the awareness of safe medication for the health of you and your family.
bibliography
[1] Department of Health and Human Services, Food and Drug Administration. Internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use; proposed amendment of the tentative final monograph; required warnings and other labeling [OL]. Fed Regist 2006; 71:77314–52.
[2]https://apps.who.int/medicinedocs/en/d/Jh2929e/6.2.html
[3] Hayward K L, Powell E E, Irvine K M, et al. Can paracetamol (acetaminophen) be administered to patients with liver impairment? [J]. British journal of clinical pharmacology, 2016, 81(2): 210-222.
[4] Bower WA, Johns M, Margolis HS, Williams IT, Bell BP. Population-based surveillance for acute liver failure. Am J Gastroenterol. 2007;102:2459-63.
[5] Yan M, Huo Y, Yin S, et al. Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions[J]. Redox biology, 2018, 17: 274-283.
[6] Lee WM. Acetaminophen and the U.S. acute liver failure Study group: lowering the risks of hepatic failure. Hepatology. 2004;40(1):6–9.
[7]https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-prescription-acetaminophen-products-be-limited-325-mg-dosage-unit
[8] Aitken P, Stanescu I, Playne R, et al. An integrated safety analysis of combined acetaminophen and ibuprofen (Maxigesic/Combogesic) in adults[J]. Journal of pain research, 2019, 12: 621.
Drug-induced Hepatology Group of Chinese Medical Association Hepatology Branch. Guidelines for the diagnosis and treatment of drug-induced liver injury[J].Chinese Journal of Liver Disease,2015,23(11):810-820.
[10] Rumack B, Heard K, Green J, et al. Effect of therapeutic doses of acetaminophen (up to 4 g/day) on serum alanine aminotransferase levels in subjects consuming ethanol: systematic review and meta‐analysis of randomized controlled trials[J]. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2012, 32(9): 784-791.
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