Recently, some netizens posted that their best friend was suffering from liver failure due to taking two cold medicines at the same time, and was in the hospital ICU for rescue. .
Source: Douban
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This post quickly became a hot search on Weibo. Many people did not expect that taking two common cold medicines together would have such serious consequences.
Actually, there are many similar tragedies in life. Some patients always feel that taking only one cold medicine is “too slow to work” and “has no effect”, and they need to eat a lot of pills to feel at ease.
As everyone knows, the ingredients of these compound cold medicines are similar, and several big-name cold medicines that we are familiar with all contain the same ingredient – acetaminophen, commonly known as “paracetamol”.
Image source: Zhanku Hailuo
This is a classic and commonly used antipyretic and analgesic ingredient. Antipyretic, is to help us reduce fever; analgesic, the role of the cold is to relieve sore throat, headache and other symptoms.
As early as the 1970s and 1980s, the U.S. Food and Drug Administration (FDA), based on a series of studies, proposed that paracetamol should be taken every 4 to 6 hours at a maximum of 1000 mg each time. The safe adult dose should not exceed 4 g per day, and the duration of continuous use should not exceed 10 days [1].
The World Health Organization also recommends that the standard therapeutic dose of acetaminophen for adults is 0.5~1g each time, every 4~6 hours, and the total daily dose should not exceed 4g; The daily dose is 20-30 mg/kg in divided doses (determined by the doctor according to the age and weight of the child) [2].
Acetaminophen, 1g per serving, has been proven to be an effective and safe therapeutic dose [3]. However, once acetaminophen is overdose, it can easily cause liver damage and liver toxicity [4].
See more medical books: How to relieve fever and relieve pain when a cold or flu strikes, are you doing 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 enzymes, and then the toxicity is eliminated by glutathione, an important “antidote” in the liver.
Now let’s see why the liver is “poisoned” with acetaminophen.
When acetaminophen reaches the liver, 85~90% of acetaminophen will be metabolized by enzyme binding and inactivated and excreted directly from the urine;
The remaining 5~9% of acetaminophen is metabolized by enzymes to N-acetyl-p-benzoquinoneimine (NAPQ1), which is hepatotoxic. This toxic guy is bound by reduced glutathione, “wrapped”, and excreted in the urine [5].
Paracetamol metabolism in the liver[5]
When acetaminophen is taken in therapeutic doses, itThe amount of NAPQ1 produced is low, and glutathione is sufficient to clear it without hepatotoxicity;
However, when acetaminophen is excessive, it will deplete glutathione in hepatocytes. Acetaminophen binds covalently and directly attacks macromolecular proteins in hepatocytes, resulting in Hepatocyte necrosis and poisoning.
Therefore, the US FDA stipulates that the maximum daily dosage of paracetamol should not exceed 4g. In excess, the hepatic glutathione limit may be exceeded, increasing the risk of liver damage by toxic metabolites [6].
For example, a certain cold medicine, each tablet contains 500mg of acetaminophen, some people take it according to the maximum amount of the instructions, take 2 tablets each time, and take it every 4 hours (6 times a day), I ate a total of 6g in 24 hours, which is more than 4g!
After all, many only know what the doctor calls “a few tablets at a time, several times a day.” How many people will calculate the total dose and ensure that it does not exceed 4g?
To this end, the US FDA issued a safety notice in 2011, limiting the unit dose of acetaminophen in prescription drugs to no more than 325mg, and adding “may cause serious liver damage” black on the label Box Warning [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 be overdose, because only a maximum of 650mg can be taken each time, 6 times a day , so that you can eat up to 3.9g per day, just less than 4g.
However, limiting prescription drug doses is only one aspect. In the actual process of drug use, there are still some “minefields” that are inevitable.
Back to the case at the beginning, the owner of the post said that “a friend took Tylenol and Fenbid at the same time”.
We only know that Tylenol contains 325mg of acetaminophen per tablet. But the landlord did not explain what kind of medicine “Fenbid” was.
Because there are actually two kinds of medicines with the trade name abbreviated as “Fenbid”, one is called “Fenbid (Ibuprofen Sustained-Release Capsules)”, the active ingredient is only ibuprofen The other is called “fenbid (phenol coffee tablets)”, each tablet contains 500mg of paracetamol.
Assuming it is Fenbid (ibuprofen sustained-release capsules), many netizens worry about whether it is safe to use ibuprofen and acetaminophen together.
However, researchers have conducted a summary analysis [8]. Adult patients taking a fixed-dose combination of acetaminophen and ibuprofen (1000mg/300mg each time) did not experience any difference between the two The serious adverse reactions related to the drug combination are mostly mild adverse reactions such as nausea and vomiting and gastrointestinal bleeding.
In this way, it is more likely that it is Fenbid (phenol coffee tablets).
1. Take Tylenol and Fenbid (phenol coffee tablets):
They are all taken at the highest therapeutic dose on the instructions: Tylenol 2 tablets at a time, 4 times a day, equivalent to 2600mg of acetaminophen; phenol coffee tablets 1 tablet at a time, 4 times a day, That is 2000mg. But the total of the two is already 4.6g, which exceeds the maximum limit of 4g/day of acetaminophen.
2. Take Tylenol and Fenbid (ibuprofen):
They are all taken according to the instructions in the therapeutic dose, and generally there will be no serious adverse reactions, but the patient may also take other compound cold medicines containing acetaminophen, but there is no explanation;
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3. Overdose of Tylenol, or overdose of both drugs.
In either case, there is a core problem: not paying attention or knowing the safe dose of acetaminophen, leading to repeated use.
In liver poisoning, nausea, vomiting, epigastric pain, and general malaise can occur, which are similar to gastrointestinal cold symptoms.
However, patients often think that “the cold is not under control” and continue to take medicine. As a result, the more the medicine is taken, the more severe the condition becomes. The symptoms of jaundice that the skin and whites of the eyes (sclera) become yellow may appear, and in severe cases, the symptoms of jaundice may appear. Bleeding gums and bruised skin!
Acetaminophen should be considered when the daily dose of acetaminophen for adults exceeds 4g and the daily dose for children exceeds 60mg/kg body weight, and nausea, vomiting, and abdominal pain occur. Phenol poisoning, immediately go to the hospital and go to the emergency room.
Once acetaminophen poisoning is suspected, liver function tests should be performed as soon as possible, which usually reveal elevated alanine aminotransferase (more than 3 times normal) or alkaline phosphatase (more than 3 times normal) 2 times the normal value);
Some critically ill patients may also have unreasonably high levels of bilirubin. The first choice for detoxification of this disease is N-acetylcysteine, which can remove a variety of free radicals in the liver. The earlier it is used, the better the effect [9].
In addition, if the patient takes the drug for less than 6 hours, the absorption of the drug into the blood can be reduced by inducing emesis, gastric lavage, and catharsis.
< i class="desc">Image source: Zhanku Hailuo
1. Have a history of liver cirrhosis and viral hepatitis.
These patients have insufficient hepatic glutathione reserves and poor detoxification.
2. People who have just drank alcohol and who have been drinking for a long time.
Ethanol is also an inducer of liver drug enzymes. Drinking alcohol while taking the drug will increase the hepatotoxic metabolites of acetaminophen and increase liver toxicity.
It is relatively safe for long-term alcoholics to take acetaminophen in a short period of time (no more than 14 days); however, if it is a heavy alcohol-dependent population, there is often malnutrition, and the utilization rate of glutathione is relatively low. Low, it is not recommended to take acetaminophen [10].
Image source: Zhanku Hailuo
3. Patients who are using anti-epileptic and anti-tuberculosis drugs.
Phenytoin, carbamazepine and other anti-epileptic drugs, as well as isoniazid, rifampin and other anti-tuberculosis drugs are all liver enzyme inducers, which will increase the hepatotoxicity of acetaminophen .
Finally, I also remind everyone that when choosing a cold medicine, be sure to read the ingredient list and dosage on the instruction manual. Many cold medicines on the market are compound preparations, including Chinese patent medicine vitamin C Yinqiao tablets, etc. These medicines contain paracetamol.
If you have already bought a combination cold medicine, do not take other combination medicines on top of it, otherwise it is likely to cause an overdose of poisoning.
I hope that the landlord’s friend will be treated well, and I hope this case can arouse everyone’s vigilance and strengthen the awareness of safe medication for the health of you and your family.
References
[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; 71:77314C52.
[2]https: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.< /p>
[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):6C9.
[7]https: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.
[9] Drug-induced liver disease group of Chinese Society of Hepatology. Guidelines for the diagnosis and treatment of drug-induced liver injury[J]. Chinese Journal of Hepatology, 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 metaanalysis of randomized controlled trials[J]. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2012, 32(9): 784-791.
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