But WHY is the combination deadly? The question is begging to be answered, yet Cecil skirts the issue to favor the powerful pharmaceutical companies? Indeed, he should have told us that TYLENOL IS REALLY A POISON to our body: that the liver totally absorbs it and then releases it in minute proportions over a period of time to mask the symptoms of our pain and misery. That’s how it works as a medicine. If the liver is saturated and totally taxed from a hard binge of alcohol, then the tylenol (poison) cannot be absorbed and is released entirely (all at once) into the body causing widespread destruction and ultimately death.
Our company pharmacist tells me that acetaminophen is one of the most abused drugs on this planet and accounts for a great number of deaths due to overdose, often accidental but still fatal. There are rare cases of people dying after a small dosage of this popular and widely used painkiller.
Death from liver failure isn’t pretty.
Don’t take this as a slam against acetaminophen or the many companies that produce it and market it under a wide number of brand names such as Tylenol. Just be careful and remember that drugs and alcohol don’t mix, ever.
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Cecil’s column can be found on-line at this link:
How can I avoid a holiday hangover?
The column (including Slug Signorino’s illustration) can also be found on pages 230-232 of Cecil Adams’ book «More of the Straight Dope».
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Umm, begging your pardon sir, but I think the OP is actually in reference to this week’s column about the interaction of alcohol and acetaminophen, when hasn’t been posted online yet.
And aspirin and ibuprofen are mentioned in the article as not mixing well with alcohol, either. Does this mean I’m not supposed to take ibuprofen the next morning after too much red wine? I hope not!
Every little bit helps - if you want to reduce the hangover the next day, eat an apple as soon as you’re done drinking - don’t wait until next morning.
The dehydration Cecil was talking about comes from the loss of potassium ions which get washed out by the alcohol - the water just follows the ions (I suspect that the alcohol inhibits the re-uptake of potassium in your kidneys rather than increase the loss). Increasing the amount of potassium - which can be found in every fruit, meat, vegetable, i.e. everything which contains cells (ergo not pretzels etc.) will lessen the effect to some amount.
Whoops! Well someone will have to post the correct link when it appears. However let me mention that the inadvisibility of mixing acetaminophen and alcohol does appear in the column cited above.
Cecil’s answer is a little superficial.
Tylenol (acetaminophen) is not itself toxic to the the liver. Enzymes in the liver break acetaminophen down into non-toxic byproducts (sulfate & glucoronide salts) which can be excreted by the kidney into the urine.
Unfortunately, while being converted to these non-toxic salts, acetominophen is converted to an intermediate metabolite called mercapturic acid, which can also be metabolized to toxic substances which cause lysis (cell membrane breakdown) and death of the liver cells. Depending upon the balance between the creation of mercapturic acid and the further breakdown of this substance into the non-toxic salts vs. toxic metabolites, mild or catastrophic damage to the liver may occur.
When too much mercapturic acid is made too fast, a sulfur-containing organic compound known as glutathione is depleted in the liver. Glutathione is necessary for mercapturic acid to be metabolized into the non-toxic salts, and lack of glutathione results in the mercapturic acid’s being metabolized to the toxic metabolites by alternative pathways.
Under ordinary circumstances, acetaminophen is broken down in a series of steps with no critical, or rate-limiting, step. However if glutathione is exhausted, the breakdown cannot proceed beyond the step requiring glutathione, and mercapturic acid levels build up rapidly, causing it to be metabolized by the alternate pathways that create the toxic metabolites.
Things that can cause buildup of mercapturic acid (MA), then, are as follows:
- Too much acetominophen being put into the system exhausts the available amount of glutathione. The liver can make new glutathione, but slowly, so MA levels build up and toxic metabolites are formed. Liver cells are lysed, and irreversible liver failure occurs. No transplant (within 1 week) = death.
- Low glutathione levels to begin with. “Safe” levels of acetominophen are formulated assuming normal glutathione levels. Poor nutrition can lead to lower levels of gluatthione, and thus to higher levels of MA building up than would occur in a well-nourished person.
Alcohol is very tricky here, and has many different effects.
Chronic, regular alcohol use actually increases the amounts of many enzymes in the liver responsible for breaking down acetaminophen and other drugs. By accelerating the conversion of acetaminophen to MA, this can aggravate the choke point effect once glutathione is exhausted. Combine this with the fact that many alcoholics get much of their “nutrition” in the form of C2H5OH (ethanol), they are at high risk for low glutathione levels, and thus more susceptible to toxicity from acetaminophen. Add in cirrhosis (pre-existing liver damage) so that they get a higher amount of acetaminophen per functioning liver cell, and their susceptibility rises even more.
Acute alcohol intoxication, on the other hand, may actually lessen the risk of acetaminophen toxicity. For reasons that are not well understood, given the choice between metabolizing ethanol, and metabolizing anything else, the liver will generally focus on the ethanol. This decreases the rate at which acetaminophen is converted to MA, so that glutathione depletion is less likely to happen. NOTE: this is theoretical, and based on anecdotal experience. Do not try this at home.
As far as being the leading cause of liver failure, nope, not even close. That honor belongs to chronic alcohol use, hepatitis C, and genetic susceptibilty. At least some of that genetic susceptibility can be explained by the gene for hemochromatosis, which is carried by approximately 10% of the Caucasian population.
Deliberate or accidental overdose of acetaminophen is a serious problem. The good news is that liver failure can be prevented, but treatment must be started within 24 hours of ingestion. Too many times, people who didn’t really intend to kill themselves awaken the next morning to realize that they feel OK, and do not seek medical attention until they become sick from impending liver failure, when it is too late. Americans assume acetaminophen is available everywhere; it is not, and therefore it is not tested for, or even considered, when someone is brought to a hospital in Europe with a history of taking a bunch of pills.
Tylenol, when taken as directed, is far safer than aspirin, or ibuprofen (or any other non-steroidal pain/fever relievers), but should be respected as a foreign substance, and taken when needed and as directed. Individuals with liver problems should consult their physicians regarding
the advisability of tylenol use.
Tylenol is metabolized in the liver. It is not tylenol itself which is the toxin, but some of the metabolites. One set of metabolites are free radicals that can cause tissue damage, mostly to kidney and liver. The enzyme systems that direct metabolism in this direction are induced (increased) by chronic alcohol intake. A second potential mechanisms may have to do with sulfate depletion. Some of the metabolites are detoxified by being attached to a sulfate group for excretion in the bile. This is the harmless pathway and the predominant pathway for metabolism. Chronic alcoholics are frequently sulfate depleted leading to diversion of tylenol down more dangerous pathways. The reason for sulfate depletion is usually nutritional. The interaction between tylenol and alcohol is not between acute alcohol ingestion and toxicity, but rather between chronic alcohol use and increased toxicity. A few drinks a day, or perhaps a few more, is what does the job, not the combination of one heavy binge and tylenol.
Acute renal failure is as much of a problem as acute liver failure from inadvertant tylenol overdose. The other problem is that the active agent (acetamenaphen)is found in a number of other drugs (vicodin, nyquil, etc) so it is easy for people to overdose themselves.
The unresolved problem is whether or not chronic ingestion of tylenol causes chronic renal failure. Chronic ingestion does not appear to injure the liver unless you take over a critical value, but it is possible that chronic ingestion does cause chronic renal failure.
I take a lot of Ibuprofen – an average of about 5 200 mg tablets per day. When my back is very sore, I take as many as 12.
Does anyone know how much risk I am taking?
Another County Heard From writes:
This is not the information I have, babe. See for example:
Emphasis added. Not saying this is the last word on the subject, but I don’t just make this stuff up.
bolding mine - ACHF
Cecil, please re-read my comment.
In response to the original question
, I posted the correct answer to the question, "What is the most common cause of liver failure. Not acute liver failure, which you chose to address, just plain liver failure. Which is what the original question was.
From Belle SH, Beringer KC, Detre KM; An Update on Liver Transplantation in the US:Recipient Characteristics and Outcome. In Clinical Transplants, Cecka JM, Pelaski PI (eds) UCLA Tissue Typing Laboratory, Los Angeles, 1995, p.19.
** = genetic predisposition or 27% - ACHF*
december, the maximum recommended daily dose for prescription-strength ibuprofen is 2400 mg/day. This assumes you are under a physician’s care and have been properly warned about potential side effects.
This amount is clearly in excess of the amount that is intended to be taken without a physician’s involvement. You should see a physician to find out why your back hurts, and to explore other treatment options.
Where have I heard that before?
Arnold, don’t we have a stock answer sticker to slap on this?
ACHF wrote: “You should see a physician to find out why your back hurts, and to explore other treatment options.”
Appreciate your advice. Have seen innumerable doctors. No definite opinikon on the cause of the back aches. The most recent advice was to use ibuprofen if that’s what works best.
Question I don’t want to think about (but should) is the long term risk of taking so much Ibuprofen.
At least I do have an annual physical…
IANAD, but I believe the risks of ibuprophen have to do with stomach irritation. This would, of course, be greatly compounded by taking it with/after alcohol, especially on an empty stomach.
December, regarding Ibuprofen, see this site from The Mayo Clinic:
It lists possible side effects as upset stomach and ulcers, liver, and kidney problems.
It also mentions that alcohol can affect ibuprofen as much as Tylenol.
Hope that helps.
Regarding the article, if the question is about liver damage, why is Slug’s picture showing kidneys?
http://www.mayohealth.org is a good, reliable source for health information on common topics for the lay person - excellent summary in your link, Irishman. Another good site for more comprehensive information is http://www.nlm.nih.gov/medlineplus .
From there, I found this more detailed discussion of ibuprofen & related medicines: http://www.nlm.nih.gov/medlineplus/druginfo/antiinflammatorydrugsnonsteroi202743.html
Approving ibuprofen for over-the-counter use was a very controversial move by the FDA. On one hand, it is nice to be able to get something for that ankle sprain, or muscle pull, on a Saturday afternoon without going to an Emergency Room. On the other hand, many people will take it for long periods of time, and in higher than recommended quantities, without ever consulting a physician.
Short-term ibuprofen use poses very little risk in healthy young or middle-aged people. Long term use greatly increases the likelihood of side effects. The most common are:
Ulcers in the stomach or duodenum, or gastritis, an allover irritation of the stomach lining. These conditions may cause heartburn, indigestion, or no symptoms at all. They may also cause bleeding into the intestinal tract, which can range from minimal to life-threatening. Unfortunately, the risk or severity of bleeding does not correlate to the presence or absence of symptoms; a life-threatening hemorrhage may be the first sign of a problem. Antacids or other meds which reduce symptoms may not reduce the bleeding risk. FWIW, after a trip through the intestines, blood usually comes out smelling awful, looking black, and wiping off as easily as tar. Alcohol is another common cause of ulcers and gastritis; the combination of ibuprofen and alcohol is more multiplicative than additive.
Kidney problems. In the most common renal complication, the kidney loses its ability to prevent large protein molecules from leaking into the urine. This can lead to a condition called nephrotic syndrome, with severe edema (fluid retention) in the legs, or in severe cases, the face, and low protein levels in the blood, and foamy urine. The kidney may also stop excreting waste products normally, allowing high levels of these to build up in the blood stream. The kidneys may rarely stop making urine altogether. Normally, stopping the ibuprofen results in a return to normal function.
Bleeding problems. Platelets are small cell fragments in your blood which help it clot by clumping together. Ibuprofen interferes with platelet clumping for about 24 hours after the last dose. This aggravates any hemorrhage from a stomach ulcer, or may complicate surgery, or increase the amount of blood lost with an injury. Ibuprofen use is one of the leading reasons for rejection of potential blood donors because of this. Chronic alcohol use can cause one to have a low number of platelets; if they also work less due to ibuprofen the bleeding risk is compounded.
december, I’m sorry to hear that preventing your back pain has been so frustrating. I would still recommend seeing a physician periodically while you are taking the ibuprofen regularly. You may get better results with prescription strength tablets (400-800 mg), have a physician familiar with your history able to discuss this with you, and, depending upon your health plan, may spend less for prescription-strength ibuprofen than for OTC-strength.
NB - everything I’ve said regarding ibuprofen applies to all drugs in the class.
I don’t drink but I have a slight
300 mg acetaminophen
20 tabs at a time max
maybe 2-3 times a day
max average is 60 tablets per day
1800 tablets per month
540,000 mg acetaminophen
27,000 mg caffeine
14,400 mg codeine
4 Checkups specifically for my Liver.
Always cleans results.
No symptoms. (maybe an irritated tummy)
Been at this intake level for about 2 years straight.
Q. Why am I not dead? (not that I want to be, what gives?)
I’m sure there is, RM Mentock, something along the lines of “the column can’t cover every bit of knowledge under the sun related to a topic due to lack of space.” I’ll try to dig up some official, Cecil-sounding wording. :;