After today's discussion on Tylenol and how easier it is to overdose from it instead of say, Ibuprofen. I looked up a couple websites.
The first is an excellent review on the pathophysiology of Tylenol and how we metabolize it. Interestingly, 90% of acetaminophen is metabolized in the liver and it also mentions that "acetaminophen poisoning is the most common cause of acute liver failure and overdose deaths."
http://emedicine.medscape.com/article/1008683-overview
This next article talks about how a man apparently took Tylenol as recommended and still had liver failure and in need of a transplant!
http://abcnews.go.com/Health/PainNews/story?id=7699582&page=1
This last one is just some more interesting history on other ways Tylenol can kill you, but not exactly...
http://en.wikipedia.org/wiki/Chicago_Tylenol_murders
I assume people metabolize acetaminophen differently. I wonder if there has been a genetic association study and the metabolism of acetaminophen, and if there has been any link between those who suffer from acute liver failure. There are several drugs that people respond very poorly to based on genetic predisposition, azathioprine for example.
ReplyDeleteSo, I have always heard that after a night of drinking, it is wiser to take ibuprofen to prevent a headache than tylenol because alcohol is already having an impact on the liver and using tylenol in conjunction with the alcohol can cause liver damage. Based on your articles, tylenol, on its own, can damage the liver, so I was wondering if you had read anything about this and whether or not this effect was dependent on the dose of tylenol taken or simply the use of tylenol in conjunction with other substances that require liver detoxification.
ReplyDeleteApparently, Tylenol alone is enough for liver toxicity to occur. However, in most cases, people would need to take more than about twice the recommended value (10-15g). Still, some people are more susceptible even by taking the recommended value. For others, the "window" between the safe therapeutic dose and the dangerous dose is just smaller with acetaminophen then for other drugs.
ReplyDeleteSo, to answer your question, I would say that Tylenol alone can cause liver damage and is probably a LOT riskier when taking it with alcohol (or even hours after) then it normally would be.
This would be different with Ibuprofen or other NSAIDS because their means of metabolism is different. More commonly, there would be negative GI (acidic properties as well as inhibition of protective prostaglandins) or renal effects (also disrupted prostaglandin mediation). But unless you already have some GI or renal issues, it should be safe at recommended doses.
Here is another article on acetaminophen toxicity:
http://www.hcvadvocate.org/hepatitis/factsheets_pdf/Acetaminophen_09.pdf
APAP toxicity is more common that one may think. It is a common additional ingredient in many OTC analgesics, and is additionally an added antipyretic in most cough and cold remedies. Also, it is also included in many narcotic analgesics, as well. This is often overseen, especially in the case of Rx drug abusers.
ReplyDeleteVicodin and Percocet are schedule III and II narcotic analgesics, respectively, that are also commonly used as recreational drugs. Both contain 325 to 750mg of APAP (depending on the brand, strength, etc), in addition to the narcotic ingredient. Abusers sometimes have no idea what they are taking, and will just swallow a handful at a time are at serious risk of overdosing on APAP. 10 grams at once is considered lethal, which is 20 regular strength Vicodin or 13-14 Vicodin ES. Complications (hepatic failure and CNS depression) are compounded if you mix in alcohol.
Also, from anecdotal experience, we get someone at UCH who ODs on APAP every once in a while. If they don't get infused with acetylcysteine (APAP 'antidote'. It should also win an award for the most terrible smelling drug ever synthesized. Think of it as liquefied rotting eggs.) soon enough, their death is quite prolonged and painful.