Hello all physiologists:
That article "How Safe are Tylenol and Advil? Helping Patients Sort Out the Risks" was such a terrible article, whose main point was just listing the negative side effects of each product and then arguing which product is better based on their respective negative side effects. In the article it said the Tylenol (acetaminophen) when overdosed on causes liver failure, and Advil (ibuprofen) when overdosed causes stomach bleeding and ulcers. However, it doesn't explain the mechanisms that transpire in order for these effects to take place, and instead the article basically ends by saying so long as you don't overdose on these products they are both perfectly safe... To which I would like to add DUH!
Wanting more information on both products and their side effects I went looking around for some answers and found to good sites that explain each products negative side effect mechanism. In the case of Advil, it is an anti-inflammatory that blocks both cyclo-oxygenase enzymes (COX-1 and COX-2). Both these enzymes have the same affinity to convert arachidonic acid to prostoglandins which then go out and cause various effects based on what the enzyme's function is. For COX-2 this function is to induce inflammation, and according to the website I looked at it is not present at baseline but increases and is inducible by inflammation. COX-1 on the other hand, possesses multiple functions one of the most important is maintaining the stomach lining. Thus, We can see why we see stomach bleeding in those who overdose on Advil, because if COX-1 is inhibited too often, the stomach lining gets weak and the gastric acids are able to eat away at the stomach wall causing ulcers, and in worst case scenarios stomach bleeding.
As for Tylenol (acetaminophen), this one is more interesting because Tylenol isn't an anti-inflammatory, it's just an analgesic. So if that's the case than why does it cause liver damage? According to the site I found it turns out that after Tylenol is metabolized it activates the nuclear receptor CAR which induces the expression of three cytochrome P450 enzymes that transform acetaminophen into NAPQI, which is a reactive and toxic metabolite. This is normally detoxified in the liver, however when one overdoses on Tylenol the NAPQI becomes to abundant for the liver to detoxify and thus the metabolite causes severe damage to the liver.
One last note, I would just like to say that the two sites you are about to visit, or not, have good information but not complete information. I think they cover enough basics which allow a person to understand the mechanism that is occurring with overdose of these drugs, but at the same time I think they have some gaps in their information that they could have filled in more. Other than that, please enjoy the websites and fill yourselves with knowledge. Also leave any comments you have below.
http://www.arthritis.co.za/cox.html
http://www.biocarta.com/pathfiles/h_AcetaminophenPathway.asp
Something that I found interesting, while being on the topic of COX-1, is that Aspirin (acetylsalicylic acid) is also considered a non-steroidal anti-inflammatory drug, but what is unique, is that it's mechanism of action is in an irreversible manner. It also tends to have an effect on the COX-1 enzymes more so than the COX-2 enzymes. So this made me wonder what the differences were between Advil and Aspirin.
ReplyDeleteAfter doing some research, I found that they function similarly, but Advil does so in lower doses. This is good for patients who tend to have a weaker digestive system.
The hypothetical question that I would like to ask regarding this topic is... If a patient who has a peptic ulcer, were to take an aspirin without knowing the side effects, then would it be a vicious cycle of causing significantly more damage to the stomach, making it continuously bleed since it is an irreversible inhibitor to COX-1 and inhibits blood clot formation?
Something that I found about the first article that you have listed is that, the explanations that they have there are correct. However though the information is very old (previously written in 99 and revised in '05) I wonder what new changes would be made to the article if it were to be written today. The article does mention both COX-1 and COX-2 enzymes and speaks about inhibiting them. What I like about the 2nd article however is the mention of COX-3 as an isoform encoded by COX-1. It states that it is only expressed in the brain. This makes me wonder that if it is very close in structure to COX-1 then anything that could hinder and/or propagate the expression of COX-1 might have an impact indirectly on the brain, if COX-3 was to receive acetaminophen.
ReplyDelete