Acetaminophen and EtOH

[Aznfarmerboi]

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I love people who wake up after drowning half a keg and a few shots of alcohol and popping a few tablets of acetaminophen for their hangover.

Or even better, people who think they are smart and pop the acetaminophen pills straight up with the drink thinking it'll prevent hangovers.

or even better, people who drink a shot of liquor to help them with their hangover.




Yeah, you can tell that i am bored from studying and tired

 

[Caverject]

bottoms up!

 

[imperial frog]

I recommend smack for hangovers.

 

[28657]

MMMM....cimetidine and APAP is my fav hangover remedy

 

[bananaface]

Acetaminophen while drinking, IBU for hangovers.

I used that line on a patient last week.

 

[Aznfarmerboi]

MMMM....cimetidine and APAP is my fav hangover remedy

I think Cimetidine is the worst GERD med out there. I wouldnt recommend it to even my worst enemies. its like cancer. if you cant afford something better, i'll give you the money. I am 100 percent anti-cimetidine

 

[28657]

Acetaminophen while drinking, IBU for hangovers.

I used that line on a patient last week.

Actually the 'taking APAP while drinking' is only true if the person rarely drinks and hasn't binged before taking the APAP. It's MUCH safer to just tell people NO APAP if you're a drinker...why risk it??

 

[Kris10h]

Can someone explain to someone who is still pre pharmacy why you wouldn't want to take apap in all cases?? Maybe thats a dumb question. I was just curious.

 

[imperial frog]

APAP is conjugated with glutathione in the liver and excreted. Excessive APAP and/or alcohol consumption depletes glutathione pushing APAP into a different pathway with the resulting APAP metabolite being toxic and can lead to death, or even worse, a severe headache.

 

[Caverject]

APAP is conjugated with glutathione in the liver and excreted. Excessive APAP and/or alcohol consumption depletes glutathione pushing APAP into a different pathway with the resulting APAP metabolite being toxic and can lead to death, or even worse, a severe headache.

You just got bumped down on the ladder of coolness with that response

 

[imperial frog]

It's either death or erectile dysfunction...I can never remember which.

 

[Trancelucent1]

LOL that response was b/c we just got abused on an exam. He's in "professional mode" hmmm...well as professional as he can get.

 

[imperial frog]

Ask a question about antibiotics and you're own your own.

 

[imperial frog]

Or dead if you you rely on my answer apparently.

 

[ButlerPharm.D.]

Don't forget that you lose Glycine and Glutamic acid before it is acetylated and excreted!!! Sorry, I had to. 🙂

 

[Aznfarmerboi]

Can someone explain to someone who is still pre pharmacy why you wouldn't want to take apap in all cases?? Maybe thats a dumb question. I was just curious.

Besides that, other stuff you have to know besides the pathway that apap is metabolized, are that apap is more widely used than aspirin, ibu, and naproxen?? (not sure but it seems that way). APAP does not treat everything and is widely confused that it does. Most studies dont recommend that you take more than 4g a day for chronic users. Midol alone has 1g. Vicodin has 500, and so on. APAP is a pretty harmless drug unless u starve urself (malnutritent) or drink a lot of alcohol in which the resulting can occur. 1.Breathing depression (Depends and is unique to the patient in my opinion) 2. Acidosis (Bicarbonate is the antidote), and 3 (What we are most worried about in alcoholics) hepatictoxicity (n-acetyl cysteine). Other than that, a liver is a fine organ and has better regeneration than most other organs though, ie compared to the kidney.


APAP noted is also a cox (Cyclooxygenase) 3 inhibitor. Unlike some drugs such as celebrex or ibuprofen, which inhibits cox 1 and/or 2, APAP is used mainly for its anti pyretic effects. unless you have inflammation, or looking for an anaglesic effect, dont even bother with it. It uses the glutathione pathway which a lot of other drugs use, but other pathway competes to metabolize it (which may make it active/inactive, therapetutic or toxic, and helps to excrete it). If you cant excrete it. . . it got problems. I think competiting pathways are sulfate conjugation and one or two other??? not sure. . . gotta revisit my med chem notes again.

okay, i got to stop ranting after studying/test.

 

[ButlerPharm.D.]

From what I remember APAP is primarily metabalized via conjugation to Glutathione. I didn't think APAP toxicity could result in Sulfate formation because Sulfate formation only occurs on Alcohols or Phenols and as we all know, APAP at toxic levels goes through a quinoneimine intermediate which does not have either of the above 2 mentioned functional groups. Pehaps I am incorrect but I don't think APAP toxicity could result in Sulfate formation.

EDIT: What I am referring to above is what would occur at toxic levels, glucoronide and sulfate formation are the major pathways of APAP metabolism at normal levels.

 

[dgroulx]

Here's some info I did for a case last year:

Our case features a person who drinks regularly, eats char broiled foods 3 times a week and smokes. Now let’s say that this person is taking acetaminophen. Acetaminophen is metabolized by CYP1E2 (major) and both CYP1A2 & CYP3A4 (minor). When these enzymes are induced, there are more enzymes available for metabolizing the drug. This will shift metabolism towards this pathway. CYP enzymes metabolize acetaminophen to a toxic metabolite called NAPQI (N-actyl-benzoquinone imine). This metabolite can be detoxified by glutathione conjugation. But, when there is more metabolite than glutathione available, proteins can form adducts with NAPQI and cause cell necrosis. With induction of the CYP enzymes, we will have more acetaminophen metabolized by this pathway and therefore more NAPQI. Drinking every day also uses up glutathione.

BTW, sulfate conjugation is a minor pathway and the non-toxic metabolite is excreted. Hydrolysis is a really minor pathway of APAP, too.

 

[ravuu]

From what I remember APAP is primarily metabalized via conjugation to Glutathione. I didn't think APAP toxicity could result in Sulfate formation because Sulfate formation only occurs on Alcohols or Phenols and as we all know, APAP goes through a quinoneimine intermediate which does not have either of the above 2 mentioned functional groups. Pehaps I am incorrect but I don't think APAP toxicity could result in Sulfate formation.

Glucuronide conjugation is the major metabolizing pathway in adults. Oxidative sulfate conjugation is the major pathway in infants. Acetaminophen can also change to an N-acetylimidoquinone intermediate and undergo Glutathione conjugation as well. I may be wrong. Please correct me if I am. I just finished this course and that's what I remember. 🙂

 

[ButlerPharm.D.]

You are correct, Glucoronide conjugation and Sulfate formation are the primary methods of metabolism and excretion for normal doses of APAP. I don't think I was clear in my original post, I was referring to what would occur at toxic levels of 7-15 gram/day. Thank you for pointing that out.

 

[pkpd]

Here's some info I did for a case last year:

Our case features a person who drinks regularly, eats char broiled foods 3 times a week and smokes. Now let’s say that this person is taking acetaminophen. Acetaminophen is metabolized by CYP1E2 (major) and both CYP1A2 & CYP3A4 (minor). When these enzymes are induced, there are more enzymes available for metabolizing the drug. This will shift metabolism towards this pathway. CYP enzymes metabolize acetaminophen to a toxic metabolite called NAPQI (N-actyl-benzoquinone imine). This metabolite can be detoxified by glutathione conjugation. But, when there is more metabolite than glutathione available, proteins can form adducts with NAPQI and cause cell necrosis. With induction of the CYP enzymes, we will have more acetaminophen metabolized by this pathway and therefore more NAPQI. Drinking every day also uses up glutathione.

BTW, sulfate conjugation is a minor pathway and the non-toxic metabolite is excreted. Hydrolysis is a really minor pathway of APAP, too.

good answer!! 👍 it is not the alternative pathway that causes toxicity. its the lack of glutathione.