Opioids Will oral N-Acetyl-L-Cysteine help prevent Acetaminohpen toxicity (i.e from Vicodin)?

[OxyChem]

In cases of Acetaminophen (Tylenol) overdose, N-Acetyl-L-Cysteine is used medically (i.e in an Emergency Room) when the liver is failing or at risk of failing as it is a precursor to Glutathione. It's basically the antidote for acetaminophen toxicity if used on time. For the average sized person, an IV of 50 grams of N-Acetyl-L-Cysteine over 24 hours is used in cases of overdoses dangerous enough to harm or shutdown the liver.

N-Acetyl-L-Cysteine is sold in vitamin stores, health-food stores, even grocery stores etc, as an oral supplement as pills or capsules between 200mg and 1200mg. If a person is taking perhaps 4 grams of Acetaminophen a day (maximum recommended daily dose), or a bit less, would taking around couple grams of the oral N-Acetyl-L-Cysteine pills/capsules have any significant benefit in terms of reducing potential damage to the liver or would substantially higher amounts of N-Acetyl-L-Cysteine be required for any benefit?

As a note, in the ER, an IV of N-Acetyl-L-Cysteine is used which basically has a bioavailability of 100%, while the oral supplement has a bioavailability of around only 10%.

Basically, I'm wondering if there is even any point to taking an oral N-Acetyl-L-Cysteine supplement as I'm not sure if ingesting 100 capsules or something ridiculous would be needed to see any benefit or if taking only a few grams would make a beneficial difference for a person taking around 4 grams of Acetaminophen in a day.

edit: spelling

 

[Mora Fiend]

Oxychem, why not negate the necessity of having something like N-Acetyl-L-Cysteine by just doing a cold water extraction on Vicodin to get the hydrocodone out and leave the acetaminophen behind?

 

[OxyChem]

Oxychem, why not negate the necessity of having something like N-Acetyl-L-Cysteine by just doing a cold water extraction on Vicodin to get the hydrocodone out and leave the acetaminophen behind?

Well yea, a CWE is pretty much always the best option but I'm generally just curious about how effective oral N-Acetyl-L-Cysteine would actually be and I can't find much in terms of specific info about it's benefits outside of true and dangerous overdose situations.

Also, from a pain management standpoint, some people actually need the added benefit of Acetaminophen in terms of relief and if someone is taking 2 or 3 grams of Acetaminophen as a daily average, I'm wondering if it would be beneficial to take an N-Acetyl-L-Cysteine supplement on a regular basis or not.

 

[i are spectre]

there is info out there for procedures regarding high apap consumption. just google it my friend. cwe can also lose some of your product. as far as i can recall, NAC will completely remove the dangerous metabolites (and/or the apap itself, i cant remember). that's what i did, just find the dosage for the amount of apap consumed to "neutralise" it. google.com

 

[OxyChem]

there is info out there for procedures regarding high apap consumption. just google it my friend. cwe can also lose some of your product. as far as i can recall, NAC will completely remove the dangerous metabolites (and/or the apap itself, i cant remember). that's what i did, just find the dosage for the amount of apap consumed to "neutralise" it. google.com

Massive amounts of conflicting info result from Googling The specific info I can find as far as how much NAC to use is in the case of severe overdose (i.e your liver IS going to die). In overdose cases, huge amounts of NAC are used, and I'm talking the equivalent of over 100+ standard large NAC supplement capsules which is why I don't know if NAC is worth it in lower amounts for someone who isn't overdosing, but simply taking around the daily maximum or less of acetaminophen. I don't think anyone is going to want to take 50 capsules of NAC a day or some crap.

If your google-fu is better than mine and you've found a reliable source that would indicate for example, how much NAC to take if 2 grams of APAP is ingested, then by all means refer me to the link!

 

[ro0ga]

This isn't an ideal way to go about it, because though NAC will help in acute APAP toxicity, NAC does NOT remove APAP from your liver, it only removes APAP's toxic metabolite NAPQI. So you need to have toxic levels of APAP in your liver before the NAC will even do anything. It's not as useful as a deterrent, but rather as a treatment if you already have tylenol toxicity. It's not good harm reduction to say, "you can take as much tylenol as you want as long as you take NAC". You're going to run into problems, because the toxic effects of tylenol take a while before it starts to harm your liver, and I don't think the NAC hangs around that long.

It probably won't hurt, but you're certainly playing with fire if you decide to keep dosing such high amounts of tylenol daily...with or without the NAC.

 

[OxyChem]

This isn't an ideal way to go about it, because though NAC will help in acute APAP toxicity, NAC does NOT remove APAP from your liver, it only removes APAP's toxic metabolite NAPQI. So you need to have toxic levels of APAP in your liver before the NAC will even do anything. It's not as useful as a deterrent, but rather as a treatment if you already have tylenol toxicity. It's not good harm reduction to say, "you can take as much tylenol as you want as long as you take NAC". You're going to run into problems, because the toxic effects of tylenol take a while before it starts to harm your liver, and I don't think the NAC hangs around that long.

It probably won't hurt, but you're certainly playing with fire if you decide to keep dosing such high amounts of tylenol daily...with or without the NAC.

So NAPQI isn't produced in any significant amount if a person takes just a couple tylenol?

 

[dokomo]

NAC is poorly tolerated when taken at effective oral doses (it can cause vomiting and other bad side effects.)

Check out this thread I made some time back about treating acetaminophen overdose with s-adenosyl methionine (SAMe.)

Its been shown to be just as (or even more effective than) NAC, even when administered orally! Plus its readily available at almost every pharmacy out there.

 

[ro0ga]

So NAPQI isn't produced in any significant amount if a person takes just a couple tylenol?

Not in significant amounts, the NAPQI that is produced is quickly conjugated by enzymes in your liver. In overdoses, the enzymes that metabolize the NAPQI become saturated and are unable to further break it down, leading to a toxic buildup which is what destroys your liver. So taking normal doses isn't going to harm you, your liver is able to keep up. It's when you start taking very large doses of APAP that you run into problems. And furthermore, a one time dose of 4,000 mg will not kill you, it's repeated doses of that amount of the course of days or weeks that causes trouble. It's doses around 8,000 mg and above that run the risk of harming you in one dose. Though it's still best to stay below the 4,000 mg mark to be safe.

I know this because during my education in pharmacy school, one of my professors was one of the countries leading researchers on the toxic effects of tylenol, so I made it a point to talk to him about it to find out "what really is the deal with tylenol..."

 

[OxyChem]

Not in significant amounts, the NAPQI that is produced is quickly conjugated by enzymes in your liver. In overdoses, the enzymes that metabolize the NAPQI become saturated and are unable to further break it down, leading to a toxic buildup which is what destroys your liver. So taking normal doses isn't going to harm you, your liver is able to keep up. It's when you start taking very large doses of APAP that you run into problems. And furthermore, a one time dose of 4,000 mg will not kill you, it's repeated doses of that amount of the course of days or weeks that causes trouble. It's doses around 8,000 mg and above that run the risk of harming you in one dose. Though it's still best to stay below the 4,000 mg mark to be safe.

I know this because during my education in pharmacy school, one of my professors was one of the countries leading researchers on the toxic effects of tylenol, so I made it a point to talk to him about it to find out "what really is the deal with tylenol..."

I see. So then, would it makes sense in terms of safety or benefit to take NAC everytime APAP is taken as well as more separately from APAP ingestion periodically based on the biological half-life of APAP so that there is no possibility of toxicity? Say a person was taking 2 grams of Acetaminophen daily, would this potentially prevent toxicity that can occur from repeated said daily use of said APAP?

So, a person takes APAP with x amount NAC then more NAC several times periodically over x amount of time and repeat all this next time APAP is taken and so on... does this even make sense? lol

 

[dokomo]

Not in significant amounts, the NAPQI that is produced is quickly conjugated by enzymes in your liver. In overdoses, the enzymes that metabolize the NAPQI become saturated and are unable to further break it down, leading to a toxic buildup which is what destroys your liver. So taking normal doses isn't going to harm you, your liver is able to keep up. It's when you start taking very large doses of APAP that you run into problems. And furthermore, a one time dose of 4,000 mg will not kill you, it's repeated doses of that amount of the course of days or weeks that causes trouble. It's doses around 8,000 mg and above that run the risk of harming you in one dose. Though it's still best to stay below the 4,000 mg mark to be safe.

I know this because during my education in pharmacy school, one of my professors was one of the countries leading researchers on the toxic effects of tylenol, so I made it a point to talk to him about it to find out "what really is the deal with tylenol..."

This is definitely correct.

It is important to point out that hepatic glutathione levels can be significantly influenced by eating habits and certain other factors, so its always important to build in room for error when dosing acetaminophen.

 

[ro0ga]

I see. So then, would it makes sense in terms of safety or benefit to take NAC everytime APAP is taken as well as more separately from APAP ingestion periodically based on the biological half-life of APAP so that there is no possibility of toxicity? Say a person was taking 2 grams of Acetaminophen daily, would this potentially prevent toxicity that can occur from repeated said daily use of said APAP?

So, a person takes APAP with x amount NAC then more NAC several times periodically over x amount of time and repeat all this next time APAP is taken and so on... does this even make sense? lol

2 grams of APAP is unlikely to cause problems, even over a period of time. Now I don't know if you drink alcohol, but throwing alcohol into the mix will complicate the issue.