Misc How Does APAP Adversely Affect the Live, but ...

[Michael_25]

But why do drugs such as codeine, hydrocodone and oxycodone not adversely affect the liver? Everyone preaches doing CWEs when doing these drugs that contain Tylenol, but don't the foregoing drugs get metabolized by the liver, thus putting it under stress when using more-than-prescribed doses?

 

[emkee_reinvented]

Good question Michael but have you tried a search yourself. I did and it looks like quite an indepht read. NCBI has some interesting info. What caught my eye was a toxic metabolite formed through one of the pathways the body uses to excrete the stuff named N-acetyl-para-benzo-quinone imine (NAPQI). Real bad mf if your a liver cell.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913076/

The fact APAP needs up to a gram to work gives me a feeling that ammount is also a factor. Or a I wrong.

 

[Michael_25]

Good question Michael but have you tried a search yourself. I did and it looks like quite an indepht read. NCBI has some interesting info. What caught my eye was a toxic metabolite formed through one of the pathways the body uses to excrete the stuff named N-acetyl-para-benzo-quinone imine (NAPQI). Real bad mf if your a liver cell.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913076/

The fact APAP needs up to a gram to work gives me a feeling that ammount is also a factor. Or a I wrong.

Thanks for the link, Emkee. But I skimmed through it and it explains liver damage from APAP, no mention of opioids where in the article. I've tried Google to find this information, but to no avail ...

 

[Wiserthanearlier]

I think that high levels of paracetamol (above 1000mg) per dose are confirmed to be toxic. Vs
high dose or even medium or very high dose of opiods arent considered toxic.

Why, these drugs are both filtered by the liver but not all drugs build up the same. Or cause as much load on the liver.

This means higher apap doses are bad as apap is heavy on the liver, where some chemicals usually attached to apap arent necessarily heavy oat all on liver

 

[Coolwhip]

Emkee nailed it. It's because of NAPQI, NAPQI is formed by the tertiary metabolic pathway. Under normal circumstances very little NAPQI is formed, but when you take excess doses of APAP the first two metabolic pathways become saturated and overwhelmed so your liver starts producing NAPQI in an effort to rid your body of the excess APAP.

It isn't that too much of any drug is bad for your liver, or the act of metabolizing things is bad for your liver, it all depends on what your liver turns those drugs into.(assuming the compound isn't hepatoxic from the start)

 

[Jekyl Anhydride]

Opioids are rare causes of drug induced liver disease and are not mentioned in large case series of clinically apparent liver injury caused by medications. In physiological, pain relieving doses, opioids have not been implicated in causing clinically apparent liver injury, acute liver failure, chronic hepatitis or vanishing bile duct syndrome.

https://livertox.nih.gov/Opioids.htm

It is possible that the implicated opioids are not directly toxic to the liver, but cause ischemic liver injury due to respiratory failure, cardiovascular collapse, shock and anoxia that can occur with severe opioid overdose. The clinical syndrome resembles acute hepatic necrosis and liver failure, but is rapidly reversible and rarely the primary cause of death from overdose.

If liver damage occurs because your heart and lungs fail, then there are bigger problems to worry about. Emkee_R. was on the right track with NAPQI being the biggest risk.

IMO Renal insufficiency is a bigger problem with high dose opioid use, rather than Hepatic issues.

 

[Jabberwocky]

^+1

Opioids are well know to be one of the least unhealthy drugs to use as far as their pharmacological action goes.

I?m not sure what the question is? The stress that APAP overdoses puts in the liver isn?t really comparable to opioids. They might be both metabolized in the liver, but the way that happens is entirely different.

 

[emkee_reinvented]

Sorry myself Michael as I was assuming the liver toxicity was common knowledge. Which it isn't but should be. And that opiods were not by any degree as bad for the liver.

How many drink alcohol and take paracetamol/ APAP without knowing the risk I wonder.

Like Tooth paste wrote opiods are actually one fine class of drugs. If you can not become addicted to them.

 

[emkee_reinvented]

Emkee nailed it. It's because of NAPQI, NAPQI is formed by the tertiary metabolic pathway. Under normal circumstances very little NAPQI is formed, but when you take excess doses of APAP the first two metabolic pathways become saturated and overwhelmed so your liver starts producing NAPQI in an effort to rid your body of the excess APAP.

It isn't that too much of any drug is bad for your liver, or the act of metabolizing things is bad for your liver, it all depends on what your liver turns those drugs into.(assuming the compound isn't hepatoxic from the start)

What about chronic users, are there concerns when dosing according to the official standards on daily basis. For sure some I know are on 2 3 grams a daily.

 

[LandsUnknown]

They are metabolized differently. There are different metabolic pathways that the liver uses to metabolize Tylenol. If the liver's resources to process the Tylenol have not been exhausted as a result of taking an overdose of Tylenol or chronic alcohol consumption, it is metabolized into compounds that are non-toxic. Therefore, recommended/prescribed dosages of Tylenol are safe. Taking more than recommended/prescribed can exhaust the liver's ability to use the safe metabolic pathways. Instead, the liver uses other pathways to metabolize it. These pathways convert the Tylenol into highly hepatoxic compounds, such as NAPQI. These compounds can cause acute liver failure, and cause your liver to shut down and require a transplant as a result (or kill you). Opiates are metabolized differently, and none of the resulting compounds are seriously hepatoxic. However, an opiate overdose also is a very dangerous and potentially deadly situation. Though, it is dangerous for different reasons (e.g. respiratory depression and depression of the cardiovascular system). It is possible that an overdose of opiates could cause damage to any cells (liver or elsewhere), because if severe respiratory depression and cardiovascular depression occurs, the cells don't get enough oxygen and blood supply.

However, responsible doctors generally prescribe amounts that are much less than the threshold of life-threatening respiratory depression and cardiovascular collapse. Though, for some reason, the recommended dosage of Tylenol is dangerously close to the threshold of potentially causing serious liver problems. According to some sources, taking just two more pills than recommended dose of Tylenol could potentially exhaust the liver's resources and result in a fatal OD The therapeutic dose of Tylenol is downright dangerously close to the threshold of a serious overdose. That's why people do CWEs when they are using more opiates than prescribed.

 

[Hodor]

Though, for some reason, the recommended dosage of Tylenol is dangerously close to the threshold of potentially causing serious liver problems.

That seems to be mostly an American thing though - the recommended maximum dose of extra-strength tylenol is 4x1000 mg/day. Here in Europe, the recommended maximum dose for APAP products is usually given as 4x500mg.

 

[emkee_reinvented]

Emkee nailed it.

Easy target, lucky shot.

 

[emkee_reinvented]

Though, for some reason, the recommended dosage of Tylenol is dangerously close to the threshold of potentially causing serious liver problems. According to some sources, taking just two more pills than recommended dose of Tylenol could potentially exhaust the liver's resources and result in a fatal OD

Due to the higher prescribed doses in US dr's realised the potential risks of APAP. Especially when taken chronically and with life expectancies increasing. They questionaded safety regarding the liver in that regards. Maybe at later age accumalated damage would occur while taking recommended doses. If I am correct they suggested adding N-acetyl-cysteine to the tablets. Scared the shit out of me harmless Paracetamol. That made me decide the European standard 2 to 3 grams daily is in no way safe eather Hodor.