Problems with long term CWE

[MrManners]

I’m just wondering if anyone knows the dangers of long term CWE use? I’m clean now but for around 4.5 years I used CWE on apap/codeine tablets daily (with a few periods of being clean in that time but not for long). I understand that some paracetamol is soluble in cold water and I’ve read anything between 0.1-7 grams/litre depending on source. I’d say over that time my average intake was 3 CWE’s per day, usually spaced a minimum of 4 hours apart. Average final solution was 30-50ml of cold water (fridge cold so probs about 2-5 centigrade) and most CWE’s were on a 32 pack of 8/500mg each time. I’ve had many, many liver function tests which have always come back clear. 3 abdominal ultrasounds with all organs having normal appearance. My main concern atm is after reading about Analgesic Nephropathy of the kidneys, where they become damaged with chronic apap/aspirin use. I’ve been getting flank pain (very, very mild) for a couple of years know and my last kidney function test was in feb this year with a egfr rate of 102. This had decreased from 120 in sept of 2019 although I realise this can fluctuate with hydration levels etc. Should I be concerned over this and tell my doctor. They already know about my past addiction. I test my urine regularly and have never had any protein found in it, nor any white or red blood cells. The only issue is the mild flank pain that comes and goes, but seeing this has been going on for at least a couple of years would I be safe to assume that 2 years of CWE’s is too little an amount of apap and time to develop this condition? Has anyone any experience in this? Thanks for reading fellow BL’s.

 

[Nurse Ratched]

It's hard to really tell what kind of damage you may be doing to your organs...if any. Flank pain ( I'm assuming leg pain as when I think of flank I think tough steak ). Could be anything really and you said you have had it for 2 years albeit it has been mild. Could just be the way you sit. So hard to help when we can only guess.

Other than that , it sounds like you are pretty healthy and your tests are coming back good. Just watch your acetaminophen intake amd keep doing the CWE's when you take the codeine tablets. Some people consume 4 grams of APAP daily, think that is the max consumption. They have to consume plain APAP tablets as they don't have a script for anything for pain. No question the stuff hates our livers. Just be careful and keep on keepin' on.

 

[Skorpio]

APAP will not really cause the nephropathy that long term use of COX inhibitors will.

There are 2 isoforms of cyclooxygenase (COX1 and COX2). They both produce slightly different suites of prostglandins. COX2, is crucial for the production of prostaglandin E2, which is responsible for tissue inflammation.

In most tissues COX2 is expressed at low levels until injury where transcription of the gene is induced and COX2 expression cranks up to aid the inflammatory response.

Unfortunately the kidneys constitutively express COX2 and rely on it for prostaglandins that maintain kidney homeostasis. This is the source of analgesic nephropathy.

APAP is a much weaker COX2 inhibitor (and these effects are really cell type dependant due to oxidation) so it seems safer for the kidneys. (it also lacks the robust epidemiological associations with kidney injury that nsaids have).

Final note, 4 grams of apap a day is an overdose. People acting like you can consume slightly less than that and avoid eventual liver damage are really gambling that their liver can repair itself quickly enough. The study below discusses people displaying biomarkers of liver damage after 1 gram of apap.

Acute Liver Failure including Acetaminophen Overdose

Acute liver failure (ALF) is a dramatic and highly unpredictable clinical syndrome defined by the sudden onset of coagulopathy and encephalopathy. Although many disease processes can cause ALF, acetaminophen overdose is the leading cause in the United ...

www.ncbi.nlm.nih.gov

 

[JessFR]

Final note, 4 grams of apap a day is an overdose. People acting like you can consume slightly less than that and avoid eventual liver damage are really gambling that their liver can repair itself quickly enough. The study below discusses people displaying biomarkers of liver damage after 1 gram of apap.

How can 4g a day be an overdose when it's literally what it says on the packets here.

From the box
"Paracetamol 500mg"
Directions adults:
1-2 (500mg-1g) tablets to be taken every 4-6 hours when required, up to 4 times daily. Maximum of 8 (4g) tablets every 24 hours"

What am I missing here?

 

[MrManners]

APAP will not really cause the nephropathy that long term use of COX inhibitors will.

There are 2 isoforms of cyclooxygenase (COX1 and COX2). They both produce slightly different suites of prostglandins. COX2, is crucial for the production of prostaglandin E2, which is responsible for tissue inflammation.

In most tissues COX2 is expressed at low levels until injury where transcription of the gene is induced and COX2 expression cranks up to aid the inflammatory response.

Unfortunately the kidneys constitutively express COX2 and rely on it for prostaglandins that maintain kidney homeostasis. This is the source of analgesic nephropathy.

APAP is a much weaker COX2 inhibitor (and these effects are really cell type dependant due to oxidation) so it seems safer for the kidneys. (it also lacks the robust epidemiological associations with kidney injury that nsaids have).

Final note, 4 grams of apap a day is an overdose. People acting like you can consume slightly less than that and avoid eventual liver damage are really gambling that their liver can repair itself quickly enough. The study below discusses people displaying biomarkers of liver damage after 1 gram of apap.

Acute Liver Failure including Acetaminophen Overdose

Acute liver failure (ALF) is a dramatic and highly unpredictable clinical syndrome defined by the sudden onset of coagulopathy and encephalopathy. Although many disease processes can cause ALF, acetaminophen overdose is the leading cause in the United ...

www.ncbi.nlm.nih.gov

I’ve had several liver function tests per year during my addiction as I was paranoid about it. I’ve never had an abnormal bio marker, not once. I’ve also paid for private ultrasound of the liver (and other organs) and the sonograther has always remarked that it looks in great health along with the portal vein and central bile duct etc. Would you assume with these regular results that I have avoided liver damage?
Thanks for putting my mind at rest about the kidneys, from what I’ve read the science is a little unclear about apap causing algesic nephropathy.

 

[Skorpio]

How can 4g a day be an overdose when it's literally what it says on the packets here.

From the box
"Paracetamol 500mg"
Directions adults:
1-2 (500mg-1g) tablets to be taken every 4-6 hours when required, up to 4 times daily. Maximum of 8 (4g) tablets every 24 hours"

What am I missing here?

I think our terms for overdose are not the same. The paracetamol box is referring to doses that would merit medical attention (ie iv n acetyl cystiene). I am referring to doses in which cell death is observed. It is likely that this can be ameliorated by the normal regeneration of the liver. Even so, I tread really lightly because I have a fairly varied diet (of substances), so if there is any easy way to baby my liver I will.

I personally will not exceed a gram of Tylenol in a sitting and use it as a second or third line treatment for pain (I usually go nsaids then weed if I am somewhere I can be high then if still in pain I will add tylenol).

I’ve had several liver function tests per year during my addiction as I was paranoid about it. I’ve never had an abnormal bio marker, not once. I’ve also paid for private ultrasound of the liver (and other organs) and the sonograther has always remarked that it looks in great health along with the portal vein and central bile duct etc. Would you assume with these regular results that I have avoided liver damage?
Thanks for putting my mind at rest about the kidneys, from what I’ve read the science is a little unclear about apap causing algesic nephropathy.

Liver function values are not the most sensitive biomarker. This is ok, because the liver is quite good at regenerating. Since you aren't mentioning evidence of fibrosis for your ultrasound results, it is likely that your liver should be fine.

That being said, if your doctors are already in the know about your addiction it possibly wouldn't hurt too much to mention the flank pain and see what they think. I guess it could send you down pricy (both money and time) rabbitholes.

 

[MrManners]

I think our terms for overdose are not the same. The paracetamol box is referring to doses that would merit medical attention (ie iv n acetyl cystiene). I am referring to doses in which cell death is observed. It is likely that this can be ameliorated by the normal regeneration of the liver. Even so, I tread really lightly because I have a fairly varied diet (of substances), so if there is any easy way to baby my liver I will.

I personally will not exceed a gram of Tylenol in a sitting and use it as a second or third line treatment for pain (I usually go nsaids then weed if I am somewhere I can be high then if still in pain I will add tylenol).





Liver function values are not the most sensitive biomarker. This is ok, because the liver is quite good at regenerating. Since you aren't mentioning evidence of fibrosis for your ultrasound results, it is likely that your liver should be fine.

That being said, if your doctors are already in the know about your addiction it possibly wouldn't hurt too much to mention the flank pain and see what they think. I guess it could send you down pricy (both money and time) rabbitholes.

See, I have over the years of my addiction searched far and wide for information relating to liver damage from chronic apap use, not overdose levels but recommended dosage levels over a lengthy period of time. There is very little information out there that I can see. It is all about acute liver injury from apap overdose. Because of this I paid to speak to a gastroenterologist to ask him about this and he didn’t believe apap use can cause fibrosis of the liver due to the mechanism of injury at therapeutic doses. Even if I take the highest estimate of 7grams per litre of paracetamol solubility your mentioned above, my average use has still been far less than the recommended therapeutic dose. It’s a tricky one, good information on this subject is hard to find.

 

[Skorpio]

Because of this I paid to speak to a gastroenterologist to ask him about this and he didn’t believe apap use can cause fibrosis of the liver due to the mechanism of injury at therapeutic doses.

Interesting. I definately would go with his info then. I do not study liver pathology in that fine of detail. I'm more in the signaling/drug metabolism realm, and certainly not an md.