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This post does not affect me personally but still thought it would be a valid subject for those who it may affect.
Many of the drugs of the benzodiazepine class suffer biotransformation in the liver and are eliminated by renal excretion, therefore, in patients with any hepatic or renal impairment the dose of such drugs should be prescribed with caution and without exaggeration, to prevent that in cases of renal failure the action of these drugs could be prolonged (increase in half-life) and cause undesirable side effects such as, for example, the use of midazolam in chronic renal failure patients postoperatively which can result in continued sedation.
Renal failure is a condition in which the kidneys lose their ability to perform their basic functions (eliminate toxic substances to the body, keep regulated the hidroelectrolyte balance of the body, regulate basic-acid balance, hormone production, excrete urine and exogenous substances such as drugs), such deficiency can be acute when loss occurs in sudden and rapid way or chronic when this loss is slow, progressive and irreversible. The latter is classified in stages, according to its evolution: 0 (risk of kidney disease by having high blood pressure or diabetes), 1 (kidney damage), 2 (kidney damage and mild glomerular filtration), 3 (moderate glomerular filtration) 4 (advanced glomerular filtration) and 5 (renal failure, requiring dialysis or transplantation).

Xfizzler 

Hey Fizz:

Are you saying that the liver processes benzos in a way that can be harmful to the kidneys? You don't question or describe the potential effect of benzos on the liver specifically in your post and I would be interested to know what, if any, direct effect benzo use may have on the liver itself.

Good thread. I hope you get some good input on this topic.

Raven

(03-09-2018, 02:18 AM)Raven Wrote: [ -> ]Hey Fizz:

Are you saying that the liver processes benzos in a way that can be harmful to the kidneys? You don't question or describe the potential effect of benzos on the liver specifically in your post and I would be interested to know what, if any, direct effect benzo use may have on the liver itself.

Good thread. I hope you get some good input on this topic.

Raven

Hi Raven!

No just pointing out the importants of exercising caution for those whose suffer from kidney disease or liver diseases. In their cases this article would pertain to them. If they absolutely had to take benzo as prescribed and suffer from liver or kidney issues. Thats all. 

Xfizzler

Benzos are not hepatotoxic drugs.
Benzos are metabolized ('broken down') by your liver (and metabolites are excreted through your kidneys), but benzos don't damage liver or kidney cells directly.

Examples of drugs that do direct damage to the liver are acetaminophen (tylenol/paracetamol) and alcohol.
It's ironic that you can purchase a deadly amount of pain killers and/or booze from a Super Market or Convenience Store without anyone raising an eyebrow.
A large Pharmacy Chain in Australia sells packs of 100 x 500mg Paracetamol tablets for $1.99   
That's 50grams.  Taking more than 10 grams at once is an overdose. Goodbye healthy liver.
I'm not pretending for one moment that benzos carry no risk, but liver & kidney failure is not one of them.

Recreational use of benzos when you have established liver or kidney disease is a whole other ball game.
It can be likened to sleep walking in a world that's going very very fast.  Will it end well? Extremely unlikely.

Benzos can be rarely hepatotoxic, and specifically the nitrobenzos (which include clonazepam) have been found to be possibly more likely to be hepatoxic than other benzos.

https://www.ncbi.nlm.nih.gov/pubmed/19005028
https://en.wikipedia.org/wiki/Nitrazepam#Liver

RG & Fizz:

Thanks for the replies. Really good information. I avoid Acetaminophen like the plague. I do, however, imbibe in a couple of beers several days per week. I really enjoy having a beer or two with friends at the end of the work day and that is one vice that I really don't want to give up. I have my blood tested twice per year and, although my ALT and AST enzymes are typically just within the recommended range, my ratio of ALT:AST is very good.

I take a single benzo dose per day when I awake in the morning and, if I do have a beer that day, then it is usually at least 8 hours later. It just makes sense to me that I should avoid having peak levels of each substance in my bloodstream at the same time.

I'm trying to be careful. I guess you could say that my goal is substance use vs. substance abuse.

Love Thy Liver! This replacement part is hard to come by.

Raven

I have been on them every day for the last 3.5 years and i had a liver toxicity test 1month ago and my liver test were all fine.
But i don`t abuse them i take 2x nitrazepam 5mg per day. Mind you i also take oxycontin everyday for 2 years (100mg) which is the reason i actually asked for the test so i was pleasantly surprised. Also i havent drunk booze in about 10 years but before the oxys i took panadeine forte for 3 years only 3-4 per day.

Both references point to one single paper published in 2009  which can be read in full here.
For mine, this paper is all over the place.
For instance, they site the case of clonazepam-induced liver injury (Am J Gastroenterol. 1988 May;83(5):576-7.)
But when you read that paper you find "It is suggested that the damage was of the metabolic idiosyncrasy type".
Back at our 2009 article and they say "idiosyncratic drug reactions do not occur in most patients at any dose"
So what are we left to conclude?
I'd say it would be something like "Clonazepam-induced liver injury does not occur in most patients at any dose".
Well, that's reassuring.

The 2009 paper also sites a mysterious paper "Chronic administration of antidepressant drugs including nitrazepam was reported to induce severe hepatic disorders"  (Seki et al., 2008)   But when you click on the link there's no mention of nitrazepam.  Hmmmm.....
As far as I know, Nitrazepam isn't considered to be a member of any class of antidepressant drugs. They're just not "Same Same".  

And to conclude my rant, comparing what happens inside a human to what happens in a cell culture incubated at 37°C in for 24hrs an atmosphere of 5% CO2 and 95% air is just plain crazy.
In their Discussion, the authors of the 2009 paper note"....it is very difficult to extrapolate from an in vitro study to in vivo in humans....."
Oh God, never a truer word were spoken!

I think we can relax. In the real world, (virtually) no-one's liver or kidney is going to collapse from a few doses of nitrazepam or clonazepam.

(03-10-2018, 08:22 AM)Richardg8092 Wrote: [ -> ]Both references point to one single paper published in 2009  which can be read in full here.
For mine, this paper is all over the place.
For instance, they site the case of clonazepam-induced liver injury (Am J Gastroenterol. 1988 May;83(5):576-7.)
But when you read that paper you find "It is suggested that the damage was of the metabolic idiosyncrasy type".
Back at our 2009 article and they say "idiosyncratic drug reactions do not occur in most patients at any dose"
So what are we left to conclude?
I'd say it would be something like "Clonazepam-induced liver injury does not occur in most patients at any dose".
Well, that's reassuring.

The 2009 paper also sites a mysterious paper "Chronic administration of antidepressant drugs including nitrazepam was reported to induce severe hepatic disorders"  (Seki et al., 2008)   But when you click on the link there's no mention of nitrazepam.  Hmmmm.....
As far as I know, Nitrazepam isn't considered to be a member of any class of antidepressant drugs. They're just not "Same Same".  

And to conclude my rant, comparing what happens inside a human to what happens in a cell culture incubated at 37°C in for 24hrs an atmosphere of 5% CO2 and 95% air is just plain crazy.
In their Discussion, the authors of the 2009 paper note"....it is very difficult to extrapolate from an in vitro study to in vivo in humans....."
Oh God, never a truer word were spoken!

I think we can relax. In the real world, (virtually) no-one's liver or kidney is going to collapse from a few doses of nitrazepam or clonazepam.

Excellent post!

(03-10-2018, 08:22 AM)Richardg8092 Wrote: [ -> ]And to conclude my rant, comparing what happens inside a human to what happens in a cell culture incubated at 37°C in for 24hrs an atmosphere of 5% CO2 and 95% air is just plain crazy.
In their Discussion, the authors of the 2009 paper note"....it is very difficult to extrapolate from an in vitro study to in vivo in humans....."
Oh God, never a truer word were spoken!

...and this is why it always pays to read the entire paper! 
Great find!