Harm Reduction Avoiding the Liver? Questions of first pass metabolism, IV / IM / Rectal admin. To prevent liver damage?

[OpiateKiller]

So I've been reading up and studying about the liver lately. On my last blood work at the doctor's I had slightly elevated liver values, which made me curious how I could prevent this. I wasn't surprised, I figured it would be worse to be honest, given my drug and alcohol history.

So apparently according to all the research I've found... IV or IM injection of drugs avoids any contact with the liver. It also stated sublingual and rectal avoid contact or possible damage to the liver.

So I mean, if this were true, why is it that people with Hep C can't shoot heroin / drugs anymore? I mean if IV drug use does no damage to the liver, why would it want to be avoided?

It seems clear that oral use of any drug, and of course alcohol as the main danger, are the common dangers for liver damage / cirrhosis..

I'm not trying to promote IV drug use, but it seems if your liver is compromised it is a healthier route of choice? Thoughts?

 

[JessFR]

People with hep c most certainly can shoot drugs. I did for a year or so when I had Hep C.

I mean sure, it's dangerous, shooting drugs always is. But it only becomes more dangerous than it might otherwise be in this context if your liver is damaged. And it can take hep c many years for that to happen.

The misconception here as I understand it. Is thinking that injection use bypasses the liver. That is not the case at all.

What it bypasses is the first pass effect that happens when you swallow a substance.

Basically if you swallow a substance, it goes through the liver before entering the rest of your system. This can cause the drug to be further metabolized before it enters your system if taken orally than via any other route. But it's only that it goes through the liver once before entering the rest of your system, not that it never goes through the liver again.

So yes, other routes with some drugs can cause less liver damage, but only less, not none. And that benefit is completely lost if that other route is injecting, because hep c is a much greater long term risk than most drugs.

A lot of drugs aren't very harmful to the liver, not by comparison to years of hep c anyway. Some like alcohol are, but opioids not so much.

Regardless of any of that though, if you have ever injected... And I mean ever. I would strongly recommend getting a hep c test if you haven't already.

That's how I found out I had Hep C in fact. I didn't find it via a routine check, my liver results on a blood test were elevated and given I was an IV drug user, that immediately prompted a hep c test, which came back positive.

Unless you drink a LOT. if you're an injection drug user. Hep c is by far the most likely reason you might have an elevated liver test.

 

[Deru]

I'm not trying to promote IV drug use, but it seems if your liver is compromised it is a healthier route of choice? Thoughts?

In some very specific cases this may have benefit. The question would be: does the increased health risks of IV use with non-sterile drugs and/or equipment outweigh the risks of further possible damage to the liver by enteral administration?

The misconception here as I understand it. Is thinking that injection use bypasses the liver. That is not the case at all

Are you thinking of the kidneys? The liver only fillters the blood coming from the stomach and intestines. As such, parenteral administration such as IV, does bypass the liver completely as far as metabolizing the drug (as far as I know, there may be exceptions.)

 

[JessFR]

In some very specific cases this may have benefit. The question would be: does the increased health risks of IV use with non-sterile drugs and/or equipment outweigh the risks of further possible damage to the liver by enteral administration?

And to that question, I would be truly stunned if the answer weren't a resounding no.

Putting aside alcohol, which is very hard on the liver. I'd say most drugs aren't nearly harmful enough to the liver to get much benefit.

I've never actually seen anyone who can tell me that their drug user seriously harmed them because of how it directly harmed their liver. At least not with most of the traditional recreation drugs that aren't alcohol.

But I've seen plenty of people either die over an od or nearly die, which is much more likely to happen with IV than most other routes. I've known plenty of people who have or had Hep C, and untreated that absolutely will damage your liver. Not the "maybe" we are talking about from the drugs themselves. Then there's also HIV. Not as common as hep c and not the killer it once was, but still way more dangerous than this liver possibility.

I don't really think there's much of a question.

Might injection use be slightly less harmful in this one specific way? Maybe. But once you factor in everything else, that tiny possible benefit is worthless IMO.

 

[Deru]

And to that question, I would be truly stunned if the answer weren't a resounding no.

Exactly. And then even if that were the case, all the other negative factors come in to play with intravenous use. I'm sure there are medically necessary reasons for this - I can't think of one reason recreational use would ever be justified - but who knows, there is always that one outlier that makes it impossible to say "always."

 

[OpiateKiller]

People with hep c most certainly can shoot drugs. I did for a year or so when I had Hep C.

I mean sure, it's dangerous, shooting drugs always is. But it only becomes more dangerous than it might otherwise be in this context if your liver is damaged. And it can take hep c many years for that to happen.

The misconception here as I understand it. Is thinking that injection use bypasses the liver. That is not the case at all.

What it bypasses is the first pass effect that happens when you swallow a substance.

Basically if you swallow a substance, it goes through the liver before entering the rest of your system. This can cause the drug to be further metabolized before it enters your system if taken orally than via any other route. But it's only that it goes through the liver once before entering the rest of your system, not that it never goes through the liver again.

So yes, other routes with some drugs can cause less liver damage, but only less, not none. And that benefit is completely lost if that other route is injecting, because hep c is a much greater long term risk than most drugs.

A lot of drugs aren't very harmful to the liver, not by comparison to years of hep c anyway. Some like alcohol are, but opioids not so much.

Regardless of any of that though, if you have ever injected... And I mean ever. I would strongly recommend getting a hep c test if you haven't already.

That's how I found out I had Hep C in fact. I didn't find it via a routine check, my liver results on a blood test were elevated and given I was an IV drug user, that immediately prompted a hep c test, which came back positive.

Unless you drink a LOT. if you're an injection drug user. Hep c is by far the most likely reason you might have an elevated liver test.

Thank you for this info, I really wasn't sure. And at the time of my blood work 8-12 beers a night was usual, and I use anabolic steroids which can elevate liver values.

But it has been a few years so I definitely plan on a Hep C test just to be safe.

I agree though unless you are very sterile and injecting pharmaceutical products filtered properly, IV drug use is much much more dangerous.

 

[OpiateKiller]

In some very specific cases this may have benefit. The question would be: does the increased health risks of IV use with non-sterile drugs and/or equipment outweigh the risks of further possible damage to the liver by enteral administration?



Are you thinking of the kidneys? The liver only filters blood coming from the stomach and intestines. As such, parenteral administration such as IV, does bypass the liver completely as far as metabolizing the drug (as far as I know, there may be exceptions.)

True, unless you follow all sterile protocols and only inject purified or properly filtered pharm grade drugs, which is very rare.

 

[JessFR]

Thank you for this info, I really wasn't sure. And at the time of my blood work 8-12 beers a night was usual, and I use anabolic steroids which can elevate liver values.

But it has been a few years so I definitely plan on a Hep C test just to be safe.

I agree though unless you are very sterile and injecting pharmaceutical products filtered properly, IV drug use is much much more dangerous.

Hopefully there's a less severe explanation, but yeah I'd definitely get checked for hep c soon.

I never did find how exactly how I got it, or even who I got it from (though I can certainly guess..). I mean obviously I got it through IV injecting, but prior to being infected I had never shared a needle. So it had to have been through shared spoons or other equipment.

My point is, hep c can be contracted even without an obvious point of exposure. If you inject at all, and you have elevated liver results, it's worth assuming that hep c could be the reason.

 

[JessFR]

Are you thinking of the kidneys? The liver only filters blood coming from the stomach and intestines. As such, parenteral administration such as IV, does bypass the liver completely as far as metabolizing the drug (as far as I know, there may be exceptions.)

Well I'm by no means an expert on this stuff, but yeah I'm pretty sure.

The liver doesn't exclusively break down substances via the portal vein, it also breaks down substances in your blood as part of the metabolic process delivered by artery.

Lets take acetaminophen as an example, it's known to cause liver damage in high doses. It is also given as IV and that has also been associated with liver damage too.

Because the liver is still exposed to the substance either way and is still involved in breaking it down. It just bypasses the first pass.

Another example, as I recall substances like chloroform and ether, which used to be used for their anesthetic properties, were withdrawn specifically because of their potential for liver damage.

Yet both were inhaled, entering the blood via the lungs.

The livers evolved expecting our primary exposure to toxins to be through ingestion. But it's by no means the only way.

 

[Deru]

Yes, it does appear certain drugs, such as acetaminophen, will make it back to the liver the second time through the circulation and still have 50 percent of the original dose needing metabolism upon reaching the liver the second time. (There's always exceptions!)

That's why I love these forums, I find all of this stuff fascinating. I know what I'll be researching for the rest of the night

I'm interested now in how much, if any, further metabolism recreational drugs like diacetylmorphine and cocaine would need by the second pass through the circulatory system.

 

[JessFR]

Some quick googling suggests that heroin is entirely metabolized into morphine by the first pass effect.

So swallowing it is probably not much different to taking oral morphine.

 

[Deru]

Yes, but if one takes heroin intravenously, would it be fully metabolized in the blood before reaching the liver in it's second pass through the circulation (and first time arriving at the liver)?

 

[JessFR]

I doubt it, heroin is metabolized extremely fast. But it's still gonna go straight to the liver through the arteries after getting to the heart after injection.

 

[Deru]

I doubt it, heroin is metabolized extremely fast. But it's still gonna go straight to the liver through the arteries after getting to the heart after injection

A small portion will inevitably make it's way to the liver through the common hepatic artery (unavoidable). I would think that would be a pretty small fraction of the total available amount that reaches arterial blood on the first pass.

 

[neversickanymore]

Yes, it does appear certain drugs, such as acetaminophen, will make it back to the liver the second time through the circulation and still have 50 percent of the original dose needing metabolism upon reaching the liver the second time. (There's always exceptions!)

Im lost here. Please clue me in on the "second pass through the circulatory system"

 

[Deru]

Im lost here. Please clue me in on the "second pass through the circulatory system"

Once the drug goes through one full circulation, artery to capillaries to vein to right side of heart to pulmonary circulation to left side of heart if we start the pass from the first stroke of the heart pushing the drug into the arterial blood stream from the left ventricle.

If we start with intravenous injection, it would be from vein to right side of heart to pulmonary circulation to left side of heart to artery to capillaries back to vein.

That could be considered "one pass" for the purposes of what we're discussing - since we're trying to discuss if a drug requires further metabolism from the liver after bypassing the liver on the first pass.

I may be missing something here, but is there an implication here that all blood is forced through the liver upon entering the aorta from the left ventricle? What about the blood that goes to the brain and upper extremities? For the arterial blood that goes down, what forces the drug itself into the common hepatic artery and not allow it to continue past it?

 

[neversickanymore]

Once the drug goes through one full circulation, artery to capillaries to vein to right side of heart to pulmonary circulation to left side of heart if we start the pass from the first stroke of the heart pushing the drug into the arterial blood stream from the left ventricle.

If we start with intravenous injection, it would be from vein to right side of heart to pulmonary circulation to left side of heart to artery to capillaries back to vein.

That could be considered "one pass" for the purposes of what we're discussing - since we're trying to discuss if a drug requires further metabolism from the liver after bypassing the liver on the first pass.

I may be missing something here, but is there an implication here that all blood is forced through the liver upon entering the aorta from the left ventricle? What about the blood that goes to the brain and upper extremities? For the arterial blood that goes down, what forces the drug itself into the common hepatic artery and not allow it to continue past it?

I am familiar with and pretty much grasp big picture arterial and venous human blood flow through their physiological and anatomical nature. But I am not familiar with substances being largely metabolized during a first pass or needing a second pass. How do one or two "passes" figure into metabolic half life?

 

[Deru]

How do you define these "passes" and how does that figure into metabolic half life?

Maybe discussing it in terms of passes is the wrong approach here.

Let's try it this way:

For parenteral administration, the drug bypasses being metabolized by the liver before reaching it's target, the receptors in the brain (yes there are other receptors throughout the body, for now we'll focus on the receptors in the brain to not make this unnecessarily complex). Not only does this increase bioavailability and result in faster onset time, but also reduces potential damage to the liver.

For intravenous injection, the drug would travel from the vein to the right atrium, then right ventricle, then pulmonary circulation, then left atrium, then left ventricle.

Upon the next beat of the heart, the aortic valve will open and the drug molecules that are in the blood in the left ventricle will then be pumped into the aorta. The drug molecules that travel through the carotid arteries will reach the target site (receptors) without ever being metabolized by the liver.

The rest of the drug molecules will be circulated through the rest of the body, organs, tissues, etc. will eventually reach the capillaries and come back from the veins and the cycle/pass repeated.

The question was originally as such: when the drug reaches the liver again, will it require further metabolism? This was in relation to the original question in the OP.

It appears very large doses of intravenous Tylenol does require further metabolism in the liver. I tried to use "second pass" to illustrate that this was not being done initially after a drug is administered via a parenteral route of administration.

There also doesn't appear to be a forced mechanism to force the drug molecules back through the liver - I am unclear exactly how this process works besides whatever finds it's way to the liver via the common hepatic artery.

I'm sure there is an incredibly simple answer to this last part - when someone says it the lightbulb will come on!

 

[neversickanymore]

Thank you for taking the time to exsplain that. I now understand what your saying.

 

[Lorne???]

It passes through the body like a trained soldier; it passes through the livet multiple times in 5 minutes.

Remember it just circulates through the body over and over

Anyway opioids aren't harmful on the liver ; my mother got hep C a long time ago, yet she has been IV'g (and sometimes IM) and her liver is so good, hep C doesn't even show up anymore because it is in remission

So don't worry about Opioids and your liver another decade you can check into it again

The important thing is to get your IV under control; what dosage do you take and do you *want* help?

Okay Luck to ya