Toxin tolerance (random bio geekery)

[cjsmith]

A while back, on a community I follow, someone asked a Princess-Bride-style question about ingesting small amounts of poison in order to develop an immunity.

Here's [LJ-CUT TEXT="the answer I would have posted if I'd had my brain handy at the time."]

Oddly, I do believe there is some merit to this idea. Not a lot, as you probably expected, but some. There are many toxins whose presence in your system is basically counteracted by your liver. Alcohol is a good example. (Granted, it's mild as toxins go.) The liver filters out alcohol, along with a variety of other substances, from your bloodstream.

A liver that is exposed to a lot of alcohol makes more filtration capability. I'm sure you've heard people mention alcohol "tolerance". The biological basis for this is that the cells in your liver will gradually build more endoplasmic reticulum (the filter). If over a span of months you stop drinking like a fish, new cells that have divided since then won't have that level of filtration capability, and your "tolerance" will decrease again.

This leaves four questions:

1) Which toxins fall into this magical category -- liver filtration power increases with exposure -- and which do not? I don't know the answer to this.

2) While you're working to get your liver to build up its filtration capability, what other damage is done to your system by ingestion of small and gradually increasing amounts of a particular toxin? For some substances, the damage will undoubtedly be far worse than it's worth to build a superliver.

3) If two toxins are in this magical category, is one just as good as the other at building tolerance (filtration capability) for both? That is, instead of eating each poison in turn, can you just drink a lot of beer? Based on my EXTREMELY rudimentary understanding of the system, my guess is you just need to drink a lot of beer. (A LOT of beer. Like, destroy-your-life levels here.)

4) What are the disadvantages of having a superliver? For example, some long-term alcoholics cannot be anesthetized for surgery. I wish I were making this up. I don't know whether local works, but sedation and general don't. Their bodies filter that stuff right out, thankyouverymuch, and they're awake when the doctor starts cutting. Most of the folk in this community are probably young and healthy, but we won't be young forever, and the horror of this is something I'm not sure I want to contemplate. This will of course also apply to many (though I don't know specifically which) medicines a person might be prescribed, making those much less effective as well. Another disadvantage is early-onset liver disease. There are likely also disadvantages I'm unaware of.[/LJ-CUT]

Any biogeeks are totally welcome to chime in here and tell me what I've left out and what I've got wrong. :-) (The general anesthesia bit above is anecdotal, but at least it's from my biology professor, who I presume has clue. Her dad went through exactly that.)

Comments

[meep.livejournal.com]

Ah, I wonder if that's why the sedation for the C-section didn't work as well as I would have liked (before Mr. D was all the way out) and I need a higher dose of novocaine.

[cjsmith.livejournal.com]

Oh yikes. O'course, some of it could simply be your own natural response, for reasons other than what your liver is up to. I apparently soak up Versed (a sedative) like nobody's business, but general anesthesia works Just Fine for me. There are sooooo many factors....

[meep.livejournal.com]

Oh yes, I felt quite a bit while they were taking me out. Thing is, if they hit you with enough stuff at the end of an operation, it pretty much wipes out the visceral memory of the pain. I remember it hurt REALLY BAD, but only in an intellectual sense. Mr. Payne, the nurse anesthetist, gave me a good dose after the boy was free and clear. Stu took two pics of me kissing the boy soon after and I was out of my gourd. That was not a pleasant sensation.

I'm not an alcoholic, but I process alcohol much faster than I did 10 years ago. I've always needed more novocaine than the dentists squirt me with initially, but it could be them being chintzy. Stu can walk around easily on high doses of morphine and/or codeine (was interesting when he had kidney stones -- the pain went away, but he had no trouble functioning, either)

[cjsmith.livejournal.com]

Mr. Payne, the nurse anesthetist

You're really not making that up? :-)

I can walk around surprisingly well on Versed. After one procedure, I was told I was the first patient ever to leave the clinic on my own two feet. I think I did a little tap dance to convince them they could skip the wheelchair. I don't know what someone's supposed to be like after the dosage I had, but the medical folks seemed surprised.

This is all fascinating stuff. I wish I had more of a clue.

[meep.livejournal.com]

Yeah, that was his name. We forebore making any jokes other than to note to him he probably got a lot of comment about his name.

For a really funny medical name, take a look at the guy who was my orthodontist (http://www.drbonebreak.com/). I babysat his twin girls, and got my parents a pricebreak on my braces.

[billeyler.livejournal.com]

I dunno. Are you trying to justify more intake of white wine in the evenings? (hic)

[cjsmith.livejournal.com]

You never know when you're going to need an immunity to iocaine powder.

[chalepa-ta-kala.livejournal.com]

Interesting! Right after I had my jaw surgery, they gave me ketorolac (Toradol, a muscle relaxant) by IV, and then oral hydrocodone (Vicodin). Nothing, and by that point I really needed enough relief so that I could sleep for a few hours. So they administered dextropropoxyphene (Darvocet) and Promethazine (Phenergan, a sedative) via IV, promising that this combo would knock me out. No such luck. The next step was morphine, and even after multiple doses through the IV, I was still awake (and in pain) hours later. Finally, after the cumulative effect of all these as well as oxycodone (Percocet) and diazepam (Valium), I was able to rest. I hope they keep this in mind for my next surgery.

[cjsmith.livejournal.com]

What an ordeal! I sure hope you can give these details to the anesthesiologist on your next go-round. A good one ought to know what to do given this data, right? ...I hope!

Vicodin doesn't seem to do squat for me either, nor does Valium, but I think that in general I react "normally" to local and general anesthetics and to sedatives. Well, okay, Versed doesn't hit me nearly as hard as they expect it to either.

I know someone for whom the local anesthetic given for LASIK does not work. It's not just faint or weak for her; it's nonexistent. What a nightmare. She says that the hardest question she has ever been asked in her life is "Do you want us to do the other eye?"

[nosrednayduj]

But what about alkies getting cirrhosis of the liver and dying of that in the end? How does "more filtration capacity" square with that?

[cjsmith.livejournal.com]

Right, early-onset liver disease. I don't know how one leads to the other, but I want to find out. :-)

[allanh.livejournal.com]

Actually, having (hopefully) just escaped it, I don't.

But please post the answer when you find out; just because I'm squeamish about it doesn't mean I'm not fascinated.

Well, my inner five-year-old is fascinated, anyway.

[recordersmith.livejournal.com]

A couple thoughts off the top of my head.

Tolerance isnt just filtration. That's one part certainly.

Several drugs are broken down by specific enzymes and therefore your tolerance for the drug will depend on whether you make the enzyme and how much. The canonic example is codeine.

Codeine doesnt do anything on its own. Your liver makes an enzyme that turns codeine into morphine, and this is what has an effect.

So, if you are one of the 6% of caucasions that do not have the gene for that enzyme, codeine will do nothing for you. Oops.

If you are one of (I dont know the percentage) who OVERexpress the enzyme, you will convert the codeine into morphine very fast--giving you a higher dose for shorter duration.

It's possible that exposure to certain toxins will create a positive feedback system where you overexpress the enzymes to degrade them. This probably depends on the specific mechanisms of the toxin.

Also, toxins that bind permanently and build up are probably not ones you want to try to build immunities to...

[plymouth.livejournal.com]

So, if you are one of the 6% of caucasions that do not have the gene for that enzyme, codeine will do nothing for you.

oooOOOooo! That explains so much!

[hnybny.livejournal.com]

Vicodin wires me like a top. If I take it after 2 PM, I won't sleep until the wee hours of the morning. I also woke up in the middle of a colonoscopy once, but that may have had more to do with my doctor being late to the OR.

[veazeyae.livejournal.com]

The ER of the liver isn't the only variable; you make 5 or 6 different ADH enzymes (ADH stands for Alcohol De-Hydrogenase). The main one converts ethanol to acetaldehyde, but together they reduce almost all alcohols to ketones and aldehydes.

Aldehydes are poisons; they contribute to liver disease, since the liver is where much of ADH is produced and used. They also circulate up to the brain, where they cause headaches, AKA hangovers.

An interesting trivia point comes from this; wines, made from yeast (and in one case, a bacteria), don't just make ethanol; wines have mostly ethanol with 2 carbons, but also 5,6,7,8... carbon alcohols that get converted to 5,6,7,8... carbon aldehydes which are more poisonous than acetaldehyde and thus cause a much worse hangover. Drinking grain alcohol or high-proof alcohol makes your head hurt much less...

[wordweaverlynn.livejournal.com]

I am fascinated! Which wine is made from bacteria? Is it the one with the "noble rot"?

[tsjafo.livejournal.com]

I've heard of instances of snake handlers or people who handle other toxic substances acquiring some immunity, snake wranglers or those who use snakes in worship come to mind. I have no proof of this, but it would be interesting if true.

[layer.livejournal.com]

the whole increasing tolerance with exposure over time is the whole premise behind allergy shots (desensitization), which apparently work for most people. of course every so often you find people who develop intolerance with increased exposure over time instead of tolerance (yes, i am one of those people), but for the most part, it should work in cases where you aren't dealing with toxins that build up in your system over time..

[moriamerri.livejournal.com]

Re: princess-bride sytle of questions: no doubt I'm gonna look silly, but I don't know what this means. Anyone care to humor me? I did google it, but I'm impatient -- I looked at some stuff about a movie "Princeess Bride" -- is that relevant? Do I need to watch the movie to understand? (If so, never mind.)

On to toxic stuff. I am NOT a bio-geek, but I do read about, talk about, and use herbs. Which can be both geeky and anti-geeky? Anyway, milk thistle is the big herb to use for liver health and for helping out those semi-functional livers. I would guess that most (maybe even all?) adults would benefit from taking some milk thistle some of the time -- cuz all of us are exposed to pretty big hits of toxic stuff -- even those of us who use only non-toxic household and bodycare products. Those on the "regular drinker" end of the spectrum of exposure could really do with lots of milk thistle for a good long time.

I once asked my accupunturist about whether she recommends it to folks who drink, just as a regular kinda thing, and she said something about that the people who really need it (at least due to heavy drinking) are probably not much interested. Still, there must be a gigantic number of social drinker who would be happy to send some nice help to their livers, I would think.

I recommend buying it in tincture form, and can babble on for really a good long while about this if anyone cares to hear more.

[tiger-spot.livejournal.com]

Yes, it's from the movie, but you don't need to see it to understand. There's a bit in there where two characters are having a confrontation over two glasses of wine, one of which is poisoned. There's some business with distractions and so forth, so it winds up that neither of them knows which is the poisoned glass. They both drink, the original poisoner falls dead -- and it is revealed that the other character poisoned both glasses and has spent the last several years building up an immunity to the poison in question.