Any info on the chemical basis for drug irritation/caustic-ness to flesh?

[cousinskeeter]

I figured this would be common info that I could google but found nothing. I also asked my very good chemist buddy who's currently overseas with a nice grant under his belt, and he couldn't give me an answer either. Keep in mind my chemistry knowledge, especially O-Chem is limited, but I can definitely understand it when explained to me.

So I am honestly curious... what is the factor(s) that contribute to certain chemicals/drugs being caustic or highly irritating to human flesh. For example literally eating away at your septum or nasal cavities.

I have been told that it doesn't have much to do with acidity or the fact that a lot of drugs come in Hcl (or similar) salt form. If that is true, then I would assume it has to do with the structure or hydrogens hanging off the molecule, and their interaction with flesh cell walls; or at least something along those lines?

Any insight into this would be lovely, I honestly did spend a lot of time looking for information on this and really found nothing besides "acidic chemicals can burn skin."

Side question: if the drug comes in HCl salt form, and it comes into contact with let's say your septum.... since your septum is moist, is there any possibility that the XXX-HCl drug dissolves and the Hydrochloric acid is now free to burn your flesh, as well as the freebase of the drug?

Thanks in advance.

 

[sekio]

local vasoconstriction & acidity combined with repeated compulsive usage without a healing period.

 

[Seppi]

pH.
Clarify: basic chemicals burn skin too.

 

[nAON]

I'm sure some of it can be mechanical irritation, ie. the size/shape of the crystals and how easily they dissolve

 

[Pomzazed]

as both above (pH in both side) and mechanical irritation (eg. oxalic acid and silica "spear" on some plants)
AND
some ligands for specific receptor too (TRPV) eg. Capsaicin

 

[Black]

Side question: if the drug comes in HCl salt form, and it comes into contact with let's say your septum.... since your septum is moist, is there any possibility that the XXX-HCl drug dissolves and the Hydrochloric acid is now free to burn your flesh, as well as the freebase of the drug?

directly, that isnt' a problem at all. you don't see a solution of NaCl irritating your mucosa because it turns to HCl and NaOH in solution. it doesn't happen. but the pH could surely be altered if for example the freebase diffuses through your membranes.

 

[cousinskeeter]

Good stuff, the answer ended up being much more simple than I expected. Occam's Razor at its best. I appreciate all the replies guys thanks a bunch!

@Black, thanks for clarifying that for me!

Only really one question I have left now: in regards to the mentioned mechanical irritation (size,shape etc of the drug), would then mechanical irritation be the main factor behind why some drugs are blatantly more irritating/burning when taken nasally? E.G. Ethylphenidate is obviously much more seriously caustic/burning/irritating etc when snorted than most others. Is the main factor behind that basically the mechanical irritation or a similar process?

Just a note, I don't ask that because I have some crazy plan to de-irritate certain drugs. I work in bioinformatics, so while my bio is solid, my chem is meh, and my computer work is obviously the strong point. My current projects are completely unrelated to drugs or pH and such I really am just extremely intrigued/curious. I was really hoping it was something cool having to do with certain structures breaking through flesh cells or perhaps a crazy binding site on the cell that sets off a reaction that phenethylamine
skeletons strongly affect. Oh well I can dream I'm still happy I got to learn some new info though!

Thanks again. (I was too embarrassed to find a colleague to ask)

 

[sekio]

directly, that isnt' a problem at all. you don't see a solution of NaCl irritating your mucosa because it turns to HCl and NaOH in solution.

NaCl is a strong base salt of a strong acid and doesn't turn to HCl/NaOH. Acid salts of amines are weak base salts of strong acids, which makes them acidic, though... and they do dissociate between acid+freebase and salt forms.

 

[Erikmen]

Interesting, I would never know this. It´s an expertise logic, explanation, so to speak..

 

[Black]

NaCl is a strong base salt of a strong acid and doesn't turn to HCl/NaOH. Acid salts of amines are weak base salts of strong acids, which makes them acidic, though... and they do dissociate between acid+freebase and salt forms.

of course. but a neutral solution of a weak base and a strong (or weak) acid stays neutral. replace the NaCl with ammonium acetate and my example still works. HCl and NaOH are just so commonly used in such a context that i couldn't resist

 

[Erikmen]

It´s just amazing how you figured this out so quickly.. I feel my lack of knowledge even though I study a bit of that when I was a freshmen in University. Should have paid more attention ..

 

[Zeds(NCO2CH2CH3)2]

Consider the pH of nasal or buccal mucosa and then look up or use a pka calculator for a given drug to determine the pka of its most ionizable group-generally amines for drugs of abuse. Consider the pka of the salt complex of the amine and understand that when you go above or below the pH of a given tissue, and you introduce something not isotonic to the tissue- secretions increase in an attempt to dilute the foreign component( osmosis concept rules).

Many times however drugs burn tissue mucosa due to binders or impurities.

One most interesting example is the burn and horrible pain introduced by the 2c-x phenylethylamines, these however most likely activate nociception via sodium channels in a different manner than typical local anesthetics like lidocaine.

It's complex but sometimes some drugs are too acidic or basic to be snorted otherwise you will be in great pain. If you've ever tried to snort something like Tianeptine (note that the carboxylic acid is first pka) then you understand how horrible acidic drugs can be on tissue mucosa..
Zedsdead

 

[Seppi]

@Zeds: -caine suffixed drugs are voltage-gated sodium channel blockers, so they don't facilitate sodium flux (i.e., activate them).
That's actually the mechanism of their analgesic properties.

 

[cousinskeeter]

Consider the pH of nasal or buccal mucosa and then look up or use a pka calculator for a given drug to determine the pka of its most ionizable group-generally amines for drugs of abuse. Consider the pka of the salt complex of the amine and understand that when you go above or below the pH of a given tissue, and you introduce something not isotonic to the tissue- secretions increase in an attempt to dilute the foreign component( osmosis concept rules).

Found a java based pka calculator app and had some fun. I must say, I now understand this aspect way better when complimented with your reply (as well as everyone elses.)

In regards to the 2c-x/xxx-caine example, that's what I was getting at. Some structures actually have their own special interaction with the cells/membrane that causes a biochemical effect separate from acids/hydrogen ions etc. I'm too lazy to loop up what I'm about to type, but I wonder if chemicals and their differences like 2c-x and xxx-caines have been studies thoroughly in regards to sodium channels etc, in hopes of developing a new beneficial drug of some sort. [Obviously of course, I mean if it would have been predictable that the 2c-x skeleton would have had this effect before they became popular]

This has been very informative. Again, appreciate the thoughtful responses. I had about 12 tabs open for period of time, just soaking in information on a lot of this stuff. I regret enjoying my required chem courses when I was taking them. It's definitely a lot more interesting and engaging than coding.

 

[Zeds(NCO2CH2CH3)2]

Yes of course cousinskeeter

And I didn't mention how they activate nociception response - they most likely do it involving similar proteins and conformational
states I should've said. If you want to get "pharmasophical"....
Trying to avoid this conversation for some reason - sodium channels are wild creatures and a solid example of how affecting conformation states of the protein can produce wildly varied response to even each as well. I'm no electrophysiologist but that is my guess, because the response from 2c-X insufflation is horrible but not as damaging as other examples of highly basic or acidic drugs..
Zedsdead

 

[cousinskeeter]

^Very intruiging. I agree probably a waste to go down that path of discussion beyond what you just said. Your last post, and all of the other responses have basically 100% answered my question as I wanted it answered. And I definitely know a little bit about how much of a bitch proteins and conformation states can be, that was similar to the study one of the potential projects I was considering getting on board with. But like I said, chem was never my strong point, so I went in the direction of statistical application to binding analysis and ancestry tracing of transcription factors. Less chem, more math, but still a nice chunk of chem to get you up to the starting line.

Thanks again though everyone! Feel free to continue discussing further even though I am satisfied.