OPANA ER insuffalation and Silicosis

[raybeez]

FWIW I asked my brother about this, he being a chemistry major and now being in medical school.

He says there would need to be a change in the chemical structure for free silica to be released, and he didn't think crushing the pill is gonna do that. He said that would be like saying sucralose causes chlorine exposure.

I have no way of knowing whether he's right, so I'm not endorsing or condoning Opana ER insufflation. But he did major in chemistry and was a tutor in the subject and is now working alongside patients in a teaching hospital.

He must have misunderstood the chemical that's in the Opana. Silicified microcrystalline cellulose is not a chemical bond between silica and cellulose. Rather, it is a mixture of free silica and microcrystalline cellulose, therefore no chemical reaction is needed to release the silica.

 

[dancingtree]

well i specifically said silicified microcrystalline cellulose. he said it was a condensed starch and found the notion that crushing the pill would release dangerous silica to be pretty laughable. not that he's right, just reporting what he said

 

[dancingtree]

Seems a bit tough to do real research on this substance, as the science sheets usually ask for a fee before you can read them. But this page says SMCC...." exhibits improved compactibility in direct compression or after wet granulation, as well as better flow" whatever that means.
http://www.highbeam.com/doc/1P3-48679714.html

This site says it's an "intimate mixture," not a blend, And that there are no covalent bonds. This would be for Prosolv, a name brand SMCC i believe
http://www.vivapur.eu/Pharma/wDeuts...prosolv_smcc_description.shtml.1264685844.wfb

sounds like we're somewhere between a chemical bond in the strictest sense and a casual blend of silicon dioxide with the cellulose.

 

[dancingtree]

What is meant by "free silica"? I would think silica of any form going into your lungs is bad.

I believe the difference is that free silica particles can enter the lungs and not be ejected by the lungs themselves, but if the silica is stuck to something else it won't behave the same way and the lungs can expel it. I don't really know though.

******
Ok I just went back to scholarly brother and said that there is no covalent bond and instead it's an "intimate mixture," between the silicone dioxide and the cellulose. He told me that even if the silicone dioxide was free, it's not "free silica," but instead is a very inert compound. <----EDIT-incorrect info. silicone dioxide is in fact "silica."

 

[arthunter888]

^^ Can you have your brother look at the exact ingredients of Opana ER (should be at the opana website)? This needs to be straightened out it seems, can anyone shed some light on this debate?

 

[raybeez]

I believe the difference is that free silica particles can enter the lungs and not be ejected by the lungs themselves, but if the silica is stuck to something else it won't behave the same way and the lungs can expel it. I don't really know though.

******
Ok I just went back to scholarly brother and said that there is no covalent bond and instead it's an "intimate mixture," between the silicone dioxide and the cellulose. He told me that even if the silicone dioxide was free, it's not "free silica," but instead is a very inert compound.

Look, regardless of whether or not the mixture is "intimate", when you snort fine powders those powders make their way into your lungs. Please read through this thread again as all of this is explained.

Furthermore, your brother clearly lacks a solid understanding of the pathophysiologyy of silicosis. When silica particles are inhaled, they are ingested by alveolar macrophage. Macrophage have lysosomes which would disperse any mixture, regardless of whether or not it's "intimate". Lysosomes even break chemical bonds as their highly acidic and oxidative environments, so they'd have no trouble busting up a mixture.

Silicosis occurs because of abnormal macrophage behaviour after they've ingested silica. They produce fibroblast growth factors which cause the tissue remodeling of the lung architecture that underlies the development of the disease.

I learned all this in first year medical school. Did your brother just start last month or something?

 

[Sturnam]

Well, the chance that it even gets into your lungs in based on particle size, among other things. The larger the particle is, the greater chance it has to be expelled from your lungs.

http://cat.inist.fr/?aModele=afficheN&cpsidt=20010467

P.S. I think the dangers being hyped are vastly overstated. Unless you're snorting multiple tables a day, for a few years, i highly doubt any harm will come from the silica.

 

[dancingtree]

Look, regardless of whether or not the mixture is "intimate", when you snort fine powders those powders make their way into your lungs. Please read through this thread again as all of this is explained.

I learned all this in first year medical school. Did your brother just start last month or something?

yes he did start last month lol.

I'm not struggling to understand that powders make their way into the lungs, it's what happens after they enter the lungs, which you addressed. If the lungs are capable of breaking chemical bonds that would indeed change the scenario.
*****

Do we know whether the lysosomes in the lungs are able to do their job and release dangerous silica particles quicker than it would take the lungs to expel the mixture of substances via mucous?

*********

This isn't much, but a fact I picked up about SMCC:

http://www.polimery.am.wroc.pl/2007/202a.pdf
Silicified microcrystalline cellulose (Prosolv) has in its composition 98% of
microcrystalline cellulose and 2% of colloidal silicon dioxide (SiO2)

I don't remember if it was this thread or a different one but someone was saying that the Opana ER pill itself contains 2% of the silicone part. But according to this, the 2% figure is the amount of colloidal silicon dioxide within the SMCC. I don't know what percentage of the ER pill is SMCC, but silicone dioxide is 2% of the SMCC presence, not 2% of the Opana ER pill. FWIW

 

[raybeez]

Well, the chance that it even gets into your lungs in based on particle size, among other things. The larger the particle is, the greater chance it has to be expelled from your lungs.

http://cat.inist.fr/?aModele=afficheN&cpsidt=20010467

P.S. I think the dangers being hyped are vastly overstated. Unless you're snorting multiple tables a day, for a few years, i highly doubt any harm will come from the silica.

If you re-read the first page in this thread you'll see that particle size has already been taken into consideration. No one is saying one pill now and then will give you silicosis.

don't remember if it was this thread or a different one but someone was saying that the Opana ER pill itself contains 2% of the silicone part. But according to this, the 2% figure is the amount of colloidal silicon dioxide within the SMCC. I don't know what percentage of the ER pill is SMCC, but silicone dioxide is 2% of the SMCC presence, not 2% of the Opana ER pill. FWIW

Re-read the first few posts in this thread! You're not contributing anything here now. All of this information has been taken into consideration in coming up with safe exposure guidelines.

-----

You guys are KILLING me over here. Particle size, maximum and minimal theoretical silica exposure levels, and a corresponding safe range of opana exposure has all been hashed out already in this thread.

Instead of posting random skepticism or quoting some kid with 30 days of med school under his belt, why not actually take the time to read 2 pages of posts and see the thought and research a number of people have put into this topic?

All you're doing is adding a bunch of garbage noise to a really important harm reduction signal.

 

[Sturnam]

If you re-read the first page in this thread you'll see that particle size has already been taken into consideration. No one is saying one pill now and then will give you silicosis.



Re-read the first few posts in this thread! You're not contributing anything here now. All of this information has been taken into consideration in coming up with safe exposure guidelines.

Thank you for that. Now go back and ACTUALLY read what I posted. And that includes a link to a scientific journal. That has relevance to this thread.

As in, most users will continue to crush and snort the pills, either due to ignorance or they don't care. I'm saying that silicosis might not even be a risk because users don't crush their pills fine enough.

Look, here is what I'm talking about.
http://www.engineeringtoolbox.com/particle-sizes-d_934.html

Scroll down to Hazardous dust particles. As you can see, different sized particles can reach different parts of the airways. If the particle is too big, it doesn't reach the airway. If it doesn't reach the airway, no disease.

And here's another example stating the same thing:
http://www.atsdr.cdc.gov/asbestos/asbestos/types_of_exposure/executive_summary.html
Under the Section "Air Samples"

Again, particle too big, doesn't get the alveolar sacs, doesn't cause silicosis.

The only question, which is probably unanswerable, is what size particles users usually snort.

Any guesses?

 

[dread]

Hm. I wonder if it would be feasible to crush the pills, then spray them slightly with water to make the powder clump together slightly, so there would be no small particles... and it would be heavier due to the moisture.

 

[Sturnam]

Well it sounds like they're particularly hard to crush in the first place (no personal experience). So I'm guessing that the particles will be bigger in general.

Plus, they might start to gel with the water.

 

[skoat]

They gel like a motherfucker if you add water to crushed powder. It becomes unusable. The ER's anyway.

 

[raybeez]

Thank you for that. Now go back and ACTUALLY read what I posted. And that includes a link to a scientific journal. That has relevance to this thread.

As in, most users will continue to crush and snort the pills, either due to ignorance or they don't care. I'm saying that silicosis might not even be a risk because users don't crush their pills fine enough.

Look, here is what I'm talking about.
http://www.engineeringtoolbox.com/particle-sizes-d_934.html

Scroll down to Hazardous dust particles. As you can see, different sized particles can reach different parts of the airways. If the particle is too big, it doesn't reach the airway. If it doesn't reach the airway, no disease.

And here's another example stating the same thing:
http://www.atsdr.cdc.gov/asbestos/asbestos/types_of_exposure/executive_summary.html
Under the Section "Air Samples"

Again, particle too big, doesn't get the alveolar sacs, doesn't cause silicosis.

The only question, which is probably unanswerable, is what size particles users usually snort.

Any guesses?

Hi Sturnam,

Sorry for coming down harsh on you. You did take the time to look through the literature and add something worth thinking about to this thread.

One of my previous posts did contain information that answers this question but when I went back to re-read it, the info isn't that obvious.

You are correct that the quantity of silica that migrates to the alveoli is related to particle size, and the question of what particle size the silica is in Opana ER is relevant to this discussion.

When I was working out what the max safe exposure limit to intranasal Opana is, I looked up the guidelines from OSHA. OSHA classifies silica particles into 3 types, amorphous, crystalline, and microcrystalline, each which comprises a range of particle sizes. For each form, OSHA has a different maximum safe exposure threshold.

When I looked up the particle size of microcrystalline cellulose, it fell within the range of microcrystalline silica. I made the assumption that "silicated microcrystalline cellulose" contains a mixture of silica and cellulose with similar particle sizes -- if it didn't, these two compounds wouldn't properly form an "intimate" mixture.

Based on this assumption, I calculated the safe exposure for Opana ER as if it contained microcrystalline silica. This translates to one Opana containing 1x to 4x the maximum safe threshold for silica exposure for a 24-hr period. The 1x to 4x covers the range of min and max theoretical silica content in an Opana.

 

[dancingtree]

raybeez:
please chill. you're not contributing anything either by showing your frustration. I brought attention to the 2% figure because at least two posters in the first page did not get what you were saying about 2% being part of the SMCC, not the total weight of the pill. Your fact was buried in many paragraphs of conjecture with 2% of the pill being SiO2.

And my question about the mixture possibly being expelled by the lungs before the lungs have a chance to break the SiO2 bond was never addressed. If that's a stupid question, it's a stupid question. But it hasn't been covered.

I'm not playing snorting opana apologist. There's plenty of info here to dissuade any thinking person from it, or at least think twice about it. You've unquestionably provided the most valuable information. You've given your conclusions, which are good conclusions. But that doesn't mean there's not more to investigate on the matter, if only for the sake of inquiry.

 

[MobiusDick]

An Understanding of the Etiology of Silicosis

I am not a pathologist, but I try to think like one when I analyze the etiology and pathophysiology of disease states; and to me, silicosis shares some of the properties of asbestosis without the mutagenicity/carcinogenicity.

Now it is essential to note that all types of asbestos are putatively not associated with asbestosis or mesothelioma. Only one very specific type of the many types of asbestos, the amphibole fibrous type of asbestos (long, straight and thin, needle-like fibers; as opposed to serpentine fibrous: curved and snakelike fibers; or non-fibrous) is the only type which seems to get stuck deep in the lungs, and causes chronic inflammation, sclerosis and scarring; and very often mesothelioma (without getting into too much theoretical oncology, many oncologists refer to malignant mesothelioma as a sentinel type of cancer, meaning it may be the original source for many of the common cancers you see today such as colorectal carcinoma or breast cancer.)

As the amphibole type of asbestos works its way through the parietal epithelium and then the visceral epithelium, and goes deeper into the lungs into the pleural mesothelium (tumors that arise from cells which originate from the pleural mesoderm are called mesothelioma), the mutagenic/carcinogenic effects of the asbestos, damage the DNA, and cellular repair enzymes cannot keep up, This causes a malignant cell and while most of the time, the immune system kills the cell, if there are too many, or the immune system is not working properly, the mutant cell may proliferate, and if the mutation is in one of the oncogenes (e.g., one of the genes associated with contact inhibition), the mutation is malignant and starts a monoclonal malignant tumor, which can metastasize by breaking off and traveling through the blood stream.

Now other types of asbestos (serpentine and crystalline), putatively, are not associated with mesothelioma, but can be associated with asbestosis (chronic inflammation, dyspnea, pyric discharge.) Also, it is worth noting that asbestosis specifically refers to interstitial (parenchymal) fibrosis from asbestos, and not pleural fibrosis or plaquing.

Now let’s compare silicone, silicates and silicosis. I am pretty sure that eronite, a natural silicate, is also associated with increased risk of mesothelioma (which is likely due to a peculiarity of its structure, and/or its interaction with DNA or replication associated molecules.) Since this is the only silicate I am aware of that has this property, it is highly unlikely that it is something to do with the silicone molecule itself, but to a property of the compound itself: [(Na2,K2,Ca)2Al4Si14O36•15H2O)].

Silicosis was originally known as Potter's Lung because the inhalation of the vast amounts of silicates associated with the manufacture of pottery was seen in Potters or assistants who worked with the kiln. (A silicate is a silicone bearing anion and hence, negatively charged, meaning the silicone molecule, at least in part, is partially oxidized.) The amount of dust inhaled daily by these people was very large, but beyond the capacity of the lung to repair itself or the damage. The lung is a resilient organ with a large amount of associated reserve capacity when you are referring to basal levels required to sustain normal life, as opposed to marathon running or sprinting. Most potters or kiln users did not get silicosis, so we can safely assume that for those that did, either the amount of inhaled material was large and/or that the inflammatory response to the silicone was abnormal. Based on the analysis of the pyric discharge, the former is certainly somehow involved as the silicone amount in the sputum was always large (I do not remember TD50 offhand.)

Now it also worth noting that Silicone [28Si14]is under Carbon [12C8} on the periodic table, and is able to form four tetrahedral bonds like carbon (and more when taking into account electrons in the d shell hence, polymeric chains like carbon, are not only theoretically possible, but have been produced (unlike in the next element in the same column of the periodic table, Germanium [72Ge32], which theoretically can form long chains, but in practice forms oxides [GeO2] to readily to polymerize without the addition of organometallic components.) So the possibility of amphibole structures is not only possible, but has been accomplished, and these do not appear to be mutagenic/carcinogenic but do appear to be more likely to cause silicosis at lower TD50 than most silicates. (and no I do not have the reference memorized, so search for it if you need it)

I am very confident that the amount and type of silicone/silicate particles in the Opana© pill is small and, if snorted, the hygroscopic properties of the binding agents make these particles get caught up in the waxy mucous discharge which these pills cause, and particularly after showering, are expelled completely when blowing your nose (or almost completely at first, but within a few days all of it clears IMHO).


If you perform my crisping technique on Opana© pills, this caking and expansion of the waxy parts still happens, but not to the same extent. You still discharge the spent material from your nose, but absorption seems quicker and sputum seems to be of a lesser volume. Most of the snorted (probably as much as 80 % from my estimates,) “uncrisped” Opana© is not absorbed parenterally from (after adsorbing to) the interstitial mucosa of the lungs and is swallowed due to increased mucous production and post-nasal buildup, which eventually works its way to the glottal area of the throat hence, most of the oxymorphone is absorbed, enterally, from the gut, where it passes through the liver and gets capped and inactivated at the 3’ end by UDP with glucuronic acid during first-pass metabolism. It is here that the oxymorphone loses at least 80-85% of its potency.

But the good news is that for anyone with even rudimentary knowledge of laboratory technique, the 40 mg tablets, when done in batches of 10, yield about 75% theoretical yield (300 mgs of the 400 mgs theoretical) by simple acid/base manipulation with polar/non-polar extraction. You can get much closer to the theoretical yield if you want to take the time, but for 10-20 minutes of quick work, 75% is not bad. The rest can be saved, combined and extracted with a more involved procedure later on.

I am not sure why the “crisping” of these pills allows for better parenteral absorption through the interstitial mucosa, but it does. It may not be not as simple as with most pills where the waxy substance congeals out of the polar material (water) during solvolysis, heating and cooling. These pills are more sensitive than most to “over-crisping” and “crisping” itself will not degrade the matrix of the pill enough to allow for injection (this is the only pill I have ever found where my crisping procedure did not degrade the matrix enough for injection.) And since I have not worked with any Opana© lately (as I have not been trying to get high all the time after curing my own depression), I never did find a simple way for the average junky to shoot an Opana© pill. Has anyone else figured a way?

MobiusDick

 

[raybeez]

And my question about the mixture possibly being expelled by the lungs before the lungs have a chance to break the SiO2 bond was never addressed. If that's a stupid question, it's a stupid question. But it hasn't been covered.

I talk about it in this post. Just to clarify, the cilia in the nasopharynx that I'm talking about extend into the upper airways. Mucus sits on top of ciliated cells, particulates get stuck in the mucus, and it is the movement of cilia that expel particles from the lung (sweeps them up, out of the lung, and into the throat where they can be swallowed). Sort of looks like a conveyor belt.

The OSHA guidelines for safe threshold of silica exposure take into account the normal biological mechanisms for clearing particulates from the lung, so basically it's factored in to my calculations earlier in the thread.

The best thing someone could do to preserve cilia function and make sure the lung's ability to clear silica is operating at 100% is to not smoke cigarettes.

 

[raybeez]

I am not a pathologist, but I try to think like one when I analyze the etiology and pathophysiology of disease states; and to me, silicosis shares some of the properties of asbestosis without the mutagenicity/carcinogenicity.

Hi MobiusDick, thanks for your post, there are a couple of really interesting points that you raise.

Now other types of asbestos (serpentine and crystalline), putatively, are not associated with mesothelioma, but can be associated with asbestosis (chronic inflammation, dyspnea, pyric discharge.) Also, it is worth noting that asbestosis specifically refers to interstitial (parenchymal) fibrosis from asbestos, and not pleural fibrosis or plaquing.

I hadn't really thought about mesothelioma coming into play here. Besides eronite, do you know if there is literature supporting a link between silica and mesothelioma (or other pulmonary malignancies?)

The lung is a resilient organ with a large amount of associated reserve capacity when you are referring to basal levels required to sustain normal life, as opposed to marathon running or sprinting. Most potters or kiln users did not get silicosis, so we can safely assume that for those that did, either the amount of inhaled material was large and/or that the inflammatory response to the silicone was abnormal. Based on the analysis of the pyric discharge, the former is certainly somehow involved as the silicone amount in the sputum was always large (I do not remember TD50 offhand.)

This is why I keep referring back to government established thresholds for daily silica exposure limits. These limits have been determined using retrospective empirical data from silica miners, looking at causal correlations between silica ppm in the air and the development of radiological signs of the disease (resembles nodular pulmonary fibrosis). The utility of these numbers is that they have been established from a large population cohorts, so they take into account the ranges of normal human biology and physiology.

I am very confident that the amount and type of silicone/silicate particles in the Opana© pill is small and, if snorted, the hygroscopic properties of the binding agents make these particles get caught up in the waxy mucous discharge which these pills cause, and particularly after showering, are expelled completely when blowing your nose (or almost completely at first, but within a few days all of it clears IMHO).

I disagree with you that the silica content is of these pills is small, and by small I mean insufficient to cause disease with frequent and long term exposure.

One really interesting point that you do raise is the gelling properties of these pills. You are 100% correct in that the waxy matrix that gels up when wet would probably serve to trap a lot of the silica particulates.

I wonder if there is some type of analytical/quantative assay that can be done to measure silica. I'd like to see 1) how much silica is actually in these pills, and 2) if you crush and snort one, then blow your nose 5 min later, how much silica is in your kleenixsnot (and how much is not)

If you perform my crisping technique on Opana© pills, this caking and expansion of the waxy parts still happens, but not to the same extent. You still discharge the spent material from your nose, but absorption seems quicker and sputum seems to be of a lesser volume. Most of the snorted (probably as much as 80 % from my estimates,) “uncrisped” Opana© is not absorbed parenterally from (after adsorbing to) the interstitial mucosa of the lungs and is swallowed due to increased mucous production and post-nasal buildup, which eventually works its way to the glottal area of the throat hence, most of the oxymorphone is absorbed, enterally, from the gut, where it passes through the liver and gets capped and inactivated at the 3’ end by UDP with glucuronic acid during first-pass metabolism. It is here that the oxymorphone loses at least 80-85% of its potency.

Well I've never done Opana so have no first hand knowledge to contribute.

But do you really think 80% gets swallowed? If so, wouldn't snorting Opana not be much better than eating it? There has to be a good chunk adsorbed through the nasal/respiratory mucosa, or people wouldn't bother using this as a route of administration...

 

[dancingtree]

I talk about it in this post. Just to clarify, the cilia in the nasopharynx that I'm talking about extend into the upper airways. Mucus sits on top of ciliated cells, particulates get stuck in the mucus, and it is the movement of cilia that expel particles from the lung (sweeps them up, out of the lung, and into the throat where they can be swallowed). Sort of looks like a conveyor belt.

The OSHA guidelines for safe threshold of silica exposure take into account the normal biological mechanisms for clearing particulates from the lung, so basically it's factored in to my calculations earlier in the thread.

The best thing someone could do to preserve cilia function and make sure the lung's ability to clear silica is operating at 100% is to not smoke cigarettes.

OK, thanks for that clarification. But does the particular ER "mixture" make some difference since it's not pure silica entering the lungs? I know you said the lysosomes can extract it, but are they able to do it before the mixture is expelled?.. the "colloidal" silicone dioxide which according to the manufacturer is not water soluble?

Thanks for your patience and for understanding that harm reduction is less effective if it can't pass through the scientific language barrier. Otherwise to most users it's just more "drugs r bad mkay," rhetoric.
**********

So if I'm understanding Mobius' post right, the shape of asbestos fibers matters when it comes to forming diseases, but in the case of silicates the shape is irrelevant and what matters is the size of the particulates and the amount of them?
**********

to set the record straight, my medical neophyte brother admitted knowing nothing about silicosis, and whether I or he represented his chemical knowledge as sufficient to contribute, I can't say. He also didn't realize that SiO2 was referred to as silica.

But his conclusions after supplied with the corrections are the same as raybeez's, that is to say that we need to know how much Si02 is in the pillz.

 

[raybeez]

OK, thanks for that clarification. But does the particular ER "mixture" make some difference since it's not pure silica entering the lungs? I know you said the lysosomes can extract it, but are they able to do it before the mixture is expelled?.. the "colloidal" silicone dioxide which according to the manufacturer is not water soluble?

I don't think the particular mixture would make a difference. Just to elaborate a bit more on the lysosome aspect:

The lung is made up of a series of branching airways that begin as quite large (primary bronchi, labelled as #29 on this image) but become smaller and smaller until they terminate into sac like structures called alveioli (see insert in top right corner, #35).

The alveoli are the only place in the lungs where exchange of O2/CO2 occurs with red blood cells, and is where the majority of alveolar macrophage live (see below for why these are important).

The cells which can expel particulate matter (ciliated respiratory epithelium) are only located in the bronchi, specifically the regions in that image that are alternating white and blue stripes. This is the main way that the upper respiratory track clears unwanted things from the lungs.

In the lower respiratory track, the lungs utilize a different strategy: alveolar macrophage. Macrophage indiscriminately phagocytose (ingest) particulates. Whatever they see, they eat. Once eaten, the macrophage send the particulate matter to an organelle called a lysosome, where it is bombarded with acid, free radicals, and enzymes capable of shredding most organic material.

The lysosomes have no problem seperating cellulose from silica (they'd digest the cellulose), but they fail to digest metals and minerals like silica. The macrophage keep eating silica but can't get rid of it, so it starts to build up. As a result, this causes them to go hayware, causing inflammation, fibrosis, and silicosis of the lung tissue.

----

A random tidbit of information - this is exactly how cholesterol causes heart disease. Macrophage in the blood eat cholesterol, can't get rid of it, become fat and heavy "foam cells", crash into the sides of arteries, and go hayware, causing fibrosis and thickening of the arteries (clogging them) .