Wikipedia:Reference desk/Archives/Science/2019 March 3

= March 3 =

Has fentanyl toxicity been attributed to poor mixing?
Now I'll admit, I've never spiked a wholesale dose of heroin with fentanyl. But it seems "obvious" to me that the source of all the overdoses we hear about is that people underestimate the difficulty of mixing things. I bet the dope dealers shake it up half a dozen times and think it's all mixed, they try a dose off the top of the package and get high the way they expect, and they never dream there's a little lump in there the size of the text on a penny (per our article: 2 mg) that will kill somebody. For all I know there could be freaky things going on with grain size or static electricity that would kill the customers even if they stirred the pot all day long. But ... how do I find a source that says what I want to say? If I could, I surely would, stand on the rock where Moses done stood... but we do have an article, if only... Wnt (talk) 01:38, 3 March 2019 (UTC)


 * The technical (and legal) term for this kind of incorrect dose is "adulteration," as defined in Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. §351(b)). A drug is "adulterated" if it's in the official catalog of regulated drugs, and its strength, purity, or quality, differs from its standard.  Here's a good place to start reading: Regulatory Information for pharmacological compounding, from the FDA.  Any entity who markets or sells drugs in the United States has to comply with rules about their process: how they manufacture (including mixing and packaging) and what ingredients they use.
 * Here are a small sample of some of the rules: Industry Guidance for documenting the manufacturing process and data standards for measuring, testing, and reporting drug potency. Reputable pharmaceuticals are made by people who follow these kinds of very specific rules: there's a procedure to make sure the drug is mixed correctly, and it's documented and enforced.
 * Anybody who deviates from those rules is probably committing a "drug crime," whether or not that person meets any particular Hollywood stereotype about drug-dealing. Especially when we're talking about fentanyl, a lot of the drug crime takes place among medical and pharmacy professionals - not necessarily in dark urban alleyways.
 * So, whether the drug has unknown dosage because it is poorly mixed by an illicit street dealer, or by a scuzzy corporation trying to save costs and offshore its manufacturing, or simply because of an honest mistake in the very complicated global supply chain of pharmaceuticals and precursor chemicals, it doesn't matter: the dose must be carefully controlled and the manufacturing process must be correctly implemented. The legal and safety rules say that doses must be carefully controlled subject to "current good manufacturing practice requirements" that are very clearly defined, and subject to regulatory oversight.
 * If you search the website of the FDA, you'll find a lot of information on drug manufacture in general; and on fentanyl in specific. In the case of fentanyl, most of the high-profile cases of adulteration come from criminal mishandling at the tail-end of the supply chain: for example, this November 2018 case involved saline bags that were labeled "fentanyl"; the dose was zero, and the real drug was being diverted by a licensed medical professional (allegedly, the real drug was diverted for illicit use elsewhere).  This is hardly the first such incident.  On the other hand, here's a 2017 indictment for a pharmaceutical outsourcing company that sold overpotent fentanyl.  The indictment alleges that a medical professional was accidentally providing almost three times too much drug to legitimate medical users; though it alleges fraud, it doesn't specifically allege a motive - but we can probably surmise "incompetence" or "negligence."  (...And if you think the fentanyl was bad, it just gets worse; in one instance, they were also selling morphine at 2400% overpotency).
 * According to DEA's May 2018 fentanyl intelligence brief, many illicit drug dealers - in other words, members of the category of stereotypical "dark alleyway" dealers - do not know the difference between fentanyl and heroin, and in several cases, have sold either drug interchangeably - in unknown quantities and dosages - to the end customer (pg. 10, "Dealers’ Lack of Knowledge...").  This is potentially more problematic than a simple incorrect dose: in some cases, the drug sellers and customers don't even know what chemical they're working with.
 * Nimur (talk) 08:30, 3 March 2019 (UTC)
 * Ah, the legal route. Didn't think of that!  The second link is interesting - the pharmacy somehow managed to compound "2,460% potent morphine sulfate" (that's American usage, 2460%).  I don't see any obvious explanation for that one.  You make a decent case for just plain stupidness as the cause. Wnt (talk) 11:43, 3 March 2019 (UTC)
 * Yet another case, featured on FDA's website, describes serious dosing errors. "The patient was inadvertently administered 2,500 mcg of fentanyl (equivalent to 50 times their prescribed dose). The report noted that the cause of the error was attributed to the prominently stated 50 mcg/mL strength, which was misunderstood as the total amount of fentanyl in the bag."
 * This mathematical mix-up between quantity and concentration might have occurred because of fatigue, insufficient training, negligence, or malice. Safety-conscious regulators have recommended clear and consistent labels to help reduce this type of accidental error.
 * When the drug is being distributed illicitly, it's nigh impossible to provide regulatory oversight for basic safety.
 * Nimur (talk) 16:05, 3 March 2019 (UTC)
 * US timeline. Drugs involved in overdose deaths.jpg In illicit use, another big factor in overdoses is that the user, and often the final seller as well, doesn't know the exact potency or makeup of what they're using. If someone thinks they're using heroin, but it's actually heroin cut with fentanyl, which is much more potent, they can easily overdose even when they are good at judging their tolerance. Since fentanyl is much more potent, it delivers more of an effect with a much smaller dose, which increases profit for dealers and suppliers. See the graph, which shows the skyrocketing incidence of overdoses involving synthetic opioids (which includes fentanyl) in the U.S.
 * Of course, addiction often leads people to do unwise things, so you also have people explicitly seeking out drug "batches" tied to overdoses because of the potency. And, as the article states, sometimes illicit non-opioid drugs are contaminated with fentanyl or other opioids as well. --47.146.63.87 (talk) 00:09, 5 March 2019 (UTC)
 * Well that is a surprising and enlightening graph that I never even thought to look at. If the overdoses from methamphetamine and cocaine have increased comparably, either these are being cut with fentanyl or else the problem has nothing to do with fentanyl at all!  How many of these overdose deaths are really just suicides? Wnt (talk) 01:23, 5 March 2019 (UTC)
 * I'm sure they are sometimes [//www.washingtonpost.com/nation/2018/12/12/cocaine-deaths-increase-amid-ongoing-national-opioid-crisis/] [//www.ohio.edu/chsp/news/meth-and-other-psychostimulant-related-overdose-deaths-grow-over-5000-percent-ohio] [//www.ajmc.com/focus-of-the-week/fentanyl-driving-overdose-deaths-in-the-us-cdc-says]. This sort of research is going to be difficult even without the various political issues involved. Nil Einne (talk) 09:18, 7 March 2019 (UTC)

On average, how far underground could a meter-wide unreinforced vertical cylindrical hole go without the rock at the bottom visibly cracking or deforming under pressure?
(non-seismically active places) Hole is empty except for air, with water pumps if needed. Above bedrock can be a pipe of artifical material for structural integrity. Sagittarian Milky Way (talk) 21:00, 3 March 2019 (UTC)
 * The thickness of the Earth's rocky crust is 30 km (20 mi) to 50 km (30 mi) on continents or 5 km (3 mi) to 10 km (6 mi) under oceans. The limiting depth of the hole surely won't extend below the loosely defined LAB (Lithosphere–asthenosphere boundary) which seismologists observe as the Gutenberg Discontinuity where shear-wave velocity decreases 90-110 km below continental crust. Please do not leave the hole unattended without a child-proof safety cover. DroneB (talk) 09:07, 4 March 2019 (UTC)


 * Rock mass rating has a graph with rock strength. 200 MPa looks to be an example value for quite a strong rock. That is about 2000 atmospheres pressure. This might be reached at about 6km deep. Some rocks are much weaker - eg coal or shale, and would deform at much more shallow depths. Graeme Bartlett (talk) 13:45, 4 March 2019 (UTC)
 * A recent practical challenge of this kind was a rescue of miners trapped 700 meters (2,300 ft) underground. The actual hole drilled was 71 cm (28 in) diameter, at 82°angle. The first 56 meters (184 ft) were cased in steel tube and 33 miners were extracted individually in a capsule 54 centimeters (21 in) in diameter. DroneB (talk) 11:13, 5 March 2019 (UTC)


 * Boreholes are drilled for kilometres into the earth's crust routinely, although obviously they are somewhat smaller. One of the issues with drilling is borehole stability as that needs to be carefully designed for - you don't just drill down leaving an open wellbore and hope for the best. A section of the borehole is drilled and then cased off to prevent collapse of the wellbore. This means that the borehole gets progressively narrower with depth. In stronger rock, you can drill uncased to some extent but you may still get break-out of the borehole wall. The deepest open cavity in the world is the Mponeng Gold Mine at 4 km below the surface but the tunnels have to be reinforced by shotcrete. In such deep mines rock bursts are a constant hazard. Mikenorton (talk) 13:45, 5 March 2019 (UTC)

milky electrons
I dimly remember reading an article page, or maybe a post on the refdesks, I think the topic was roughly terahertz technology and it was about some effect or some metamaterial. It said something like, to the electrons, you see, metal and semiconductors look milky (by analogy with optics, apparently), but there's a way to make it such that the bulk of material in which they travel will look clear (I don't remember how or to what end.) I'm sure I'm not hallucinating this. Does someone by chance know what I'm talking about or knows the area of physics or technology in which this analogy is commonly employed and makes physical sense? Aecho6Ee (talk) 23:31, 3 March 2019 (UTC)


 * false alarm, found it: Ballistic_conduction. Thanks everyone Aecho6Ee (talk) 00:15, 4 March 2019 (UTC)