@Smokin Joe@Cyber LibertyNever argue with a man carrying a calculator....
Oh, I had my calculator going too. (LOL)
I had already used my calculator to figure out that the reporter in TomSea's posted article had assumed the figure of 2.1 mg as the lethal dose. But I did not have the
Human LD50 data that Joe found. I wonder how they got the data, BTW. They certainly did not get it from testing regular scientific volunteers. This is why good human LD50 data is usually pretty hard to get. (Maybe they got it from autopsies and other reports from centering on other kinds of "volunteers." I'll have to check out the citations that Joe's Wikipedia article has.)
Let me 'splain why the data still bother me:
1) Based on a human LD50 of 0.03 mcg/kg, the standard 70-kg guy would, indeed, have a
50-percent chance of dying from a transdermal (patch) or sublingual (lozenge) of 2.1 mg. As Joe's post ultimately reveals, the LD50 figure presented by Wikipedia is obviously the one the reporter used to come up with the figure of
26 million
deaths. (Even reporters and police officers have calculators, of course; some can even convert mass units as well as Joe and I can.) However, if the LD50 figure is correct at 0.03 mcg/kg, the number of deaths from 118 pounds of contraband fentanyl would be at most 50 percent of 26 million, i.e., would be
less than
13 million. The reporter overlooked this--which means the reporter is wrong if the Wikipedia figure Joe found is the correct human LD50.
2) I furthermore submit that contraband fentanyl would be used only by narcotics addicts--probably rather hard-core narcotics addicts for the most part, in fact. As it turns out, these drug addicts are actually pretty hard to kill with narcotics, even accidentally. This makes a huge difference in lethality.
To illustrate the weird phenomenon of opioid tolerance: the normal human body's physiological demand for complete pain relief (say, relief of pain from failed back surgery) is 100 "morphine equivalents" per day. However, some years ago, I inherited a bunch of chronic pain patients, handed off to me from a group of retired docs who had started their chronic pain patients on narcotics at (or more likely well below) 100 morphine equivalents per day but had wound up having to ramp up their doses over several years due to the insidious problem of opioid tolerance. Many of these patients were needing way more than 100 morphine equivalents per day. A few of these patients were needing 20 TIMES the normal physiological demand for narcotic pain management by the time they came to me. These doses would be
immediately lethal several times over for an opioid-naive patient. One fellow was
taking--not diverting to the black market!--
over 2800 morphine-equivalent milligrams of narcotics per day. When I forced these opioid-habituated guys into weaning programs, it was pretty rough for them. Their pain would come back with a fury even with modest weaning. The weaning would also trigger horrible withdrawal symptoms, mainly in the GI tract.
One of the reasons why I am presenting all of this is to point out that narcotics, although wonderfully important in many medical/surgical situations, are insidiously dangerous, often life-ruining things. However, the main reason why I am laying this out on this particular thread is to remind TBR members and lurkers that the reporter is way off in his sensationalistic estimate. Not only is that reporter off by a factor of two, but he is more likely off by a factor of four or five. (Again, it's because the targeted users of contraband fentanyl are not the "Standard 70-kg Adult." It's not that the 70-kg weight standard is an invalid assumption, but the fact that the target population is not our society's standard, "clean and sober" medical patient--not even close. The overall social problem is so bad that we can't even make very useful guesses--unless our guesses are "useful" for selling exciting newspapers.)
3) Next, let me point out an unrelated reason why I frankly worry about the LD50 being cited by Wikipedia as low as 0.03 mcg/kg, i.e., as low as 2.1 mg per standard subject. When I looked up fentanyl in my most recent prescribing reference, I discovered that it is approved for chronic pain cases at 2.4 mg transdermally per day. This transdermal strategy bypasses the liver's "first-pass effect," and it also flattens out the blood concentrations of the drug (dosing it slowly at 0.1 mg/hr), but a subject's liver function (necessary for processing and excretion of the drug) would still appear to be a safety concern for the scenario of repetitive or continuous administration of the drug. Given the fact of such metabolic unknowns, it would appear that the approved slow-dosing approach might become uncomfortably close to the official LD50 (especially if the approved adult patient is well under 70 kg!). So, has the LD50 been reliably, precisely measured? Or has it been merely
inferred from a complicated mess of death data? (I realize that the guidelines for fentanyl dosing are designed to take pharmacokinetics into account--and I would be inclined to trust the guidelines more than I would trust the "measured" (?) LD50--but I am mainly saying that don't like the fact that the reported LD50 number is so low.)
What is even more worrisome (irksome) in my opinion, if the cited LD50 is correct, is the fact that sublingual administration of fentanyl for bad cancer pain is approved for the standard adult patient at 1.6 mg over only fifteen minutes--i.e., practically instantaneous dosing at a
putatively near-lethal dose. This dosing strategy is approved up to four times per day to be administered
only in conjunction with another longer-acting narcotic. (Oooops.) Again, is the LD50 for fentanyl really as low as 2.1 mg for the standard adult population? If it is, how can the medically approved dosing be safe enough to be approved? (Pain is bad stuff. Cancer is a bad disease. But shouldn't physicians be clearly telling their pain-wracked patients that the approved analgesia could very well [perhaps very easily] kill them?)
4) Finally, let me point out something else that is curious about the human LD50 cited as 0.03 mcg/kg (the number that forms the whole basis for my discussion). I have been reading an official DEA PDF that presents toxicity data from mouse studies of both fentanyl and one of its more toxic relatives, acetyl fentanyl. (The acetyl form is apparently in circulation in the black market.) The DEA document (July, 2015) claims that in the mouse studies, the LD50 for fentanyl was determined to be 62 mg/kg.
This is 2 million times higher than the figure that Smokin Joe found for humans. Different species can have remarkably different responses to toxins, but I have never heard of a disparity this great in a comparison between mammals. So, I just don't buy it. I'll bet it's off by a factor of one million. (Milligrams, micrograms, grams, and kilograms--
What difference does it make?)
***
Anyway, the whole thing is a mess.
