5 ms·

This may be fallacious, but I am automatically dismissive when a drug from one area of medicine is recruited as a treatment for a completely disjoint disorder.

This may be fallacious, but I am automatically dismissive when a drug from one area of medicine is recruited as a treatment for a completely disjoint disorder. I need a somewhat plausible sounding mechanism of action, even if it's hypothetical. Because it fits a pattern I've observed where a drug is discovered, and it's on the cover of every magazine as a panacea[0], and then it doesn't pan out and it fades back into the small niche where it actually works. So I dismissed HCQ and Ivermectin out of hand. [0]: Interferon was on the cover of TIME in ~1980 as a cancer cure. (EDIT: but I'm not an MD, just a crazy person who likes reading pubmed, so my views are pure superstition)

shakna 5y ago
Interferon is still used as a cancer therapy today. [0] Quite a number of drugs are highly effective in different fields of study. [0] https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/interferon https://www.cancerresearchuk.org/about-cancer/cancer-in-gene...
- deleted 5y ago
  [deleted]
rbanffy 5y ago
IIRC HCQ was flagged in computational models as promising, but the concentrations required to have an actual effect are a large multiple of the lethal doses. There is a ton of politically driven disinformation around. Brazilian president Bolsonaro pushed both as treatments while, we now know, government representatives were stalling direct purchases from labs while negotiating vaccines with intermediaries in order to profit from sales to the government.
- cheaprentalyeti 5y ago
  >...but the conentrations required to have an actual effect are a large multiple of the lethal doses..." Which was the excuse they gave when they designed actual drug trials that gave patients lethal doses and ignored the testimony of doctors who found it useful at sub-lethal doses. And therefore a drug used by tens of millions of people a year(if not more) for the past five decades was declared too dangerous to use. Addendum: I wound up arguing with someone that thus-and-such a trial was actually using what was considered an overdose in 2017 and they would not look at the entry in the PDR.
ekianjo 5y ago
> I am automatically dismissive when a drug from one area of medicine is recruited as a treatment for a completely disjoint disorder. I guess you have never heard of Viagra.
- zetalyrae 5y ago
  But viagra has a plausible-sounding (to me, I am not an MD) mechanism of action. Whereas in the first paper[0] about chloroquine for COVID, the claim is: >This drug has multiple activities, one of which is to alkalise the phagolysosome, which hampers the low-pH-dependent steps of viral replication, including fusion and uncoating. Other mechanisms of antiviral activity are poorly explained. Which sounds like limited evidence. [0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134866/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134866/
  - ekianjo 5y ago
    > Other mechanisms of antiviral activity are poorly explained. You would be surprised how many drugs have an unclear mechanism of action. If you think we know everything in Biology you might want to revise your judgment.
    - s5300 5y ago
      Maybe I'm wrong, but I really want to be able to mostly correctly presume that the average HN user over the age of like... 20(?) probably has vague knowledge of the fact we don't understand the mechanism of things like acetaminophen (Tylenol) and most anesthetics... Furthermore, most chemical engineering/pharmacy students learn that with today's regulations, acetaminophen would've never been approved. Do we think that's a good thing? I don't. That said, I still very much agree with the parent poster's view.
      - jwbwater 5y ago
        Anyone that has ever taken a class in molecular biology or biophysics knows that it's ridiculously complex. Many drugs that look promising in vivo or in animals fail to perform in humans. Empirical evidence is what counts. Even targeted enzyme inhibitors are made by a shotgun approach. Synthesize 1000s of candidates and try them all to see which ones work best in vivo and then try those in animals and then try those winners in humans.
nradov 5y ago
This article explains the suspected mechanism of action. I'm not claiming that ivermectin is actually effective, but the biochemistry is at least plausible. https://www.sciencedirect.com/science/article/pii/S0166354220302011 https://www.sciencedirect.com/science/article/pii/S016635422... In general small molecule drugs often hit multiple different pathways. It's not reasonable to put them into neat little buckets.
- zetalyrae 5y ago
  Good point. As I said, it may be fallacious reasoning on my part :) I suppose what this underscores is: biology is immensely complex and first-principles thinking can only get you so far. Eventually, you need to test things with a big RCT to know what's going on.
s5300 5y ago
Quite unfortunately, the general public, and thus elected officials, do not appear to be capable of this sort of logical deduction.
- loopz 5y ago
  Why would they without expertise in the medical field? It's not something to dismiss out of hand either.
jwbwater 5y ago
A plausible mechanism of action is no where near good enough. Molecular biology is crazy complicated and lots of things that sound plausible don't work (and maybe do the opposite). I'll take "it works, but we don't know why" over "this is why we think it might work" every time.
- ksaj 5y ago
  There are actually a number of drugs where they specifically state the actual mechanism of action is unknown, but they do know from proper and continued clinical trials that the drug does indeed work. A lot of pain killers are in that category. Here is a list of 68 drugs that are known to work, but apparently we don't know how or why: https://en.wikipedia.org/wiki/Category:Drugs_with_unknown_mechanisms_of_action https://en.wikipedia.org/wiki/Category:Drugs_with_unknown_me...
  - deleted 5y ago
    [deleted]
copperx 5y ago
Interferon is a cancer cure (albeit limited to specific kinds, and abysmally low complete cure rates -- but a cure nonetheless for some people).
rsynnott 5y ago
> This may be fallacious, but I am automatically dismissive when a drug from one area of medicine is recruited as a treatment for a completely disjoint disorder. I mean, it sometimes works, and obviously it's a very attractive idea (no need to wait on slow trials; drug is already assessed for safety) but precisely because it's such an attractive idea people seem to be overly credulous about it.

shakna 5y ago

Interferon is still used as a cancer therapy today. [0] Quite a number of drugs are highly effective in different fields of study. [0] https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/interferon https://www.cancerresearchuk.org/about-cancer/cancer-in-gene...

deleted 5y ago
[deleted]

rbanffy 5y ago

IIRC HCQ was flagged in computational models as promising, but the concentrations required to have an actual effect are a large multiple of the lethal doses. There is a ton of politically driven disinformation around. Brazilian president Bolsonaro pushed both as treatments while, we now know, government representatives were stalling direct purchases from labs while negotiating vaccines with intermediaries in order to profit from sales to the government.

cheaprentalyeti 5y ago
>...but the conentrations required to have an actual effect are a large multiple of the lethal doses..." Which was the excuse they gave when they designed actual drug trials that gave patients lethal doses and ignored the testimony of doctors who found it useful at sub-lethal doses. And therefore a drug used by tens of millions of people a year(if not more) for the past five decades was declared too dangerous to use. Addendum: I wound up arguing with someone that thus-and-such a trial was actually using what was considered an overdose in 2017 and they would not look at the entry in the PDR.

ekianjo 5y ago

> I am automatically dismissive when a drug from one area of medicine is recruited as a treatment for a completely disjoint disorder. I guess you have never heard of Viagra.

zetalyrae 5y ago
But viagra has a plausible-sounding (to me, I am not an MD) mechanism of action. Whereas in the first paper[0] about chloroquine for COVID, the claim is: >This drug has multiple activities, one of which is to alkalise the phagolysosome, which hampers the low-pH-dependent steps of viral replication, including fusion and uncoating. Other mechanisms of antiviral activity are poorly explained. Which sounds like limited evidence. [0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134866/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134866/
- ekianjo 5y ago
  > Other mechanisms of antiviral activity are poorly explained. You would be surprised how many drugs have an unclear mechanism of action. If you think we know everything in Biology you might want to revise your judgment.
  - s5300 5y ago
    Maybe I'm wrong, but I really want to be able to mostly correctly presume that the average HN user over the age of like... 20(?) probably has vague knowledge of the fact we don't understand the mechanism of things like acetaminophen (Tylenol) and most anesthetics... Furthermore, most chemical engineering/pharmacy students learn that with today's regulations, acetaminophen would've never been approved. Do we think that's a good thing? I don't. That said, I still very much agree with the parent poster's view.
    - jwbwater 5y ago
      Anyone that has ever taken a class in molecular biology or biophysics knows that it's ridiculously complex. Many drugs that look promising in vivo or in animals fail to perform in humans. Empirical evidence is what counts. Even targeted enzyme inhibitors are made by a shotgun approach. Synthesize 1000s of candidates and try them all to see which ones work best in vivo and then try those in animals and then try those winners in humans.

nradov 5y ago

This article explains the suspected mechanism of action. I'm not claiming that ivermectin is actually effective, but the biochemistry is at least plausible. https://www.sciencedirect.com/science/article/pii/S0166354220302011 https://www.sciencedirect.com/science/article/pii/S016635422... In general small molecule drugs often hit multiple different pathways. It's not reasonable to put them into neat little buckets.

zetalyrae 5y ago
Good point. As I said, it may be fallacious reasoning on my part :) I suppose what this underscores is: biology is immensely complex and first-principles thinking can only get you so far. Eventually, you need to test things with a big RCT to know what's going on.

s5300 5y ago

Quite unfortunately, the general public, and thus elected officials, do not appear to be capable of this sort of logical deduction.

loopz 5y ago
Why would they without expertise in the medical field? It's not something to dismiss out of hand either.

jwbwater 5y ago

A plausible mechanism of action is no where near good enough. Molecular biology is crazy complicated and lots of things that sound plausible don't work (and maybe do the opposite). I'll take "it works, but we don't know why" over "this is why we think it might work" every time.

ksaj 5y ago
There are actually a number of drugs where they specifically state the actual mechanism of action is unknown, but they do know from proper and continued clinical trials that the drug does indeed work. A lot of pain killers are in that category. Here is a list of 68 drugs that are known to work, but apparently we don't know how or why: https://en.wikipedia.org/wiki/Category:Drugs_with_unknown_mechanisms_of_action https://en.wikipedia.org/wiki/Category:Drugs_with_unknown_me...
- deleted 5y ago
  [deleted]

copperx 5y ago

Interferon is a cancer cure (albeit limited to specific kinds, and abysmally low complete cure rates -- but a cure nonetheless for some people).

rsynnott 5y ago

> This may be fallacious, but I am automatically dismissive when a drug from one area of medicine is recruited as a treatment for a completely disjoint disorder. I mean, it sometimes works, and obviously it's a very attractive idea (no need to wait on slow trials; drug is already assessed for safety) but precisely because it's such an attractive idea people seem to be overly credulous about it.