[FRIAM] ivermectin, nope

[Steve Smith]

Eric -
>>
>> I understand Hydroxychloroquine to have been used widely in
>> developing (equatorial) countries as an antiviral (in particular
>> Malaria) \
>>
> Not antiviral, Steve.  Plasmodium isn’t even a bacterium; it is a
> protozoan.  One of us, gooble gobble.

yes to protozoan, I shortcut a bit too much...   I was mostly
referencing the anecdotal experience of a friend who did 2 years in
Africa in the 90s as a Peace Corps volunteer.   He contracted Malaria
and was prescribed a series of rounds of Hydroxychloroquine as the
remedy (against the protozoa responsible).   The doses he was given were
so strong as to have many (short term) negative side-effects especially
heaped on top of his malaria symptoms.  I think he even had a couple of
heavy rounds a year or more after returning to knock down flare-ups.  

According to him, Hydroxycholoroquine was (among Americans/Europeans in
Africa in his circle) treated as a broad-spectrum preventative/cure to
*many things* including many viruses.   It isn't clear that was good
medicine or by some measure more a placebo with limited long-term
side-effects they can throw an anything with limited negative
consequences?   I can't imagine what it feels like to be a 3rd world MD
trying to raise public health against terrible odds while also dealing
with first-world do-gooders (or badders like arms and diamond dealers)
who have (relatively) minor problems given their overall state of health
and access to prime health care before and after living there.  Maybe
throwing synthetic Quinine at first-worlders was an easy thing to do to
get them out of the office?

The kind of conflation I offered up could easily feed/explain those who
have (or still are) pushed synthetic Quinine as a remedy for Covid-19. 
My bad.  My daughter ( a virologist studying Flavis) would not be
pleased.  She is also rabidly ant-anti-vaxx and anti-anti-science,
though she is having a crisis of trust with medical science (as a
system, not a science).

As you point out, the mechanism seems to involve raising the pH enough
to interfere with reproduction of the protozoan or some viruses, and it
is too easy to conflate en-vivo with en-vitro contexts.  Like Trump's
idea of injecting bleach (or whatever he *actually* said that was easily
refactored into something that bluntly brain-dead).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128816/

I was surprised to discover that 2 liters of Tonic Water is assumed to
be an equivalent dose to the prescribed standard dose of Quinine in pill
form.  I have to admit to a significant fondness for Gin and Tonic, but
I don't know that I could maintain that level of consumption for more
than a day or two.  One liter sounds a lot more reasonable.   At my
preferred 1/3 gin, 1/3 Tonic, 1/3 ice that leads to a mere 3-4 jiggers
of gin a day?

- Steve

>  
>
> Don’t mean to be a pedant.  But to the extent that we think things
> work for reasons, major domain distinctions are likely affect what we
> think deserves time to follow up.
>
> I have a colleague who gave a talk at SFI once (on metastasis in
> cancers), in which as a supporting tangent to an argument about
> difficulty, he commented that he had had fungal toenail infection
> since teenage, when as an athlete he had developed it from locker room
> showers in England, and in the subsequent decades been unable to get
> rid of it.  His next sentence: “And that’s a different _kingdom_!”
>  But the least different from us you can get without going to the
> animals, and that was enough to drastically lower the interventions
> available for it.  His point: imagine how much harder it is to get rid
> of a cancer cell line that is your own personal genome, mostly.  (Be
> your own, personal, genome.)
>
> Also, on Nick’s question about parasites.  I haven’t read the studies
> showing antiviral activity of ivermectin in vitro (I am not as good a
> person as REC, by a lot, but we knew that), but from what I have read,
> I gather that they drowned the virus in ivermectin, presumably in
> whatever cell culture they were growing it in.  But I would be amazed
> if any of those studies deliberately included cell parasites in the
> medium, so that ivermectin’s knocking them out would affect the
> ability of some unrelated virus to replicate in cells that perhaps
> that parasite doesn’t even touch.
>
> Again, of course, in the world where, as Masha Gessen says of the
> cynical society under autocracies, “Anything is possible and nothing
> is true”, the fact that ivermectin is claimed to be antiviral at
> drowning doses in vitro with no parasites, and then by coincidence the
> same drug is claimed to be antiviral at doses many orders of magnitude
> smaller in people in countries where you have a lot less ability to
> referee study methods if you don’t live there, but where there could
> be different parasites, makes this connection completely comme il faut  
>
> We know that at some sufficiently strong concentration, ethanol, and I
> assume either vinegar or baking-soda solution, will also be antiviral
> against almost anything.  (Whether vinegar or baking soda will depend
> on whether capsule denaturation is acid-catalyzed or base-catalyzed,
> but probably it will be one or the other.)  But of course, we know why
> you can’t get to those concentrations in a live animal.  That just
> isn’t interesting, because there isn’t anything singular about it.
>  The obscure drugs are singular, particularly if they are “anti
> parasitical”, given the above comment about how delicate a matter it
> can be to clear something that is phylogenetically not so far from you.
>
> Btw, the use of “parasite” in pharmacology again makes the hair on the
> back of my neck stand up.  What _kind_ of parasite?  Protists and
> predatory lenders?  Bacteria and fungi?  Tapeworms?  I feel like, for
> any of these drugs that do actually have some efficacy, there is
> probably a more specific word for what they cover that could be used,
> and would aid in guessing-games about their likely off-label scope.
>  When efficacy is real, and against classes of things that really
> don’t have much in common, that becomes even more interesting.  
>
> Eric
>
>
>
>
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