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Chloroquine and Hydroxychloroquine as treatments for Covid-19

Discussion in 'Epidemics (including Covid-19)' started by Samuel, Mar 11, 2020.

  1. Samuel

    Samuel Senior Member (Voting Rights)

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    Mod note: This thread has been renamed and some posts moved from the thread: The biology of coronavirus COVID-19 - including research, vaccines, treatments
    ____________________

    https://www.unboundmedicine.com/medline/citation/32074550/full_citation

    vvv
    The coronavirus disease 2019 (COVID-19) virus is spreading
    rapidly, and scientists are endeavoring to discover drugs
    for its efficacious treatment in China. Chloroquine
    phosphate, an old drug for treatment of malaria, is shown
    to have apparent efficacy and acceptable safety against
    COVID-19 associated pneumonia in multicenter clinical
    trials conducted in China. The drug is recommended to be
    included in the next version of the Guidelines for the
    Prevention, Diagnosis, and Treatment of Pneumonia Caused by
    COVID-19 issued by the National Health Commission of the
    People's Republic of China for treatment of COVID-19
    infection in larger populations in the future.
    ^^^

    i wonder if we could look at those guidelines and pick out anything relevant to m.e. and m.e. comorbidities to create information for pwme.

    also an ignorant question: i wonder if chloroquine causes fluoroquinolone-like issues, or is bad for those who were poisoned with fluoroquinolones.
     
    Last edited by a moderator: Mar 25, 2020 at 10:39 AM
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  2. hinterland

    hinterland Senior Member (Voting Rights)

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    Not an ignorant question at all. I don't know if chloroquine is structurally similar to quinolone drugs, but I think possibly yes. Chloroquine and hydroxychloroquine are 4-aminoquinolines, and 4- quinolone is a compound derived from quinoline.

    I too have had a serious adverse reaction to fluoroquinolone drugs in the past that still affects me today, and ever since I've been more hypersensitive to any drugs or nutritional supplements that I put into my body. So I don't expect I'd tolerate chloroquine very well and be wary of it for myself.

    Probably the most well know, and significant, potential long-term side effect of chloroquine drugs is retinopathy (causing loss of vision), they can also cause hearing problems in some people.

    The range of potential side effects is listed here:
    https://www.drugs.com/sfx/chloroquine-side-effects.html
     
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  3. Caesar

    Caesar Established Member (Voting Rights)

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    Location:
    Norway
    Australian researchers to test possible cure for COVID-19 on human patients
    A team of Australian researchers say they may have found a cure for the novel coronavirus and hope to have patients enrolled in a nationwide trial by the end of the month.
    https://www.9news.com.au/national/c...eensland/7c0ea555-add8-48a4-96c6-48c3083aebba

    Drugs used to treat HIV and malaria could be used to tackle the coronavirus, according to scientists in Australia.
    A team of infectious disease experts at the University of Queensland in Brisbane say they have seen two existing medications manage to wipe out COVID-19 infections.
    Chloroquine, an anti-malarial drug, and HIV-suppressing combination lopinavir/ritonavir have both reportedly shown promising results in human tests and made the virus 'disappear' in infected patients.
    https://www.dailymail.co.uk/news/ar...-Australian-researchers-CURE-coronavirus.html
     
  4. boolybooly

    boolybooly Senior Member (Voting Rights)

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    Last edited: Mar 18, 2020
  5. lunarainbows

    lunarainbows Senior Member (Voting Rights)

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    Is this the same as hydroxychloroquine - ie can that be used instead?
     
  6. boolybooly

    boolybooly Senior Member (Voting Rights)

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    Its potentially nasty stuff but I wonder how it works?

    Talking about structure, since it is an analogue of quinine it makes me wonder whether something as simple as tonic water might also be helpful!

    I know that is a very speculative idea but as things stand who knows!? Its a question worth answering IMHO.

    Personally I like the taste so I got a bottle from my supermarket, cant hurt, as long as I lay off the gin...

    Its a bit premature to start panic buying Schweppes though!
     
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  7. boolybooly

    boolybooly Senior Member (Voting Rights)

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    If my google-fu serves me well then they are subtly different since Wikipedia shows it has a different structure with an added hydroxy moiety and appears to be an analogue of Chloroquine.

    https://en.wikipedia.org/wiki/Hydroxychloroquine
    https://en.wikipedia.org/wiki/Chloroquine

    Hydroxychloroquine -[​IMG] Chloroquine -[​IMG] Quinine - [​IMG]

    This changes its pH and polarisation of electronegativity within the molecule; as I understand it that matters because it may effect its behaviour in the body especially solubility, diffusion and ease of crossing membranes and also pharmacology.

    We dont know if Chloroquine works for sure but it looks like several small trials have had positive outcomes, so the next step is bigger trials and I am sure they are working on it. Its impossible to know if Hydroxychloroquine would also work without trying it, ditto other more distantly related analogues like quinine, which is a long shot but would have the advantage of being widely available. Depends on what mechanism is involved.

    The Aussies and Chinese are both using Chloroquine of some description, but I have added a precautionary edit to my post above as I dont know exactly what or how it is being administered but we do know the Chinese have been using Chloroquine phosphate.
     
  8. minimus

    minimus Established Member

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    The attached study was published a day or two ago by a group of French doctors on the use of hydroxychloroquine and azithromycin to treat hospitalized Covid-19 patients.

    The study has a number of problems, most of which the authors acknowledge:
    • It was not placebo-controlled or double-blinded.
    • The sample size is quite small at 36.
    • Six out of 26 patients in the treatment arm were lost to follow-up, three because they had to be put into the ICU and one because they died.
    • The outcome measure -- the percent of patients who tested negative by nasopharyngeal PCR for SARS-Cov-2 six days after study entry -- may not correlate that well with a patient's clinical outcome. It is plausible that a patient could clinically deteriorate and die because of a cytokine storm or a secondary bacterial infection after they test negative for the coronavirus.
    • The authors do not explain that clearly why they chose this outcome measure, so it is possible it was cherry picked from a range of other measures (e.g. change in oxygen saturation, body temperature, or breaths per minute, etc.)
    On the plus side, the PCR test is at least objective in nature, so maybe less prone to placebo effects and observer bias than a subjective outcome measure. In addition, the patients in the treatment arm were on average significantly older (51) and therefore presumably more prone to severe illness because of their age than controls, who were on average 37 years old.

    The authors found that 70% (14/20) of the treated patients had a negative PCR test 6 days after study inclusion vs. 12.5% (2/16) for controls.

    The authors also found that the combination of hydroxychloroquine and azithromycin appeared to be more effective in clearing the virus -- with 6 out of 6 patients testing negative by PCR on day 6.
     

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  9. Cheshire

    Cheshire Moderator Staff Member

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    The main author of this study has been all over the French media claiming that he has found the solution to the COVID 19 crisis, without any precaution. I do not think this is a responsible attitude, given all the limitations of this trial, and wouldn't trust someone with such a poor sense of integrity.
     
    Last edited: Mar 19, 2020
  10. Kalliope

    Kalliope Senior Member (Voting Rights)

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    The Norwegian Medicines Agency has been notified of hoarding of Plaquenil and on Monday introduced rationing of the drug.

    - Last week there was no shortage, but then the Norwegian Medicine Agency began receiving reports from the pharmacies that they were starting to run out of hydroxychloroquine and introduced rationing. There are no restrictions on health institutions, but individuals are not allowed to do so now, he points out.


    Dagens medisin: Helsepersonell tar medisin på rasjoneringslista for å unngå smitte
    google translation: Health professionals take medicine on ration list to avoid infection
     
  11. Kalliope

    Kalliope Senior Member (Voting Rights)

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  12. Solstice

    Solstice Senior Member (Voting Rights)

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    Apparently mixed with azithromycine(zithromax in us i think) it gives even better results.
     
  13. boolybooly

    boolybooly Senior Member (Voting Rights)

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  14. boolybooly

    boolybooly Senior Member (Voting Rights)

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    @lunarainbows about that hydroxychloroquine (HQC) question.

    TLDR chloroquine (CQ) looks more effective as a virus blocker, but HCQ may have helpful anti-inflammatory properties as well as blocking the virus but not quite as well as CQ.

    "Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro" Liu et al
    https://www.nature.com/articles/s41421-020-0156-0
    This second quote from the same paper adds to the mechanism mentioned on TWiV.
    EEs are early endosomes; ELs are endolysosomes.

     
    Last edited: Mar 21, 2020
  15. Cheshire

    Cheshire Moderator Staff Member

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    About the Chloroquine trial



     
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  16. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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  17. boolybooly

    boolybooly Senior Member (Voting Rights)

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    I am very sorry to read this. What I think this man and woman did not appreciate is that Chloroquine is potentially very toxic. Even a cursory investigation of side effects on google would show that it is not something to be trifled with.

    The advice for treatment sems to indicate that it is not suitable for over 65s which is probably why the medical interest in the less effective but less toxic hydroxychloroquine.

    This sounds like probably a dosage error rather than impurities due to being vetinary grade. Its a saying in toxicology that the dose makes the poison.
     
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  18. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I doubt this was a dosage problem. You can almost certainly eat a gram of chloroquine without any symptoms. I suspect this fish treatment had something else really toxic in it.
     
  19. boolybooly

    boolybooly Senior Member (Voting Rights)

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    Maybe, 1g of pharmaceutical grade is apparently normal for malaria treatment initiation, though this article in Forbes states they both took a teaspoonful, whatever it was.

    https://www.forbes.com/sites/taraha...quine-after-trump-touts-drug-for-coronavirus/
    Sourced from an NBC tweet.


    Which if chloroquine phosphate was as dense as sugar would mean 5g at least and it is likely to be denser judging from the chemical properties, since molecular weight of the phosphate is 417.92 whereas sugar is only 342.3 and it has 5-6 water of hydration but I cant see hydration info for CQP.
    http://www.inchem.org/documents/pims/pharm/chloroqu.htm#SectionTitle:3.3 Physical properties
    https://pubchem.ncbi.nlm.nih.gov/co...hate#section=Chemical-and-Physical-Properties

    My logic for the dose theory is that as a fish keeper I am told Koi are quite sensitive fish and highly prized and very expensive. My reasoning is that koi treatments would be of a relatively high quality which is why I suspect on balance the dose did it but am sure I dont know.

    Side effects include hypoglycemia and heart arrhythmias or failure as well as hypersensitivity.
    https://reference.medscape.com/drug/aralen-chloroquine-phosphate-chloroquine-342687#0

    Its a terrible tragedy whatever the reason.
     
    Last edited: Mar 24, 2020 at 6:45 PM
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  20. alex3619

    alex3619 Senior Member (Voting Rights)

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    Moved from this thread Coronavirus - worldwide spread and control
    _______________

    http://www.virology.ws/2020/03/19/h...viral-load-and-symptoms-in-covid-19-patients/

    I only just realized how dramatically hydroxychloroquine, a cheap drug, lowers viral load for Covid-19. This makes the drug more highly likely to be useful in my view, though not without risks. One of the issues is that people might get worn down over time by the virus, but the virus is around for a far shorter time on this drug.
     
    Last edited by a moderator: Mar 25, 2020 at 8:16 PM
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