Chloroquine and Hydroxychloroquine as treatments for Covid-19

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

 

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

 

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

 

FYI as posted in another thread the medics in and around Wuhan and other regions in China have also been trialling Chloroquine phosphate (same [edit : type of] drug the Aussies are trying) and Gao et al are preparing to report positive results. So, fingers crossed.

https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.01047/_pdf

 

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

 

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!

 

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 - Chloroquine - Quinine -

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.

 

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.

 

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

 

https://twitter.com/user/status/1240786150803062784

 

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

 

"New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?"
https://www.sciencedirect.com/science/article/pii/S0924857920300881?via=ihub#bib0062

Also
"Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19?"
https://www.ncbi.nlm.nih.gov/pubmed/32179150

 

@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.

 

https://www.nbcnews.com/health/heal...oroquine-attempt-prevent-coronavirus-n1167166

Man dies after ingesting chloroquine in an attempt to prevent coronavirus

 

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.

 

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.

 

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.
https://twitter.com/user/status/1242238700995710977


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.

 

Moved from this thread Coronavirus - worldwide spread and control
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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.