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Our mission statement Arrow. One that I find particularly amusing, for personal reasons, is the idea of complexing zinc ions. I say that because over 20 years ago, I was on a project targeting a particular phosphatase enzyme I know, I know, it was as doomed as all the other phosphatase work from that era. Our lead compound was pretty similar to chloroquine, which is interesting because I was working for Bayer at the time — there were still plenty of such structures from way back in the compound collection.
Unfortunately, none of the analogs we made were active in the slightest, so I did what I should have done right at the start and ordered up some of the original powder sample for more stringent analysis. And so to today. There has as yet been no well-controlled trial, and unfortunately the effects seen are still the sort of thing that can look exciting but disappear when you look closely. I mean that. It happens all the time — ask anyone else who does drug research for a living.
Better trials are cranking up right now: please, wait for those.
Chloroquine and hydroxychloroquine do have pretty significant adverse effects at high doses. Which make sense, since these compounds accumulate in the lysosomes, due to their high logP and basicity. The side effects are modest for most, especially on a 10 days or less regimen. But in general, chloroquine can be considered safe, at least for standard malaria therapy. I might be a bit more concerned about the combination of chloroquine plus azithromycins for certain patients, as both drugs may lead to QT prolongation.
The report I read said dosage is mg once a week, and a fatal dose is only 5 times that. Plus it bioaccumulates, has a long half-life in your body. Also, it is a bodyweight-sensitive dose, so if you are a small person, take a smaller dose. Thankfully, overdose at the same high level is a very rare occurrence. Great write-up on a dubious therapy.
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People are gearing up favipiravir too, on similarly preliminary signs. But favipiravir is known to be teratogenic and to whack red-cell production. If effective, is there any chance the indiscriminate use to cause the surge of a COVID Chloroquine resistant strain?
D, et. It does, however, immediately suggest that a larger and stricter trial be run. It was the combination of chloroquine and azithromycin that appeared to be effective. Any thoughts on why that might be? Looking at pubchem, azithromycin does quite a lot of things in quite a lot of systems. These results merit further testing. I would think it would be evident fairly quickly if there was something significant there. It looks like there were a total of 6 patients in the chloroquine.
Definitely enough to want to do a real study, not enough for the president of the united states to tout from the bully pulpit. People are still looking into a significant role of a secondary bacterial infections in a virus infection.
Chloroquine, Past and Present | In the Pipeline
It is therefore very important to include antibacterial drug for lung infections such as azithromycin in the treatment. Reports earlier were that bacterial pneumonia was oddly not a common sequel of the viral infection in China. The most dreaded complication is staphylococcal pneumonia, which develops days after the initial presentation of viral pneumonia. MRSA is a drug-resistant Staph aureus. We will either win under Trump or lose under Trump. Love it or hate it but it is what it is. Please clarify. It seems to me that those are indeed the possible outcomes. To be fair, I suppose it could be undecided at the time Trump leaves office.
In Poland, chloroquine has been officially approved for use in COVID and our generic drug company Adamed has promised to ramp up production.
We knew in that hydroxychloroquine treats lung cells infected with SARS-coronavirus. Was this a case of throwing everything at the wall and hoping something sticks, or is there some history with antimalarials and viruses that made it an interesting test case? People in here may know better, but chloroquine was known as an antiviral and, I believe, is used as an HIV treatment.
I guess it was a drug repurposing strategy using FDA approved drugs that revealed chloroquine and many others. Chloroquine screws up endosomes, and that plasmodium parasite as it cannot stash away excess of iron left after gobbling up all that hemoglobin. Endosomes also happen to play key role in the virus particles getting into cell — internalizing that receptor-bound virus. Biologists who develop transfection vectors, even nonviral one, often use chloroquine to look at the mechanism of the nucleic acid getting inside the cell and being released from the endosomes.
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The immunosuppressive effects of chloroquine are probably of the same origin. Excellent question. When you are a biologist interested in a new screen, new biology etc — you often start screening a collection of existing drugs some companies sell plates with all approved drugs. This way any hit will already have lots of data attached to it PK, safety, pharmacology etc. There have been in vitro, in vivo and clinical trials using chlorine for a long time.
I read an article, a few weeks ago, about a doctor, in , who was researching the effect of Chloroquine on the Sars virus. He had excellent results, but before they could do larger studies the SARS virus epidemic ended, and his research was put on the back burner, replaced by something more urgent. Corona virus in RNA type and replicates with Trancription 2. Transcription requires Amonoacids and specfic codons triplets nucleotide for example AUG always initiates Transcription and Tremination codons terminate Transcription, 3.
Intitiating codon has affinity to Hydroxyl group and terminating codons have affinity to phosphate group.
The phosphate moeity in chloroquin phosphate attaches to terminating codons and increase number of terminating codons, thus incducing termination of transcription, I do not have practial experiment on this and does not have data to prove this , However this is most reasonable explanation. On some of those early anti-malarials that caused permanent staining or not I wondered what the treated patients looked like under ultraviolet light! One minor quibble — malaria and trypanosomes are quite distinct parasites.