Posted on 04/29/2020 9:20:23 AM PDT by SeekAndFind
The spread of the pandemic disease COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has now reached almost every country of the world, with over 3.11 million cases and over 217,000 deaths as of April 29, 2020.
Most patients have mild or asymptomatic disease, but 20% or so of patients have more severe disease. Overall, critical or very severe disease occurs in about 5% of patients.
These patients have cardiac arrhythmias, acute kidney disease, pulmonary edema, septic shock, and acute respiratory distress syndrome (ARDS). Other vital organs are also affected in some patients, such as the heart, kidneys, liver, or digestive tract, causing multi-organ damage. Individuals who are older or have underlying medical conditions are at high risk for severe disease and death.
In the absence of a vaccine or new therapeutic agent, older approved drugs are being explored to test if they can be repurposed against COVID-19. Experiments show that the SARS-CoV-2 virus was inhibited by the antimalarial chloroquine and its derivative, hydroxychloroquine in vitro. Both drugs have been commercially produced for the treatment of malaria for decades. Hydroxychloroquine is also used in the treatment of several autoimmune disorders like systemic lupus erythematosus (SLE).
Clinical trials showed both drugs performed better than the control group in controlling pneumonia and preventing it from worsening, improving the findings on lung imaging, accelerating seroconversion, and shortening the course of the disease.
The drugs may act by blocking the entry of the virus into the host cell, could inhibit glycosylation, and increase the pH of endosomes and lysosomes. Their immunosuppressive characteristics may also dampen the cytokine storm that is now believed to underlie many of the manifestations of COVID-19.
The drugs have been approved by the US Food and Drug Administration (FDA) for emergency treatment of COVID-19. However, despite their demonstrated safety and effectiveness, these drugs may have serious side effects like diarrhea, pain in the abdomen and arrhythmias, as well as retinal damage. One study showed a higher risk of liver and kidney damage when these drugs were used in COVID-19.
The threshold above which toxicity occurs, the limit for effectiveness, and side effects must be clearly understood to achieve an optimal dosing regimen, especially for high-risk subgroups.
The current study looked at eight different types of cells in culture, namely, the retina, myocardium, lung, liver, kidney, endothelium, and intestinal epithelium. These were incubated with either chloroquine or hydroxychloroquine at a range of doses (0.017 to 1000 μM) for 72 hours.
The incubating device can perform long-term imaging of dynamic cell changes, taking photographs every 3 hours, and thus inform the investigators about the pattern of cell proliferation.
The scientists also found the selectivity index SI for both drugs along with the predicted tissue concentration by the use of the physiologically-based pharmacokinetic model (PBPKM), for each target organ.
The study found that hydroxychloroquine is significantly safer than chloroquine at the heart, liver, lung, and kidney. Chloroquine at over 30 μM was significantly toxic to the cells at 48 hours. Hydroxychloroquine showed significant toxicity to the cells at 100 μM at 48 hours. At over 300 μM, most cells died within 3 hours.
Comparison of the concentration at which half the cells showed cytotoxic effects at 48 and 72 hours showed that at over 300 μM of either drug, all eight cell lines showed signs of severe and rapid toxicity. The heart, kidney, and intestinal cell lines were most sensitive to chloroquine (and the first two to hydroxychloroquine too), with the concentration required to produce toxicity in half the cells being less than 20 μM.
The CC50 decreased over time for both drugs suggesting that the toxicity was due to drug accumulation. However, the SI of hydroxychloroquine is higher than that of chloroquine for most cell types.
The SI indicates the safe range of activity of the drug. The effective concentration at which hydroxychloroquine kills half the viral particles of SARS-CoV-2 (EC50) is less than that of chloroquine by almost eight-fold, and the CC50 is also lower.
The PBPK models showed what would happen if standard courses of the two drugs were given: hydroxychloroquine 600 mg twice a day for one day followed by 200 mg twice a day from days 2 to 5, or chloroquine 500 mg twice a day for seven days. The maximum tissue concentrations were calculated.
This showed that the highest concentrations of chloroquine resulted from the accumulation of the drug in the liver and the lung, at 3 times that of the heart. For hydroxychloroquine, the highest concentration is in the lung rather than in the liver, kidney, or heart.
They also calculated the ratio of the tissue trough concentration to the CC50 (RTTCC) to compare the risk of toxicity of the two drugs in each tissue. They found that the RTTCC was 6-87 times higher for chloroquine compared to hydroxychloroquine for the lung, heart, kidney, and liver.
The promising antiviral activity of chloroquine and hydroxychloroquine has led to their widespread adoption against COVID-19. However, it is important to remember that they have toxicities directed against different types of cells in the body. These toxic actions are time- and dose-dependent, which means that the drugs should be given for only a short time to prevent cumulative toxicity.
Different cell types react differently to the drugs. For instance, liver and intestinal cell types have the greatest sensitivity to chloroquine but lung and intestine to hydroxychloroquine. The importance of the distribution of the drug is revealed as a factor affecting its toxicity. The PBPK model has shown that hydroxychloroquine has a better safety profile compared to chloroquine.
It is noteworthy that a recent report contradicts this, which might be the result of complex differences in the way the drugs behave in the living body as opposed to in vitro systems.
The use of the RTTCC allows the investigators to monitor the whole process of proliferation and to differentiate the effects on different tissues. The researchers emphasize the need to perform ECG monitoring throughout the period of usage of these drugs, even if the patient doesn’t show signs of severe disease and if the person shows symptoms of impaired vision.
The study does not give any clearcut evidence for or against the use of these drugs in COVID-19 but suggests that it adds value to their study in clinical and preclinical trials.
This has been known for decades, with a little less detail.
Kids overdosing on chloroquine was why hydroxychloroquine was invented decades ago, was too easy to OD.
It’s harder to overdose on hydroxychloroquine but it’s more expensive
Thank goodness they’re researching this brand new, never-before studied medication. After all, we know nothing about it. Except that it’s toxic, toxic I tell ya.
Like pretty much every substance in the world. WATER KILLS.
btt
No mention of zinc
The medical community knows damn good and well that hydroxychloroquine is safe.
My daughter takes it for lupus, as do hundreds of thousands of others.
Were my daughter to develop pneumonia, she would be given azithromycin.
Pharmacists have been advising people to take zinc at the start of a cold for decades. The common cold is a corona virus variation.
There is only one reason to doubt the efficacy and safety of these drugs: the left does not want an easy cure for COVID-19.
The left wants the nation quarantined and the economy trashed for political power.
The left is prolonging this crisis for the defeat of Trump. NOTHING LESS.
Remdesivir causes liver damage-
“Experimental virus drug, Remdesivir, stopped after side effects in 18 patients”
The authors said Remdesivir was “not associated with a difference in time to clinical improvement,” compared to the control.
After a month, 13.9 percent of the patients on Remdesivir had died, compared to 12.8 percent of those in the control group.”
Since hte media love poo pooing HCQ by pointing out one or two negative studies- let’s see what Remsidiver trials have shown:
“First trial for potential Covid-19 drug shows it has no effect
WHO draft put online states remdesivir does not benefit severe coronavirus patients”
“Remdesivir, a drug thought to be one of the best prospects for treating Covid-19, failed to have any effect in the first full trial, it has been revealed.
The drug is in short supply globally because of the excitement it has generated. It is one of the drugs Donald Trump claimed was “promising”.
In a “gold standard” trial of 237 patients, some of whom received remdesivir while others did not, the drug did not work. The trial was also stopped early because of side-effects”
Why is this doctor combining the two pills? Hydroxychloroquine is the one being prescribed.
Here is what they always leave otu when claimign that HCQ ‘may be’ dangerous
“It can cause severe side effects IF NOT TAKEN PROPERLY OR UNDER MEDICAL SUPERVISION OR GUIDELINES,”
When taken under the supervision of a doctor, the drug is very very safe- far safer than other drugs- that are taken daily in the millions without masses of people suffering side effects
When HCQ is taken and proper observations are taken while on the drug it is very very safe- Doctors prescribe far more dangerous drugs every day- and people are told what to watch for, and what to report if a symptom should crop up- they are even given a read out when they pick up their medication that tells them to report any of a whole slew of symptoms
RE: It can cause severe side effects IF NOT TAKEN PROPERLY OR UNDER MEDICAL SUPERVISION OR GUIDELINES,
*THAT* is a strawman argument by those who opposed the use of the drug. NOBODY, NOT especially Trump, is advocating the taking of Hydroxychloroquine without Medical Supervision.
“The study found that hydroxychloroquine is significantly safer than chloroquine at the heart, liver, lung, and kidney.”
“They also calculated the ratio of the tissue trough concentration to the CC50 (RTTCC) to compare the risk of toxicity of the two drugs in each tissue. They found that the RTTCC was 6-87 times higher for chloroquine compared to hydroxychloroquine for the lung, heart, kidney, and liver.”
“The PBPK model has shown that hydroxychloroquine has a better safety profile compared to chloroquine.”
As I keep pointing out, these two DIFFERENT drugs have different side effects. Why? Because they are DIFFERENT drugs!
which is exactly why I posted that- the left will not explain that to the people- they just insist the drug is ‘dangerous’ - too dangerous to approve for widespread use- which is a blatant lie-
The Evil on the left is sickening- people are dying by the 10’s of 1000’s because of them- as a direct result of them not using a safe effective drug that can and should be used to halt this pandemic in it’s tracks-
Chloroquine was used in the initial study and was found to have an antiviral effect, without zinc, against SARS-CoV. Chinese researchers substituted HCQ as it was available to them. There is a third quinoline, quinacrine (or mepacrine in other countries, trade name, Atabrine), which although unavailable in US can be made by compounding pharmacists. It is feared more dangerous than the others.
[[“The study found that hydroxychloroquine is significantly safer than chloroquine at the heart, liver, lung, and kidney.”]]
But even still- chloroquine has been used by millions and millions of people- billions of times- hundreds of billions of times over the years- with no issues or slight issues, because doctors monitor for problems and stop or reduce the drug IF any symptoms show up- chloroquine has saved millions of lives- how many lives has it taken when under medical supervision?
Chemo drugs are far more dangerous than this drug- yet chemo is still given to millions every single day- under medical supervision, and even given outside the hospital and tell patients to monitor for symptoms themselves-
The opposition to HCQ- a drug with much less side effects than chloroquine, is just Satanic in nature- there’s no other explanation as to why people would oppose such a safe cost effective life saving drug during a pandemic when 10’s of 1000’s are dying fro something that is entirely preventable or fixable-
Silver ions and vitamin C. Much less so
The addition of the Hydroxyl group made the chloroquine safer, but did not change its active effect. Neither Aralen nor Plaquenil can be used without close doctor supervision.
I am not sure what is your point in emphasizing the differences between them. If my doctor elected to use Aralen instead of Plaquenil, I know of no reason to be concerned. In malaria and amoebiasis therapy the drugs have different dosages but are considered alternatives. Parasites resistant to one are resistant to the other.
ITS VERY ‘FUNNY’ THAT THESE SAME PEOPLE,DO NOT BAT AN EYE AT OTHER WIDELY PRESCRIBED TREATMENTS THAT CAN MORE EASILY KILL YOU
SUCH AS CHEMOTHERAPY
SUCH AS JUST ABOUT ANY OTHER MAJOR WIDELY PUSHED PHARMA DRUGS
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