The truth of France's Coronavirus treatment ( hydroxychloroquine )

Hydroxychloroquine (HCQ), sold under the name Plaquenil among others, may be a medication used for the prevention and treatment of certain sorts of malaria.[1] Specifically it's used for chloroquine-sensitive malaria.[2] Other uses include treatment of atrophic arthritis , lupus, and porphyria cutanea tarda.[1] it's taken orally .[1] it's also getting used as an experimental treatment for coronavirus disease 2019 (COVID-19).[3]

Common side effects include vomiting, headache, changes in vision and muscle weakness.[1] Severe side effects may include allergies .[1] Although all risk can't be excluded it remains a treatment for rheumatic disease during pregnancy.[4] Hydroxychloroquine is within the antimalarial and 4-aminoquinoline families of medication.[1]

Hydroxychloroquine was approved for medical use within the us in 1955.[1] it's on the planet Health Organization's List of Essential Medicines, the safest and best medicines needed during a health system.[5] The wholesale cost within the developing world is about US$4.65 per month as of 2015, when used for atrophic arthritis or lupus.[6] within the us the wholesale cost of a month of treatment is about US$25 as of 2020.[7] within the uk this dose costs the NHS about £ 5.15.[8] In 2017, it had been the 128th most prescribed medication within the us with quite five million prescriptions.[9]
Medical use
Hydroxychloroquine treats malaria, systemic LE , rheumatic disorders like atrophic arthritis , porphyria cutanea tarda, and Q fever .[1]

In 2014, its efficacy to treat Sjögren syndrome was questioned during a double-blind procedure involving 120 patients over a 48-week period.[10]

Hydroxychloroquine is widely utilized in the treatment of post-Lyme arthritis. it's going to have both an anti-spirochaete activity and an anti-inflammatory activity, almost like the treatment of atrophic arthritis

Contraindications
The drug label advises that hydroxychloroquine shouldn't be prescribed to individuals with known hypersensitivity to 4-Aminoquinoline compounds.[12] There are a variety of other contraindications[13] [14] and caution is required if patients have certain heart conditions, diabetes, psoriasis etc.

Side effects
The most common adverse effects are a light nausea and occasional stomach cramps with mild diarrhea. the foremost serious adverse effects affect the attention .

For short-term treatment of acute malaria, adverse effects can include abdominal cramps, diarrhea, heart problems, reduced appetite, headache, nausea and vomiting.

For prolonged treatment of lupus or arthritis, adverse effects include the acute symptoms, plus altered eye pigmentation, acne, anaemia, bleaching of hair, blisters in mouth and eyes, blood disorders, convulsions, vision difficulties, diminished reflexes, emotional changes, excessive coloring of the skin, deafness , hives, itching, liver problems or liver failure, loss of hair, muscle paralysis, weakness or atrophy, nightmares, psoriasis, reading difficulties, tinnitus, skin inflammation and scaling, skin rash, vertigo, weight loss, and infrequently enuresis . Hydroxychloroquine can worsen existing cases of both psoriasis and porphyria.

Eyes
Main article: Chloroquine retinopathy
One of the foremost serious side effects may be a toxicity within the eye (generally with chronic use).[15] People taking 400 mg of hydroxychloroquine or less per day generally have a negligible risk of macular toxicity, whereas the danger begins to travel up when an individual takes the medication over 5 years or features a cumulative dose of quite 1000 grams. The daily safe maximum dose for eye toxicity are often computed from one's height and weight using this calculator. Cumulative doses also can be calculated from this calculator. Macular toxicity is said to the entire cumulative dose instead of the daily dose. Regular eye screening, even within the absence of visual symptoms, is suggested to start when either of those risk factors occurs.[16]

Toxicity from hydroxychloroquine could also be seen in two distinct areas of the eye: the cornea and therefore the macula. The cornea may become affected (relatively commonly) by an innocuous cornea verticillata or vortex keratopathy and is characterized by whorl-like corneal epithelial deposits. These changes bear no relationship to dosage and are usually reversible on cessation of hydroxychloroquine.

The macular changes are potentially serious. Advanced retinopathy is characterized by reduction of acuity and a "bull's eye" macular lesion which is absent in early involvement.

Overdose
Due to rapid absorption, symptoms of overdose can occur within a half an hour after ingestion. Overdose symptoms include convulsions, drowsiness, headache, heart problems or coronary failure , difficulty breathing and vision problems.

Hydroxychloroquine overdoses are rarely reported, with 7 previous cases found within the English medical literature. In one such case, a 16-year-old girl who had ingested a couple of hydroxychloroquine 200mg presented with tachycardia (heart rate 110 beats/min), hypotension (systolic vital sign 63 mm Hg), central systema nervosum depression, conduction defects (ORS = 0.14 msec), and hypokalemia (K = 2.1 meq/L). Treatment consisted of fluid boluses and dopamine, oxygen, and potassium supplementation. The presence of hydroxychloroquine was confirmed through toxicologic tests. The patient's hypotension resolved within 4.5 hours, serum potassium stabilized in 24 hours, and tachycardia gradually decreased over 3 days.[17]

Interactions
The drug transfers into breast milk and will be used with care by pregnant or nursing mothers.[citation needed]

Care should be taken if combined with medication altering liver function also as aurothioglucose (Solganal), cimetidine (Tagamet) or digoxin (Lanoxin). HCQ can increase plasma concentrations of penicillamine which can contribute to the event of severe side effects. It enhances hypoglycemic effects of insulin and oral hypoglycemic agents. Dose altering is suggested to stop profound hypoglycemia. Antacids may decrease the absorption of HCQ. Both neostigmine and pyridostigmine antagonize the action of hydroxychloroquine.[18]

While there could also be a link between hydroxychloroquine and haemolytic anaemia in those with glucose-6-phosphate dehydrogenase deficiency, this risk could also be low in those of African descent.[19]

Specifically, the FDA drug label for hydroxychloroquine lists the subsequent drug interactions [12]:

Digoxin (wherein it's going to end in increased serum digoxin levels)
Insulin or antidiabetic drugs (wherein it's going to enhance the consequences of a hypoglycemic treatment)
Drugs that prolong QT interval and other arrhythmogenic drugs (as Hydroxychloroquine prolongs the QT interval and should increase the danger of inducing ventricular arrhythmias if used concurrently)
Mefloquine and other drugs known to lower the convulsive threshold (co-administration with other antimalarials known to lower the convulsion threshold may increase risk of convulsions)
Antiepileptics (concurrent use may impair the antiepileptic activity)
Methotrexate (combined use is unstudied and should increase the frequency of side effects)
Cyclosporin (wherein an increased plasma cylcosporin level was reported when used together).
Pharmacology
Pharmacokinetics
Hydroxychloroquine has similar pharmacokinetics to chloroquine, with rapid gastrointestinal absorption and elimination by the kidneys. Cytochrome P450 enzymes (CYP2D6, 2C8, 3A4 and 3A5) metabolize hydroxychloroquine to N-desethylhydroxychloroquine.[20]

Pharmacodynamics
Antimalarials are lipophilic weak bases and simply pass plasma membranes. The free base form accumulates in lysosomes (acidic cytoplasmic vesicles) and is then protonated,[21] leading to concentrations within lysosomes up to 1000 times above in culture media. This increases the pH of the lysosome from 4 to six .[22] Alteration in pH causes inhibition of lysosomal acidic proteases causing a diminished proteolysis effect.[23] Higher pH within lysosomes causes decreased intracellular processing, glycosylation and secretion of proteins with many immunologic and nonimmunologic consequences.[24] These effects are believed to be the explanation for a decreased immune cell functioning like chemotaxis, phagocytosis and superoxide production by neutrophils.[25] HCQ may be a weak diprotic base which will undergo the lipid cell wall and preferentially concentrate in acidic cytoplasmic vesicles. the upper pH of those vesicles in macrophages or other antigen-presenting cells limits the association of autoantigenic (any) peptides with class II MHC molecules within the compartment for peptide loading and/or the next processing and transport of the peptide-MHC complex to the cell wall .[26]

Mechanism of action
Hydroxychloroquine increases[27] lysosomal pH in antigen-presenting cells. In inflammatory conditions, it blocks toll-like receptors on plasmacytoid dendritic cells (PDCs).[citation needed] Hydroxychloroquine, by decreasing TLR signaling, reduces the activation of dendritic cells and therefore the inflammatory process. Toll-like receptor 9 (TLR 9) recognizes DNA-containing immune complexes and results in the assembly of interferon and causes the dendritic cells to mature and present antigen to T cells, therefore reducing anti-DNA auto-inflammatory process.

In 2003, a completely unique mechanism was described wherein hydroxychloroquine inhibits stimulation of the toll-like receptor (TLR) 9 family receptors. TLRs are cellular receptors for microbial products that induce inflammatory responses through activation of the innate system .[28]

As with other quinoline antimalarial drugs, the mechanism of action of quinine has not been fully resolved. the foremost accepted model is predicated on hydrochloroquinine and involves the inhibition of hemozoin biocrystallization, which facilitates the aggregation of cytotoxic heme. Free cytotoxic heme accumulates within the parasites, causing their deaths.

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coronavirus: Australia joins growing list of nations to ban all foreign visitors.

In an attempt to slow the spread of the coronavirus, Prime Minister Scott Morrison of Australia on Thursday barred all foreign citizens and nonresidents from entering the country, becoming the newest world leader to enact a wide-sweeping travel ban since the pandemic was declared.

The ban will become beginning on Friday and follows similar orders in Canada and New Zealand.

Mr. Morrison said he had consulted with Prime Minister Jacinda Ardern of latest Zealand about the ban said it had been “essential to require that further step so as to limit the spread of the coronavirus.”

“We have already seen a really significant reduction within the visit Australia by noncitizens and residents,” he added, citing the very fact that 80 percent of cases within the country are linked to overseas travel.

Australia has recorded 568 cases and 6 deaths, a figure that reflects the country’s still-limited testing protocols, experts said.

Australian citizens and residents are still ready to enter the country from abroad, but must quarantine themselves for 14 days upon returning.

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The Trump administration on Wednesday broadened the government’s response to the coronavirus pandemic and spelled out the primary details of a $1 trillion economic package, asking Congress for an infusion of $500 billion for direct payments to taxpayers and $500 billion in loans for businesses.

President Trump invoked a seldom-used wartime law that permits the govt to press American industry into service to build up production of medical supplies. He said he would send two hospital ships to ny and California.

He also directed federal agencies to suspend all foreclosures and evictions until the top of April because the full economic toll of the crisis began to line in round the world. And he agreed with Canada to prevent all nonessential traffic across the northern border.

After weeks of playing down the outbreak, Mr. Trump appeared on Wednesday to completely embrace the scope of the calamity, saying he saw himself as a wartime president and invoking memories of the efforts made by Americans during war II.

“Now it’s our time,” Mr. Trump said at a press conference at the White House. “We must sacrifice together because we are beat this together, and that we will come through together. It’s the invisible enemy.”

Entire sectors of the American economy are shutting down, threatening to crush businesses, put many people out of labor and forcing lawmakers to think about a huge financial bailout that might dwarf the federal government’s response to the 2008 crisis.

The scale of the matter is unlike anything Washington has faced before: The financial crisis, which sent unemployment skyrocketing to 10 percent, centered on foreclosures and therefore the banking sector while this crisis is springing from dozens of place directly , as restaurants and movie theaters pack up , factories close and airplanes, public trains and buses run nearly barren of passengers.

Economists fear that by the time the coronavirus pandemic subsides and economic activity resumes, entire industries might be exhausted , proprietors across the country could lose their businesses and many workers could find themselves jobless.

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