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ASMIYAH M.

CURRIE 04/07/2020

HYDROXYCHLOROQUINE

As indicated by CNN PHILIPPINES, The possibility of utilizing hydroxychloroquine to treat Covid-19 in the
midst of the novel coronavirus pandemic has started malignity and difference among government
officials and researchers.

There have been indications that the drug is effective in treating or preventing Covid-19, but the tests
haven't endured the due diligence of extensive clinical trials.

Hydroxychloroquine additionally known by the brand name Plaquenil - and its simple, chloroquine, are
gotten from quinine, which French scientific experts in 1820 segregated from the bark of the cinchona
tree, as indicated by Medicines for Malaria Venture. In 1934, German researchers made the engineered
chloroquine as a component of a class of against intestinal sickness, MMV said. Hydroxychloroquine is
the less-poisonous variant of chloroquine.

It's unclear. In labs it has demonstrated some efficacy against the severe acute respiratory syndrome
coronavirus responsible for the present pandemic. But the White House's coronavirus response
coordinator, Dr. Deborah Birx, has said that efficacy in test tubes doesn't mean it will work in humans.

Studies on humans have presented conflicting conclusions. For instance, a small Chinese study said the
prognosis was "good" but the drug requires further investigation. Meanwhile, a French study combining
the drug with a popular antibiotic.

While health experts say it's best to wait until clinical trials determine if hydroxychloroquine is safe and
effective in treating Covid-19,

Mode of action: Hydroxychloroquine increases lysosomal pH in antigen-presenting cells. In


inflammatory conditions, it blocks toll-like receptors on plasmacytoid dendritic cells
(PDCs).

Target site: The exact mechanisms of hydroxychloroquine are unknown. It has been shown that
hydroxychloroquine accumulates in the lysosomes of the malaria parasite, raising the
pH of the vacuole. This activity interferes with the parasite's ability to proteolyse
hemoglobin, preventing the normal growth and replication of the
parasite.Hydroxychloroquine can also interfere with the action of parasitic heme
polymerase, allowing for the accumulation of the toxic product beta-hematin.
Hydroxychloroquine accumulation in human organelles also raise their pH, which
inhibits antigen processing, prevents the alpha and beta chains of the major
histocompatibility complex (MHC) class II from dimerizing, inhibits antigen
presentation of the cell, and reduces the inflammatory response.
ASMIYAH M. CURRIE 04/07/2020

Dosing: 200 mg tablet

Malaria

Prophylaxis

Indicated for prophylaxis of malaria in geographic areas where chloroquine resistance


is not reported

400 mg (310 mg base) PO weekly, starting 2 weeks before exposure and continued
for 4 weeks after departure from endemic area OR

Weight-based dosing: 6.5 mg/kg (5 mg/kg base) PO once weekly, not to exceed 400
mg (310 mg base), starting 2 weeks before exposure and continued for 4 weeks after
leaving the endemic area.

Coronavirus Disease 2019 (COVID-19) (Off-label)

Data available as of March 24, 2020

Note: Limited data available; no drug is FDA approved to treat COVID-19

Hydroxychloroquine may be considered for use as part of an investigational protocol


for patients with COVID-19

Side effect: Headache, dizziness, diarrheal, stomach cramps, vomiting

Monitoring: Hydroxychloroquine tests

Before starting on hydroxychloroquine your doctor may take a blood test to check
that your liver and kidneys are working normally, but you won't need any regular
blood tests during the treatment. Your doctor will ask you about any problems with
your eyesight and may suggest you have a vision test.

LOPINAVIR

According to a journal by Neil M. Ampel, MD et al. (2020), there are no drugs documented to be
effective to treat patients with COVID-19 arising from coronavirus SARS-CoV-2 infection. However,
lopinavir (a protease inhibitor clinically available for HIV-1 infection) has shown in vitro activity against
SARS-CoV, and a study of lopinavir plus the protease inhibitor ritonavir demonstrated clinical efficacy for
human severe acute respiratory syndrome (SARS). To determine whether lopinavir- will be successful for
COVID-19, researchers conducted a randomized open- trial at a single hospital in Wuhan, China, starting
on January 18, 2020. They assigned 199 adult patients with SARS-CoV-2 infection, radiographically
confirmed pneumonia, and an oxygen saturation of <94% or a partial pressure of oxygen <300 mm Hg to
receive standard care alone or with oral lopinavir-ritonavir (400 mg–100 mg) twice daily for 14 days.
ASMIYAH M. CURRIE 04/07/2020

Lopinavir-ritonavir recipients and those receiving standard care did not differ significantly in time to
clinical improvement (median, 16 days), duration of intensive care unit stay, days of mechanical
ventilation, or days of oxygen support. Patients who received lopinavir-ritonavir had lower 28-day
mortality (19% vs. 25%), but the between-group difference was not significant. SARS-CoV-2 RNA
concentrations in throat swabs obtained over time did not differ between the two groups.

Mechanism of action Lopinavir/ritonavir inhibits the HIV protease


enzyme by forming an inhibitor-enzyme complex
thereby preventing cleavage of the gag-pol
polyproteins. Immature, non- infectious viral
particles are subsequently produced

Target site Lopinavir is a moderate inhibitor of CYP3A4 and


the combination of lopinavir with ... that no
relevant induction is provoked in the target cells of
HIV-1 therapy.

Dosing Usual Adult Dose for HIV Infection

Once-daily dosing regimen: Lopinavir 800 mg-


ritonavir 200 mg orally once a day

Twice-daily dosing regimen: Lopinavir 400 mg-


ritonavir 100 mg orally twice a day

Side effect Diarrhea, headache, nausea, vomiting, stomach


upset, drowsiness, dizziness, a bad taste in the
mouth, and trouble sleeping may occur. If any of
these effects persist or worsen, tell your doctor or
pharmacist promptly.

monitoring Therapeutic drug monitoring of lopinavir/ritonavir


given alone or with a non-nucleoside reverse
transcriptase inhibitor.

AZITHROMYCIN

According to news article, in another study, posted on medRxiv, which has not yet been peer-reviewed,
Chinese scientists from Renmin Hospital of Wuhan University, in Wuhan, China, gave
hydroxychloroquine to patients with only mild infections who were free of medical issues, similar to the
Gautret study. Results revealed that the 31 patients who received the medication reported a decrease
of their symptoms 24 hours earlier than control group patients. In fact, signs of pneumonia increased in
25 of the 31 patients in the control group against 17 of 31. As noted in several of the comments
ASMIYAH M. CURRIE 04/07/2020

associated with the manuscript, there are issues related to the translation of the paper, thus clouding
interpretations of some of the results. The paper also appears to focus more on pneumonia than COVID-
19. However, these issues may be cleared up or addressed once the paper finishes the peer-review
process.

Many researchers are warning that despite the recent approval of this drug for use against COVID-19,
questions remain as to the efficacy of this treatment. As Dr Molina and colleagues note: “Ongoing
randomized clinical trials with hydroxychloroquine should provide a definitive answer regarding the
alleged efficacy of this combination and will assess its safety.”

To date there are no found drugs or pharmaceuticals that can truly cure or treat Covid-19 effectively.
Most of these experimental drugs especially the antivirals are actually toxic and have been known to
have caused deaths in Covid-19 patients. There are a number of safer drugs and herbs and TCM
preparations being researched and undergoing clinical trials and we will be covering on these shortly.

warns all that there is so much fake news and misinformation being released by government agencies
and health authorities and even so called pharma and drug companies merely for reasons to pacify the
public, for political and security reasons and also for reasons of greed and money.

Mechanism of action Azithromycin prevents bacteria from growing by


interfering with their protein synthesis. It binds to
the 50S subunit of the bacterial ribosome, thus
inhibiting translation of mRNA. Nucleic acid
synthesis is not affected.

Target site Azithromycin is modification of the 23S rRNA


target, most often by methylation.

Dosing injection, lyophilized powder for reconstitution


500mg/vial
tablet
250mg,500mg
oral suspension
100mg/5mL
200mg/5mL

Side effect Diarrhea, nausea, abdominal (belly) pain, vomiting,


headache

monitoring Azithromycin reversibly binds to the bacterial


ribosome and inhibits protein synthesis. The drug
has an absolute oral bioavailability of 35−42% in
healthy volunteers and people with cystic fibrosis
and a long half-life due to extensive uptake in
ASMIYAH M. CURRIE 04/07/2020

tissue, particularly lung, tonsil and prostate.

DARUNAVIR

According to an article news, POZ that the maker of HIV med Prezista (darunavir) warned against reports
that the drug could be used to treat COVID-19, the disease caused by the novel coronavirus.

“Johnson & Johnson [J&J] has no evidence that darunavir has any effect against the virus that causes
COVID-19,” “Based on preliminary, unpublished results from a previously reported in vitro experiment, it
is not likely [darunavir] will have significant activity against [the novel coronavirus] when administered
at the approved safe and efficacious dose for the treatment of HIV-1 infection.”

Mechanism of action Darunavir has activity against HIV-1. Mechanism of


Action: Darunavir inhibits the HIV protease
enzyme by forming an inhibitor-enzyme complex
thereby preventing cleavage of the gag-pol
polyproteins. Immature, non-infectious viral
particles are subsequently produced

Target site Darunavir is known to bind to two distinct sites on


the enzyme: the active site cavity and the surface
of one of the flexible flaps in the protease dimer.
Darunavir is an N,N-disubstituted
benzenesulfonamide bearing an unsubstituted
amino group at the 4-position, used for the
treatment of HIV infection.

Dosing Tablet
75mg
150mg
400mg
600mg
800mg

oral suspension
100mg/mL

Side effect diarrhea, nausea, vomiting, heartburn,


stomach pain, weakness, headache,
skin rash, or changes in the shape or location of
body fat (especially in your arms, legs, face, neck,
breasts, and waist)
ASMIYAH M. CURRIE 04/07/2020

monitoring Therapeutic drug monitoring of darunavir/ritonavir


in pregnancy.

Bibliography
Hydroxychloroquine and Covid-19: an explainer. (April 06 2020). CNN.

Inpatient Use of Mobile Continuous Telemetry for COVID-19 Patients Treated with Hydroxychloroquine
and Azithromycin. (april 2020).

Duddu, P. (30 MARCH 2020). Coronavirus treatment: Vaccines/drugs in the pipeline for COVID-19.

F1000Prime recommendation of A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-


19. (March 20, 2020).

MARMOR, M. F. (2020). COVID-19 and Chloroquine/Hydroxychloroquine: is.

Owens, B. (april 1 2020). Excitement around hydroxychloroquine for treating COVID-19 causes
challenges for rheumatology. The Lancet.

Reference:

https://www.rxlist.com/prezista-side-effects-drug-center.htm#overview

https://medlineplus.gov/druginfo/meds/a607042.html

https://www.webmd.com/drugs/2/drug-1527-3223/azithromycin-oral/azithromycin-250-500-mg-
oral/details

https://www.healthline.com/health/azithromycin-oral-tablet

https://www.webmd.com/drugs/2/drug-5482/hydroxychloroquine-oral/details

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