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Review Article http://doi.org/10.18231/j.ijirm.2020.021
Empirical pharmacotherapy of COVID-19
R. Arbind Kumar Choudhary1*, L Madhan2, R Mani3, Isaac Christians Moses4
1
Assistant Professor, 2Professor and HOD, 3Dean, 4Special Officer, Dept. of Pharmacology, Government Erode Medical College &
Hospital, Erode, Tamil Nadu, India
*Corresponding Author: R. Arbind Kumar Choudhary
Email: arbindkch@gmail.com
Abstract
Researchers are studying several types of drugs to treat the novel coronavirus or COVID-19 that has spread to over 200 countries,
taking a massive human toll of nearly 2.6 lakh as of Wednesday morning. About 37 lakh positive cases have been identified,
including almost 50,000 cases in India. Most drugs being worked upon are repurposed and are largely anti-viral drugs used
previously to treat other conditions. For instance, Favipiravir, or Avigan was used to treat influenza in Japan. Likewise, Remdesivir
was tested on Ebola. Another treatment, while not a drug, that has shown promise is plasma therapy. The method uses convalescent
plasma which is extracted from the blood of recovered COVID-19 patients. This plasma contains antibodies that neutralize SARS-
CoV-2.Hydroxychloroquine and Chloroquine have not been shown to be safe and effective for treating or preventing COVID-19.
They are being studied in clinical trials for COVID-19, and temporary use during the COVID-19 pandemic for treatment of the
virus in hospitalized patients
Keywords: Empirical Pharmacotherapy, COVID-19, Remdesivir, Favipiravir, Chloroquine.
Introduction coronavirus, severe acute respiratory syndrome
The COVID-19 pandemic outbreak is unprecedented, but coronavirus 2, 2019-nCoV, SARS-CoV-2, SARS-CoV,
the global attention draws on the lessons learned from MERS-CoV, and COVID-19 in combination with
other disease outbreaks over the past era.1 As part of treatment and pharmacology.
WHO’s response, to promote activated to accelerate 1. For treatment of COVID-19, consider convalescent
diagnostics, vaccines and therapeutics for this novel plasma, IL-6 antagonists.
coronavirus. WHO is playing excellent job to improve 2. Patients taking angiotensin-converting enzyme
coordination between scientists and global health (ACE) inhibitors and angiotensin receptor blockers
professionals, accelerate the R&D process, and develop (ARBs) should continue them. Data regarding
new norms and standards to learn from and improve upon antimalarials are limited, and the drugs are not
the global response. As the COVID-19 pandemic it is benign. Before trials emerge, this article synthesizes
continues to spread across the world, killing thousands what little we know Narrative review of 18 articles
and bringing economies to their knees, doctors, scientists on pharmaceutical therapy for COVID-19.
and governments are on the lookout for safe and effective
treatments to help those who are sick. Most serious issue Remdesivir
is COVID-19 is that there is, as yet, no cure.2 This is an intravenous antiretroviral drug that was
Antiviral drugs that directly affect the coronavirus's developed to block infection with related coronaviruses
ability to thrive inside the body. and even Ebola, and is one of the drugs the WHO is
Drugs that can calm the immune system - patients helping to investigate. Recent found Remdisivir has
become seriously ill when their immune system shown to work against SARS-CoV-2 in cells in a dish in
overreacts and starts causing collateral damage to the a lab as well as in mice infected with the virus in some
body Antibodies, either from survivors' blood or made in clinical trials its show the exceptionally reduction in the
a lab, that can attack the virus. duration of the treatment of covid19 patient Remdesivir
A prospective literature review was performed using specifically targets key viral proteins particles which
google scholar and PubMed, scientific reports and lay involved in making new copies of the virus and prevents
press editorials. Identify relevant publication between them from function.3 Remdesivir has already been used
November, 2019 to April 2020. Search keyword included in some COVID-19 patients in the US and appears safe,
Covid-19 Special Issue, April, 2020;1(2):23-27 23R. Arbind Kumar Choudhary et al. Empirical pharmacotherapy of COVID-19
but large trials are needed to really know if this is the which has been developed by the Japanese company
case meanwhile many Indian pharmaceuticals company Toyama Chemical, which named it Avigan, and has been
were asked trails on Indian community by ICMR. tested by Wuhan University in China. In a study of 240
patients with pneumonia, although not severe cases, this
Lopinavir/Ritonavir drug was given to half of them while the other half were
This is a protease inhibitor drug used in combination given Umifenovir an antiviral used in Russia. 7 Those
with or without NRTIs vs NNRTIs. Against viruses like given Favipiravir saw that symptoms of fever and cough
HIV. It works in a similar way to remdesivir by blocking disappeared earlier but a similar number in each group
key viral proteins called “proteases”. There has been ended up needing oxygen or respirators, concluding that
much talk, but little evidence, that a pair of HIV drugs - Favipiravir was the "preferred" of the two drugs. As
lopinavir and ritonavir - would be effective at treating reported in the MIT Technology Review, owned by the
coronavirus. There has been some evidence they can Massachusetts Institute of Technology (MIT), there have
work in the laboratory, but studies in people have been been few (and no conclusive) studies on the benefits of
disappointing.5 The combination did not improve using certain compounds in the fight against coronavirus
recovery; reduce deaths or lower levels of the virus in with Favipiravir. Glenmark developed the drug’s API
patients with serious Covid-19. Recent trials have shown and formulations internally. Following the regulatory
lopinavir–ritonavir treatment did not act significantly to approval, the new trial will assess the product in Covid-
accelerate clinical improvement of the patient include 19 patients with mild to moderate infection.
reducemortality, or diminish throat viral RNA detect
ability in patients with serious Covid-19 and Ribavirin
asymptomatic. These early data should inform future It is too toxic at required doses: Ribavirin is a guanosine
studies to assess this and other medication in the analog that interferes with the replication of RNA and
treatment of infection with SARS-CoV-2. Whether DNA viruses. However, the antiviral activity of ribavirin
combining lopinavir–ritonavir with other antiviral agents, is not limited to interference with polymerases, that is,
as has been done in SARS5, 20 and is being studied in the structure of ribavirin also interferes with RNA
MERS-CoV, 15 might enhance antiviral effects and capping that relies on natural guanosine to prevent RNA
improve clinical outcomes remains to be determined degradation.8 Moreover, to further promote the
Nucleoside analogues: Not recommended. 6 destabilization of viral RNA, ribavirin inhibits natural
High conservation of the viral RdRp(RNA- guanosine generation by directly inhibiting inosine
dependent RNA polymerase) and low tolerance for monophosphate dehydrogenase in a pathway that is vital
mutations at key residues, resistance against NIs due to for the production of the guanine precursor to guanosine.
mutations in the viral RdRp has been observed in CoVs A large number of clinical studies and retrospective
and other RNA viruses. Treatment with combinations of analyses that will come from the 2019‐nCoV outbreak
potent anti-CoV NIs could increase the barrier to will put the controversy of ribavirin efficacy in a broader
resistance and enhance efficacy, especially if additive or context.9
synergistic interactions occur.
Antimalarial, e.g., Chloroquine and
Favipiravir Hydroxychloroquine
Trials of favipiravir underway. Favipiravir is effective as Based on extremely limited data,
it acts by inhibiting the virus from copying its genetic FDA granted emergency authorization for
material. It was discovered while searching for drugs to hydroxychloroquine. Both can be toxic, even lethal.10
treat a common flu and has strong inhibitory activity on Both are anti-malarial drug, my local hospital trails on
RNA-polymerase RNA, which is dependent on most Covid-19 for 10 days with 200 milligrams of
viruses with RNA genomes. Among them, influenza hydroxychloroquine three times a day. Some were also
viruses have been shown to be sensitive to this new given the antibiotic azithromycin. After six days, the
antiviral drug, including strains with genetic resistance to treated patients had a lower viral load than patients at
neuraminidase inhibitors, as per the Chinese authorities another center who did not receive that treatment,
Favipiravir to be a "clearly effective" antiviral drug
Covid-19 Special Issue, April, 2020;1(2):23-27 24R. Arbind Kumar Choudhary et al. Empirical pharmacotherapy of COVID-19
although with such a small sample the conclusions of the persons with known case of retinopathy, known
study cannot be taken as definitive. hypersensitivity to hydroxychloroquine, 4-
Both of these drugs used to treat malaria and some aminoquinoline compounds
extend autoimmune disease lupus. Reproposing is
emerge drastically and Chloroquine has been screened NSAIDs and Corticosteroids
against lots of different infections because in- vitro study Patients be infected with COVID-19 but remain
shown its block viruses – including SARS-CoV-2 - from asymptomatic for 10 days we could inject a patient who
getting enter into cells prevent infection. Chloroquine has was already infected without being aware of this. There
not been demonstrated to have effectiveness at is few research available in this area. It is plausible that
preventing disease and there is limited evidence so far the Glucocorticoids injected for musculoskeletal
that it can work for COVID-19, despite receiving a lot of conditions may have an impact on the potential B and T
hype from President Donald Trump. cell responses. It is unlikely this would be profound or
Caution should be taken with chloroquine as it can prolonged as most patients have only one injection.
have significant side effects in certain people and may Corticosteroid injections are performed locally with a
even block the immune response – the desired result in view to managing local symptoms but it is important to
lupus treatment. In-vitro studies have shown that recognize that the corticosteroid is absorbed from the
chloroquine is effective against several viruses, including local site and there is hypothalamic pituitary axis
severe acute respiratory syndrome coronavirus (SARS- suppression of ACTH and cortisol for up to 4 weeks
CoV). Multiple mechanisms of action have been following the administration of a single injection. Friedly
identified for chloroquine that disrupts the early stage of et al studied this effect in spinal injections and found that
coronavirus replication.11 Moreover, chloroquine affects methylprednisolone and triamcinolone injections resulted
immune system activity by mediating an anti- in pituitary suppression in 41% of patients at 3 weeks 12.
inflammatory response, which might reduce damage due This effect was not demonstrated with betamethasone or
to the exaggerated inflammatory response. At the time of dexamethasone compared to controls. It would be
the SARS epidemic, chloroquine was suggested as a drug sensible–if there was a need for a corticosteroid
that could be used to treat this infection. However, injection–to consider the use of betamethasone other
randomised, double-blind, controlled studies in humans management options or to defer the injection until the
to evaluate its efficacy for this use were not done, and the risk associated with this pandemic is reduced.
true clinical efficacy of chloroquine in treating
coronavirus infections was not established. Advisory 1. Avoid routine use.
guideline by ICMR (Indian Council of Medical Research, 2. Consider in refractory septic shock, severe acute
New Delhi) on the use of hydroxychloroquine as respiratory distress syndrome.
prophylaxis for SARS-CoV-2 infection Asymptomatic 3. Ibuprofen, Indomethacin, aspirin, Naproxen and
healthcare workers involved in the care of suspected or paracetamol/acetaminophen all reduced antibody
confirmed cases of COVID-19. production, but Ibuprofen has the greatest effect
Asymptomatic household contacts of laboratory 4. Both paracetamol and ibuprofen use are predictors
confirmed cases Dose: Asymptomatic healthcare workers for more respiratory problems with bacterial
involved in the care of suspected or confirmed cases of community acquired pneumonia, but nothing is
COVID-19: 400 mg twice a day on Day 1, followed by known re COVID-19
400 mg once weekly for next 7 weeks; to be taken with 5. If there is an indication for a corticosteroid injection,
meals. Asymptomatic household contacts of laboratory consider the use of betamethasone, consider other
confirmed cases: 400 mg twice a day on Day 1, followed management options or defer the injection until the
by 400 mg once weekly for next 3 weeks; to be taken risk associated with this pandemic is reduced.
with meals.
Biologics, e.g., Tocilizumab and Sarilumab
Exclusion / Contraindications Consider if cytokine release syndrome.
The drug is not recommended for prophylaxis in children
under 15 years of age. The drug is contraindicated in
Covid-19 Special Issue, April, 2020;1(2):23-27 25R. Arbind Kumar Choudhary et al. Empirical pharmacotherapy of COVID-19
Convalescent Plasma which ACE2 is suppressed may determine the severity of
In this procedure, blood is drawn from a person who has the resulting lung injury.
recovered from COVID-19 sickness. The serum is For instance, if there is a complete absence of ACE2,
separated and screened for virus-neutralizing antibodies. following viral entry, the circulating level of Ang II goes
The blood serum, which is rich in antibodies, it is then up, causing pulmonary injury in a bird flu model. In a
administered to a COVID-19 patient showing severe mouse model, infection with the virus causes the level of
symptoms. Unlike regular blood donation in which ACE2 in the heart to drop. People with SARS-CoV-2
donors have to wait for red blood cells to replenish show the same trend, with higher myocardial
between donations, plasma can be donated more inflammation levels. 15This is similar to and recorded
frequently, as often as twice a week, it said. This therapy since the earlier SARS epidemic. This has sparked new
is not simple to harness its has so may ethical barriers, interest in experiments with losartan in COVID-19, and
primarily due to the difficulty of obtaining significant in the use of recombinant ACE2 to regulate the RAA.
amounts of plasma from survivors corona virus. In
diseases like COVID-19, where most of the patients with Conclusion
severe symptoms with comorbidity and aged, and often There is currently no vaccine or treatment for COVID-
suffer from other medical conditions such as 19. Symptoms of a coronavirus usually go away on their
hypertension, diabetes, and so on, the effectiveness own. If symptoms feel worse than a common cold,
remains questionable. Few, a study in China found the contact your doctor. He or she may prescribe pain or
therapy effective, albeit on small sample size, in treating fever medication. The FDA is currently advising people
corona-virus patients. Trial was conducted with 200 ml to be cautious of websites and stores selling products that
dose of convalescent plasma was administered to 10 claim to prevent, treat or cure COVID-19. Additionally,
adult COVID-19 patients with severe symptoms. 13 The do not take any form of chloroquine unless it has been
patients witnessed significant improvement with the prescribed for you by your family doctor and purchased
disappearance of the virus reported among seven patients from a legitimate source.
without any severe adverse side-effects.in very short span
of time, the sick acquires only temporary passive Source of Funding
immunization. It lasts only till the time the injected None.
antibodies remain in the bloodstream—usually less than a
week.14 The good news is three critically ill COVID-19 Conflict of Interest
Indian-American patients in Houston are also showing None.
signs of recovery after they were transfused with the
blood plasma from recovered patients. Based on prior References
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