So as it relates to the science and practice of pharmacy
any drug approved for use in any condition not only to treat Covid-19 but any
illness or condition; has to be supported by rigorous studies which are
properly designed and conducted and would have to support the safe
administration of that agent for humans.
So medications go through different phases of trials to see
if a drug is suitable for use in the care of humans. Before these clinical
trials you have preclinical research to assess and test treatments these are
primarily conducted in animals. After these pre-clinical animal research, clinical
trials are conducted in humans and go through five phases to see if the drug is
safe and actually work in humans.
The five phases include phase 0_____ drug is assessed to
see how it works and is given to about 10-15 persons
Phase 1________ finds the best dose at which the entity
works with minimal side effects
Phase 2_______the drug is then compared to the standard
care available. This assesses which therapy works best and up to 100 persons
are enrolled in this phase.
Phase 3________these are trials in which the drug is
compared to standard care, all participants in the trial are similar so that if
there are any changes in outcome it is not due to chance but due to the fact
that the drug does work. A drug can be approved for use in the population by
the FDA at this phase. (currently the case with the vaccines being used
internationally since about December 2020)
Phase 4______at this point the drug is then observed in a
larger population in amounts of hundreds to thousands. At this phase the long-lasting
or short-lived side-effects can be observed in larger groups of participants.
So Pharmacists utilise treatments or try to promote only
drugs that have been approved for use by these bodies like the FDA, CDC and
European bodies.
So what was happening due to the deadly nature of the Covid
-19 and the desperate search for a cure or to save lives, scientists and
clinicians were examining the lifecycle of the virus to see at which point
successful attempts could have been done to interrupt the cycle and cure the
illness.
The table below outlines the different opportunities for
intercepting the virus’ activity that were being investigated and also where in
the lifecycle a few of the agents we know act.
|
Potential Therapeutic Interventions |
|
Rationale for Use of Drugs |
|
Entry via the coronavirus spike attachment to the human angiotensin 2
receptor in lungs, small intestines |
|
Broad entry inhibitors (primarily hydroxychloroquine and chloroquine) |
|
|
|
|
|
Translation of viral RNA and production of 2 large polyproteins |
|
Interference with host factors involved in translation |
|
Proteolysis of the polyproteins into 16 nonstructural proteins,
including 2 proteases, RNA-dependent RNA polymerase, helicase, and
exonuclease, which checks accuracy of |
|
Inhibition of proteolysis |
|
Replication and transcription of viral RNA |
|
Protease inhibitors |
|
Release of new virions |
|
Interference with host factors
involved in virion release |
Adapted
Source: Denison, 2020; de Wit et al., 2016, Guo Y-R et al., 2020
Abbreviations: ACE, angiotensin converting enzyme; ARBs, angiotensin 2
receptor blockers
aInvestigational agent
Some agents
are promising, while others are not performing well clinically, the care
remains mostly supportive.
The National Institutes of Health
released Covid-19 treatment guidelines these cover critical care, therapeutic options under investigation,
and concomitant medications.
“The treatment guidelines panel
concluded that insufficient data are available to make a recommendation
regarding use of chloroquine or hydroxychloroquine as single agents outside
clinical trials.” This was primarily due to the cardiac effects where the Q-T
phase in heart activity was prolonged.
Lopinavir/rotinavir (proteinase
inhibitors) should not be used outside clinical trials. For Jamaica these medications
are reserved for specific populations and so this restriction was welcomed for
our territory.
Statins or
ACE inhibitors/ARBs should not be started as treatment for COVID-19 this
approach was being used because of the affinity of the virus for the
Angiotensin receptors so blocking these receptors was a strategy being
investigated.
Ivermectin is
an anthelmintic agent but because of its ability to inhibit the replication of
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cell cultures
there was a rush for its use. As I explained before this activity was in
pre-clinical research in-vitro (not in humans). For human use and effectiveness
it had to be used in too a large dose (100 times higher than the safe dose that
is approved for use in humans), there was a warning issued in April 2020 by the
FDA that use of ivermectin in humans for Covid-19 treatment was not allowed.
Use of the
investigational nucleotide analogue remdesivir, has been approved for use in
patients who needed supplemental oxygen and not those on ventilators. The
Government of Jamaica was lobbied by PSJ under our Immediate Past President Dr.
Ernestine Watson last year to assist in making the drug readily available for
use in the island as it greatly improved the survival of patients once given
early enough in the illness.
No difference
was identified between use of NSAIDs or acetaminophen for fever reduction and
so those patients could continue therapy. Advice about systemic corticosteroids
is similar to other guidelines — no routine use other than in the acute
respiratory distress syndrome (ARDS) setting.
Dexamethasone,
a corticosteroid, was found to improve survival in hospitalized patients who
require supplemental oxygen, with the greatest effect observed in patients who
require mechanical ventilation. Therefore, the use of dexamethasone is strongly
recommended in this setting.
In the
earliest stages of infection, before the host has mounted an effective immune
response, anti-SARS-CoV-2 antibody-based therapies may have their greatest
likelihood of having an effect.
The
anti-SARS-CoV-2 monoclonal antibodies bamlanivima and casirivimab
plus imdevimab are available through Emergency Use Authorizations for
outpatients who are at high risk for disease progression.
Vaccines
So based on
the Nature of the Covid-19 disease the only way to cure it is to use a vaccine.
At the moment there are different types of vaccines inactivated vaccines,
live-attenuated vaccines, and protein subunit vaccines, and protein subunit
vaccines. The Food and Drug Administration (FDA) has issued an Emergency Use
Authorization (EUA) for use of vaccines which were in the Phase 3 stage of
trials as we have seen with Moderna, Pfizer and Astra Zeneca vaccines.
MRNA vaccines
These are vaccines which are made using a new technology. These mRNA vaccines have strands of genetic material called mRNA inside a special coating. That coating protects the mRNA from enzymes in the body that would otherwise break it down. It also helps the mRNA enter the dendritic cells and macrophages in the lymph node cells near the vaccination site.
The mRNA strands
gives instructions to the cell on how to make the spike protein that is
specific to the SARS-CoV-2. Only a part of the protein is made so there is no
harm to the person who is vaccinated it only stimulates the immune system to
fight the virus. It never enters to cell to change anyone’s DNA or other
genetic material of the cell.
Like all vaccines, COVID-19 mRNA vaccines have been rigorously tested
for safety before being authorized for use in the United States.
Often patients are concerned about live vaccines. mRNA vaccines are not live vaccines and do not use an infectious element, so they carry no risk of causing disease in the person vaccinated.
Researchers have been studying them for decades so research has been taking place with this technology in clinical trials for influenza, Zika, rabies and cytomegalovirus (CMV). Technological advancements in RNA biology so challenges with stability, safety and minimised immune response have been overcome.
This mRNA
technology has been investigated in numerous preclinical and clinical
studies to cancer treatment to stimulate immune responses targeted at
clearing or reducing malignant tumors, due to the antigen response.
Benefits of RNA
mRNA vaccines have several
benefits compared to other types of vaccines including use of a non-infectious
element,
- Shorter manufacturing times, and potential for targeting of multiple diseases.
- mRNA vaccines can be developed in a laboratory using a DNA template and readily available materials.
- This means the process can be standardized and scaled up, making vaccine development faster than traditional methods.
- In addition, DNA and RNA vaccines typically can be moved most rapidly into the clinic for initial testing.
- In the future, mRNA vaccine technology may allow for one vaccine to target multiple diseases
We at the PSJ
have confidence in the vaccination effort that the government of Jamacia will
be seeking to undertake in April 2021 so that we are lobbying the government to
adjust legislations so that Pharmacists can be recognised as providers of
immunisation for the Adult population so that we can assist with their goal of
vaccinating the Jamaican population in April 2021 of this year.
Before this
occurs PSJ will be undertaking an
islandwide training of pharmacists as immunisers in anticipation for this initiative.
So the Jamaican government can count on pharmacists being ready to help
increase the uptake of persons getting vaccinated because of this training that
PSJ will be undertaking. This will be similar to our international counterparts
who are utilising pharmacists to ensure the success of their campaigns.
References
Phases of Clinical Trials.
https://www.nccn.org/patients/resources/clinical_trials/phases.aspx
Vaccines and Immunisations:
Recipient Education. U.S. National Institutes of Health. 2021 January 16th
Available
Sanders JM,
Monogue ML, Jodlowski TZ, et al. Pharmacologic treatments for coronavirus
disease 2019 (COVID-19): a review. JAMA. 2020:
10.1001/jama.2020.6019. [Epub in advance of print, April 13, 2020]
Yang SNY,
Atkinson SC, Wang C, et al. The broad spectrum antiviral ivermectin targets the
host nuclear transport importin alpha/beta1 heterodimer. Antiviral Res. 2020;177:104760.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/32135219.
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020;178:104787. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32251768.
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