Pharmacology

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Pharmacology

Pharmacological aspects

22  articles in this collection
Written by Mathias Castonguay, Laurie-Anne Duquette, Camille Blouin, Johann Graham, 

The Use of Corticosteroids in Adrenal Insufficiency

The World Health Organization has recently advised against corticosteroids use in COVID-19 patients, unless indicated for another reason, as in adrenal insufficiency (AI). Indeed, both patients with primary or secondary AI are at higher risk of developing infections, precipitating an adrenal crisis. No specific protocol has been studied for AI patients in the context of […]

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06/05/2020

Understanding the Role of Vitamin D

Does vitamin D supplementation have a role in COVID-19? A striking observation about COVID-19 is the greater severity among different populations. Indeed, statistics show that older age, non-Caucasian individuals, male gender, obesity and patients with multiple comorbidities have poorer outcomes. Moreover, most respiratory viruses peak during winter. Vitamin D deficiency, which is more prevalent in […]

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05/17/2020

Is Testosterone a Good or a Bad Guy?

Worldwide epidemiology studies have found higher number of cases of SARS-CoV-2 in men. Moreover, male gender carries a worse prognosis, especially in younger adults. Two opposing theories about androgens have been proposed to explain the gender gap. Testosterone as a promoter of COVID-19 infection: Transmembrane protease serine 2 (TMPRSS2) is a cellular co-receptor required for […]

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05/11/2020

Corticosteroids and Other Medications in Preterm Labour

Antenatal corticosteroids for fetal lung maturation Studies that have shown worse outcomes for infected patients with the prolonged use of high-dose corticosteroids did not consider baseline morbidity. However, in an antenatal setting, the doses are much smaller and the exposure is not prolonged.  Antenatal steroids must be used with prudence particularly in critically ill pregnant […]

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04/13/2020

Treatment Options for Pregnant Women

Confirmed cases should be treated in a negative pressure isolation room when available. Critically ill patients should be placed in left lateral decubitus. Treatment options include oxygen therapy, hydration, and empirical antibiotic therapy. The use of antiretroviral therapy and chloroquine is under investigation. Target saturation is ≥ 95%.   Is hydroxychloroquine safe in pregnancy? Some […]

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04/15/2020

Summary of Emerging Treatment Options

Investigational Drugs Results in favor of the use* Results not in favor of the use** Efficacy proven Antiviral agents Chloroquine∆,1-3 ✓ ✓ Hydroxychloroquine∆,4-11 ✓ ✓ Hydroxychloroquine + Azithromycin∆,5,7,8,10 ✓ ✓ Ivermectin12 N/A N/A Favipivir13,14 ✓ Lopinavir-Ritonavir15,16 ✓ Oseltamivir17 ✓ Remdesivir18,19 ✓ ✓ Convalescent plasma20 ✓ Supporting agents Anakinra (IL-1 receptor antagonist) N/A N/A Baricitinib (JAK […]

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04/26/2020

Rationale for the Use of Interferons in New Pandemic

Before COVID-19 Interferons are among the earliest cytokines produced during a viral infection2 and generate a cascade that culminates in controlling viral replication and inducing an adaptive immune response.3  Type 1 interferons (IFN-1) have frequently been studied against coronaviruses, having the most antiviral properties. They can be subdivided in α, β, ε, ω and κ […]

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05/06/2020

Should We Discontinue ACE-I and ARB?

Despite some evidence of up-regulation of ACE2 by RAAS inhibition, with its theoretically associated higher susceptibility to COVID-19 infection and increased viral load, there is currently no data suggesting a causal relationship between ACE2 activity and COVID-19 associated mortality; therefore, based on currently available data, the assumption of a causal relationship between ACE-I or ARB […]

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04/03/2020

Rationale of Favipiravir Against New Pandemic

Before COVID-19: Favipiravir is approved in Japan and China for treating severe influenza virus, as well as a promising prophylaxis and treatment of Ebola virus and treatment of Fever with Thrombocytopenia Syndrome.1   It was shown to be safe in several human clinical trials for influenza.1  It is renowned for its broad anti-RNA virus action1, and […]

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04/12/2020

Prophylactic Anticoagulation in Sepsis Induced Coagulopathy

LMWH (low molecular weight heparin) at a prophylactic dose may reduce mortality in patient with markedly elevated D-dimers (6 upper limit normal) or  a SIC (sepsis-induced-coagulopathy criteria) ≥4, as 28-day mortality rates were statistically lower for patients meeting these criterias. Higher doses should be considered in patient with a high body mass index.  Rationale of […]

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04/07/2020

The Use of Remdesivir in Severe Cases

What is Remdesivir? Remdesivir (or GS-5734) is a nucleoside analogue with antiviral activity developed by Gilead Sciences. It inhibits viral RNA replication by incorporating itself in the nascent viral RNA chain. It was originally developed for the treatment of Ebola virus infection, for which it was judged to be less effective than the monoclonal antibody […]

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04/06/2020

Rationale of Antiparasitic Drug Ivermectin as an Agent Against Novel Coronavirus

Before COVID19: Ivermectin has been known for its antiviral properties in vitro, as demonstrated in multiple studies: It inhibits viral replication of several alphaviruses and flaviviruses, including yellow fever virus, dengue, West Nile Virus, Venezuelan equine encephalitis virus (VEEV), influenza1,3 and Chikungunya virus4, via its effect on Importin α/β1, a protein that enables the importation […]

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04/07/2020

Transplantation of Mesenchymal Stem Cells in Critically Ill Patients

Before COVID-19 Mesenchymal stem cells (MSCs) are multipotent, self-renewing stromal cells present mainly in the bone marrow and adipose tissue, that are able to differentiate into various cell types, including myocytes, adipocytes, osteoblasts and chondrocytes.2 MSCs have shown their effectiveness in immune-mediated inflammatory diseases2: They have been recognized to have immunomodulatory, immunosuppressive, and regenerative effects, […]

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04/16/2020

Tocilizumab for Cytokine Storm

What is Tocilizumab? Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor, initially indicated only for use in patients with moderate and severe rheumatoid arthritis, but has now been FDA approved for other conditions including cytokine release syndrome, a notable side effect of CAR-T cell therapy.    Cytokine storm in Covid-19 ? The […]

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04/14/2020

How Immune Response to Previous Coronaviruses Pandemics May Help

Innate Immune Responses: Overall genomic similarity is observed between SARS-CoV2 and the 2 other viruses. Early elevation of pro-inflammatory cytokines were found in SARS-CoV2 infection but also in SARS-CoV and MERS-CoV pandemics. This suggests a potential similar cytokine storm-mediated disease. Type 1 interferon response is suppressed by both SARS-CoV and MERS-CoV viruses during infection by […]

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04/12/2020

Potentials and Potencies of JAK Inhibitors

Janus kinase (JAK) inhibitors reduce inflammation by inhibiting cytokine signaling. Their potential role in managing the cytokine storm leading to acute lung injury, acute respiratory distress syndrome and death have been evoked. 1,2 Their biggest concern is that the inhibition of a wide variety of inflammatory cytokines includes INF-a, which is important in fighting virus.1 […]

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04/13/2020

Angiotensin II for Treatment of Vasodilatory Shock

Pro-inflammatory processes in ARDS disrupt ACE function in the pulmonary endothelium. Thus, Ang-1 (angiotensin I) cannot be hydrolyzed to Ang-2. Excess Ang-1 contributes to hypotension via 4 physiological mechanisms: (1) decrease in smooth muscle contraction, (2) metabolism into Ang-(1-7) to agonize vasodilatory MAS and AT2 receptors (3) Activation of NO production (4) Impairs hydrolysis of […]

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04/06/2020

Bringing Colchicine Back

Colchicine’s background The therapeutic use of colchicine is well-established in gout and familial Mediterranean fever. Its primary mechanism of action is the inhibition of microtubule polymerization. Other mechanisms of action are not fully understood. Colchicine interferes with several inflammatory pathways. Immunomodulatory and anti-inflammatory effects are partly through: Inhibition of NALP3 inflammasome responsible for caspase-1 activation […]

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04/04/2020

Rationale of Old Antimalarial Drugs Against New Pandemic

Before COVID-19: Chloroquine has demonstrated its antiviral properties in vitro in the past against SARS-CoV-1 and MERS-CoV.1,2,3 It inhibits replication of several viruses in pH-dependent steps including members of the flaviviruses, retroviruses and coronaviruses.2 Immunomodulatory effects of chloroquine suppress the production/release of TNF-α and IL-6, which mediate the inflammatory responses in several viral diseases.2 Hydroxychloroquine […]

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04/01/2020

Should NSAIDs Be Avoided?

Evidence of possible harm was associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) in acute respiratory infections (ARI).1,2,3,4,5 A review of case-control studies suggests higher rates of complications.2,3 Observational studies suggest further increased risks of acute myocardial infarction and stroke, in addition to the risk associated with ARI itself.4,5  Meanwhile NSAIDs are already known […]

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04/04/2020

Effects of Corticosteroids in Lung Injury

Theoretically, corticosteroids suppress lung inflammation in acute lung injury and acute respiratory distress syndrome (ARDS). However, by inhibiting host immune responses they also inhibit pathogen clearance. Possible harm was shown with its use in other respiratory infections including: Delayed viral clearance (SARS-CoV and MERS-CoV) Increased secondary infection (influenza) Increased mortality and length of stay in […]

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04/01/2020

Lopinavir-Ritonavir in Severe Cases

No benefit was observed with lopinavir-ritonavir treatment in addition to standard of care in hospitalized adult patients with severe COVID-19. No significant difference in the time to clinical improvement or mortality at 28 days was shown between the lopinavir-ritonavir group and the standard of care group.  Viral RNA was detectable in similar percentages of patients […]

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04/01/2020