The treatment of SARS-CoV2 with antivirals and mitigation of the cytokine storm syndrome: the role of gene expression.

In the absence of a vaccine, the treatment of SARS-CoV2 has focused on eliminating the virus with antivirals or mitigating the cytokine storm syndrome (CSS) that leads to the most common cause of death: respiratory failure. Herein we discuss the mechanisms of antiviral treatments for SARS-CoV2 and treatment strategies for the CSS. Antivirals that have shown in vitro activity against SARS-CoV2, or the closely related SARS-CoV1 and MERS-CoV, are compared on the enzymatic level and by potency in cells. For treatment of the CSS, we discuss medications that reduce the effects or expression of cytokines involved in the CSS with an emphasis on those that reduce IL-6 because of its central role in the development of the CSS. We show that some of the medications covered influence the activity or expression of enzymes involved in epigenetic processes and specifically those that add or remove modifications to histones or DNA. Where available, the latest clinical data showing the efficacy of the medications is presented. With respect to their mechanisms, we explain why some medications are successful, why others have failed, and why some untested medications may yet prove useful.

So Many Antihyperglycemics: How to Choose? A Practical Approach.

Guidelines from around the world have stressed the importance of glycemic control in the management of patients with type 2 diabetes (T2DM) to reduce the risk of developing complications. To achieve this goal, both lifestyle and pharmacologic therapies are available. There are 9 classes of antihyperglycemic therapies available in Canada and each class provides a different mechanism of action to address the pathophysiology of T2DM. Metformin remains the first choice for pharmacologic therapy. Thereafter, individualization is essential. If there is significant hyperglycemia at diagnosis, initial combination therapy should be considered. The choice of therapy after metformin depends on a number of factors with the first consideration being the presence or absence of cardiovascular disease. If present, an agent with proven cardiovascular benefit should be added. Otherwise, individualization should be based on desired glycemic lowering, risk of hypoglycemia, effect on weight, cardiovascular effects, other side effects and accessibility.