Prevention of risks associated with inappropriate use/unnecessary consumption of medicines.

In the code of public health, misuse is defined as intentional and inappropriate use of a medicine or product, which is not in accordance with the terms of the marketing authorisation or the registration as well as with good practice recommendations. Very often this involves an individual or the interaction of several individuals including the patient, his/her carers, prescriber(s) and/or dispensers. Misuse is common; it is the source of medicinal adverse effects for which a significant part is avoidable. Medicines initially prescribed or dispensed in the context of their marketing authorization (MA) can also be the subject of primary dependency and misappropriation. Companies which develop medicines nationally make declarations to the ANSM (French National Agency for the Safety of Medicines and Health Products) and implement measures to limit non-compliant use of their products. Recently, the coronavirus disease-2019 (COVID-19) pandemic has highlighted the influence and societal impact of drug misuse. The finding of the existence of systemic misuse, the impossibility of proposing simple solutions leads us to propose two main areas for improved information and the training of users and health professionals in medicines in the context of multi-faceted interventions: prevention of misuse on the one hand and its identification and treatment on the other hand.

[Diabetes and COVID-19]. / Diabète et COVID-19.

According to previous reports, diabetes seems to be associated with serious clinical events due to COVID-19. But is diabetes per se a risk factor of being infected by the virus? We discuss these points. Data about the antidiabetic drugs are scarce. Dipeptidylpeptidase-4 (DPP-4) is found as both a cell surface protein ubiquitously expressed in many tissues and as a soluble molecule found in serum/plasma, fluids. DPP-4 is involved in infection of cells by some viruses. We relate data about the use of DPP-4 inhibitors in diabetic patients. We conclude relating French and international recommendations in people with diabetes.

Drugs acting on renin angiotensin system and use in ill patients with COVID-19.

Some concerns about the prescription of drugs acting on the renin-angiotensin system (angiotensin-converting enzyme 1 (ACE1) inhibitors, ACEi; angiotensin II type 1 receptor blockers, ARB) have emerged due to SARS COV2 and COVID-19 pandemic. These very legitimate questions are directly the consequence of the recent recognition of the fundamental role of ACE2 (angiotensin-converting enzyme 2) in COVID-19 infection. Indeed, SARS COV2 utilizes ACE2 as a membrane receptor to enter target cells. Consequently, the putative impact of drugs modulating the renin-angiotensin system on the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection emerged. As a membrane-bound enzyme (carboxypeptidase), ACE2 inactivates angiotensin II and therefore physiologically counters its effects. Due to a different structure compared with ACE1, ACE2 is insensitive to ACEIs. In vitro, both ARBs and ACEi appear able to upregulate ACE2 tissue expression and activity but these results were not confirmed in Humans. The exact impact of both ARBs and ACEis on COVID-19 infection is definitively known and preliminary results are even in favor of a protective role confers by these drugs. Due to the crucial role of ACE2, some groups support the hypothesis that a modulation of ACE2 expression could represent a valuable therapeutic target could confer protective properties against inflammatory tissue damage in COVID-19 infection. So, studies are currently ongoing to test the impact of elevated ACE2 membrane expression, administration of ARB and infusion of soluble ACE2. In summary, based on the currently available evidences and as recommended by several medical societies, ACEi or ARB should not be systematically discontinued because to date no safety signal was raised with the use of these drugs.

Diabetes and COVID-19

Summary According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs – including those targeting DPP4-related pathways – produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance.

Genesis of an emergency public drug information website by the French Society of Pharmacology and Therapeutics during the COVID-19 pandemic.

On March 16, 2020, the French Society of Pharmacology and Therapeutics put online a national Question and Answer (Q&A) website, https://sfpt-fr.org/covid19 on the proper use of drugs during the COVID-19 pandemic. The working group 'Drugs and COVID-19' was composed of a scientific council, an editorial team, and experts in the field. The first questions were posted online during the first evening of home-confinement in France, March 17, 2020. Six weeks later, 140 Q&As have been posted. Questions on the controversial use of hydroxychloroquine and to a lesser extent concerning azithromycin have been the most consulted Q&As. Q&As have been consulted 226 014 times in 41 days. This large visibility was obtained through an early communication on Twitter, Facebook, traditional print, and web media. In addition, an early communication through the French Ministry of Health and the French National Agency for Medicines and Health Products Safety ANSM had a large impact in terms of daily number of views. There is a pressing need to sustain a public drug information service combining the expertise of scholarly pharmacology societies, pharmacovigilance network, and the Ministry of Health to quickly provide understandable, clear, expert answers to the general population's concerns regarding COVID-19 and drug use and to counter fake news.

Renin-angiotensin-aldosterone system and COVID-19 infection.

With the multiplication of COVID-19 severe acute respiratory syndrome cases due to SARS-COV2, some concerns about angiotensin-converting enzyme 1 (ACE1) inhibitors (ACEi) and angiotensin II type 1 receptor blockers (ARB) have emerged. Since the ACE2 (angiotensin-converting enzyme 2) enzyme is the receptor that allows SARS COV2 entry into cells, the fear was that pre-existing treatment with ACEi or ARB might increase the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection. The present article discusses these concerns. ACE2 is a membrane-bound enzyme (carboxypeptidase) that contributes to the inactivation of angiotensin II and therefore physiologically counters angiotensin II effects. ACEis do not inhibit ACE2. Although ARBs have been shown to up-regulate ACE2 tissue expression in experimental animals, evidence was not always consistent in human studies. Moreover, to date there is no evidence that ACEi or ARB administration facilitates SARS-COV2 cell entry by increasing ACE2 tissue expression in either animal or human studies. Finally, some studies support the hypothesis that elevated ACE2 membrane expression and tissue activity by administration of ARB and/or infusion of soluble ACE2 could confer protective properties against inflammatory tissue damage in COVID-19 infection. In summary, based on the currently available evidence and as advocated by many medical societies, ACEi or ARB should not be discontinued because of concerns with COVID-19 infection, except when the hemodynamic situation is precarious and case-by-case adjustment is required.