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Drugs acting on renin angiotensin system and use in ill patients with COVID-19.
Therapie. 2020 Jul-Aug; 75(4):319-325.T

Abstract

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.

Authors+Show Affiliations

Service de pharmacologie, université de Caen-Normandie, UNICAEN, CHU de Caen Normandie, EA 4650, 14000 Caen, France. Electronic address: alexandre-j@chu-caen.fr.University Grenoble Alpes, centre régional de pharmacovigilance de Grenoble, Inserm, HP2, 38000 Grenoble, France.Service de pharmacologie, université de Rouen Normandie, UNIROUEN, CHU de Rouen Normandie, UMR Inserm U1096 EnVI, 76000 Rouen, France.Service d'hypertension artérielle et thérapeutique PCVM, UMR 1027 université Toulouse 3, CHU Rangueil, 31000 Toulouse, France.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32553503

Citation

Alexandre, Joachim, et al. "Drugs Acting On Renin Angiotensin System and Use in Ill Patients With COVID-19." Therapie, vol. 75, no. 4, 2020, pp. 319-325.
Alexandre J, Cracowski JL, Richard V, et al. Drugs acting on renin angiotensin system and use in ill patients with COVID-19. Therapie. 2020;75(4):319-325.
Alexandre, J., Cracowski, J. L., Richard, V., & Bouhanick, B. (2020). Drugs acting on renin angiotensin system and use in ill patients with COVID-19. Therapie, 75(4), 319-325. https://doi.org/10.1016/j.therap.2020.05.009
Alexandre J, et al. Drugs Acting On Renin Angiotensin System and Use in Ill Patients With COVID-19. Therapie. 2020;75(4):319-325. PubMed PMID: 32553503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Drugs acting on renin angiotensin system and use in ill patients with COVID-19. AU - Alexandre,Joachim, AU - Cracowski,Jean-Luc, AU - Richard,Vincent, AU - Bouhanick,Béatrice, AU - ,, Y1 - 2020/05/20/ PY - 2020/5/4/received PY - 2020/5/15/accepted PY - 2020/6/20/pubmed PY - 2020/9/2/medline PY - 2020/6/20/entrez KW - Arterial hypertension KW - Renin-angiotensin-aldosterone system SP - 319 EP - 325 JF - Therapie JO - Therapie VL - 75 IS - 4 N2 - 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. SN - 1958-5578 UR - https://www.unboundmedicine.com/medline/citation/32553503/Drugs_acting_on_renin_angiotensin_system_and_use_in_ill_patients_with_COVID_19_ DB - PRIME DP - Unbound Medicine ER -