Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Five-Membered Nitrogen Heterocycles Angiotensin-Converting Enzyme (ACE) Inhibitors Induced Angioedema: An Underdiagnosed Condition.

Version 1 : Received: 1 February 2024 / Approved: 2 February 2024 / Online: 2 February 2024 (11:53:14 CET)

A peer-reviewed article of this Preprint also exists.

Papapostolou, N.; Gregoriou, S.; Katoulis, A.; Makris, M. Five-Membered Nitrogen Heterocycles Angiotensin-Converting Enzyme (ACE) Inhibitors Induced Angioedema: An Underdiagnosed Condition. Pharmaceuticals 2024, 17, 360. Papapostolou, N.; Gregoriou, S.; Katoulis, A.; Makris, M. Five-Membered Nitrogen Heterocycles Angiotensin-Converting Enzyme (ACE) Inhibitors Induced Angioedema: An Underdiagnosed Condition. Pharmaceuticals 2024, 17, 360.

Abstract

Angiotensin-converting enzyme (ACE) inhibitors are used primarily in the treatment of hypertension, heart failure, and in the acute phase of myocardial infarction. Lisinopril [N2-[(1S)-1-car-boxy-3-phenylpropyl]-L-lysyl-L-proline], enalapril [(S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline] and ramipril [2-aza-bicyclo-[3.3.0]-octane-3-carboxylic acid] are all five-membered heterocycles and three of the most prevalent ACE inhibitors in clinical use worldwide. ACEi-induced angioedema (ACEi-AE) is clinically characterized by self-limited edema of the dermis and subcutaneous lipid tissue, localized on face skin, oral mucosa and tongue in most cases. However, severe episodes of intestinal AE misdiagnosed as acute appendicitis and laryngeal AE requiring incubation have been reported. The pathophysiology of ACEi induced-AE is attributed to the accumulation of bradykinin, which is a potent vasodilator with proinflammatory activity that is normally degraded by angiotensin-converting enzyme (ACE) and aminopeptidase P; however, a small proportion of treated patients is affected. Given that patients do not respond to anti-H1 antihistamines and steroids, the early clinical recognition and the ACEi discontinuation are the treatment of choice for the long term management of ACEi-AE.

Keywords

angiotensin-converting enzyme(ACE); angiotensin-converting enzyme inhibitors (ACEi); angioedema; bradykinin mediated angioedema; tratement of ACEi induced AE

Subject

Medicine and Pharmacology, Immunology and Allergy

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