PMID- 38543146
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240330
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 17
IP  - 3
DP  - 2024 Mar 10
TI  - Five-Membered Nitrogen Heterocycles Angiotensin-Converting Enzyme (ACE) 
      Inhibitors Induced Angioedema: An Underdiagnosed Condition.
LID - 10.3390/ph17030360 [doi]
LID - 360
AB  - Angiotensin-converting enzyme (ACE) inhibitors are used primarily in the 
      treatment of hypertension, heart failure, and in the acute phase of myocardial 
      infarction. Lisinopril [N(2)-[(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. ACE inhibitor-induced angioedema (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 ACE inhibitor-induced 
      angioedema 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, early clinical recognition and 
      discontinuation of the ACE inhibitors are the treatments of choice for the 
      long-term management of ACE inhibitor- induced angioedema. The search period of 
      the present review was set up until November 2023, and its aim is to shed light 
      on the broader context of ACE inhibitor-induced angioedema, exploring aspects 
      such as clinical presentation, pathophysiology, and therapeutic considerations in 
      this potentially life-threatening condition. The exploration of alternative drug 
      options such as angiotensin II receptor blockers, the potential association of 
      coadministration of DPP-4 inhibitors with ACE inhibitors, the presentation of 
      angioedema and the significant clinical importance of this condition are also 
      discussed. By focusing on the chemical structure of ACE inhibitors, specifically 
      their nitrogen-based heterocycles-an attribute shared by over 880 drugs approved 
      by the FDA within the pharmaceutical industry-this review emphasizes the pivotal 
      role of nitrogen scaffolds in drug design and underscores their relevance in ACE 
      inhibitor pharmacology.
FAU - Papapostolou, Niki
AU  - Papapostolou N
AUID- ORCID: 0000-0003-3950-3089
AD  - Allergy Unit, 2nd Department of Dermatology and Venereology, National and 
      Kapodistrian University of Athens, University General Hospital 'Attikon', 12462 
      Athens, Greece.
FAU - Gregoriou, Stamatios
AU  - Gregoriou S
AUID- ORCID: 0000-0002-7585-1032
AD  - 1st Department of Dermatology and Venereology, "Andreas Syggros" Hospital for 
      Skin and Venereal Diseases, National and Kapodistrian University of Athens, 16121 
      Athens, Greece.
FAU - Katoulis, Alexander
AU  - Katoulis A
AUID- ORCID: 0000-0001-8189-7486
AD  - Allergy Unit, 2nd Department of Dermatology and Venereology, National and 
      Kapodistrian University of Athens, University General Hospital 'Attikon', 12462 
      Athens, Greece.
FAU - Makris, Michael
AU  - Makris M
AUID- ORCID: 0000-0003-2713-2380
AD  - Allergy Unit, 2nd Department of Dermatology and Venereology, National and 
      Kapodistrian University of Athens, University General Hospital 'Attikon', 12462 
      Athens, Greece.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20240310
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC10974338
OTO - NOTNLM
OT  - angioedema
OT  - angiotensin-converting enzyme (ACE) inhibitors
OT  - bradykinin
OT  - nitrogen-based heterocycles
OT  - pharmacology
COIS- The authors declare no conflict of interest.
EDAT- 2024/03/28 06:45
MHDA- 2024/03/28 06:46
PMCR- 2024/03/10
CRDT- 2024/03/28 01:23
PHST- 2024/01/31 00:00 [received]
PHST- 2024/03/04 00:00 [revised]
PHST- 2024/03/08 00:00 [accepted]
PHST- 2024/03/28 06:46 [medline]
PHST- 2024/03/28 06:45 [pubmed]
PHST- 2024/03/28 01:23 [entrez]
PHST- 2024/03/10 00:00 [pmc-release]
AID - ph17030360 [pii]
AID - pharmaceuticals-17-00360 [pii]
AID - 10.3390/ph17030360 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2024 Mar 10;17(3):360. doi: 10.3390/ph17030360.