Bradykinin Metabolism and Drug-Induced Angioedema

Abstract

Bradykinin (BK) metabolism and its receptors play a central role in drug-induced angioedema (AE) without urticaria through increased vascular permeability. Many cardiovascular and diabetic drugs may cause BK-mediated AE. Angiotensin-converting enzyme inhibitors (ACEIs) and neprilysin inhibitors impair BK catabolism. Dipeptidyl peptidase-IV (DPP-IV) inhibitors reduce the breakdown of BK and substance P (SP). Moreover, angiotensin receptor blockers, thrombolytic agents, and statins may also induce BK-mediated AE. Understanding pathophysiological mechanisms is crucial for preventing and treating drug-induced AE.

Angioedema Following Tenecteplase for Acute Ischemic Stroke

“…Additionally, Black patients may be at increased risk due to genetic polymorphisms of the metallopeptidases required to break down bradykinin. 3 Studies have also suggested that the location of the infarct may increase the risk of angioedema after thrombolytic administration, noting that patients with infarcts involving the insular region show greater angioedema events. 5 Current American Heart Association/American Stroke Association guidelines recommend initial treatment with intravenous corticosteroids, antihistamines, and general supportive care measures.…”

“…1,2 While the incidence of angioedema after thrombolytic therapy is 2% to 8% in the general population, the risk is 6× higher for patients also taking angiotensin-converting enzyme (ACE) inhibitors. 3 ACE inhibitors block the ability for ACE to inactivate bradykinin, resulting in a slower rate of bradykinin degradation, enhanced biologic activity, and increased ability to induce angioedema. Additionally, ACE inhibitors block the ability of ACE to degrade substance P, another mediator linked to angioedema.…”

A challenging case of bradykinin-mediated angioedema with airway obstruction: management and therapeutic strategies

“…Often the clinical history and presentation of this entities overlaps and the failure to respond to therapeutic should incite the search of another pathophysiologic mechanism. The laboratory study did not find any abnormalities, and the clinical response only after the institution of icatibant and tranexamic acid was evident associated with failure of antihistaminics and corticosteroids which points to the diagnosis of BK-mediated angioedema [ 17 , 18 ]. Tranexamic acid is an easily available and effective treatment and may prove to be important while waiting for more specific and less accessible treatment as icatibant and C1INH concentrate [ 19 ].…”