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The Journal of Allergy and Clinical... 2017
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Humans
PubMed: 29122164
DOI: 10.1016/j.jaip.2017.07.040 -
The Western Journal of Emergency... Jul 2019Angioedema is defined by non-dependent, non-pitting edema that affects several different sites and is potentially life-threatening due to laryngeal edema. This narrative... (Review)
Review
Angioedema is defined by non-dependent, non-pitting edema that affects several different sites and is potentially life-threatening due to laryngeal edema. This narrative review provides emergency physicians with a focused overview of the evaluation and management of angioedema. Two primary forms include histamine-mediated and bradykinin-mediated angioedema. Histamine-mediated forms present similarly to anaphylaxis, while bradykinin-mediated angioedema presents with greater face and oropharyngeal involvement and higher risk of progression. Initial evaluation and management should focus on evaluation of the airway, followed by obtaining relevant historical features, including family history, medications, and prior episodes. Histamine-mediated angioedema should be treated with epinephrine intramuscularly, antihistaminergic medications, and steroids. These medications are not effective for bradykinin-mediated forms. Other medications include C1-INH protein replacement, kallikrein inhibitor, and bradykinin receptor antagonists. Evidence is controversial concerning the efficacy of these medications in an acute episode, and airway management is the most important intervention when indicated. Airway intervention may require fiberoptic or video laryngoscopy, with preparation for cricothyrotomy. Disposition is dependent on patient's airway and respiratory status, as well as the sites involved.
Topics: Airway Management; Algorithms; Angioedema; Anti-Inflammatory Agents, Non-Steroidal; Blood Coagulation Factors; Bradykinin; Bradykinin B2 Receptor Antagonists; Bronchodilator Agents; Emergency Service, Hospital; Epinephrine; Glucocorticoids; Histamine; Histamine Antagonists; Humans; Peptides; Plasma; Urticaria
PubMed: 31316698
DOI: 10.5811/westjem.2019.5.42650 -
Journal of Investigational Allergology... 2016Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep... (Review)
Review
Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms. Histamine is the mediator in acquired angioedema of unknown etiology (idiopathic histaminergic acquired angioedema), whereas in other forms the main mediator is bradykinin. Angioedema can be caused by C1-inhibitor deficiency (C1-INH-hereditary angioedema and C1-INH-acquired angioedema), mutations in coagulation factor XII (FXII-hereditary angioedema), and treatment with angiotensin-converting enzyme inhibitors (ACEI-acquired angioedema). Etiology remains unclear in acquired angioedema (idiopathic nonhistaminergic acquired angioedema) and in 1 type of hereditary angioedema (hereditary angioedema of unknown origin). Several treatments are licensed for hereditary C1-INH deficiency. Plasma-derived and recombinant C1-INHs, the bradykinin receptor blocker icatibant, and the plasma kallikrein inhibitor ecallantide have been approved for on-demand treatment to reverse angioedema symptoms. Attenuated androgen and plasma-derived C1-INH are approved for prophylaxis.
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Complement C1 Inhibitor Protein; Humans
PubMed: 27470642
DOI: 10.18176/jiaci.0087 -
Molecules (Basel, Switzerland) Jul 2019Hypertension is considered a major public health issue due to its high prevalence and subsequent risk of cardiovascular and kidney diseases. Thus, the search for new... (Review)
Review
Hypertension is considered a major public health issue due to its high prevalence and subsequent risk of cardiovascular and kidney diseases. Thus, the search for new antihypertensive compounds remains of great interest. Snake venoms provide an abundant source of lead molecules that affect the cardiovascular system, which makes them prominent from a pharmaceutical perspective. Such snake venom components include bradykinin potentiating peptides (proline-rich oligopeptides), natriuretic peptides, phospholipases A, serine-proteases and vascular endothelial growth factors. Some heparin binding hypotensive factors, three-finger toxins and 5' nucleotidases can also exert blood pressure lowering activity. Great advances have been made during the last decade regarding the understanding of the mechanism of action of these hypotensive proteins. Bradykinin potentiating peptides exert their action primarily by inhibiting the angiotensin-converting enzyme and increasing the effect of endogenous bradykinin. Snake venom phospholipases A are capable of reducing blood pressure through the production of arachidonic acid, a precursor of cyclooxygenase metabolites (prostaglandins or prostacyclin). Other snake venom proteins mimic the effects of endogenous kallikrein, natriuretic peptides or vascular endothelial growth factors. The aim of this work was to review the current state of knowledge regarding snake venom components with potential antihypertensive activity and their mechanisms of action.
Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Bradykinin; Humans; Hypertension; Hypotension; Peptides; Snake Venoms
PubMed: 31370142
DOI: 10.3390/molecules24152778 -
BMC Nephrology May 2023Intradialytic hypotension (IDH) is a common clinical complication and is associated with increased morbidity and mortality in patients undergoing maintenance... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Intradialytic hypotension (IDH) is a common clinical complication and is associated with increased morbidity and mortality in patients undergoing maintenance hemodialysis (MHD). The pathogenesis of IDH has been attributed to the rapid reduction of plasma volume during hemodialysis and the inadequate compensatory mechanisms in response to hypovolemia, such as the lack of vasoconstriction. This may be due to the increased production of vasodilators, such as bradykinin. In this study we test the hypothesis that bradykinin B receptor blockade prevents intradialytic hypotension.
METHODS
We performed a post-hoc analysis of a double-blind, placebo-controlled, randomized, 2 × 2 crossover clinical trial comparing the continuous infusion of icatibant, a bradykinin B receptor blocker, and placebo during hemodialysis. Icatibant or placebo was infused for 30 min before and during hemodialysis in 11 patients on MHD.
RESULTS
Seven of the patients had IDH, defined as a reduction of systolic blood pressure equal to or greater than 20 mmHg during hemodialysis. Stratified analysis, based on the presence of IDH, revealed that icatibant prevented the decrease in blood pressure compared to placebo in patients with IDH [blood pressure at average nadir (2.5 h after hemodialysis): Placebo,114.3 ± 8.9 vs. icatibant, 125.6 ± 9.1 mmHg, mean ± S.E.M]. Icatibant did not affect blood pressure in the group of patients without IDH.
CONCLUSION
Bradykinin B2 receptor blocker may prevent the occurrence of IDH. Further studies should evaluate the hemodynamic effects of icatibant during hemodialysis and the symptomatology associated with IDH.
Topics: Humans; Receptors, Bradykinin; Bradykinin; Hypotension; Renal Dialysis; Blood Pressure
PubMed: 37170244
DOI: 10.1186/s12882-023-03192-4 -
American Journal of Physiology.... Apr 2000The kinin peptide system in humans is complex. Whereas plasma kallikrein generates bradykinin peptides, glandular kallikrein generates kallidin peptides. Moreover, a... (Comparative Study)
Comparative Study
The kinin peptide system in humans is complex. Whereas plasma kallikrein generates bradykinin peptides, glandular kallikrein generates kallidin peptides. Moreover, a proportion of kinin peptides is hydroxylated on proline(3) of the bradykinin sequence. We established HPLC-based radioimmunoassays for nonhydroxylated and hydroxylated bradykinin and kallidin peptides and their metabolites in blood and urine. Both nonhydroxylated and hydroxylated bradykinin and kallidin peptides were identified in human blood and urine, although the levels in blood were often below the assay detection limit. Whereas kallidin peptides were more abundant than bradykinin peptides in urine, bradykinin peptides were more abundant in blood. Bradykinin and kallidin peptide levels were higher in venous than arterial blood. Angiotensin-converting enzyme inhibition increased blood levels of bradykinin, but not kallidin, peptides. Reactive hyperemia had no effect on antecubital venous levels of bradykinin or kallidin peptide levels. These studies demonstrate differential regulation of the bradykinin and kallidin peptide systems, and indicate that blood levels of bradykinin peptides are more responsive to angiotensin-converting enzyme inhibition than blood levels of kallidin peptides.
Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antibody Specificity; Arteries; Bradykinin; Chromatography, High Pressure Liquid; Coronary Disease; Cross Reactions; Endothelium, Vascular; Female; Humans; Hydroxylation; Hyperemia; Jugular Veins; Kallidin; Male; Middle Aged; Peptidyl-Dipeptidase A; Radioimmunoassay; Renal Veins; Vasodilation
PubMed: 10749777
DOI: 10.1152/ajpregu.2000.278.4.R897 -
Clinical Reviews in Allergy & Immunology Jun 2018Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic... (Review)
Review
Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic review, we searched PubMed, EMBASE, and Scopus to provide an overview of the efficacy of different treatment options for the abovementioned subtypes of refractory non-hereditary AE with or without wheals and with normal C1INH. After study selection and risk of bias assessment, 61 articles were included for data extraction and analysis. Therapies were described for angiotensin-converting enzyme inhibitor-induced AE (ACEi-AE), for idiopathic AE, and for AE with wheals. Described treatments consisted of ecallantide, icatibant, C1INH, fresh frozen plasma (FFP), tranexamic acid (TA), and omalizumab. Additionally, individual studies for anti-vitamin K, progestin, and methotrexate were found. Safety information was available in 26 articles. Most therapies were used off-label and in few patients. There is a need for additional studies with a high level of evidence. In conclusion, in acute attacks of ACEi-AE and idiopathic AE, treatment with icatibant, C1INH, TA, and FFP often leads to symptom relief within 2 h, with limited side effects. For prophylactic treatment of idiopathic AE and AE with wheals, omalizumab, TA, and C1INH were effective and safe in the majority of patients.
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Humans; Omalizumab; Progestins; Tranexamic Acid; Treatment Outcome
PubMed: 27672078
DOI: 10.1007/s12016-016-8585-0 -
Skin Therapy Letter Jan 2018Hereditary angioedema is characterized by severe, episodic edema of the subcutaneous and mucosal tissue. The disease carries significant morbidity and mortality due to... (Review)
Review
Hereditary angioedema is characterized by severe, episodic edema of the subcutaneous and mucosal tissue. The disease carries significant morbidity and mortality due to involvement of the gastrointestinal tract and upper airway. Recent advances in the treatment of hereditary angioedema include new techniques used to isolate and purify human-derived C1 inhibitor, the production of a recombinant form of C1 inhibitor, and the development of drugs that target the kallikrein-kinin pathway. This paper reviews the mechanisms, efficacy, and adverse reactions associated with these medications.
Topics: Angioedemas, Hereditary; Bradykinin; Complement C1 Inhibitor Protein; Humans; Peptides
PubMed: 29357215
DOI: No ID Found -
Naunyn-Schmiedeberg's Archives of... Mar 2022Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that preferentially infects... (Review)
Review
Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that preferentially infects the respiratory tract. Bradykinin (BK) is a hypotensive substance that recently emerged as one of the mechanisms to explain COVID-19-related complications. Concerning this, in this review, we try to address the complex link between BK and pathophysiology of COVID-19, investigating the role of this peptide as a potential target for pharmacological modulation in the management of SARS-CoV-2. The pathology of COVID-19 may be more a result of the BK storm than the cytokine storm, and which BK imbalance is a relevant factor in the respiratory disorders caused by SARS-CoV-2 infection. Regarding this, an interesting point of intervention for this disease is to modulate BK signaling. Some drugs, such as icatibant, ecallantide, and noscapine, and even a human monoclonal antibody, lanadelumab, have been studied for their potential utility in COVID-19 by modulating BK signaling. The interaction of the BK pathway and the involvement of cytokines such as IL-6 and IL1 may be key to the use of blockers, even if only as adjuvants. In fact, reduction of BK, mainly DABK, is considered a relevant strategy to improve clinical conditions of COVID-19 patients. In this context, despite the current unproven clinical efficacy, drugs repurposing that block B1 or B2 receptor activation have gained prominence for the treatment of COVID-19 in the world.
Topics: Bradykinin; COVID-19; Drug Repositioning; Humans; Interleukin-6; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35089406
DOI: 10.1007/s00210-022-02206-6 -
Drug Development Research Feb 2021The severe acute respiratory syndrome coronavirus-2 (SARS-COV-2), a novel coronavirus responsible for the recent infectious pandemic, is known to downregulate... (Review)
Review
The severe acute respiratory syndrome coronavirus-2 (SARS-COV-2), a novel coronavirus responsible for the recent infectious pandemic, is known to downregulate angiotensin-converting enzyme-2 (ACE2). Most current investigations focused on SARS-COV-2-related effects on the renin-angiotensin system and especially the resultant increase in angiotensin II, neglecting its effects on the kinin-kallikrein system. SARS-COV-2-induced ACE2 inhibition leads to the augmentation of bradykinin 1-receptor effects, as ACE2 inactivates des-Arg9-bradykinin, a bradykinin metabolite. SARS-COV-2 also decreases bradykinin 2-receptor effects as it affects bradykinin synthesis by inhibiting cathepsin L, a kininogenase present at the site of infection and involved in bradykinin production. The physiologies of both the renin-angiotensin and kinin-kallikrein system are functionally related suggesting that any intervention aiming to treat SARS-COV-2-infected patients by triggering one system but ignoring the other may not be adequately effective. Interestingly, the snake-derived bradykinin-potentiating peptide (BPP-10c) acts on both systems. BPP-10c strongly decreases angiotensin II by inhibiting ACE, increasing bradykinin-related effects on the bradykinin 2-receptor and increasing nitric oxide-mediated effects. Based on a narrative review of the literature, we suggest that BPP-10c could be an optimally effective option to consider when aiming at developing an anti-SARS-COV-2 drug.
Topics: Angiotensin-Converting Enzyme 2; Animals; Bradykinin; COVID-19; Humans; Peptide Fragments; Renin-Angiotensin System; Snake Venoms; COVID-19 Drug Treatment
PubMed: 32761647
DOI: 10.1002/ddr.21732