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Urticaria and Angioedema
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Jenny M Stitt, Stephen C Dreskin
Acute attacks of HAE are most effectively treated with supplemental C1 inhibitor, a bradykinin B2 receptor antagonist (e.g., icatabant), or a kallikrein inhibitor (e.g., ecallantide) (Cicardi et al. 2010, Parikh and Riedl 2011, Zuraw et al. 2010, Antoniu 2011). The choice of medication is often based on availability. When these medications are not available, symptomatic care and airway monitoring for laryngeal edema should be provided. Administration of fresh frozen plasma, which contains C1 inhibitor, can also be considered; however there is significant concern that FFP may worsen ongoing AE in some patients (Dreskin 2012). The patient’s airway should be monitored, and if there is concern for laryngeal edema and stridor or respiratory distress is evident, the patient should undergo endotracheal intubation. If intubation is unsuccessful due to angioedema, emergent cricothyroidotomy may need to be performed. Other supportive care measures may include intravenous fluids and antiemetics for gastrointestinal symptoms, as well as analgesics for pain.
Lanadelumab for the treatment of hereditary angioedema
Published in Expert Opinion on Biological Therapy, 2019
Among additional therapeutic strategies in early phase trials, orally active bradykinin B2 receptor antagonists are promising options and they are expected to be preferred by patients due to the easy route of administration. To this regard, a novel orally bioavailable non-peptide small molecule B2 receptor antagonist, PHA-022121, is now under development by the drug company Pharvaris (founded by the team which successfully developed icatibant) and is entering clinical phase I studies, after in vitro results highlighted that this drug is able to inhibit bradykinin B2 receptors with higher affinity, selectivity and potency than icatibant and is characterized by good oral bioavailability and metabolic stability [39].
Icatibant for the treatment of hereditary angioedema with C1-inhibitor deficiency in adolescents and in children aged over 2 years
Published in Expert Review of Clinical Immunology, 2018
Henriette Farkas, Kinga Viktória Kőhalmi
Icatibant (formerly, Hoe140) is a synthetic peptidomimetic drug consisting of 10 amino acids (H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH), produced by solid-phase peptide synthesis [47]. Its structure is similar to that of bradykinin, except for the presence of five non-proteinogenic amino acids, and it acts as a competitive, highly selective antagonist of the bradykinin B2 receptor [46].
Biological therapy in hereditary angioedema: transformation of a rare disease
Published in Expert Opinion on Biological Therapy, 2020
Hilary Longhurst, Henriette Farkas
PHA‑022121 is a novel proprietary small-molecule antagonist of the bradykinin B2 receptor. Based on preclinical experimental data and modeling, this compound is predicted to be effective for oral treatment and prevention of HAE attacks [74].