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Hematologic Drugs
Published in Radhwan Nidal Al-Zidan, Drugs in Pregnancy, 2020
Risk Summary: It should be used with caution because the pregnancy experience in humans is limited, and the reproduction studies in animals have shown the risk of developmental toxicity associated with the use of Icatibant.
Cardiac Inhibition of Angiotensin Converting Enzyme: Role of Kinins
Published in Malcolm J. Lewis, Ajay M. Shah, Endothelial Modulation of Cardiac Function, 2020
Wolfgang Linz, Gabriele Wiemer, Bernward A. Schölkens
Vavrek and Stewart (1985) discovered that substitution of D-phenylalanine for proline at position 7 of BK converted it into a specific antagonist for B2 kinin receptors. A short time later icatibant (HOE 140) was discovered, which at the present time is one of the most potent, stable and long-lasting specific B2 kinin receptor antagonists (Henke et al., 1990; Hock et al., 1991; Wirth et al., 1991; Bao et al., 1991). Using icatibant it was clearly shown that the beneficial effects of ACE-inhibition in myocardial ischemia were abolished (Table 15-3 and 4). Icatibant given alone aggravated ischaemia-induced effects in the isolated rat heart (Linz et al., 1992). On the other hand, given in the absence of ischaemia, icatibant (10−10 mol/1) induced no changes either in the cardiovascular parameters measured (left ventricular pressure, dP/dtmax, heart rate, conorary flow) or in myocardial metabolism (release of lactate dehydrogenase, creatine kinase, lactate, myocardial content of glycogen, ATP and creatine phosphate). Toxicological studies in rats where icatibant was given intravenously or subcutaneously in large doses of 10 mg/kg/d for 4 weeks showed no adverse effects, indicating that B2 kinin receptor blockade with icatibant may interfere with kinin-induced cardiac effects only when acute severe myocardial ischemia occurs.
Drug Therapy in Laryngology and Head and Neck Surgery
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Swelling of the face and lips, and occasionally of the larynx, occurs in angioneurotic oedema of allergic origin. Antihistamines and corticosteroids are prescribed and, if life-threatening, 1 mL/1:1000 adrenaline can be administered subcutaneously. The non-allergic type results from a serum deficiency of the C1 esterase inhibitor protein. An acute attack is treated with an intravenous injection of 1000 units of C1 esterase inhibitor protein (derived from human plasma). This can also be given prior to surgery for prophylaxis. Conestat alfa (contraindicated if allergic to rabbits) and icatibant are also licenced in treating acute attacks of hereditary angioedema in adults with C1 esterase inhibition.1 Long-term prophylaxis is achieved with epsilon aminocaproic acid or its derivative tranexamic acid or with androgen methyltestosterone or its derivative danazol. These stimulate the production of C1 esterase inhibitor protein.
Safety of medications for hereditary angioedema during pregnancy and lactation
Published in Expert Opinion on Drug Safety, 2023
Andrew Yeich, Ahmed Elhatw, Zaynab Ashoor, Kristen Park, Timothy Craig
We suspect that for rescue treatment other therapies, such as icatibant, which is now generic, will be safe, but further data are essential before suggesting use during pregnancy. Thus far only case reports are available demonstrating safety during pregnancy for icatbant, but the short duration of action suggests it should be safe. Until further data are available the authors suggest that for rescue 20 units per kg intravenously should be given as early as possible during the attack, and for every attach, to abort the attack as soon as possible. The WAO Guidelines suggest that 500 and 1000 units is adequate for acute therapy, but objective data conflict with this suggestion, and some of the authors of the guidelines persist is this suggestion based on custom rather than objective evidence.
Clinical and genomic characterisation of a fatal Puumala orthohantavirus case with low levels of neutralising antibodies
Published in Infectious Diseases, 2022
Anne Tuiskunen Bäck, Johan Rasmuson, Therese Thunberg, Gregory Rankin, Julia Wigren Byström, Charlotta Andersson, Andreas Sjödin, Mattias Forsell, Clas Ahlm
The patient initially received intravenous penicillin G under the suspicion of a bacterial pneumonia, as well as rehydration therapy, nasal cannula oxygen supplementation, and paracetamol intravenously. A chest X-ray demonstrated a minimum of unilateral pleural effusion. At day two post-onset of fever (POF) an anti-PUUV IgM rapid test (Reascan, Reagena, Helsinki, Finland) and a PUUV-specific quantitative RT-PCR from serum were found positive, and penicillin-treatment was discontinued. Day three POF the patient detoriated including developed hypotension with a systolic pressure of 50 mmHg. The patient became anuric and was transferred to the intensive care unit for vasoactive drug treatment, intubation and mechanical ventilation. During day four POF the circulatory dysfunction worsened with pronounced capillary leakage and vasoplegia. Cardiac ultrasound revealed hypovolemia but with normal biventricular function. The patient developed refractory circulatory shock and a single dose of the bradykinin receptor inhibitor icatibant (30 mg) was given subcutaneously, although without any apparent beneficiary effect. The patient succumbed in circulatory shock with multiorgan failure 12 h later.
Select hyperacute complications of ischemic stroke: cerebral edema, hemorrhagic transformation, and orolingual angioedema secondary to intravenous Alteplase
Published in Expert Review of Neurotherapeutics, 2018
A frightening and potentially fatal complication after the administration of IV alteplase is the development of acute orolingual angioedema. The incidence of this rare adverse reaction is between 0.2% and 5.1% [88]. The severity of this condition varies from mild to potentially fatal leading to compromise of a patient’s airway. Alteplase-mediated angioedema is characteristic of a bradykinin-mediated reaction, causing localized laryngeal, mucosal, lingual, and upper airway soft tissue swelling thought to be due to vasodilatation and increased vascular permeability. Current guidelines from the 2018 AHA/ASA stroke guidelines recommend stopping alteplase infusion and holding ACEIs. This is to be followed by administering 125 mg of IV methylprednisolone, 50 mg of IV diphenhydramine, and 50 mg of IV ranitidine or 20 mg of IV famotidine [74]. Finally, if the angioedema continues to progress then it is recommended to administer epinephrine 0.3 mL subcutaneously or 0.5 mL by nebulizer [74]. It is important to acknowledge that these recommendations are based on expert opinion and not high level data. Icatibant is a bradykinin B2 receptor antagonist FDA approved for the treatment of hereditary angioedema but also appears to be effective for alteplase-mediated angioedema [89]. It is reasonable to consider administering icatibant if other treatments are not effective. Clearly if there is evidence of impending respiratory failure intubation should proceed without delay.