icatibant and Airway-Obstruction

Hereditary angioedema (HAE) is a potentially life-threatening autosomal dominant disease characterized by recurrent episodes of oedema, commonly occurring in the skin, abdomen, and upper respiratory tract. After many years during which limited treatment options were available, a range of newer therapies with proven efficacy have been approved in Europe by the European Commission for the treatment of HAE attacks. However, due to differing legislation and financial restrictions, these treatment options are not available in all countries. Home therapy and self-administration of treatment are recommended in order to minimize the burden of disease upon the patient, with the ideal treatment option being effective, well-tolerated, and easy to prepare and administer. Recently, the Hereditary Angioedema International Working Group (HAWK) consensus recommended early, on-demand treatment for HAE. This article reviews the current treatment options available, and considers the need for treatment guidelines to recommend the appropriate therapy.

Topics: Airway Obstruction; Angioedemas, Hereditary; Anti-Inflammatory Agents, Non-Steroidal; Bradykinin; Complement C1 Inhibitor Protein; Costs and Cost Analysis; Europe; Health Knowledge, Attitudes, Practice; Hospitalization; Humans; Insurance Coverage; Insurance, Pharmaceutical Services; Legislation, Drug; Peptides; Practice Guidelines as Topic; Practice Patterns, Physicians'; Self Administration

Responses to bradykinin (BK) were investigated in the pulmonary vascular bed of the cat under conditions of controlled pulmonary blood flow and constant left atrial pressure when lobar arterial pressure was elevated to a high steady level. Under elevated-tone conditions, BK caused dose-related decreases in lobar arterial pressure. After administration of Hoe-140, a BK B2-receptor antagonist, vasodilator responses to BK were reduced in a selective manner. Vasodilator responses to BK were unchanged by atropine, glibenclamide, meclofenamate, or bronchial occlusion, suggesting that responses are not dependent on the activation of muscarinic receptors or K+ATP channels, the release of vasodilator prostaglandins, or changes in bronchomotor tone. The nitric oxide (NO) synthase inhibitors N omega-nitro-L-arginine benzyl ester and N omega-nitro-L-arginine reduced vasodilator responses to BK in a selective manner, indicating that responses to BK are mediated in part by the release of NO. Methylene blue, an inhibitor of the activation of soluble guanylate cyclase, increased lobar arterial pressure and decreased responses to BK. The increases in lobar arterial pressure in response to methylene blue were partially reversed by the administration of superoxide dismutase, indicating that generation of O2- may inactivate basally released NO. The duration of the response to BK was enhanced by the guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor Zaprinast, suggesting that responses to BK involve increases in cGMP levels. Responses to BK were enhanced by captopril, indicating that BK is rapidly inactivated by kininase II in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Airway Obstruction; Amino Acid Oxidoreductases; Animals; Bradykinin; Bronchi; Cats; Methylene Blue; Nitric Oxide Synthase; Pulmonary Circulation; Purinones; Vasodilation