title: Assessment of systemic adverse reactions induced by ophthalmic beta-adrenergic receptor antagonists.
abstract: To assess quantitatively the risks of ophthalmic beta-blocking agents for cardiovascular and respiratory adverse reactions, we analyzed the binding kinetics of beta-blocking agents to the beta-1 and beta-2 adrenoceptors. The relationship between the occupancies for beta-1 and beta-2 adrenoceptors and the effects on the exercise pulse rate or the forced expiratory volume in one second (FEV1) after topical administration of carteolol, befunolol, timolol and betaxolol was analyzed using a ternary complex model. The beta-1 and beta-2 receptor occupancies after ophthalmic administration were calculated to be quite high as well as those after oral administration. The maximum occupancies for beta-1 and beta-2 receptors after ordinary ophthalmic administration were 52% and 88% for carteolol, 52% and 61% for befunolol, 62% and 82% for timolol, and 44% and 3% for betaxolol, respectively. Concave relationships were obtained between a decrease in exercise pulse rate and the beta-1 receptor occupancy and between a decrease in FEV1 and beta-2 receptor occupancy, respectively. Nasolacrimal occlusion was estimated to decrease the exercise pulse rate and FEV1 by 65% and 50%, respectively. The beta-1 and beta-2 adrenoceptor occupancies were proved to be the most appropriate indicators for cardiac and pulmonary adverse reactions evoked by ophthalmic beta-blocking agents.
authors: Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Japan.
authors: Y
authors: Y
authors: Yamada
authors: R
authors: R
authors: Takayanagi
authors: K
authors: K
authors: Tsuchiya
authors: K
authors: K
authors: Ito
authors: H
authors: H
authors: Ohtani
authors: Y
authors: Y
authors: Sawada
authors: T
authors: T
authors: Iga
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects* / Q000378:metabolism; D015784:Betaxolol / Q000009:adverse effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000378:metabolism; D002354:Carteolol / Q000009:adverse effects / Q000378:metabolism; D015444:Exercise; D005541:Forced Expiratory Volume / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects*; D009883:Ophthalmic Solutions; D011412:Propanolamines / Q000009:adverse effects / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012120:Respiration Disorders / Q000139:chemically induced / Q000378:metabolism; D012189:Retrospective Studies; D013999:Timolol / Q000009:adverse effects / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C006034:befunolol; D013999:Timolol; D002354:Carteolol; D015784:Betaxolol