Systemic P-Adrenoceptor Function and Ophthalmic P-Adrenergic Blockers

pproximately 80% of ophthalmic P-adrenergic blockers are systemically absorbed through conjunctival capillaries and the nasal mucosa. This absorption avoids hepatic first-pass metabolism, making the systemic bioavailability of ophthalmic drugs comparable to that of intravenously administered drugs (1). Investigations of ophthalmic P-adrenergic blockers in healthy volunteers have confirmed the systemic effects of minute amounts of drug instilled in the conjunctiva (2,3), but evaluation of /3-adrenoceptor function in patients with cardiovascular pathology has not been performed. We report a case in which the hemodynamic effects of chronic use of a 0.5% ophthalmic solution of the nonselective /3-adrenoceptor antagonist levobunolol (Betaganm; Allergan, Irvine, CA) were quantified with the isoproterenol sensitivity test (4,5). Case Report A 65-yr-old man (86 kg, 172 cm) was admitted for coronary artery bypass grafting (CABG). Originally, the patient was enrolled in a study of p-adrenoceptor function in patients with ischemic heart disease. The study had been approved by the regional ethics committee and written, informed con- sent was obtained. The investigation was completed in ac- cordance with the protocol, but the patient was later ex- cluded when it was realized that he was treated with an ophthalmic /3-adrenergic blocker. After the investigation, the patient was informed about the results and he gave in- formed consent to a subsequent genotyping to elucidate whether he was a slow metabolizer of /3-adrenergic blockers. The medical history included hypertension, a myocardial infarction 10 yr previously, and glaucoma. Medical treat- ment consisted of diltiazem 120 mg X 3, isosorbide dinitrate 40 mg X 2, furosemide 40 mg X 2, and topical levobunolol 0.5% one drop daily in each eye. Preoperative electrocardiogram showed sinus rhythm and left ventricular hypertrophy with ischemia. Arterial blood pressure was 175/70 mm Hg. Coronary angiography dis- closed three-vessel disease. Left ventricular ejection fraction