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 • " Am. J. Ophthalmoi 102:606-611 (1986). Most (80%) of a
 p "-.
 topically administered eyedrop volume drains through the
 nasolacrimal duct becoming systemically absorbed° Approxi-
 mately 40% to 70% of a dose of systemic beta adrenergic
 blockers (propranolol) administered orally undergoes a first-
 pass hepatic metabolism before reachln_ the systemic circu-
 lation. A beta-adrenergic antagonist administered in eyedrop
 form does not undergo such first-pass metabolism, and may
 behave like an intravenous drug dose. Shell, J_W._
 Pharmacokinetics of topically applied opthalmic drugs, Surv.
 Ophthaimol. 26:207-218 (1982).
 17. Serious adverse respiratory events from topical
 beta blockers (FDA defined) consists of respiratory arrest,
 _. respiratory failure, respiratory distress, dyspnea, broncho-
 spasm, asthma, wheezing, bronchitis, apnea, pulmonary edema,
 diminished pulmonary functions and exacerbation of preexisting
 respiratory disease. For purposes of analysis, reports of
 asthma, shortness of breath, wheezing_ and bronchospasm were
 classified as bronchcspasm=related events. Serious adverse
 cardiovascular events were defined as follows: cardiac arrest,
 myocardial infarctions engines chest pain, arrhythmia_
 bridycardia_ tach_cardia, palpitations, heart failu:e_
 ..... cardiospasm/ cerebrovascular accidents syncopes unspecified
 cardiovascular disorders, and exacerbation of preexisting
 cardiovascular disease. Reports of hypes:tension, dizziness,
 headache, andohypotension not resulting in syncope were not
 considered to be serious. |

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