Therapeutic and systemic side effects of ocular beta-adrenergic antagonists in anesthetized dogs.
Beta adrenergic antagonists, while useful in the treatment of glaucoma, can be absorbed transocularly causing a variety of systemic side effects. An adequate animal model which simultaneously indicates the intraocular pressure lowering effects as well as the systemic effects of ocularly applied beta-adrenergic antagonists would be highly useful. The pentobarbital anesthetized dog, instrumented to record blood pressure (BP) and heart rate (HR) and in which intraocular pressure (IOP) was measured with a pneumatonometer, was investigated. Isoproterenol iv dose-response curves were run and IOP measured before and hourly for 3 hr following ocular application of 50 microliters 0.5% RS-52367 (a Syntex beta-adrenergic antagonist), or dH2O control. Timolol and RS-52367 produced similar decreases in IOP. However, timolol decreased basal BP and HR, markedly inhibited isoproterenol-induced BP and HR responses, and also decreased contralateral IOP. Systemic effects of RS-52367 were far more mild. Since both the IOP lowering and systemic beta-adrenergic antagonist properties of timolol were elicited, the anesthetized dog appears to be an excellent animal model for examining the effects of beta-adrenergic antagonists applied topically to the eye.
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D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D011412:Propanolamines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013999:Timolol / Q000009:adverse effects / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C048219:RS 52367; D013999:Timolol