Assessment of systemic effects of different ophthalmic β-blockers in healthy volunteers

Abstract

Systemic beta-blockade after single doses of ophthalmic beta-blockers (one drop in each eye) was investigated in healthy volunteers in two randomized, double-blind, crossover, placebo-controlled studies. beta-Blockade was evaluated by displacement of the bronchodilator (specific airway conductance), positive chronotropic (heart rate), and tremorogenic (finger tremor amplitude) dose-response curve for inhaled isoproterenol. In study 1, 0.5% betaxolol, 0.6% metipranolol, and 0.5% timolol were tested in 16 subjects. Compared with placebo, all beta-blockers resulted in a significant systemic beta-blockade (p greater than 0.05); the increasing order of potency was betaxolol, metipranolol, and timolol. In study 2, 2% butylamino-phenoxy-propanol-acetate (BPPA; a noncardioselective but topically oculoselective drug) and 1% timolol were investigated in 12 subjects. Placebo and BPPA showed no differences (p greater than 0.05), whereas timolol resulted in a significant beta-blockade (p less than 0.05). Topical oculoselectivity is an important aspect of drug safety of beta-blocking eyedrops. Measure of tremor is appropriate to evaluate beta 2-blockade.

Assessment of bronchial effects following topical administration of butylamino‐phenoxy‐propanol‐acetate, an oculoselective beta‐ adrenoceptor blocker in asthmatic subjects.

“…The hypothesis derived from previous studies in normal subjects that BPPA does not cause bronchoconstriction in asthmatics was confirmed by our data on sGaw, and with limitation, our data on FEV1 (Bauer et al, 1991;Maclure et al, 1987). The quantitative assessment of the bronchial 13-adrenoceptor blockade as well as the ,Badrenoceptor blocking effects on heart rate and muscle tremor can be assessed more accurately by measuring the displacement of the ,3-agonist dose-response curves in normal subjects (Bauer et al, 1991;Tattersfield & Keeping, 1979).…”

“…The quantitative assessment of the bronchial 13-adrenoceptor blockade as well as the ,Badrenoceptor blocking effects on heart rate and muscle tremor can be assessed more accurately by measuring the displacement of the ,3-agonist dose-response curves in normal subjects (Bauer et al, 1991;Tattersfield & Keeping, 1979). In our study the subjects with a fall in FEV1 following BPPA and/or placebo, received all doses of the challenge regime because they had definitely unchanged traces of sGaw.…”

“…The rapid oxidation in the systemic circulation to inactive carboxylic acid metabolites explains the lack of systemic P-adrenoceptor blockade following ocular administration (Sugrue et al, 1988). Studies in healthy volunteers showed that BPPA was as effective as timolol in reducing IOP but did not antagonize the dose-response of inhaled isoprenaline on airway calibre, heart rate, and finger tremor (Bauer et al, 1991 …”

Resting pulse rates in a glaucoma clinic: the effect of topical and systemic beta-blocker usage

“…[3][4][5][6][7][8] This is probably due to the good bioavaliablity of topical beta-blockers 22 therefore easily affecting the body systemically. An aspect of beta-blocker therapy, not widely considered in the literature, is the effect of combining oral and topical beta-blockers.…”

“…Topical beta-blockers have a well-established role in the reduction of intraocular pressure; 1,2 however, their side effects are also well documented, potentially affecting both cardiac [3][4][5][6][7][8] and respiratory functions. 3,4,[9][10][11] In recent years new agents such as prostaglandin analogues have been developed with a better safety profile, as well as comparable efficacy, [12][13][14][15] leading to beta-blockers not now necessarily being the first-line treatment in glaucoma.…”