Interaction between timolol eyedrops and oral nicardipine or oral diltiazem in healthy Japanese subjects.

OBJECTIVE: Timolol is widely used for the topical therapy of glaucoma. Adverse cardiovascular effects include slowing of the heart rate and weakening of myocardial contractility. We investigated pharmacodynamic interactions with respect to cardiovascular and ocular responses between timolol ophthalmic solution and either nicardipine, which does not directly inhibit cardiac conduction, or diltiazem, which does. METHODS: Two studies utilized a randomized, double-blind, Latin-square, placebo-controlled design involving four separate treatments given at least 1 week apart. Eight healthy male Japanese volunteers received a single drop of 0.5% timolol or artificial tears in each eye with or without a single oral dose of nicardipine (40 mg), and with or without a single oral dose of diltiazem (60 mg). Subjects exercised on a bicycle ergometer before and 1.5 and 3 h after dosing. At these times, heart rate and blood pressure were measured at rest and after exercise. The intraocular pressure was measured at rest. RESULTS: One drop of 0.5% timolol per eye significantly reduced the exercise-induced increase in heart rate and blood pressure, and intraocular pressure at rest. The timolol ophthalmic solution suppressed the reflex sympathetic cardiac stimulation that resulted from the primarily vasodilative action of nicardipine. No additional reduction in heart rate occurred when the ophthalmic timolol solution was administered in conjunction with diltiazem. The concomitant use of timolol and nicardipine or diltiazem did not induce an additional reduction in intraocular pressure. Oral nicardipine or diltiazem did not reduce intraocular pressure. Care should be taken when using topical timolol in patients with cardiovascular or respiratory diseases.

Short-term effects of nicardipine and propranolol on ocular and systemic hemodynamics in healthy Japanese subjects.

Ocular perfusion is a critical factor in ischemic ocular diseases, and blood flow in the ophthalmic artery has a pronounced effect on perfusion. To evaluate the effects of dihydropyridine calcium channel blocker and nonselective beta-adrenergic antagonist on ocular perfusion, we investigated the short-term effects of single oral doses of nicardipine (40 mg) and propranolol (40 mg) on the blood flow velocity in the ophthalmic artery, intraocular pressure (IOP), systemic blood pressure, and heart rate in nine healthy Japanese male volunteers in a double-blind, placebo-controlled study using color Doppler imaging. Parameters were evaluated before and 60 and 120 minutes after administration. Nicardipine significantly increased the maximum systolic velocity and time-averaged blood flow velocity compared with placebo without significant increase in the resistance index. Propranolol had no significant effects on Doppler parameters. Propranolol exhibited a great reduction in IOP from placebo values. Systolic blood pressure and heart rate were significantly reduced by propranolol. Nicardipine significantly increased heart rate. These results suggest that nicardipine increased ophthalmic blood flow, but propranolol did not.

Ophthalmic artery flow velocity after physical exercise in healthy men.

This study was conducted to evaluate the effects of physical exercise on blood flow velocity in the ophthalmic artery of healthy men. Color Doppler imaging, which permits rapid noninvasive imaging of the ophthalmic artery, was performed in 11 healthy male adult volunteers to compare pre- and post-exercise measurements of blood flow velocity. After submaximal physical exercise, systolic blood flow velocity (Vmax) and time-averaged blood flow velocity (Vmean) increased significantly, but returned to pre-exercise levels 5-10 minutes after the completion of physical exercise. There were no significant changes in minimum end-diastolic blood flow velocity (Vmin), resistance index (RI) or pulsatility index (PI). The RI and PI parameters are considered to reflect vascular resistance. Our results indicate that submaximal physical exercise increased the blood flow velocity, but did not alter the resistance index of the ophthalmic artery.

[The variability of blood velocity in the ophthalmic artery with color Doppler imaging].

Non-invasive measurements of blood velocities of the ophthalmic artery (BVA) in color Doppler imaging (CDI) are increasingly used to assess the influence of disease on the hemodynamics of the eye. Such measurements are only valid when compared to spontaneous variability. Therefore, the aim of this study was to examine the variability of BVA in healthy subjects. Within-a-day short-term variability was assessed from measurements obtained during one day from 5 healthy young male subjects as the coefficient of variation (CV) of 10 consecutive measurements. Between-days variability was assessed by comparing measurements made on three different days at one month intervals. The left and right BVA were measured five consecutive times to evaluate the difference in BVA between left and right eyes in 5 healthy young male subjects. In the within-a-day variability, mean CV in maximum systolic BVA (V max), minimum end diastolic BVA (V min), time-averaged BVA (V mean), resistive index (RI), and pulsatility index (PI) were found to be 6.6%, 14.0%, 14.9%, 3.2%, and 17.4%, respectively. The between-days variability was just as high as the within-a-day variability. There was significant difference in BVA between left and right eyes in two of the five subjects. We concluded that the within-a-day variability and the between-days variability of BVA measured using CDI are reproducible. The CDI can be used to assess the influence of disease and drugs on the hemodynamics of the eye.