Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles / Efeitos do maleato de timolol, do levobunolol e da apraclonidina sobre a pressão intraocular, o diâmetro pupilar, a pressão sanguínea e a frequência cardíaca, em cães da raça Beagle

The aim of this study was to evaluate changes in intraocular pressure (IOP), pupil size (PS), blood pressure (BP), heart rate (HR), and ECG variables (Pms wave PmV, PR interval, QRS complex, RMV wave and QT intervals) over time during the instillation of 0.5% timolol, 0.5% levobunolol and 0.5% apraclonidine in clinically normal dogs. Ten adult beagles were used. Baseline values were measured at 8a.m., 2p.m. and 8p.m., for three consecutive days. A waiting period of 10 days between the administrations of each drug was established. For 15 consecutive days, the drug being tested was instilled in one eye of each dog twice a day (7a.m. and 7p.m.). The parameters were evaluated at the aforementioned times on days 3, 6, 9, 12 and 15. Data were statistically compared using the Bonferroni test and one-way repeated measures analysis of variance (P<0.05). The Pearson test was used to evaluate any correlation between QT interval, HR and BP. The tested drugs did not find a decrease in IOP. A significant decreased in PS was observed in almost all dogs following levobunolol administration, relative to the control eye. A significant decrease in HR was observed on day 3 following levobunolol treatment, while apraclonidine induced an increase on day 15. Blood pressure was reduced in all measurement time points following apraclonidine treatment. A negative correlation between QT interval and HR was only observed in dogs treated with timolol. In conclusion, levobunolol was the only drug that induced significant alterations in PS. Apraclonidine was the only drug that induced systemic hypotension. Timolol was the only drug to that induced a negative correlation between QT and HR.(AU)

O objetivo deste estudo foi avaliar as mudanças na pressão intraocular (PIO), no diâmetro pupilar (DP), na pressão sanguínea (PS), na frequência cardíaca (FC) e nas variáveis eletrocardiográficas (onda Pms, PmV, intervalo PR, complexo QRS, onda RmV e intervalo QT), ao longo do tempo da instilação do timolol 0,5%, do levobunolol 0,5% e da apraclonidina 0,5% em cães clinicamente normais. Dez Beagles adultos compuseram o estudo. Valores basais foram mensurados às oito,, 14 e 20 horas, durante três dias consecutivos. Foi instituído um período de espera de 10 dias entre a administração de cada fármaco. Durante 15 dias consecutivos, um olho de cada animal recebeu uma gota de cada um deles, a intervalos de 12 horas (às sete e às 19 horas). Os parâmetros foram avaliados nos momentos acima referidos, nos dias três, seis, nove, 12 e 15. Os dados foram comparados estatisticamente empregando-se o teste de Bonferroni após análise de variância para medidas repetidas (P<0,05). Teste de Pearson foi utilizado para correlação entre o intervalo QT com a FC e a PS. Não se encontrou diminuição da PIO. Observou-se redução significativa do DP na quase totalidade dos animais que receberam levobunol, relativamente ao olho controle. Diminuição significativa da FC foi vista ao terceiro dia após a administração do levobunolol, enquanto apraclonidina induziu aumento no 15º dia. A pressão arterial foi reduzida em todos os momentos com a apraclonidina. Observou-se correlação negativa entre o intervalo QT e a FC apenas nos indivíduos tratados com o timolol. Em conclusão, levobunolol foi o único fármaco que induziu alterações significativas no DP. A apraclonidina foi o único fármaco que induziu hipotensão sistêmica significativa. O timolol foi o único a ensejar correlação negativa entre o intervalo QT e a FC.(AU)

Acute Central Horner Syndrome Diagnosed by 0.5% Apraclonidine Test: The Usefulness of the Apraclonidine Test

No abstract available.

A Pharmacologic Pupillary Test in the Diagnosis of Diabetic Autonomic Neuropathy

PURPOSE: To screen for diabetic autonomic neuropathy of the pupil using 0.5% apraclonidine and 0.1% pilocarpine and to evaluate the early diagnostic value of this pharmacologic pupillary test by assessing the relationship between pupillary and cardiovascular autonomic neuropathies. METHODS: A total of 22 diabetic patients were recruited. Baseline pupillary diameter (PD) and the difference in PD between the test eye and the control eye before and after instillation of apraclonidine and pilocarpine were measured. All patients also underwent cardiovascular autonomic function (CAF) testing. RESULTS: Baseline PD in room light correlated with duration of diabetes mellitus (DM, p=0.049) and the presence of DM retinopathy (DMR, p=0.022). Eleven patients (50%) had positive apraclonidine tests, and two patients had positive pilocarpine tests. The patients who had positive pilocarpine tests also had positive apraclonidine tests. Patients who had a positive pupillary test had a significantly higher rate of positive CAF tests (p=0.032). CONCLUSIONS: Pupillary autonomic neuropathy was related to the duration of diabetes and the degree of DMR. There was also a significant correlation between pupillary autonomic neuropathy and cardiovascular autonomic neuropathy (CAN). Also, sympathetic nerve dysfunction occurred prior to parasympathetic dysfunction in this study. A simple pharmacologic pupillary test can help manage complications in diabetic patients because patients with pupillary autonomic dysfunction have an increased risk of CAN.

Prophylactic Use of Brimonidine or Apraclonidine for Intraocular Pressure Elevation following Laser Iridotomy

PURPOSE: The purpose of this study was to evaluate and compare the prophylactic effect of brimonidine 0.2% and apraclonidine 0.5% in preventing intraocular pressure(IOP) elevation in patients undergoing laser iridotomy. METHODS: The 24-hour, placebo-controlled, randomized, clinical trial was conducted to determine the efficacy of brimonidine 0.2% and apraclonidine 0.5% in controlling IOP after combined argon and Nd:YAG laser peripheral iridotomy. The 110 eyes(56 eyes with angle closure glaucoma, 54 eyes with narrow occludable angle) were randomized to receive brimonidine 0.2%, apraclonidine 0.5% or artificial tear(as placebo) 20 minutes before the procedure. IOP was measured before and 1, 2, and 24 hours after the procedure by masked observer using Goldmann applanation tonometry. The difference between preoperative(baseline) IOP and the highest postoperative IOP was recorded as the maximum IOP rise. RESULTS: The mean of maximum IOP rise was 1.1+/-5.6 mmHg in the brimonidine group, 1.0+/-2.9 mmHg in the apraclonidine group and 4.7+/-7.6 mmHg in the placebo group. There was statistically significant decrease in IOP in both drug groups compared to the placebo group(p0.05). CONCLUSIONS: Both brimonidine 0.2% and apraclonidine 0.5% were significantly effective in preventing IOP spike following laser iridotomy procedure. There was a tendency toward less efficacy with brimonidine 0.2% compared to apraclonidine 0.5%, but this was statistically insignificant.

Brimonidine 0.2% versus Apraclonidine 0.5% for Controlling Intraocular Pressure Elevation after Q-switched Nd:YAG Laser Posterior Capsulotomy

PURPOSE: To compare the effectiveness of 0.2% brimonidine tartrate and that of 0.5% apraclonidine hydrochloride for controlling IOP elevation after Nd:YAG laser capsulotomy. METHODS: Thirty eyes were given with 0.2% brimonidine (group 1) and fourteen eyes with 0.5% apraclonidine (group 2) before and after the procedure. Fifteen eyes served as untreated controls (group 3). Intraocular pressure and visual acuity were measured preoperatively and 1 hour, 3 hours, 24 hours, and 1 week postoperatively in all cases. RESULTS: The postoperative mean intraocular pressures of group 3 (14.97+/-3.58, 16.47+/-3.93 mmHg) at 1 hour and 3 hours were statistically significant higher than those of group 1 (11.23+/-3.43, 11.50+/-3.01mmHg), and those of group 2 (10.79+/-3.51, 11.57+/-3.03 mmHg)(p< 0.05), but, there were no statistically significant differences in mean IOP at 1 hour and 3 hours between group 1 and group 2 (P=0.569, P=0.610). At 1 hour and 3 hours, there was no case of IOP elevation of 5 mmHg above baseline in group1 and group 2. but, there were 5 cases (33.3%) at 1 hour and 6 cases (40%) at 3 hours in group 3. CONCLUSIONS: This result suggests that 0.2% brimonidine and 0.5% apraclonidine are equally effective for preventing acute IOP elevation after Nd:YAG laser capsulotomy, that is, 0.2% brimonidine is an effective and well-tolerated agent for preventing acute IOP rises after Nd:YAG laser posterior capsulotomy.

The Effect of Apraclonidine Hydrochloride 0.5%Ve rsus 1%for Controlling Intraocular Pressure Elevation after Nd :YAG Laser Posterior Capsulotomy

Previous reports have shown that Nd:YAG laser capsulotomy is associated with elevated intraocular pressure(IOP). Topical apraclonidine hydrochloride has been shown to be effective in preventing postlaser pressure spikes. This study was designed to compare the effect of apraclonidine hydrochloride 0.5%versus 1% in controlling IOP elevation after Nd:YAG laser posterior capsulotomy. Fourteen eyes were treated with 0.5%apraclonidine(Group 1), twenty eyes with 1%apraclonidine(Group 2)and fifteen eyes without apra-clonidine(Group 3)in Nd:YAG laser posterior capsulotomy. The mean post-operative IOP at 1 to 3 hours of Group 3(15.0+/-3.6 mmHg, 16.0+/-4.3 mmHg) was higher than Group 1(10.8+/-3.5 mmHg, 11.6+/-3.0 mmHg)and Group 2 (11.2+/-3.0 mmHg, 12.7+/-2.3 mmHg)(P0.05). This result suggests that 0.5%and 1%apraclonidine are equally effective in preventing IOP rise and 0.5%apraclonidine can be a useful adjunct in preventing IOP elevation following Nd:YAG laser posterior capsulotomy.

The Effects of 0.5% Apraclonidine on Optic Nerve Head and Peripapillary Retinal Microcirculation

To examine the effects of 0.5% apraclonidine on optic nerve head (ONH) and peripapillary microcirculation, scanning laser Doppler flowmetry was performed before and 1 honr, and 3 hours after administration of 0.5% apraclonidine in 10 healthy subjects. In each occasion, 3 scans were obtained. Hemodynamic parmeters (volume, flow, and velocity0 were found at 8 locations, 4 in the neural rim and 4in the peripapillary retina. The intraocular pressure was reduced significantly in apraclonidine-treated eyes by 15.4% (p<.05) at 1 hour and 30.1% (p<.01)at 3 hours after administration. There was no significant change in the volume, flow or velocity of ONH and peripapillary retinal blood flow after apraclonidine administration. In conclusion, single-dose of topical apraclonidine 0.5% in healthy subjects does not have adverse effects on the microcirculation in ONH and peripapillary retina.

The Effect of 1 % Apraclnidine on Intraocular Pressure Following Argon Laser Iridotomy and Laser Trabeculoplasty

We studied the effect of 1% apraclonidine (Iopidine(R)) on the ocular hypotensive action and its ocular side effects following laser surgery for glaucoma. One hundred twenty patients with primary angle closure glaucoma underwent argon laser peripheral iridotomy and 40 patients with primary open angle glaucoma were treated with laser trabeculoplasty. Mean lOP of eyes instilled with 1% apraclonidine fell by 16% 3 hours after instillation in laser iridotomy cases and by 28% 3 hours after instillation in trabeculoplasty cases. lOP elevation greater than lO mmHg was found in 18 eyes (30%) of the control group in iridotomy cases and 4 eyes (40%) in trabeculoplasty cases, but none in the apraclonidine group in both treated cases for the first three hours. Apraclonidine reduced the incidence and magnitude of potentially harmful lOP elevations after laser irdotomy and trabeculoplasty.

Effect of apraclonidine hydrochloride on the attack of Posner-Schlossman syndrome

The intraocular pressure (IOP) of glaucomatocyclitic crisis with the attack fell 50.3%, from 37.8 +/- 8.2 mmHg to 18.8 +/- 4.8 mmHg, 4 hours after instillation of 1% apraclonidine. Glaucomatocyclitic crisis showed a more significant hypotensive response to 1% apraclonidine than primary open-angle glaucoma (24.8%, from 43. 1 +/- 8.1 mmHg to 32.4 +/- 7.5 mmHg after 4 hours). The intraocular pressure decrease percentage was similar regardless of the initial level of intraocular pressure. Clinically significant changes in mean systolic and diastolic blood pressures, were not observed, however, a mild decrease in the pulse rate was noted. And the local mydriatic effect on the pupillary diameter was significant. Apraclonidine, 1% might be newly indicated to control the IOP rise of glaucomatocyclitic crisis. Further studies on the possible mechanism of the prostaglandin mediated hypotensive effect of 1% apraclonidine are suggested.

Effect of Apraclonidine Hydrochloride on the Acute Intraocular Pressure Rise after Argon laser Iridotomy

To determine the effect of apraclonidine hydrochloride on the acute intraocular pressure (IOP) rise after argon laser iridotomy (ALl), a double-masked comparative study was carried out. Twenty-nine eyes (20 patients) with angle-closure glaucoma underwent ALL Eighteen eyes were treated with apraclonidine and the remainder received placebo 1 hour before and immediately after ALl. The mean IOP increase in the apraclonidine group was lower than that in placebo group at each postlaser intervals (p<0.01). Although average value of maximal increases of IOP after ALl in apraclonidine group was 4 mmHg, that in placebo group was 16mmHg. 27.3% (3 out of 11 eyes) in placebo group experienced IOP rise greater than or equal to 10 mmHg, however, that kind of IOP rise was not found in apraclonidine group (0 out of 18 eyes) (p

Morphological Changes in the Ciliary Epithelium of Pigmented Rabbits by Intravitreal Injection of Apraclonidine

The effects of clonidine that is an alpha2-adrenergic agonist are complex in that the intraocular responses are biphasic and dose dependent. The mechanisms of the ocular hypotensive responses to clonidine in the treated and the contralateral untreated eyes seemed to be dependent on the central activity of clonidine and the intact peripheral adrenergic system. Apraclonidine is a clonidine derivative which penetrates into the blood-brain barrier minimally and lowers the intraocular pressure significantly not accompanied by systemic side effects such as change in blood pressure and pulse rate. The main purpose of the present study is to use apraclonidine to elucidate the influence of the central and peripheral sympathetic activity in the change of the morphology of the ciliary nonpigmented epithelium in the pigmented rabbits 0.1 cc of 1% apraclonidine was injected into the vitreous cavity of pigmented rabbits after removal of 0.1 cc of aqueous humor from the anterior chamber and the eyes were enucleated on 1, 3, 5, 7 days after injection. The eyes were observed with light microscopic examination. 1. In the 1st day's specimen, swollen nonpigmented epithelium and increased pigments were noted in the treated eye. 2. In the treated eye on the 5th day, vacuole like appearances under the nucleus of the nonpigmented epithelium were noted. 3. Except for the appearance of slightly increased pigmented granules in the 3rd and 5th day's specimen, there were no significant changes in any of the nontreated eyes. 4. The mechanism of the hypotensive response of apraclonidine seemed to be dependent on the alpha2-adrenergic receptors which are located in the eye, not on the central nor on the peripheral adrenergic system.

Morphological Studies on the Rabbits Ciliary Epithelium by Apraclonidine

Apraclonidine is a potent alpha-adrenergic agonist that, like clonidine, is relatively selective for alpha-2 receptors. Apraclonidine has been shown to lower intraocular pressure by diminishing aqueous humor formation. The purpose of this study is to know the morphological changes in the ciliary epithelium by apraclonidine against aqueous formation. In group I, two drops of 1% apraclonidine hydrochloride were instilled on the right eye of the pigmented rabbits and the eyes were enucleated on 1,2.6 and 24 hours after instillation to find out the duration of action of the drug and the tissue response. In group II, one drop was instilled twice daily for seven days on the right eye and the eyes were enucleated on 1, 2 and 5 days after cessation of the instillation observing the cumulative effect of the drug and the tissue response. These eyes were studied with electron mIcroscopIc examiation. As a result, widening of cell membranes(basal infoldings) of the non-pigmented epithelium(NPE) were observed. This change was recovered with time, and seems to be the principal morphological changes of apraclonidine against aqueous formation in the ciliary body. In group II, the cellular changes were minimal except for well developed rough endoplasmic reticulum representing resumed secretary function of the cell.

The Effects of 1% Apraclonidine in Preventing the Intraocular Pressure Rise FolIowing Argon Laser Surgery in Glaucoma

The effect of 1% apraclonidine(Lopidine) in preventing transient rising of intraocular pressure following argon laser peripheral iridotomy or argon laser trabeculoplasty was evaluated in a prospective, randomised, double-masked study. Forty-two eyes(42 patients) with glaucoma underwent argon laser peripheral iridotomy or argon laser trabeculasty. They were randomised into two groups; the apraclonidine group(twenty-one eyes) receiving 1% apraclonidine hydrochloride, and the control group(twenty-one eyes). The apraclonidine group was treated with one drop of 1% apraclonidine hydrochrolide one hour before and immdiately after laser surgery. We measured intraocular pressure before the operation and hourly for the first three hours after the operation, after one day, and after one week. Elevation of intraocular pressure after laser surgery was found in 13 eyes(61.9%) of the control group and 5 eyes(23.8%) of the apraclonidine group. Elevation greater than 10 mmHg was found in 3 eyes of the control group but none in the apraclonidine group.

Inhibition of the Apraclonidine induced Reduction of Intraocular Presure by Topical Suprofen in Normal Human Eyes

We studied the effect of prostaglandin synthesis inhibitor on the ocular hypotensive action of apraclonidine in a prospective, double-masked study. Twenty normal volunteers were studied. Suprofen, cyclooxygenase;nhibitor and apraclonidine were applied to one eye, and normal saline and apraclonidine to the other eye. Intraocular pressure(IOP) was then measured hourly in both eyes for 7 hours. The results showed significant reduction in mean IOP of both eyes one hour after apraclonidine application. The differences of IOP between the suprofen-treated eyes and control eyes were significant at 2 hours following treatment(p<0.05), reached maximum at 3 to 4 hours(p<0.01) and lasted until 7 hours(p<0.05). In suprofentreated eyes, there was less reduction of mean IOP than in control eyes. These results suggest that this reduction of IOP is at least in part mediated by prostaglandins or other cyclooxygenase products, since suprofen inhibits the ocular hypotensive effect of topically applied apraclonidine.

Effect of apraclonidine hydrochloride on acute introacular pressure rise after argon laser iridotomy

To determine the effect of apraclonidine hydrochloride on the acute intraocular pressure (IOP) rise after argon laser iridotomy (ALI), a double-masked comparative study was carried out. Twenty-nine eyes (20 patients) with angle-closure glaucoma underwent ALI. Eighteen eyes were treated with apraclonidine, and the remainder received a placebo 1 hour before and immediately after ALI. The mean IOP increase in the apraclonidine group was lower than that in the placebo group at each postlaser interval (p or = 10 mmHg. However, that kind of IOP rise was not found in the apraclonidine group (0 out of 18 eyes) (p < 0.01). Ocular or systemic side effects were not found in a series of examinations in both groups. Therefore, apraclonidine proved to be effective in lowering the IOP rise after ALI.

The Effects of 1% Apraclonidine(Iopidine) on Intraocular Pressure in Normal Persons

Apraclonidine(Iopidine, p-aminoclonidine hydrochloride, ALO 2145) is a peripheral alpha 2 agonist. We evaluated the effect of apraclonidine on IOP and its systemic or ocular side effects in normal subjects. We measured IOP, BP(systolic and diastolic), pulse rate, pupillary size, palpebral fissure width and checked the ocular side effects, such as conjunctival blanching, irritation, and headache, etc. Mean IOP of eyes instilled with 1% apraclonidine fell by 20 +/- 8.5%, from 15.5 +/- 3.9mmHg to 12.4 +/- 2.6 mmHg, 3 hours after instillation. The effect remained up to 7 hours after instillation(p<0.01). Mean IOP of the fellow eyes did not show statistically significant difference, compared with the baseline; but when compared with the placebo group, there was a slight but statistically significant difference(p<0.01) from 3 hours to 7 hours after instillation. There was no significant difference between the eyes instilled with 1% apraclonidine and the placebo in terms of the mean systolic and diastolic BP, pulse rate, pupillary size and palpebral fissure width. Conjunctival blanching was noted in 51.6% of the eyes instilled with 1% apraclonidine. Other side effects noted were headache(25.8%), lid elevation sense(16.1%), lid drooping sense of the fellow eye(6.4%), nausea(9.7%), and irritation(3.2%).