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)

Effects of topical levobunolol or fixed combination of dorzolamide-timolol or association of dorzolamide-levobunolol on intraocular pressure, pupil size, and heart rate in healthy cats / Efeitos da aplicação tópica do levobunolol, da combinação fixa de dorzolamidatimolol ou da associação de dorzolamida com levobunolol sobre a pressão intra-ocular, o diâmetro pupilar e a freqüência cardíaca em gatos saudáveis

The effects of topical levobunolol with the fixed combination of 2 percent dorzolamide-0.5 percent timolol and the association of 2 percent dorzolamide with 0.5 percent levobunolol on intraocular pressure (IOP), pupil size (PS), heart rate (HR), and conjunctival hyperemia in eighteen halthy cats were investigated and compared. IOP, PS, HR, and conjuntival hyperemia were daily recorded at three times (9a.m., 2p.m., and 6p.m.). Three groups were formed (n=6), and one eye of each animal was randomly selected and treated with topical levobunolol (L), or commercial combination of dorzolamide-timolol (DT), or the association of dorzolamide with levobunolol (DL). The first day (0) consisted of recording of baseline values. On the next four consecutive days, drugs were instilled at 8a.m. and 8p.m. and measurements were taken at the same times fore cited. Comparing with the baseline values, all evaluated parameters significantly decreased (P<0.001). Conjuntival hyperemia was not seen. Levobunolol significantly declined IOP, PS, and HR in normal cats, and showed a stronger effect in lowering HR, when compared to dorzolamide-timolol effect. No synergistic effect in IOP declining was noted when levobunolol dorzolamide was added to levobunolol.

Estudaram-se e compararam-se os efeitos do levobunolol, da combinação fixa de dorzolamida 2 por cento-timolol 0,5 por cento e da associação de dorzolamida 2 por cento com levobunolol 0,5 por cento sobre a pressão intra-ocular (PIO), o diâmetro pupilar (DP), a freqüência cardíaca (FC) e a hiperemia conjuntival em 18 gatos saudáveis. PIO, DP, FC e hiperemia conjuntival foram aferidos diariamente, em três horários distintos (9h, 14h e 18h). Três grupos foram formados (n=6) e um olho de cada animal recebeu, aleatoriamente, uma gota de levobunolol (L), ou a combinação comercial à base de dorzolamida-timolol (DT), ou a associação de dorzolamida com levobunolol (DL). Parâmetros basais foram aferidos no primeiro dia (dia 0). Nos quatro dias consecutivos, os fármacos foram instilados às 8h e 20h e os parâmetros aferidos nos mesmos horários. Todos os parâmetros decresceram significativamente em relação aos valores basais (P<0,001) e não se observou hiperemia conjuntival. O levobunolol reduziu significativamente a PIO, o DP e a FC e o foi o fármaco que mais reduziu a FC. Não se observou efeito sinérgico na redução da PIO quando a dorzolamida foi adicionada ao levobulol.

Adverse drugs reactions associated with glaucoma medications

We undertook a non-concurrent prospective study of 191 Puerto Rican patients from August 1993 to April 1994. All patients had open angle glaucoma (OAG) (age ranged from 50 to 80 yrs; mean = 65 yrs). Patient's symptomatology associated to side effects of their glaucoma medicadons was reviewed. Incidence percent of ocular and/or systemic side effects per medication were: levobunolol 45.0; betaxolol 42.0; timolol 27.3; pilocarpine 100; dipivefrin 14.0; and acetazolamide 250 mg 64.1. Incidence percent of ocular and/or systemic side effects of topical beta-blockers used with concomittant medications were determined. Ocular side effects were more frequent in patients using levobunolol 44.2 than in those patients using betaxolol 42.0, 8.5 of patients using levobunolol did report systemic side effects. No systemic side effects were reported by patients using betaxolol. Ocular side effects in patients using pilocarpine were frequent (100); whereas the frequency of systemic side effects was low (6.1). Systemic side effects were common in patients using carbonic anhydrase inhibitors. These results suggest that non-selective and cardio-selective topical Beta-blockers, differ in their ocular or systemic side effects