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 anti-glaucoma drugs on resistive index of the medial long posterior ciliary artery using color Doppler imaging in Beagle dogs

Color Doppler imaging (CDI) was carried out to evaluate the effects of anti-glaucoma drugs on ophthalmic circulation using CDI-derived resistive index (RI) values. CDI was performed on nine Beagle dogs, and RI values were calculated for the medial long posterior ciliary artery before and after the administration of anti-glaucoma drugs. A significant increase in RI values was found after topical administration of levobunolol (p < 0.05) or dipivefrin (p < 0.05). Pilocarpine showed no effects on RI values after topical administration. The results suggest that some anti-glaucoma drugs could affect ophthalmic blood flow.

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

Effect of topical antiglaucoma drugs on corneal epithelium wound healing in rabbits

Topical antiglaucoma drugs had been used frequently in treatment of different types of glaucoma. Some of these drugs cause inhibition of corneal epithelial wound healing. So, this study aimed to determine the toxic effect of topical antiglaucoma drugs on corneal epithelium of the rabbit. In the present study, seven antiglaucoma drugs [[1] Timolol maleate 0.5%; [2] Apraclonidine HCI 0.5%; [3] Dipvefrin HCI 0.1%; [4] Betoxolol HCI 0.5% [5] Levobunolol HCI 0.5%, [6] Befunolol HCI 0.5%, and [7] Pilocarpine HCI 2%] in their therapeutic concentrations were applied to the cornea of the rabbit which undergone mechanical removal of the epithelium 8 mm in diameter.The rate of healing of conreal wound in saline treated controls was found significant if compared with antiglaucoma drugs.Drugs 5,6,7 demonstrated more rapid healing than drugs 1, 2, 3, 4. In this study, anti glaucoma drugs appear to have toxic effect on the corneal epithelial wound healing specially drug 2 followed by drugs 1, 3, 4

Estudo comparativo do efeito do timolol, do betaxolol e do levobunolol sobre a curva diária de pressäo intra-ocular de pacientes glaucomatosos / Comparative study of timolol, betaxolol and levobunolol by the diurnal curve pressure in glaucomatous patients

Estudou-se os mesmos pacientes glaucomatosos sem dano do nervo óptico, comparativamente pela CDPo, a açäo hipotensora ocular de 3 drogas: maleato de timolol, betaxolol e levobunolol. O estudo foi precedido de uma CDPo sem medicaçäo. A análise estatística comparativa entre os 3 fármacos näo mostrou diferenças significativas em relaçäo à hipotensäo ocular que cada droga produziu. Näo havendo contra-indicaçäo, a escolha de um deles deve ser feita baseada no senso clínico

Ocular Hypotensive Effect of Levobunolol Hydrochloride

To estimate the clinical efficacy of a newly developed beta1 and beta2 - adrenoreceptor antagonist, levobunolol hydrochloride (Betagan), fifty six patients (96 eyes) with various types of glaucoma were enrolled in this study and were treated twice a day with 0.5% Betagan. Intraocular pressure (lOP), visual acuity, pupil size and cup/disc ratio were measured before and after Betagan treatment, at week 1, 2, 4, 8 and 12. The patients were also examined to check the subjective or objective local adverse reactions. All the patients showed significant reduction of lOP throughout the observation period without significant change of visual acuity, pupil size and cup/disc ratio. Additive hypotensive effect of Betagan was also noted when it was added to pilocarpine. In some patients, however, stinging sensation with tearing, photophobia, or foreign body sensation and punctate corneal erosion were noted after Betagan treatment; those were mild and transient.

Estudo duplo mascarado sobre o uso tópico de levobunolol e maleato de timolol em pacientes com glaucoma crônico simples ou hipertenso ocular / Double masked study of levobunolol an timolol maleate in chronic open angle glaucoma or ocular hypertension patients

A açäo hipotensa ocular, eficácia e segurança da soluçäo de levobunolol a 0,5% foram comparadas com o maleato de timolol a 0,5% quando administrado duas vezes ao dia em 37 pacientes com glaucoma crônico simples ou hipertensäo ocular, por um período de 3 meses. Os pacientes em tratamento prévio foram submetidos a um período de eliminaçäo das drogas, que variou de 4 a 14 dias conforme a medicaçäo que estavam utilizando. As seguintes variáveis foram avaliadas no exame inicial e no decorrer dos 3 meses: história clínica e eletrocardiograma (só no exame inicial), freqüência cardíaca, pressäo arterial, acuidade visual, pressäo intra ocular, biomicroscopia, oftalmoscopia e campo visual (só nas visitas inicial e final). Foram considerados parâmetros para avaliar a eficácia da droga; Po, escavaçäo, papilar e campo visual; e quanto à segurança ocular: acuidade visual, biomicroscopia e oftalmoscopia. A segurança sistêmica' foi avaliada pelas alteraçöes ocorridas na freqüência cardíaca e pressäo arterial sistólica, tomando por base o exame inicial. Noventa por cento dos pacientes do grupo do levobunolol e 94% do maleato de timolol completaram com sucesso o estudo. Em todas as visitas houve uma diminuiçäo significante da média da Po no grupo do levobunolol. Uma diminuiçäo similar foi vista também no grupo do maleato de timolol. Näo houve uma diferença significante quanto à eficácia dos dois tratamentos. Em ambos os grupos houve uma diminuiçäo na média da pressäo arterial e freqüência cardíaca, sendo que sta näo foi clinicamente significativa

The Diurnal Variation and the Hypotensive Effect of Combined Therapy of Levobunolol and Dipivefrine in the Healthy Koreans and the Patients with Open Angle Glaucoma

The diurnal variation of introcular pressure was measured in 40 eyes of 20 healthy Koreans and in 50 eyes of 25 patients with chronic open angle glaucoma and ocular hypertension with and without levobunolol and dipivefrine. The intraocular pressure was measured every 1 hour from 8:00 o'clock by the same examiner using with Goldmann applanation tonometry. The levobunolol, a new beta-adrenoceptor antagonist effective in the long-term treatment of glaucoma and the dipivefrine, a prodrug of epinephrine which is alpha-and beta-adrenergic agonist, both decrease intraocular pressure despite of opposite pharmacologic actions. Several clinical studies have demonstrated additional effect when an epinephrine compound is added to timolol, a beta-blocker antagonist, theraphy. It is the most important issue that determination of the time of instillatiolt related to the time of maximum effec: of the drugs and the time of the highest intraocular pressure in a day in every each patient. The authors obtained the following results; 1) In the control group, the mean intraocular pressure was 15.3 +/- 1.377 mmHg, the highest was 17.3 +/- 0.924 mmHg at 10 o'clock AM and the lowest was 13.7 +/- 1.764 mmHg at 3 o'clock PM. The diurnal variation was 3.60 +/- 1.743 mmHg.(p=0.002). 2) In the patient group, the mean intracular pressure was 28.5 +/- 1.606 mmHg, the highest was 31.4 +/- 2.986 mmHg at 10 o'clock AM and the lowest was 26.1 +/- 0.836 mmHg at 4 o'clock PM. The diurnal variation was 5.31 +/- 1.101 mmHg.(p=0.0001). 2) The lowering effect of intraocular pressure by the instillation of 0.5% levabunolol and 0.1% dipivefrine was statistically significant(p=0.0001) both in the control group and patient group. In the patient group, the maximum effect was made at 5 hours after instillation of the drugs with 28% decrease. 4) The distribution of the highest intraocular pressure in the patient group was as following: 23 eyes at 10 o'clock AM, 11 eyes at 9 AM, 9 eyes at 11 AM, 3 eyes at 8 AM, 3 eyes at noon and 1 eye at 4 o'clock PM.

Influence of beta-adrenoceptor antagonists on spontaneous rate and on force of contraction of isolated rabbit atria.

The influence of beta-adrenoceptor antagonists on the spontaneous rate and on force of contraction of the myocardium was studied independently on spontaneously beating right and electrically driven isolated left atria of rabbit. On spontaneous rate, practolol had sympathomimetic effect only, N-isopropylmethoxamine (IMA), had both sympathomimetic as well as depressant effects, whereas alprenolol, procinolol, bunolol and H 35/25 had depressant effects only in higher concentrations. The order of potency was procinolol greater than bunolol greater than alprenolol greater than H 35/25 greater than and IMA. On the contractions of isolated left atria, all beta-adrenoceptor antagonists produced concentration-dependent depressant effect. In relation to procinolol, these agents were 5-125 times less potent for depressing the contractions of left atria by 15% and the order of beta-potency was procinolol greater than alprenolol greater than bunolol = H 35/25 greater than IMA greater than and practolol. The present results indicate that the depressant effects of beta-adrenoceptor antagonists on spontaneous rate of right atria and on contraction of isolated left atria are not related to each other.