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At least 307 records · Page 17Linked to original sources

PubMed1992

Effect of nasolacrimal occlusion on timolol concentrations in the aqueous humor of the human eye.

We studied the effect of manual nasolacrimal occlusion on the concentration of timolol in the aqueous humor of eyes of patients undergoing cataract extraction. Aqueous humor samples were obtained at various times after timolol maleate instillation from patients with or without 5 min of nasolacrimal occlusion; aliquots were assayed by HPLC. In patients receiving occlusion treatment, average timolol concentrations were statistically greater than those in control patients both between 15 and 90 min after instillation and also at 180 min. Pharmacokinetic analysis indicated that occlusion increased the concentration of timolol in the aqueous humor 1.7 times. In both groups, timolol concentrations were highest approximately 1 h after instillation. The decline in aqueous humor timolol concentrations occurred at similar rates in both groups.

Aged↗

PubMed1993

Dual sorption model for the nonlinear percutaneous permeation kinetics of timolol.

The nonlinear percutaneous permeation kinetics of timolol were studied in vitro with human cadaver skin. In the sorption isotherm (equilibrium) study, the plots of the amount of timolol per unit area of epidermis versus aqueous timolol concentration in equilibrium were curvilinear as the dual sorption model predicts. In the penetration study, several aqueous timolol concentrations were maintained in the donor cell for 25 h. The lag-time was prolonged as the timolol concentration in the donor cell was decreased. The change in the lag time was analyzed by a newly proposed method with the lag-time prolongation factor that is calculated from the parameter values obtained in the sorption isotherm study. The ratio of the lag-time to lag-time prolongation factor was of the same magnitude, indicating that the dual sorption model explains the nonlinear percutaneous permeation kinetics of timolol. Finally, the diffusion parameter for the mobile solute was estimated by fitting the data of the cumulative amount excreted into receptor cell versus time to the numerical solution of the dual sorption model. The observed data were roughly compatible with the values predicted by the dual sorption model.

Administration, Cutaneous↗

PubMed1980

Timolol eye drops: bradycardia or tachycardia?

26 eyes of 14 patients--8 with primary open angle glaucoma, 6 glaucoma suspects--were treated for at least 6 months with either twice daily timolol 0.25% in both eyes or twice daily timolol 0.50% in one eye. None of the patients received concomitant local or oral drugs. Special attention was paid to tachyphylaxis and to blood pressure and pulse rate. We could detect a slight although not significant tendency to tachyphylaxis (1-2 mm Hg) after 1 week of timolol treatment. It takes at least 1-2 weeks to reach the initial I.O.P. level after withdrawal of timolol therapy. Blood pressure did not change significantly. The pulse rate showed a slight although not significant tendency to decrease (a few beats/minute), but we detected a reflex tachycardia (10 beats/minute) after withdrawal of timolol therapy which was very significant. This rebound phenomenon has not been referred to in the literature. It seems reasonable to conclude that one should take care in treating glaucoma patients with concomitant arrhythmias with timolol eye drops.

Adult↗

PubMed1995

Oxygen-induced retinopathy in the newborn rat: effects of hyperbarism and topical administration of timolol maleate.

BACKGROUND: Lesions resembling those of human retinopathy of prematurity can be provoked in newborn Wistar rats by exposure to an FiO2 of 80% for the first 5 days of life followed by 5 days recovery under room-air conditions. METHODS: We evaluated the effects of moderate hyperbarism (+60.75 kPa, i.e. 455 mmHg or 0.6 atm) and topical administration of 0.25% timolol maleate on oxygen-induced retinopathy (OIR) in this experimental model. RESULTS: OIR (including neovascularization in most cases) was observed in 100% of the retinas of normobaric oxygen-reared ratlings that did not receive timolol. OIR was less frequent in oxygen-reared ratlings treated with hyperbarism (60%) or timolol (65%). Hyperbaric oxygen supplementation combined with timolol treatment during both the hyperoxic and room-air phases reduced the incidence of OIR to 30%. There was no sign of vasoproliferation in any of the retinas from the latter three groups. CONCLUSIONS: The highly significant protective effects of hyperbarism and timolol observed in this study are not fully understood. We speculate that vasoconstriction induced by the hyperbarism reduces the amount of oxygen that reaches the retina from the choroid during O2 supplementation, while an increased ocular perfusion pressure caused by timolol-induced reduction of the intraocular pressure might decrease the stimulus to vasoproliferation that normally occurs with room-air recovery.

Administration, Topical↗

PubMed1994

Topical timolol, corneal epithelial permeability and autofluorescence in glaucoma by fluorophotometry.

UNLABELLED: Corneal epithelial permeability and autofluorescence were measured by fluorophotometry in patients with open-angle glaucoma or ocular hypertension to quantify the epithelial function of the cornea and to evaluate its metabolic activity in 24 patients using daily timolol and 11 not using timolol. The findings were compared with those in age-matched healthy controls. Permeability values in patients using timolol were 1.9 times higher than in patients not using timolol and 2.5 times higher than in healthy controls (Mann-Whitney test P < 0.001). Values for patients not using timolol did not differ from those for healthy controls (P = 0.15). Corneal autofluorescence values in each patient group were higher than in healthy controls (P = 0.002). CONCLUSIONS: (1) open-angle glaucoma or ocular hypertension alone does not affect corneal epithelial permeability; (2) daily instillation of timolol causes impairment of the corneal epithelial barrier; (3) open-angle glaucoma or ocular hypertension are likely to induce an increase of corneal autofluorescence.

Administration, Topical↗

PubMed1980

[The effect of timolol and dipivalyl-epinephrine in the treatment of the elevated intraocular pressure (author's transl)].

Twenty-seven patients with ocular hypertension or open angle glaucoma were tested to see if, and to what extent, timolol and dipivalyl-epinephrine produced a supplementary reduction of intraocular pressure. In a shortterm study, 14 patients were tested with timolol (0.1%) and dipivalyl-epinephrine (0.25%). Simultaneous application of both substances produced a statistically more significant reduction of intraocular pressure than either timolol (0.1%) or dipivalyl-epinephrine (0.25%) alone. In 13 patients a comparison was made between patients who received both timolol (0.25%) and dipivalyl-epinephrine (0.1%) bis x and patients who received only timolol (0.25%) bis x over a period of 6, 9 and 12 weeks. Both substances used in combination produced a statistically more significant reduction in intraocular pressure than timolol (0.25%) bis x alone. The simultaneous application of an alpha and beta-adrenergic agonist and beta-adrenergic antagonist is not contradictory. The results are discussed on the basis of the mode of action of the applied substances.

Drug Therapy, Combination↗

PubMed1982

The IOP-lowering effect of timolol in simple and capsular glaucoma. A multicenter study in Finland.

Timolol maleate eye drops (0.25% and 0.5%) were used alone or in combined treatment in 220 patients with simple or capsular glaucoma. A highly significant (P less than 0.001, mean -9.4 mm Hg,-29%) decrease in the intraocular pressure (IOP) was seen in 196 (164 simple, 32 capsular) patients in the beginning of the study using timolol alone. (Inadequate control timing, deviation from the treatment definition, or adverse reactions caused the exclusion of the data of 24 patients). A total of 180 patients (151 simple, 29 capsular) completed the 6-month study. At the end of the study an IOP less than 22 mm Hg was seen in 103 (57.2%, 91 simple, 12 capsular) patients treated with timolol alone. During the follow-up period there was no significant difference in the IOP-lowering effect of timolol in the simple and the capsular group using timolol alone. Combined treatment was needed by 39 of 180 patients who completed the study. It was needed more than twice as often in the capsular group (12 patients, 41.4%) as in the simple group (27 patients, 17.9%). The IOP increased above 25 mm Hg in one-fourth of these 39 patients during the follow-up period, but there was no significant difference between the simple and the capsular group. Six patients dropped out of the study because of side-effects possibly related to timolol therapy.

Acetazolamide↗

PubMed1982

Timolol treatment of chronic open-angle glaucoma and ocular hypertension. A 2.5-year multicenter study.

Maintenance effect of topical timolol was investigated for 2 years in a group of 125 glaucomatous and ocular hypertensive patients (231 eyes) who had been successfully treated with timolol alone during a 6-month period preceding this trial. Intraocular pressure (IOP) was controlled with timolol alone in 135 of 183 eyes (74%) that completed the study. At the end of the trial 142 eyes (78%) showed an IOP of less than 22 mmHg. Other glaucoma medication had to be added to timolol treatment in 18% of ocular hypertensive and 35% of glaucomatous eyes because of IOP elevation. Elevation of IOP seemed to be due to worsening of glaucoma rather than to decreased efficacy of timolol. None of the ocular hypertensive patients developed visual field defects but in ten glaucomatous patients progression of existing visual field defects was observed in association with elevated IOP. Transient adverse effects were observed in 13% of cases, but timolol treatment had to be stopped in only five cases (4%) because of side effects.

Adult↗

PubMed2003

Spectrophotometric methods for determination of enalapril and timolol in bulk and in drug formulations.

Two simple and accurate spectrophotometric methods for determination of timolol and enalapril maleate are described. The first method is based on chelate formation with palladium(II) chloride in buffered medium. The second method is based on the formation of the colored complex between palladium(II), eosin, and the two cited drugs using methylcellulose as surfactant to increase the solubility and intensity of the formed complexes. Under optimum conditions the complexes showed maximum absorption at 369.4 nm and 362.8 nm for timolol and enalapril maleate, respectively, in the first method and 552.2 and 550.6 nm for the second method. Apparent molar absorptivities were 1.8 x 10(3) and 1.3 x 10(3) and Sandell's sensitivities were 5.9 x 10(-4) and 2.7 x 10(-4) for timolol and enalapril maleate in the first method; in the second method molar absorptivities were 2.8 x 10(4) and 1.1 x 10(4) while Sandell's constants were 9.1 x 10(-3) and 2.3 x 10(-3) for timolol and enalapril maleate. The solutions of the complexes obeyed Beer's law in the concentration ranges 20-200 micro g mL(-1) and 50-300 micro g mL(-1) for timolol and enalapril maleate, respectively. In the second method, because the reaction was more sensitive the ranges were reduced to 1.6-16 micro g mL(-1) for timolol 8-56 micro g mL(-1) for enalapril maleate. The proposed methods were applied to the determination of the two drugs in their pharmaceutical formulation.

Antihypertensive Agents↗

PubMed1999

The favorable effect of topical betaxolol and timolol on glaucomatous visual fields: a 2-year follow-up study.

BACKGROUND: It has been suggested that beta-adrenergic antagonists might have mechanisms of action other than ocular hypotensive effects affecting the visual function in glaucoma patients and that betaxolol might protect the visual field better than others. A randomized, double-blind study was conducted to compare the effects of betaxolol and timolol on visual fields of glaucoma patients. METHODS: Sixty-four glaucoma patients were treated with either 0.5% betaxolol or 0.25% timolol eyedrops twice daily. The Octopus visual field performance was followed up for 2 years and analyzed to find diffuse and localized changes. We analyzed the change in the mean sensitivity (MS) and performed a cluster analysis and clinical assessment of the visual fields in both treatment groups. RESULTS: The mean sensitivity (MS) improved significantly and equally in both treatment groups. There was a tendency towards more improved clusters in the betaxolol group than in the timolol group and more worsened cluster in the timolol group than in the betaxolol group, but the difference was not statistically significant. The clinical assessment also showed no statistically significant difference between the two groups. CONCLUSION: In the present study both betaxolol and timolol had a favorable effect on the visual fields of glaucoma patients. There was no statistically significant difference between betaxolol- and timolol-treated patients either in the change in mean retinal sensitivity or in the change in localized scotomatous areas.

Administration, Topical↗

PubMedDate not supplied

Comparative study on the combined effects of bunazosin and nipradilol or timolol on intraocular pressure in normotensive rabbits.

PURPOSE: To compare the ocular hypotensive effect of nipradilol and timolol in combination with bunazosin in rabbits. METHODS: The intraocular pressure (IOP) in normal rabbits was measured using an applanation pneumatonograph. Nipradilol, timolol, and bunazosin were instilled, individually or in combination, into the inferior conjunctival sac. RESULTS: Nipradilol (0.25%), timolol (0.5%), and bunazosin (0.01%) individually lowered IOP. The IOP-lowering effects of both nipradilol and timolol were significantly enhanced by the combined application of bunazosin (0.01%). In the presence of 5% timolol or 0.1% bunazosin, IOP was further lowered by the addition of nipradilol. The IOP-lowering effect of nipradilol was partly inhibited by pretreatment with c-PTIO (10 mM), a nitric oxide (NO)-trapping agent. CONCLUSIONS: The present study demonstrated that the IOP-lowering effects of nipradilol are due to beta- and alpha1-blocking and NO-donating actions, and bunazosin has an additive effect on the IOP-lowering effect of nipradilol or timolol.

Adrenergic alpha-Antagonists↗

PubMed1988

Prophylaxis of post-myocardial infarction dysrhythmias by long-term timolol therapy.

The antiarrhythmic efficacy of timolol maleate was assessed in 94 patients with acute myocardial infarction. No significant differences were noted between early treatment with timolol and placebo in the mean and peak hourly ventricular premature complex rates, ventricular premature complex couplets, or runs. However, compared to the placebo treatment, there was a significant (p less than 0.001) 66% reduction in the relative fraction of early-cycle ventricular premature complexes 7 to 9 days after initiation of timolol therapy and a more prolonged significant (p less than 0.001) 73% reduction in the fraction of early-cycle supraventricular complexes throughout the 28-day timolol and placebo comparison period. The frequency distribution of QRS duration was significantly different between the placebo- and timolol-treated patients, with the mean duration 8 msec longer in the placebo-treated patients (p = 0.008). Adverse effects from early administration of timolol did not differ from those in the placebo-treated patients.

Cardiac Complexes, Premature↗

PubMed1986

Acute myocardial infarct size reduction by timolol administration. The International Collaborative Study Group.

A multicenter, randomized, double-blind study was performed to evaluate the effects of timolol administered early during the evolution of acute myocardial infarction. Of 144 patients entered into the trial, 73 were assigned to timolol and 71 to placebo. The 2 groups were well matched at baseline. The timolol group had reduced myocardial ischemia and infarct size as measured by an accelerated reduction of ST-vector magnitude, a significant reduction of creatine kinase (CK) release and significantly smaller changes in QRS vector variables. The predicted maximal QRS vector change and cumulative CK release for any given initial ST-vector magnitude was significantly reduced in the timolol-treated patients. Furthermore, QRS evolution time and CK release time were significantly reduced after intravenous timolol, as were the need for analgesics and the pain scores. Timolol treatment was well tolerated overall.

Adult↗

PubMed1986

A double-masked comparison of betaxolol vs timolol in the treatment of open-angle glaucoma.

We conducted a six-month prospective, double-masked randomized trial comparing betaxolol with timolol at 0.25% and 0.5% concentrations in the treatment of primary open-angle glaucoma in 38 patients. To qualify, patients had to demonstrate an average intraocular pressure in at least one eye of greater than or equal to 26 mm Hg without treatment. The median intraocular pressure was consistently lower in the timolol group than in the betaxolol group (after four weeks of therapy, it was 20.2 mm Hg for timolol vs 22.5 mm Hg for betaxolol; P less than .04). Adjunctive therapy was required in eight patients in the betaxolol group compared to one in the timolol group (P less than .05). Betaxolol appears to be a clinically effective and safe agent in the treatment of open-angle glaucoma. However, the magnitude of the decrease in intraocular pressure with it may not be as great as that with timolol and there may be a greater need for adjunctive therapy with it than with timolol.

Adult↗

PubMed1979

Effects of the beta-adrenergic blocking agents propranolol and timolol on canine cardiac refractory periods.

The effects of d,1-propranolol and 1-timolol on cardiac refractory periods (RP) were compared in 14 phentobarbital-anesthetized dogs using endocavitary His bundle electrograms and programmable electrical stimulation. Beta-blocking agents were injected at cumulative doses in each dog at 3 day intervals. A control group (6 dogs) received 4 successive saline injections at the same time intervals. RP measurements at a constant drive rate were done before and 10 minutes after each dose of either drug or saline. Propranolol and timolol produced a dose-dependent increase of atrial and atrioventricular nodal refractory periods; dose-response curves were parallel. Depending on the parameter chosen timolol exerted an 8--36 times more potent effect than propranolol. The effects of propanolol and timolol on ventricular effective (VERP) and functional (VFRP) RP were measured in 6 dogs. Both drugs increased VFRP significantly, but saline had the same effect. Only the higher doses of timolol increased VERP significantly. These data confirm that blockade of myocardial beta-adrenergic receptors exerts predominant effects on supraventricular refractoriness and that in anesthetized dogs timolol has more potent beta-blocking properties than does propranolol.

Animals↗

PubMed1992

Improving the safety of topically applied timolol in the pigmented rabbit through manipulation of formulation composition.

The objective of this study was to compare the efficiency of various formulations in maximizing the ratio of ocular to systemic absorption of topically applied timolol in the pigmented rabbit. Formulations of various pHs, tonicities, and concentrations of benzalkonium chloride, EDTA, poly(vinyl alcohol), poly(vinylpyrrolidone), hydroxypropylcellulose, and Na hyaluronate were tested. Ocular absorption was determined by monitoring the timolol concentration in various anterior segment tissues 30 min after instillation of timolol solution, while systemic absorption was determined by monitoring the time course of timolol concentration over 120 min. Timolol was assayed by reversed-phase HPLC. Lowering the solution tonicity to 80 mosmol kg-1 and incorporating polymers into the formulation were the only approaches that promised to improve the safety of topically applied timolol, since they afforded the desired increase in ocular absorption and reduction in systemic absorption. Lowering the solution pH to 6.4 and increasing the tonicity of the solution to 600 mosmol kg-1 reduced systemic absorption but caused either no change or a decrease in ocular absorption. Raising the solution pH to 8.4 and incorporating 0.025% benzalkonium chloride and 0.5% EDTA into the formulation led to an undesirable increase in systemic absorption although ocular absorption was also increased. In the final analysis, the net effect of formulation changes on the ratio of ocular to systemic absorption depended on the interplay of changes in solution drainage; permeability of the cornea, conjunctiva, and nasal mucosa; and fraction of drug in the preferentially absorbed form.

Administration, Topical↗

PubMed1983

Efficacy of combining timolol with other antiglaucoma medications.

The ocular hypotensive effects of timolol and a carbonic anhydrase inhibitor (acetazolamide or methazolamide) are partially additive; that is, concurrent administration of these drugs produces a clinically useful reduction in intraocular pressure which is greater than the effect of either medication alone, but less than the arithmetic sum of the effects of the individual drugs. Similarly, concurrent administration of timolol and a miotic agent (pilocarpine, carbachol, or echothiophate iodide) produces a clinically useful response in most glaucoma patients. In contrast, the ocular hypotensive effects of timolol and epinephrine are poorly additive. Only a minority of patients maintain a substantial, longterm reduction in intraocular pressure when timolol is added to a regimen of epinephrine or vice versa. Ophthalmologists prescribing timolol or epinephrine for patients receiving the other drug are urged to use a therapeutic trial to one eye for several weeks to determine the efficacy of concurrent treatment. The addition of timolol to the medical regimen of patients uncontrolled on maximum tolerated antiglaucoma therapy (a miotic agent, epinephrine and a carbonic anhydrase inhibitor) reduces intraocular pressure substantially in one-third to one-half of the cases.

Acetazolamide↗

PubMed1994

The direct vascular relaxing action of betaxolol, carteolol and timolol in porcine long posterior ciliary artery.

The vascular relaxing properties of three beta adrenoceptor antagonists, betaxolol, carteolol and timolol, currently used in the treatment of glaucoma, were characterized, compared and contrasted in the porcine long posterior ciliary artery. Isolated arterial ring segments precontracted with increased extracellular KCl (plus 40 mM) or the thromboxane analog, U-46619 (3 x 10(-7) M), were relaxed in a concentration-dependent fashion by betaxolol, carteolol, timolol or nitroprusside. In vessel segments depolarized with increased extracellular KCl, EC50 values indicated that the intrinsic relaxant sensitivity to betaxolol was equal to that of nitroprusside, six-fold greater than that of carteolol, and ten-fold greater than that of timolol. Similarly, the maximum relaxation occurring at equimolar concentrations (10(-4) M) for the beta adrenoceptor antagonists was betaxolol > carteolol = timolol. Qualitatively similar results were noted in ring segments of the rabbit external iliac artery precontracted with increased extracellular KCl (plus 30 mM). Under conditions in which specific receptor-linked events are absent and voltage-gated Ca++ entry is maximized, the Ca++ concentration response relationship in porcine long posterior ciliary artery was shifted to the right in an apparent competitive manner by betaxolol, reflecting a 5.6-fold reduction in the sensitivity to Ca++. Conversely, nitroprusside reduced the Ca++ sensitivity three-fold in a noncompetitive fashion; not only shifting the Ca++ concentration response relationship to the right, but also depressing the maximum by 57%. Porcine long posterior ciliary arterial segments precontracted to a similar degree with U-46619, in which voltage-gated Ca++ entry is only one component of many specific cell signalling transduction mechanisms contributing to the precontraction, exhibited a sensitivity to betaxolol that was six-fold less than to nitroprusside, but two-fold greater than to timolol and 20-fold greater than to carteolol. These results are consistent with an obvious direct vascular relaxing capacity for beta adrenoceptor antagonists that primarily represents a capacity for inhibiting voltage-gated Ca++ entry in vascular smooth muscle. Additionally, the differential potencies of these three beta adrenoceptor antagonists characterized in this study suggests that this property is much more likely to contribute to any potentially beneficial effects of betaxolol than carteolol or timolol.

Animals↗