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PubMed1980

The place of timolol in the practice of ophthalmology.

Timolol has become so populat with ophthalmologists that it is prescribed 44% of the time when an anti-glaucoma drop is needed. This popularity is due to its newness and the publicity it has received, its effectiveness in most types of glaucoma, and the apparent scarcity of side effects. This paper looks at the first 489 patients treated with timolol at Wills Eye Hospital and the side effects encountered. These include blurring of vision, burning and pain, bradycardia and heart failure, hallucinations, dilated pupils, headaches, dizziness, hypotony, allergy, asthma, impotence, drowsiness, anxiety, emotional lability, and nausea.

Aged↗

PubMed1981

The effect of timolol and acetazolamide on transient intraocular pressure elevation following cataract extraction with alpha-chymotrypsin.

Elevated intraocular pressure (IOP) early after cataract extraction with alpha-chymotrypsin is a well-described, common occurrence. To study the incidence of pressure increase and the efficacy of medical therapy, IOP was monitored every 12 hours beginning on the first postoperative day in 68 patients after otherwise uncomplicated intracapsular cataract extraction performed with one milliliter of alpha-chymotrypsin and wound closure with multiple sutures. Patients were randomly assigned to one of three groups: treatment with oral acetazolamide, treatment with topical timolol, or no treatment. Without prophylactic treatment, the prevalence of pressure elevation at 24 hours postoperatively was 69% with IOP greater than or equal to 25 mm Hg; 29% with IOP greater than or equal to 40 mm Hg. This was independent of the type of sutures used (10--0 nylon or 9--0 silk). The patients of four different surgeons had similar rates of occurrence of postoperative glaucoma. Both timolol and acetazolamide were essentially equally effective in lowering IOP in these patients. No adverse side effects were observed. With these effective treatments available if needed, we believe that routine monitoring of the IOP by applanation tonometry during the early postoperative course provides a good opportunity for reducing the risk of complications from excessive intraocular pressure.

Acetazolamide↗

PubMed1991

Effect of apraclonidine in long-term timolol users.

A double-blind, randomized study was undertaken to determine if the alpha-agonist apraclonidine has an additive effect in eyes treated with long-term timolol. Seventeen patients (15 with primary open-angle glaucoma, 1 with pigmentary glaucoma, and 1 glaucoma suspect) on long-term timolol treatment in both eyes received a single dose of apraclonidine in one eye and a placebo in the other. Aqueous flow and intraocular pressure were compared in the treated and untreated eyes. There was no statistically significant difference in pretreatment aqueous flow between the two eyes. When flow in the apraclonidine-treated eyes (1.39 +/- 0.41 microliter/min, mean +/- standard deviation) was compared with that of the untreated eyes (1.66 +/- 0.38 microliter/min), a statistically significant difference was found (P less than 0.01). Apraclonidine reduced intraocular pressure by 1.3 mmHg (P = 0.05). The implications of these findings on the understanding of the mechanism of action of adrenergic drugs in the human eye is discussed.

Adrenergic alpha-Agonists↗

PubMed2006

[In vivo assessment of corneal epithelial toxicity of timolol with benzalkonium chloride using very-high-frequency ultrasound imaging].

PURPOSE: To assess in vivo the corneal epithelial damage caused by a topical toxic medication using a 60-MHz ultrasound device. MATERIAL: and methods: A solution of timolol with 0.01% benzalkonium chloride (BAC) was applied twice a day in the test eyes of ten rabbits, and a BAC-free solution of timolol in the control eyes, for 56 days. We used a 60-MHz ultrasound device to evaluate the epithelial damage in BAC-exposed eyes, compared to control eyes. The clinical and ultrasound examinations were performed every week, and the histological analysis at the end of the experiment. RESULTS: The clinical findings were conjunctival redness, corneal staining and instability of the tear film. In vivo VHF ultrasound revealed a thinning of the epithelium of test eyes (from 40.9+/-1,6 microm at D0 to 31.8+/-3.4 microm at D56; p=0.0006 for D0 vs D56), while the epithelium of control eyes remained unchanged. Ultrasound epithelial thickness was correlated with corneal staining (at D34 and D56; p=0.0025 and 0.0377, respectively) and histological epithelial pachymetry (p=0.0176 for control and 0.0505 for tested epithelium). Moreover, we report qualitative VHF ultrasound imaging of early epithelial damage. CONCLUSION: This new device could be very useful in ocular toxicity evaluation as a reproducible and reliable tool for multicentric clinical research.

Animals↗

PubMed2004

Effectiveness of levobetaxolol and timolol at blunting retinal ischaemia is related to their calcium and sodium blocking activities: relevance to glaucoma.

Glaucoma is a chronic optic neuropathy in which retinal ganglion cells die over a number of years. The initiation of the disease and its progression may involve an ischaemic-like insult to the ganglion cell axons caused by an alteration in the quality of blood flow. Thus, to effectively treat glaucoma it may be necessary to counteract the ischaemic-like insult to the region of the optic nerve head. Studies on the isolated optic nerve suggest that substances that reduce the influx of sodium would be particularly effective neuroprotectants. Significantly, of the presently used antiglaucoma substances, only beta-blockers can reduce sodium influx into cells. Moreover, they also reduce the influx of calcium and this would be expected to benefit the survival of insulted neurones. Betaxolol is the most effective antiglaucoma drug at reducing sodium/calcium influx. Our electroretinographic data indicated that topical application of levobetaxolol to rats attenuated the effects of ischaemia/reperfusion injury. Timolol was also effective but to a lesser extent. Based on these data we conclude that beta-blockers may be able to blunt ganglion cell death in glaucoma, and that levobetaxolol may be a more effective neuroprotectant than timolol because of its greater capacity to block sodium and calcium influx.

Animals↗

PubMed2004

Chemometric determination of amiloride hydrochloride, atenolol, hydrochlorothiazide and timolol maleate in synthetic mixtures and pharmaceutical formulations.

Different chemometric methods such as classical least squares (CLS), principal components regression (PCR) and partial least squares with one dependent variable (PLS-1) applied on UV spectral data (0 D) and on their first derivatives (1 D) were evaluated for the simultaneous quantification of samples containing mixtures of amiloride hydrochloride, atenolol, hydrochlorothiazide and timolol maleate. Their performances were compared by means of ANOVA tests, which evidenced that 0 D-PCR, 0D-PLS-1, 1D-PCR, 1D-PLS-1, were reproducible and gave statistically similar results, while 0 D-CLS and 1D-CLS displayed higher variances than the former and failed to comply with the Levene's variance homogeneity test at different stages of the method comparison and validation process. The four statistically equivalent procedures were successfully applied to the analysis of synthetic samples with two to four analytes and to commercial tablet preparations containing amiloride hydrochloride and hydrochlorothiazide alone or in association with atenolol or timolol maleate.

Amiloride↗

PubMed1984

Effects of propranolol and timolol on left ventricular volumes during exercise in patients with coronary artery disease.

The hemodynamic effects of beta-receptor blocking agents on the ejection fraction of patients with coronary artery disease during exercise have been studied previously using radionuclide techniques. Left ventricular volume measurements and the peak systolic pressure/end-systolic volume (PSP/ESV) index have been shown to be variables of left ventricular function that are less influenced by preload and afterload than is ejection fraction. Left ventricular volumes and PSP/ESV were therefore measured in 18 patients with proven coronary artery disease in the control state and after 2 weeks of daily maintenance therapy with either 240 mg propranolol or 60 mg timolol. Values at rest and during symptom-limited upright exercise were compared using the first pass technique and a multicrystal scintillation camera. Left ventricular volumes were measured by the area-length method. Because there was no difference between the propranolol and timolol groups, the results for both groups were combined. The ejection fraction at rest after beta-receptor blocker treatment was not significantly different from pretreatment measurements because of an increase in both end-diastolic and end-systolic volumes (p less than 0.01). However, the value for peak systolic pressure/end-systolic volume (PSP/ESV) index at rest was lower after treatment. The exercise ejection fraction was greater after treatment (p less than 0.01), owing to an increase in end-diastolic volume and unchanged end-systolic volume. In addition, there was a significant improvement in the directional change in the PSP/ESV ratio between rest and exercise from pretreatment to treatment (-1.1 +/- 2.5 to +0.2 +/- 1.2, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1996

Continuous intraocular pressure measurement by telemetry in alpha-chymotrypsin-induced glaucoma model in the rabbit: effects of timolol, dorzolamide, and epinephrine.

The aim of this study was to set-up and validate the use of a radio-telemetry system in order to record IOP in chronic ocular hypertensive animals. The transmitter of a miniaturized radio-telemetry system was implanted in rabbits, and its catheter was tunnelled subcutaneously to the superior conjunctival sac and inserted into the midvitreous. Implantation was performed in chronic ocular hypertensive rabbits induced by an injection of alpha-chymotrypsin into the posterior chamber of the eye. The effects of 0.5% timolol maleate, 2% dorzolamide hydrochloride and 1% epinephrine were assessed and compared after topical administration in this model. Implanted radio-telemetric system into the vitreous allowed IOP measurement for more than 6 months. In this study, circadian IOP kinetic profiles were monitored in all animals over 24 h for 3 weeks. Timolol maleate was found significantly potent in reducing IOP, while changes depended on the nyctemeral period. Dorzolamide hydrochloride induced a very large IOP reduction and was found to be also well effective at night. We evidenced a biphasic time-dependent effect after topical epinephrine, with a long lasting IOP increase occurring after the administration. This change was found to be related to side effects resulting from a poor ocular tolerance of this drug in the rabbit, leading to either a complete eye closure or a higher blinking rate. By using our method, we confirmed the pressure pulses and undershoots occurring during blinking. Radio-telemetry in chronic glaucoma rabbits appears as a refined method to assess anti-glaucoma drug activity, 24 hours a day, for long-term periods in unrestrained animals, while also providing information on the ocular side effects of eye drops.

Adrenergic beta-Agonists↗

PubMed1980

Urinary metabolites of timolol from humans and laboratory animals. Syntheses and beta-adrenergic blocking activities.

Syntheses are reported for three metabolites (2-4) of timolol (1) formed by oxidative metabolism of the morpholine ring. GLC-MS comparisons are presented which establish that the two metabolites whose structures were previously in question are identical with their synthetic counterparts 2 and 3. In 2, metabolic oxidation of the 4-morpholinyl group of 1 had occurred at the carbon next to oxygen to give the 2-hydroxy-4-morpholinyl moiety, whereas in 3, the morpholine of 1 has been oxidized one step further and then ring opened to produce the N-(2-hydroxyethyl)glycine substituent. Biological testing of synthetic samples of the three major metabolites from human urine (3, 4, and 6) indicated that only 4, in which the morpholine moiety has been degraded to a 2-hydroxyethylamino group, had significant beta-adrenergic blocking activity (one-seventh that of timolol in anesthetized dogs).

Adrenergic beta-Antagonists↗

PubMed1998

A comparison of the efficacy and tolerability of dorzolamide and acetazolamide as adjunctive therapy to timolol. Oral to Topical CAI Study Group.

PURPOSE: To compare the efficacy and tolerability of dorzolamide to acetazolamide. METHODS: Following a timolol and acetazolamide run-in, 105 patients with elevated intraocular pressure (IOP) were randomized to dorzolamide or acetazolamide, in addition to timolol, for 12 weeks. RESULTS: More patients receiving acetazolamide discontinued due to clinical adverse experiences than patients receiving dorzolamide; 13 (25%) vs. 1 (2%); p<0.001. The prevalence of systemic adverse experiences for the dorzolamide group dropped by 50% by Week 12, but remained unchanged for the acetazolamide group, as compared to baseline; p<0.001. Ocular burning/stinging was more common in the dorzolamide group (21% vs. 0%; p<0.001). The mean trough IOP at Day 1 and Week 12 were 20.5 mmHg and 21.8 mmHg for the dorzolamide group, and 20.4 mmHg and 20.5 mmHg for the acetazolamide group. The mean peak IOP at Dayl and Week 12 were 18.9 mmHg and 20.0 mmHg for the dorzolamide group, and 18.7 mmHg and 18.6 mmHg for the acetazolamide group. CONCLUSIONS: Mean IOP was slightly lower (by approximately 1 mmHg) with acetazolamide, while dorzolamide demonstrated much better tolerability.

Acetazolamide↗

PubMed1993

Doppler ultrasonography of the central retinal artery in normals treated with topical timolol.

Using high-resolution Duplex scanning it is possible to evaluate the blood flow velocity in the central retinal artery of eyes of normal individuals. The flow velocity can be divided into its systolic and diastolic phases. Topical timolol maleate 0.5%, a non-selective beta-adrenergic receptor blocking agent, was then administered to one eye in each of the normals and the flow velocity was again recorded. The flow velocity improvement was significant, with a 43.58% increase in the systolic phase and a 61.53% increase in the diastolic phase. The diastolic component increased from 49.29% to 55.56%. The increased flow velocity may be due to a vasodilatory effect of timolol. The technique is briefly described and the significance of the results discussed.

Adult↗

PubMed1995

Doppler ultrasonography of the central retinal artery in patients with diabetes and vascular disease treated with topical timolol.

Using high-resolution duplex scanning it is possible to evaluate the blood flow velocity in the central retinal artery of the eye. Four different patient groups were studied with this technique: normals, diabetics with a decreased flow, diabetics with an increased flow and vascular patients with a decreased flow. The eyes of these patients were then treated with topical timolol and the flow measured again. An increase in the flow was found in three of the four groups. This increased flow velocity may be due to a vasodilatory effect of timolol. The results are presented and discussed.

Administration, Topical↗

PubMed1999

The lack of efficacy of topical beta-blockers, timolol and betaxolol on intraocular pressure in Nigerian healthy volunteers.

PURPOSE: The beta-adrenoceptor antagonists are commonly used drugs in ophthalmic and medical practice. While beta-blockers may show reduced antihypertensive efficacy in African patients, the effect of beta-blockers on intraocular pressure (IOP) in African healthy volunteers is less well known. METHODS: This single-masked, placebo-controlled, randomised study was conducted to investigate the response of healthy Nigerian volunteers to a single drop of the beta-adrenoceptor antagonists timolol and betaxolol. Twenty-five volunteers participated in the study; however, only 19 were able to complete the study. The concentrations of the beta-blocker used were 0.0625%, 0.125%, 0.25% and 0.5%. One eye of the volunteers was used while the other eye served as control. The baseline IOP was documented and IOP measured hourly over 6 h. Pupillary size, corneal sensitivity and visual acuity were also assessed. Cardiovascular parameters were also documented hourly (blood pressure, heart rate, pulse rate). RESULTS: Only 0.5% concentrations of both beta-adrenoceptor antagonists caused any significant IOP reduction in normal volunteers (p < 0.05). The maximal falls were -2.33 +/- 2.2 mmHg and -1.23 +/- 0.6 mmHg with timolol and betaxolol, respectively. The IOP reduction produced lasted for only 4 h, after which the IOP returned to baseline. There was also an overshoot of the IOP above the baseline values in all the volunteers (+2.0 to +2.3 mmHg). There was no significant change in the cardiovascular parameters. There was no effect on the pupillary size, visual acuity or corneal sensitivity. There was no significant change in IOP and cardiovascular parameters in the placebo group. CONCLUSIONS: Both beta-adrenoceptor antagonists caused an attenuated IOP reduction in African normal volunteers, compared with values reported in Caucasians. There was a rebound intraocular hypertensive effect demonstrated with both beta-adrenergic antagonists in blacks.

Administration, Topical↗

PubMed1981

The effect of prolonged administration of propranolol and timolol on the growth and the heart of growing rabbits.

1. The effect of prolonged administration of beta-adrenoreceptor-blocking agents was studied in growing rabbits. Equivalent doses of propranolol and timolol were given parenterally for 8 weeks. 2. Animals given propranolol had a significantly lower heart rate than that in the controls. After subcutaneous injection, plasma propranolol levels were twice those obtained after intraperitoneal injection. 3. Growth rate of animals given propranolol intraperitoneally was significantly less than controls, whereas animals given propranolol subcutaneously or timolol intraperitoneally grew normally. Reduced growth rate was associated with reduced food intake and was not related to the beta-adrenoreceptor-blocking activity of the drugs. 4. At the end of the experiment the heart and other organs were examined. beta-Adrenoreceptor blockade produced no significant changes in ventricular size or water content, and no significant changes in ultrastructure were found.

Animals↗

PubMed1982

The prophylactic effect of timolol versus propranolol and placebo in common migraine: beta-blockers in migraine.

A multicentre double-blind, cross-over trial was planned to evaluate the prophylactic effect of timolol in migraine. The effectiveness of the drug was compared to propranolol and placebo. In the Norwegian part of the trial described in this paper, 18 patients completed the study. The data suggest that timolol is equivalent in effectiveness to propranolol in migraine prophylaxis. Firm conclusions should not be drawn until the results from the multicentre trial are available.

Adolescent↗

PubMed1991

[Effect of betaxolol and timolol on visual fields in glaucoma patients].

In a prospective, randomized, double-masked study, primary open-angle glaucoma patients were treated twice daily with either betaxolol 0.5% or timolol 0.5%. Patients received a pretreatment baseline examination following a 2 week washout period; they were then examined after 3 and 6 months of treatment. Each examination included visual field measurements with an Octopus automated perimeter and intraocular pressure measurement. The visual fields of the betaxolol group showed on the average a pronounced tendency toward improvement (MD decrease of 2.05 dB); visual fields in the timolol group showed a slight tendency toward improvement (MD decrease of 1.56 dB). The difference between these 2 trends after 6 months was statistically not significant (p greater than or equal to 0.05, U-test). Both drugs lowered intraocular pressure, there was no significant difference between the two drugs (p greater than or equal to 0.05, U-test).

Betaxolol↗

PubMed1988

[Comparison of the effectiveness and safety of levobunolol and timolol in ocular hypertension and chronic open-angle glaucoma].

Twenty-six patients with open-angle glaucoma or ocular hypertension were studied in a concomitant double-masked clinical trial lasting three months, in which the ocular hypotensive efficacy and safety of levobunolol (0.5%) and timolol (0.5%), topically administered twice daily, were compared. At all follow-up examinations there was a significant decrease in mean intraocular pressure from baseline in both treatment groups, with no significant difference between them in this regard. Few changes were seen in either treatment group in cup/disk ratio, visual fields, visual acuity, biomicroscopy, or ophthalmoscopy. In both groups slight decreases in mean blood pressure were observed. Levobunolol and timolol were similarly effective and safe in reducing intraocular pressure in patients with chronic open-angle glaucoma and those with ocular hypertension.

Adult↗

PubMed1983

[Increase in visual field defects under long-term timolol treatment in patients with open-angle glaucoma - observations from an ophthalmology practice].

The authors report on 6 patients with open-angle glaucoma who were treated with Timolol eye drops for 2 years. During this period the intraocular pressure was normal at all times. In spite of this a deterioration in visual fields occurred, in some of the cases associated with reduced vision. It is emphasized that these patients form part of a larger group comprising 30 individuals. In the remaining 24 patients no deterioration of the visual field or vision was found during the 2 years of treatment with Timolol.

Aged↗