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PubMed1981

Timolol and metoprolol. A diurnal study of the ocular and systemic effects in glaucoma patients.

A comparison of the diurnal effects of timolol 0.5% and metoprolol 3.0% eye drops on the intraocular pressure, blood pressure and heart rate in 10 glaucoma patients was performed in a double-masked cross-over study. Both agents produced a significant ocular hypotensive effect for more than 12 h. Timolol appeared to be more potent after 4 and 7 h. No significant difference in hypotensive action was present between timolol and metoprolol 1, 12 and 24 h after treatment. The mean arterial pressure was significantly lowered after 1 and 4 h with timolol and after 1 h during metoprolol therapy. Both agents reduced the heart rate after 1 h. Measurements of plasma concentration of ocular applied timolol and metoprolol showed in 4 patients levels of plasma timolol high enough to induce minimal systemic beta-blockade.

Aged↗

PubMed1993

Plasma and aqueous humour concentrations and systemic effects of topical betaxolol and timolol in man.

Plasma and aqueous humour concentrations and systemic effects of timolol and betaxolol were studied after ocular administration in 45 patients scheduled for extracapsular cataract extraction and intraocular lens implantation. The patients were divided randomly into three groups and received 40 microliters of either 0.5% betaxolol, 0.25% timolol or placebo into the lower cul-de-sacs of both eyes. Blood samples were collected over a period of 4 h and blood pressure and heart rate were monitored during the study. Aqueous humour samples were aspirated at the beginning of the operation. Plasma and aqueous humour concentrations of timolol and betaxolol were analyzed using a sensitive radioreceptor assay. The mean plasma concentrations of betaxolol were lower than those of timolol. The concentration of betaxolol in the aqueous humour was twice as high as the concentration of timolol. Both drugs produced a significant decrease in heart rate. In the timolol group a decrease in heart rate was found 15 min after drug administration, and in the betaxolol group after one hour.

Absorption↗

PubMed1980

Timolol in operated closed-angle glaucoma.

Tonometry in 9 eyes (7 patients) provides some evidence that timolol eye drops are useful in improving control of pressure in eyes operated for closed-angle glaucoma. In cases 1 and 2 (Figs, 1 and 2) this beta 1 and 2 blocker reduced pressure consistently. Case 3 (Fig. 3) showed that timolol 0.5% twice daily was as effective as pilocarpine 2% or 4% with adrenaline 1%. The effect of timolol 0.5% in case 4 (Fig. 4) and case 6 (Fig. 6) was additive to pilocarpine and adrenaline; in case 5 (Fig. 5) it probably improved the effect of adrenaline, but in cases 4 and 5 there may have been some loss of effect with time. Case 7 (Fig. 7) showed a good effect of timolol, reversed on withdrawal, but pressure fell again in spite of continued withholding of timolol. Timolol will be especially valuable in the control of pressure if an operation involving iridectomy has not been completely successful in open-angle glaucoma or more especially in closed-angle glaucoma because it has no effect on the pupil. Miotics will tend to produce posterior pupillary synechiae because aqueous humour will go through the iridectomy, not under the edge of the pupil. The danger will be greater in eyes with closed-angle glaucoma because the pupil is closely applied to the anterior lens surface, which will also tend to produce irritative iridocyclitis.

Epinephrine↗

PubMed1995

Latanoprost administered once daily caused a maintained reduction of intraocular pressure in glaucoma patients treated concomitantly with timolol.

The long term effects of two dose regimens of latanoprost (PhXA41) administered to eyes concomitantly treated with timolol which had not adequately been controlled by timolol alone were compared. A total of 50 patients, 17 with primary open angle glaucoma and 33 with capsular glaucoma, were recruited from five clinics. All had glaucomatous visual field defects and an intraocular pressure (IOP) of at least 22 mm Hg despite treatment with 0.5% timolol twice daily. Patients were randomised to two treatment groups. In one group 0.006% latanoprost was given twice daily, in the other group placebo was given at 8 am and latanoprost at 8 pm for 3 months, with concomitant timolol treatment in both groups. Average daytime IOP (mean (SD)) at baseline (on timolol alone) and after 4 and 12 weeks' treatment was 24.8 (3.6), 16.8 (4.3), and 15.7 (2.4) mm Hg respectively with once daily application of latanoprost and 24.9 (2.9), 18.1 (3.0), and 18.0 (3.6) mm Hg respectively with latanoprost twice daily. No clinically significant side effects were observed during treatment. Latanoprost causes a marked and sustained IOP reduction in eyes which are also being treated with timolol. Latanoprost given once daily is at least as effective and probably superior to a twice daily dose regimen.

Aged↗

PubMed2000

Changes in ocular surface caused by antiglaucomatous eyedrops: prospective, randomised study for the comparison of 0.5% timolol v 0. 12% unoprostone.

AIM: To study changes induced in ocular surface epithelia and the tear film by antiglaucomatous eyedrops. A beta blocker (0.5% timolol) and a novel prostaglandin F(2alpha) metabolite related drug (0.12% unoprostone) were examined in a prospective, randomised fashion. METHODS: 40 patients were randomly assigned to use either 0. 5% timolol (timolol group) or 0.12% unoprostone eyedrops (unoprostone group) twice a day for 24 weeks. In addition to routine ocular examinations, corneal epithelial integrity (vital staining tests, tear film break up time (BUT), anterior fluorometry, specular microscopy) and tear function (Schirmer's test, cotton thread test, tear clearance test (TCT)) were examined before and after the treatment. RESULTS: Both eyedrops caused significant reduction in intraocular pressure from the baseline levels. No significant changes were noted in corneal integrity in both groups, except a decrease in BUT at 20 weeks in the timolol group. The timolol group demonstrated significant decreases in Schirmer's test, tear clearance test, and tear function index (Schirmer's test value multiplied by clearance test); however, no such changes were noted in the unoprostone group. CONCLUSION: While unoprostone eyedrops caused no adverse effects on the corneal epithelial integrity and tear function, timolol caused significant impairments in tear production and turnover.

Adrenergic beta-Antagonists↗

PubMed1985

Effect of timolol on changes in serum potassium concentration during acute myocardial infarction.

One hundred and six patients with acute myocardial infarction admitted to hospital within four hours after the onset of symptoms were randomised to treatment with intravenous timolol (54 patients) or placebo (52 patients). Serum potassium concentrations were estimated at frequent intervals during the first 24 hours of admission. Patients in both treatment groups, who did not receive subsequent diuretic treatment, had a transient rise in serum potassium concentration, which was maximal after four hours. This rise was abolished by diuretic treatment in the placebo group but not in the timolol group, in which there was a pronounced and prolonged rise in serum potassium concentration. The change in serum potassium concentration in the first four hours after admission correlated with cumulative creatine kinase release in the placebo group, but not in the timolol group. Hypokalaemia (serum potassium concentration less than or equal to 3.5 mmol/l) occurred in 15 (28.8%) patients in the placebo group and in seven (13%) in the timolol group and was independent of infarct size. The frequency of hyperkalaemia was not increased in the timolol group. By increasing the serum potassium concentration and preventing hypokalaemia, the use of intravenous timolol early in acute myocardial infarction may have important clinical effects in addition to reducing infarct size.

Clinical Trials as Topic↗

PubMed2006

Circadian intraocular pressure control with dorzolamide versus timolol maleate add-on treatments in primary open-angle glaucoma patients using latanoprost.

PURPOSE: To compare the 24-hour efficacy of dorzolamide and timolol maleate administered twice daily to primary open-angle glaucoma patients whose intraocular pressure (IOP) could not be adequately controlled with latanoprost monotherapy. METHODS: In this double-blind prospective crossover clinical comparison trial, 36 primary open-angle glaucoma patients with uncontrolled IOP despite treatment with latanoprost applied once daily were administered timolol and dorzolamide twice daily. The treatment sequence was randomized. All patients underwent measurements for four 24-hour tonometric curves: at baseline and after each 4-week period of treatment. The IOP measurements were taken at 06:00, 09:00, 12:00, 15:00, 18:00, 21:00, 24:00 and 03:00 h. The between-group differences were tested for significance by means of parametric analysis of variance at each time point and circadian curve. The peak values within circadian curve were defined. The mean of the exact amount and percentage of additional IOP reductions from baseline were evaluated and success rates (a minimum of 10% reduction) were determined for both drug regimens. RESULTS: The mean peak/circadian curve IOPs were 23.4 +/- 2.2/21.8 +/- 2.2 mm Hg at dorzolamide baseline, 23.3 +/- 2.2/21.7 +/- 2.1 mm Hg at timolol baseline, and reduced to 20.2 +/- 1.7/18.7 +/- 1.7 mm Hg and 20.7 +/- 2.4/19.4 +/- 1.6 mm Hg, respectively. When added to latanoprost, both dorzolamide and timolol lowered IOP at circadian curve significantly (p < 0.05). Dorzolamide reduced baseline IOP values at each time point. Timolol also significantly reduced baseline IOP values at all time points except at 03:00. The mean of the exact amount and percentage of reduction in IOP at circadian curve and 5 out of 8 time points were significantly greater with dorzolamide add-on treatment (p < 0.05). The successful reduction rates were 86% for the dorzolamide group and 61% for the timolol group (p = 0.016; chi(2) test). CONCLUSION: Both of the combinations are effective in lowering IOP, the exact amount and percentage of reduction is greater with the latanoprost + dorzolamide regimen, especially at night-time.

Antihypertensive Agents↗

PubMed1979

[Clinical experiences with timolol eye drops].

Three groups of chronic simple glaucoma (group I: newly adjusted patients; group II: previously satisfactorily pressure-regulated patients; group III: previously notsatisfactorily pressure-regulated patients) received treatment with Timolol eye drops for 4 months. In 34 eyes the intra-ocular pressure could be lowered below 22 mm Hg by Timolol alone, whereas 10 eyes additionally had to be treated with 1% epinephrine. The higher the initial pressure effect, the more pronounced the pressure-lowering properties of Timolol became. Especially in the first 2 weeks, less in the following 14 weeks, Timolol showed a loss in effectiveness. The application of Timolol instead of carbonic anhydrase inhibitors with acute angle-closure glaucoma and secondary glaucoma was successful. Timolol eye drops were tolerated very well. There were no local or systemic side effects.

Adult↗

PubMed1978

Hemodynamic, reflexive, and metabolic alterations induced by acute and chronic timolol therapy in hypertensive man.

The hemodynamic, cardiovascular, and metabolic effects of acute (intravenous) and prolonged (four weeks oral) timolol treatment were assessed in 16 patients with mild or moderate essential hypertension. Fifteen patients completed the outpatient study and ten showed a fall in mean arterial pressure of at least 10 mm Hg. They also demonstrated a significant fall in supine systolic (7%), diastolic (9%), and mean arterial pressure. Hemodynamic evaluation was performed in 13 patients and cardiac index was found to be reduced with both intravenous (20%) and oral timolol (13%). There was no correlation between the decrease in cardiac index and arterial pressure. Calculated total peripheral resistance rose with intravenous timolol and returned toward, but not below, pretreatment values with the oral therapy. Left ventricular ejection rate also fell significantly with intravenous timolol but returned toward pretreatment levels with oral therapy. Plasma renin activity was reduced similarly with both modes of administration and its reduction also did not correlate with the fall in arterial pressure. Plasma volume fell in eight of 13 patients. Reflexive responses to the Valsalva maneuver were considerably modified by both intravenous and oral timolol but responses to 50 degrees upright tilt and handgrip were not. Timolol is an effective oral antihypertensive agent with similar hemodynamic and metabolic effects to propranolol.

Administration, Oral↗

PubMed1986

The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects.

The propensity of systemic beta-adrenergic blockers to cause bronchoconstriction in patients with reactive airway disease is well recognized. A study was carried out to determine the prevalence of sensitivity to ophthalmic timolol in 24 asthmatic subjects at our institution and to determine the effect of ophthalmic betaxolol, a cardioselective beta-blocker efficacious in the treatment of glaucoma, in 8 subjects who were timolol-sensitive. Subjects received topical timolol 0.5%; ventilatory function, blood pressure, and heart rate were monitored over a 90-min period. The mean FEV1 fell from 2.47 to 1.93 L by 30 min after drug treatment to a minimal value of 1.86 L (-27.8%). There was a corresponding fall in FVC from 3.68 to 3.09 L by 30 min with a minimal value of 3.00 L(-20.7%). FEV1/FVC ratio also fell from 66.9 to 61.0% by 30 min, reaching a minimum of 60.0%. In 14 subjects (58.3%), the fall in FEV1 was greater than or equal to 20%, with a mean fall of 38.7% by 30 min and a maximal fall of 44.9%. The severity of timolol-sensitivity correlated with the extent of reduction in baseline percent predicted FEV1 and FVC and with exercise-induced bronchospasm. In addition, the administration of timolol reduced the bronchodilator response to below the pretimolol value. In 8 of the timolol-sensitive patients who underwent a double-blind crossover challenge with ocular instillation of betaxolol 1% and saline, betaxolol was well-tolerated and did not affect ventilatory function over a 4-h observation period. In addition, it did not prevent the FEV1 response to inhaled bronchodilator.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1997

Temporal variation in the effects of ophthalmic timolol on cardiovascular and respiratory functions in healthy men.

This study examined the effects of ophthalmic timolol and time of administration on cardiovascular and respiratory functions in healthy young male volunteers. Eight participants (mean age +/- standard deviation, 22 +/- 0.9 years) received either 50 microL of 0.5% timolol or placebo in the lower conjunctival sacs of both eyes in the morning or evening. Intraocular pressure, blood pressure, heart rate, and respiratory functions, including percent forced expiratory volume in 1 second and peak expiratory flow rate, were then measured for 3 hours after drug administration. Timolol reduced intraocular pressure and cardiovascular function at both administration times. However, a timolol-induced reduction in respiratory function was observed only in the evening: percent forced expiratory volume in 1 second, peak expiratory flow rate, and expiratory flow rate at 75% vital capacity were reduced by 3%, 7%, and 12%, respectively, 3 hours after administration. These results indicate that ophthalmic timolol reduces cardiovascular and respiratory functions in healthy young male subjects and that bronchial sensitivity to timolol differs between morning and evening.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

A randomized, comparative open-label study on the efficacy of latanoprost and timolol in steroid induced ocular hypertension after photorefractive keratectomy.

PURPOSE: To evaluate the effect of 0.005% latanoprost and 0.50% timolol for the treatment of steroid-induced ocular hypertension (SIOH) after excimer laser photorefractive keratectomy (PRK). METHODS: In this comparative, open-label study we enrolled 29 patients who received steroid therapy after PRK and developed intraocular pressure (IOP) elevation within 30 days of treatment. Fifteen were randomized to 0.005% latanoprost (group A) and 14 to 0.50% timolol (group B). IOP measurements were scheduled at 1, 3, 7, 15, 30, 60, 90 and 120 days of therapy. RESULTS; We did not find any real differences between latanoprost and timolol except at the 7-day and 15-day timepoints, when latanoprost reduced IOP significantly more than timolol (p=0.033, 0.035, respectively). After 7 days of therapy two of the 14 timolol-treated patients had high IOP (24 and 26 mmHg) but these promptly returned to normal when latanoprost was added. No significant differences were observed in the ocular side effects considered. CONCLUSIONS: 0.005% latanoprost is as safe and effective as 0.50% timolol in the treatment of SIOH after PRK. Both drugs provide a significant and stable IOP reduction in the majority of patients after short-term treatment. These findings are encouraging for the use of latanoprost in the management of SIOH after PRK, although further trials are necessary to consider it as a primary treatment.

Administration, Topical↗

PubMedDate not supplied

Effects of L-NAME and timolol on aqueous IL-1beta, IL-6, IL-8, TNF-alpha and NO levels after Nd:YAG laser iridotomy in rabbits.

PURPOSE: Pro-inflammatory cytokines are produced by tissues and play a vital role in the host inflammatory response and uveitis. Nitric oxide (NO) can be produced in large amounts as a response to experimentally-induced uveitis or cytokines. In this study, we measured the levels of pro-inflammatory cytokines such as interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and free-radical in aqueous humor after Nd:YAG laser iridotomy in rabbits, and investigated whether timolol maleate an anti-glaucoma drug, or a NO synthase inhibitor, NG-nitro-L-arginine methyl esther (L-NAME) had an inhibitory effect on these molecules, since L-NAME is a known anti-inflammatory agent in rabbits. METHODS: Bilateral experimental Nd:YAG laser iridotomy (power 7.5 mJ, mode single burst, aiming beam 4) was performed on 18 rabbits under general plus topical anesthesia. Aqueous humor samples were taken by clear corneal paracentesis preoperatively, and 1 and 24 h postoperatively. Six rabbits (12 eyes) were given bilateral topical timolol maleate 0.5% (Timoptic) drop b.i.d. (group 1), six rabbits (12 eyes) received bilateral 0.1 ml subconjuntival injections of L-NAME (150 mg/kg) (group 2), and six rabbits (12 eyes) were treated with topical balanced salt solution (BSS) b.i.d. (control). RESULTS. Preoperative cytokine and NO levels were comparable in the three groups, with no significant differences. In addition, there was no significant difference in baseline cytokine levels between the right and left eyes. In all groups, pre- and postoperative mean IL-1beta levels were below the detection limit of the assay (<5.0 pg/ml). In the control group, postoperative mean IL-6, IL-8 and NO levels were significantly higher after Nd:YAG laser iridotomy than before (for each, p < 0.01). Timolol and L-NAME both inhibited the rise in IL-8 and TNF-alpha levels. Timolol also inhibited the rise in IL-6 but not NO. L-NAME had an inhibitory effect against NO, but not IL-6. CONCLUSIONS: L-NAME has an inhibitory effect on IL-8, TNF-alpha and NO, but not on IL-6. Timolol had inhibitory effects on IL-6, IL-8 and TNF-alpha, but not on NO. These preliminary experimental results might help in assssing the effect of Nd:YAG laser iridotomy in aqueous humor, and to understand the inhibitory effects of timolol and L-NAME against these molecules.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

The efficacy and safety of timolol maleate versus brinzolamide each given twice daily added to travoprost in patients with ocular hypertension or primary open-angle glaucoma.

PURPOSE: To compare the efficacy and safety of timolol maleate 0.5% versus brinzolamide 1% when added to travoprost 0.004% in patients with ocular hypertension or primary open-angle glaucoma. DESIGN: A prospective, double-masked, randomized, active-controlled, parallel comparison. METHODS: Qualified patients at Visit 1 were placed on travoprost dosed every evening for 4 weeks and then were randomized at baseline (Visit 2) to the addition of timolol maleate or brinzolamide each given twice daily. Patients returned to clinic at Week 4 (Visit 3) for a safety visit and Week 12 (Visit 4) for an efficacy visit. At Visits 2 and 4 the intraocular pressure (IOP) was measured at 08:00, 12:00, and 16:00 hours. RESULTS: Ninety-seven patients on brinzolamide had a baseline diurnal IOP of 21.5+/-2.2 mmHg and 95 on timolol maleate had 21.3+/-2.5 mmHg, each added to travoprost. The diurnal mean IOP at Week 12 was 18.1+/-2.7 mmHg for brinzolamide and 18.1+/-3.0 mmHg for timolol maleate (p=0.96). There was no statistical difference found between treatment groups in the absolute level of pressure, or in the reduction in IOP from baseline, at each time point or for the diurnal curve (p>0.05). There was no significant difference for any adverse event between groups (p>0.05), with the most common side effect being conjunctival hyperemia in 15/97 (16%) brinzolamide and 6/95 (6%) timolol treated patients (p=0.06). CONCLUSIONS: This study showed that brinzolamide provides similar safety and efficacy compared to timolol maleate when added to travoprost.

Antihypertensive Agents↗

PubMed1984

Effects of timolol on intraocular pressure following ocular adrenergic denervation.

The effects of timolol on the elevation of intraocular pressure induced by orogastric water-loading were studied in conscious pigmented rabbits which had undergone unilateral, superior cervical ganglionectomy. Each rabbit was studied without timolol treatment and with unilateral 2% timolol treatment, either to the innervated eye or to the denervated eye, 90 min before water-loading. Timolol, applied to the innervated eye, significantly reduced the elevation of intraocular pressure in that eye, but not in the fellow eye. Timolol, applied to the denervated eye, did not affect the elevated intraocular pressure in either the denervated or the fellow eye. These results demonstrate that ocular adrenergic innervation participates in the mechanism of ocular hypotensive action of timolol in water-loaded pigmented rabbits.

Animals↗

PubMed1984

Effect of topical epinephrine and timolol on ocular and optic nerve blood flow in phakic and aphakic rabbit eyes.

The effects of 4% epinephrine bitartrate and 0.5% timolol on ocular and optic nerve blood flow were studied in phakic and aphakic rabbit eyes using a radioactive microsphere (85Sr) technique. Either epinephrine or timolol was given topically as eight drops in the hour immediately preceding blood flow measurements (one drop every 7.5 minutes). Epinephrine decreased anterior uveal blood flow in both phakic and aphakic eyes, whereas timolol exhibited no effect. Retinal and choroidal blood flow were not affected by either timolol or epinephrine in phakic eyes. In aphakic eyes, epinephrine increased choroidal blood flow without altering retinal blood flow, whereas timolol increased both retinal and choroidal blood flow. Optic nerve blood flow was increased in epinephrine treated phakic and aphakic eyes and also in timolol treated aphakic eyes.

Animals↗

PubMed1984

The effects of separate and combined topical treatment with timolol maleate and trifluormethazolamide on the intraocular pressure in normal rabbits.

The effects of separate and combined topical treatment with timolol maleate and trifluormethazolamide (TFM) on the intraocular pressure (IOP) were studied in normotensive rabbits. Timolol had a distinct, albeit small, dose related hypotensive effect. Unilateral application of timolol resulted in dose related decrease in IOP in the untreated fellow eye. These effects could be observed only by using a protocol that reduces the contribution of individual and diurnal variations to the overall variability in IOP in the rabbit. Topical treatment with TFM caused a reduction in the calculated outflow pressure of 32%, similar to that observed after systemic administration of acetazolamide and methazolamide. At the concentration and dosage employed here there was no significant difference between the hypotensive effects of timolol and TFM. The maximal decrease in the calculated outflow pressure for the different doses of timolol varied between 24% to 37%. The hypotensive effect of the combined timolol and TFM treatment (delta IOP = -2.4 +/- 0.4 mmHg, n = 12) was greater than that observed in rabbits treated with TFM alone (delta IOP = -1.6 +/- 0.5 mmHg, n = 12). The increment was smaller than the initial effect of either drug alone.

Administration, Topical↗

PubMed1986

Cardiovascular effects of ophthalmic timolol.

We studied cardiovascular effects related to ophthalmic timolol maleate, a beta-adrenergic blocker commonly used to treat chronic glaucoma. Twenty normal subjects were randomly assigned to two double-blind treatment groups each with ten subjects. One group received two drops of ophthalmic timolol (0.5%) twice daily for 4 weeks, and the other received two drops of placebo (artificial tears) twice daily for 4 weeks. Ophthalmic timolol significantly decreased resting and maximal exercise heart rate after the first dose and maximal exercise heart rate during chronic dosing. Chronic timolol administration reduced oxygen consumption at maximal exercise and blunted the augmentation in exercise capacity seen during chronic placebo therapy. Cardiac sympathetic tone and inotropy were reduced after ophthalmic timolol treatment. Despite the presence of drug-induced cardiovascular effects, the plasma levels of timolol were often undetectable and never exceeded 2.8 ng/mL.

Adult↗