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PubMed1982

Clinical implications of reported timolol-induced side effects.

Since its approval by the Food and Drug Administration (FDA), timolol has been widely used for the treatment of open-angle glaucoma. Contrary to the clinical trials before FDA approval, many reports of possible ocular and systemic side effects have now appeared. Cardiovascular, respiratory, and gastrointestinal systemic effects occur relatively often and are attributable to beta-adrenergic antagonism, but central nervous system (CNS) effects are not so explainable. The most frequent ocular side effects are instillation pain and blurred vision, often requiring discontinuation of timolol. Superficial punctate keratitis and associated reduced corneal sensitivity have been reported and pose a risk for affected contact lens wearers. The incidence of side effects in two prospective studies was about 20%, with some 40% of those having to discontinue timolol. Of optometric interest are reports that timolol increases the electro-oculogram (EOG) ratio (Arden Index), and that it may be used to lower intraocular pressure in acute angle closure when pilocarpine alone is unsuccessful.

Adrenergic beta-Antagonists↗
PubMed2005

A three-month, multicenter, double-masked study of the safety and efficacy of travoprost 0.004%/timolol 0.5% ophthalmic solution compared to travoprost 0.004% ophthalmic solution and timolol 0.5% dosed concomitantly in subjects with open angle glaucoma or ocular hypertension.

PURPOSE: The primary objective of this study was to compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% fixed combination to the concomitant administration of travoprost 0.004% (TRAVATAN) and timolol 0.5% in subjects with open angle glaucoma or ocular hypertension. METHODS: This was a randomized, multicenter, double-masked, active-controlled, parallel group study. Three hundred sixteen patients with open angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.004%/timolol 0.5% ophthalmic solution fixed combination once daily in the morning or concomitant administration of timolol 0.5% once daily in the morning and travoprost 0.004% ophthalmic solution once daily in the evening. The efficacy and safety of the fixed combination were compared with concomitant therapy over three months. The primary efficacy outcome measure was mean intraocular pressure. RESULTS: Both travoprost 0.004%/timolol 0.5% fixed combination and the concomitant administration of travoprost 0.004% and timolol 0.5% produced statistically significant reductions from baseline in IOP, with mean IOP ranging from 15.2 to 16.5 mm Hg in the patients using travoprost 0.004%/timolol 0.5% fixed combination compared with 14.7 to 16.1 mm Hg in the concomitant group. The upper 95.1% confidence limit for the differences in mean IOP (fixed combination minus concomitant) was < or =1.5 mm Hg at 7 of 9 visits, including all three 8 AM time points, 24-hours post-dose. Mean IOP reductions from baseline ranged from 7.4 to 9.4 mm Hg in the fixed combination group compared with 8.4 to 9.4 mm Hg with concomitant therapy. Safety analysis demonstrated equivalent safety between the two treatment groups. CONCLUSIONS: A fixed combination of travoprost 0.004% and timolol 0.5% produced clinically relevant IOP reductions in patients with open angle glaucoma or ocular hypertension that were comparable to concomitant therapy with its components. Safety and tolerability of the fixed combination were also equivalent to concomitant therapy. Travoprost 0.004%/timolol 0.5% fixed combination offers IOP reduction equivalent to concomitant therapy, with potential benefits that include convenience (fewer bottles and drops per day), improved compliance, cost savings (based on fewer co-payments), and elimination of potential washout effects.

Aged↗
PubMed1982

Timolol eyedrop-induced severe bronchospasm.

A patient with glaucoma simplex and chronic pulmonary obstruction was treated with the non-selective beta-adrenergic blocking agent timolol in ophthalmic solution of 0.25% for 11/2 years, when he had daily asthma attacks. In a provocation test, forced expiratory volume in the first second was reduced by 56% and bradycardia was induced after application of two drops of timolol eyedrops 0.25%. The severe systemic side-effects of timolol, when used as eyedrops, are related to the liver bypass and perhaps to the fast absorption from the cornea. It is suggested that when timolol ophthalmic solution is given for the first time to glaucoma patients with chronic obstructive pulmonary disease, they should be observed for one hour with special reference to difficulty in breathing.

Aged↗
PubMed1983

Effect of timolol on clinical features and echocardiographic assessment of left ventricular function in hyperthyroidism.

The effect of timolol, a beta-adrenoceptor blocking drug on the clinical status, thyroid status and left ventricular function as measured by serial M-mode echocardiographic recordings was assessed in a double-blind randomised study in 18 hyperthyroid patients. A significant clinical improvement was documented after 2 weeks of timolol treatment compared with placebo. There was no evidence that timolol impaired peripheral monodeiodination of thyroxine (T4). There were significant increases in left ventricular fractional shortening (Fr. Sh.) and velocity of circumferential shortening (Vcf) as well as a significant decrease in the left ventricular systolic internal dimension (LVIDs) (all P less than 0.01) in the untreated thyrotoxic patients compared with a normal euthyroid control group. After timolol treatment (2/52) there were significant increases in LVIDs and LVIDd and a significant decrease in Vcf (all P less than 0.05). No further changes occurred after a further 2/52 treatment with carbimazole. The cardiac data suggest that both an augmented sympathetic drive and a direct effect of thyroid hormone on myocardial contractility are mediators of the haemodynamic changes in hyperthyroidism.

Adult↗
PubMedDate not supplied

Studies on interaction of timolol, hydrochlorothiazide and amiloride in the rat.

1. The acute effects of hydrochlorothiazide, amiloride, timolol and their combinations on diuresis and arterial pressure were studied in rats. 2. Timolol did not modify the diuretic and saluretic effects of hydrochlorothiazide and/or amiloride and had no diuretic or antidiuretic effects alone. 3. At a single dose of 1.25 mg/kg, p.o., timolol alone had no antihypertensive effect in spontaneously hypertensive rats. 4. The antihypertensive effect of hydrochlorothiazide + amiloride + timolol was significantly greater than with any of the drugs alone.

Amiloride↗
PubMed2004

Preventive effect of lacrimal occlusion on topical timolol-induced bronchoconstriction in asthmatics.

AIM: To evaluate the potential preventive role of lacrimal occlusion on the topical timolol-induced bronchoconstriction in asthmatics. METHODS: This was a prospective and single-masked study. Fourteen volunteer subjects with asthma were included. Collagen plugs were inserted into both canaliculi on one side to inhibit lacrimal drainage. The effect of lacrimal occlusion on lung function tests was measured before and 60 min after the instillation of a timolol drop in unplugged and plugged eyes. The spirometric measurements include forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, and mid expiratory flow-rate (FEF25-75). RESULTS: The timolol (0.5%) drop administration into the eye caused a significant decrease in pulmonary functions in patients with asthma in whom the lacrimal punctae had not been occluded by collagen plug. P values were 0.008 for FVC and 0.001 for FEV1 and FEF25-75. The occlusion of the lacrimal duct by intracanalicular plugs significantly reduced this decrease in pulmonary function. P values were 0.6 for FVC, 0.8 for FEV1, and 0.5 for FEF25-75. The lacrimal occlusion did not affect heart rate and blood pressures. Three subjects complained of epiphora. CONCLUSIONS: Lacrimal occlusion with intracanalicular collagen plugs may almost completely prevent the bronchoconstriction caused by topical timolol in asthmatics by inhibiting or decreasing systemic absorption of the medication.

Administration, Topical↗
PubMed1979

Timolol maleate in treatment of open angle glaucoma.

The effect of Timolol maleate on the intraocular pressure in open angle glaucoma has been examined in 37 patients, of these simple glaucoma in 26 (48 eyes), capsular glaucoma in 9 (14 eyes) and chronic secondary glaucoma in 2 patients (2 eyes). These cases constituded a group which was relatively difficult to manage. The average pressure reduction caused by Timolol maleate alone was about 23%. In 18 patients the intraocular pressure was adequately controlled on Timolol as the only drug and in 10 on additional drug therapy. Five patients failed on drug treatment, and the remaining four failed on one eye while the fellow eye was well regulated. Tonography indicates that the effect is caused by a reduction of the aqueous humour production. Side effects of locally applied Timolol maleate have not been observed. This drug may be the drug of choice in many instances.

Adult↗
PubMed1981

Lysozyme, alfa-1-antitrypsin and serum albumin in tear fluid of timolol treated glaucoma patients with and without symptoms of dry eyes.

Determination of tear lysozyme, alfa-1-antitrypsin and serum albumin was performed in the tear fluid of 24 glaucoma patients on maintenance treatment with timolol. In 7 patients with symptoms of dry eye decreased levels of tear lysozyme and increased levels of alfa-1-antitrypsin and serum albumin were disclosed in contrast to 17 timolol treated patients without dry eyes and to healthy controls. The timolol treated patients with ocular dryness also showed hyperosmolality of tear fluid, abnormal corneal staining with rose bengal and decreased break-up time and Schirmer-I-test. It is concluded that decreased concentration of tear lysozyme in glaucoma patients on topical treatment with timolol may indicate some impairment of the tear gland function provoked by the treatment.

Aged↗
PubMed1981

Initial and long-term effects of metoprolol and timolol on the intraocular pressure. A comparison in healthy subjects.

The effect of 3% metoprolol and 0.5% timolol eye drops on the intraocular pressure (IOP) was compared in healthy subjects. The effect of a single dose was determined up to 48 h after administration of the drug before and after 2 weeks' treatment twice daily with the test drug. The study was performed as a randomized, double-masked cross-over study. Both drugs caused significant reductions in IOP with a maximal effect 2 to 8 h after administration of the drug. Timolol reduced the mean IOP from 14.8 to 10.7 mmHg after 2 h. The corresponding figures for metoprolol were 14.1 and 11.5 mmHg. There was no clear cut effect in the untreated eye for either drug. The effect of one drop timolol lasted for at least 48 h. The duration of one drop metoprolol was 36 h, but there was a marked reduction of the effect between 8 and 12 h after administration of the drug. Both drugs caused a smaller pressure reduction when the effect of one drop was followed for 48 h after to weeks' treatment compared to the initial response. This "escape" was of the same order for both drugs. It has been concluded that the composition of metoprolol eye drops used in the present study is less efficient than timolol as an ocular hypotensive agent.

Adult↗
PubMed1982

Additive intraocular pressure reducing effect of topical timolol during systemic beta-blockade.

The effect on intraocular pressure (IOP) of topical timolol was studied in 30 patients with arterial hypertension treated with oral alprenolol, metoprolol or timolol. No patient had any known eye disorder. Topical administration of timolol induced a significant reduction of IOP regardless if the patients had systemic beta-blockade or not. Treatment with topical timolol alone was equally effective in reducing IOP as combined topical and oral therapy. Patient compliance was checked with plasma concentrations of the different beta-blockers.

Administration, Oral↗
PubMed1985

The effect of ocular pigmentation on intraocular pressure response to timolol.

The one-hour intraocular pressure (IOP) response to topical ocularly applied timolol was studied in darkly and lightly pigmented eyes. One drop of 0.25% 1-timolol was applied to one eye of ten subjects with brown and ten subjects with blue iris color. In the treated and untreated eyes with blue iris color the IOP fell significantly from the baseline value, whereas no pressure reduction was obtained either in the treated or untreated eyes with brown iris color. Beta-blocking agents are known to accumulate in pigment-containing ocular structures. The lack of a one-hour pressure response to timolol in darkly pigmented eyes observed in our study may refer to the reduction of 1-timolol in the biophase due to excessive pigment binding.

Adult↗
PubMed1987

The pharmacokinetics of ocularly applied timolol in rabbits.

[3H]timolol derived radioactivity and beta-antagonistic activity in the aqueous humour, iris, ciliary body and blood in rabbits were analyzed by liquid scintillation counting (LSC) and radioreceptor assay (RRA) after ocular timolol. After ocular application of tracer labelled timolol, the radioactivity decreased slowly in the iris (Kel = 0.05 h-1) and ciliary body (Kel = 0.02 h-1). In the aqueous humour the elimination rate was faster (Kel = 0.57 h-1). The beta-antagonistic activities of the aqueous humour and plasma decreased rapidly when compared to LSC values. The ethanol extractable pool of the beta-antagonistic activity from the iris and ciliary body was only a few percent of the corresponding LSC estimates. The kinetics of beta-antagonistic activity extractable from iris and ciliary body was identical with that in the aqueous humour. Timolol concentrations in the untreated rabbit eye were sufficiently high to lower the intraocular pressure.

Animals↗
PubMed1988

A comparison of betaxolol and timolol in open angle glaucoma and ocular hypertension.

In a randomized, double-masked study, 41 patients with primary open-angle glaucoma or ocular hypertension were treated with betaxolol 0.5% or timolol 0.5% drops for 26 weeks. The average decrease in intraocular pressure (IOP) over the total study period was significant with both betaxolol (-6.3 mmHg) and timolol (-7.2 mmHg) in patients receiving no adjunctive therapy. There was no difference between betaxolol and timolol with respect to changes from baseline IOP. Significantly decreased mean brachial arterial pressure (MAP) was seen only with timolol, although the difference between the two groups was not significant. Pulse, pupil size, and basal tear secretion were unchanged in both groups. Burning upon instillation of the drops was more frequent with betaxolol.

Adrenergic beta-Antagonists↗
PubMed1993

The effect of betaxolol and timolol on postoperative intraocular pressure.

Postoperative intraocular pressure (IOP) elevation is a well documented phenomenon after cataract surgery. Many pharmacological agents have been used to prevent this complication. We conducted a randomized double-blind, placebo-controlled study to evaluate the effect of topical betaxolol and timolol on postoperative IOP after extracapsular cataract extraction and intraocular lens implantation. One hundred and twenty patients were randomly divided into three groups. At the end of the operation, the patients were given one drop of 0.5% betaxolol, 0.5% timolol or placebo solution into the lower cul-de-sac of the operated eye. IOP was measured preoperatively and five and twenty-four h postoperatively. There was a significant rise in IOP in the placebo and betaxolol groups but not in the timolol group five h postoperatively. IOP was significantly higher in all groups twenty-four h after the operation than preoperatively. Betaxolol did not have any significant effect on the postoperative IOP, but timolol was effective in preventing the early IOP rise. The differences in the antagonist effects of these drugs and the possible role of beta 2-receptors in mediating the aqueous humour flow are discussed.

Betaxolol↗
PubMed2004

A 12 week study comparing the fixed combination of latanoprost and timolol with the concomitant use of the individual components in patients with open angle glaucoma and ocular hypertension.

BACKGROUND: To compare the intraocular pressure (IOP) lowering effect and safety of the fixed combination of latanoprost and timolol with that of the concomitant use of the individual components. METHODS: A 12 week, double masked, randomised, crossover, multicentre study of patients with open angle glaucoma or ocular hypertension and IOP controlled on ocular hypotensive treatment (mean < or =21 mmHg). Patients received either a once daily morning dose of the fixed combination of latanoprost 0.005% and timolol 0.5% or once daily evening latanoprost 0.005% and twice daily timolol 0.5% for six weeks and then switched to the other combination. The primary efficacy endpoint was the within-patient difference in diurnal IOP between fixed and unfixed treatment combinations after six weeks of treatment; a one sided 97.5% confidence interval (CI) for the mean difference in IOP <1.0 mmHg indicated the fixed combination was not inferior to the unfixed combination. Adverse events were recorded at each visit. RESULTS: In all, 190 patients were included in observed cases analyses (93 fixed to unfixed combination; 97 unfixed to fixed combination). Mean IOP at baseline was 16.9 mmHg in both groups. The mean diurnal IOP was 17.0 mmHg after fixed combination treatment and 15.9 mmHg after unfixed combination therapy (p<0.0001). The difference in mean within-patient diurnal IOP was 1.1 mmHg favouring the unfixed combination (95% CI 0.8 to 1.4 mmHg). Both treatments were tolerated well. CONCLUSIONS: Although the primary efficacy endpoint was not met, once daily administration of the fixed combination of latanoprost and timolol was found to be safe and effective. The fixed combination provides a convenient alternative to the three instillations required with the individual components.

Adrenergic beta-Antagonists↗
PubMed1981

Study of the additive effect of timolol and epinephrine in lowering intraocular pressure.

A randomised, double-masked clinical study was conducted in patients with primary open-angle glaucoma to determine if timolol and epinephrine have an additive effect in lowering intraocular pressure. Sixteen patients were randomly assigned to one of 2 treatment sequences (timolol alone, supplemented after 2 weeks with epinephrine, and vice versa). An initial additive effect in lowering intraocular pressure was found in both sequences. However, after several weeks of combined therapy complete loss of additive effect was found. Patients who were treated first with epinephrine for 2 weeks and then supplemented with timolol had significantly lower intraocular pressures for at least 2 weeks than patients in the reverse treatment sequence. Epinephrine treatment alone caused a significant increase in facility of outflow, but this effect did not occur with simultaneous timolol treatment. The results are discussed in terms of possible fundamental beta and alpha adrenergic influences on aqueous dynamics and their potential clinical relevance.

Adult↗
PubMed1987

A comparison of the effects of oral nadolol and topical timolol on intraocular pressure, blood pressure, and heart rate.

We compared the effects of oral nadolol 20 mg once daily and topical timolol 0.25% twice daily on the intraocular pressures of 22 glaucoma suspects, in a 12 week double-masked crossover study. Both nadolol and timolol reduced intraocular pressure (p less than 0.001). The reductions in intraocular pressure did not differ significantly after two weeks and four weeks of treatment. Nine of these subjects underwent treadmill exercise tests in order to compare the effects of nadolol and timolol on the cardiovascular system. The effects of the two treatments on blood pressure were comparable, but nadolol caused a significantly greater reduction in heart rate than timolol at rest (p less than 0.05). Nadolol reduces intraocular pressure effectively and may prove a useful alternative treatment for chronic simple glaucoma.

Administration, Oral↗
PubMed1996

Sublingual timolol--an alternative to topical medication in glaucoma?

AIMS: To assess whether timolol drops lower a raised intraocular pressure (IOP) when given sublingually. This route of administration would be useful for glaucoma patients who are unable to instil their own drops--for example, because of stroke, poor vision, arthritis, poor coordination, or blepharospasm. METHODS: A placebo controlled randomised, double masked, crossover study was undertaken in the glaucoma clinic of a large teaching hospital. Twelve patients with ocular hypertension with IOPs over 21 mm Hg, normal optic discs, and full visual fields were examined by Humphrey perimetry. Single dose units of timolol maleate 0.5% drops and normal saline drops were given by instillation in one eye or sublingually. The IOP of both eyes, pulse rate, and blood pressure were all measured before and after each type of drop and route of administration. RESULTS: Two hours after instillation of timolol in one eye, the IOP in the treated eye was reduced by a mean of 8.5 mm Hg (p = 0.0000), and by 1.66 mm Hg in the fellow eye (p = 0.03). Two hours after sublingual instillation of timolol, the IOP was reduced by 7.55 mm Hg in the study eye (p = 0.0000) and by 7.7 mm Hg in the fellow eye (p = 0.0000). There was an equal amount of reduction in pulse rate by either route, but there was no significant change in blood pressure. CONCLUSIONS: The results show that, at least after 2 hours, sublingual treatment is almost as effective as topical treatment in lowering a raised IOP.

Administration, Sublingual↗