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At least 667 records · Page 37Linked to original sources

PubMed2001

Lack of long-term drift in timolol's effectiveness in patients with ocular hypertension.

PURPOSE: To report the change over time in intraocular pressure in patients treated with topical timolol or placebo. METHODS: Ninety patients with untreated ocular hypertension, defined as elevated intraocular pressure and normal visual fields, were randomly assigned to treatment and prospectively observed at 3-month intervals for up to 10 years in a double-masked fashion. The study end point was one eye showing reproducible glaucomatous field defects; patients were also withdrawn if one eye showed intraocular pressure of 35 mm Hg or higher. For each treatment group and visit, the mean and median of all intraocular pressure measurements were calculated. Medians were also calculated for the timolol group, assuming a worst-case scenario in which all patients who reached the end point, or intraocular pressure of 35 mm Hg or more, were assumed to show higher intraocular pressure than those remaining in the study. Distributions of slopes for intraocular pressure over time were compared between treatment groups. RESULTS: Means and medians of follow-up intraocular pressure over time did not differ between timolol- and placebo-treated patients. This was also true when assuming a worst-case scenario. Slopes of intraocular pressure over time did not differ statistically between treatment groups. CONCLUSIONS: In agreement with other masked and controlled studies and in conflict with uncontrolled ones, the present study did not demonstrate long-term drift of intraocular pressure in patients with ocular hypertension treated with topical timolol.

Adrenergic beta-Antagonists↗

PubMed2002

Direct enantiomeric resolution of some cardiovascular agents using synthetic polymers imprinted with (-)-S-timolol as chiral stationary phase by thin layer chromatography.

Molecular imprinted polymers (MIPs) of S-timolol were prepared as chiral stationary phases (CSPs) in thin layer chromatography (TLC). The resolution of the enantiomers of some cardiovascular drugs, including propranolol, atenolol, timolol, nadolol, nifedipine and verapamil were investigated on these CSPs. A mobile phase system of either methanol or acetonitrile was used and the effects of acetic acid content of the mobile phases were also investigated. The best resolution was achieved for enantioseparation of propranolol, timolol and atenolol on plates based on MIP of (-)-S-timolol using methacrylic acid as functional monomer (alpha = 1.52, 1.6, 1.59) respectively, using acetonitrile containing 5% acetic acid and (alpha = 1.47, 1.52, 1.5) in methanol containing 1% acetic acid as mobile phases. The results obtained show that TLC based on MIPs could be applied in the direct separation of several beta-adrenergic drugs. As the side chains on beta-blockers are similar, it is possible that this method could also be used for the resolution of other racemates in this family of drugs. Racemic drugs structurally related to print molecule, were completely resolved into two spots with the MIP plates. In general the retention of (+)-R-isomers was greater than that of (-)-S-isomers, indicating lower stereoselectivity of the MIPs to the dextrorotatory isomers. The method offers a rapid, sensitive and reliable method for quality control for these drugs.

Adrenergic beta-Antagonists↗

PubMed2001

[Effect of pH on the permeability of timolol maleate across isolated rabbit cornea].

AIM: To study the effect of pH on the transcorneal permeability of timolol maleate (TM). METHODS: The apparent distribution coefficients of TM were determined. The permeability of TM across isolated rabbit cornea was measured using in vitro method at various pH. RESULTS: The partition coefficient and pKa of TM were 63.63 and 9.17 respectively. At neutral pH, the apparent permeation coefficient of TM was 1.43 x 10(-5) cm.s-1. When the pH varied from 6.65 to 9.20, the cumulative amount for timolol transcorneal penetration increased 1.3 times and the lag time decreased more than 19-folds. The calculated permeability coefficients of ionized and un-ionized timolol were 1.29 x 10(-5) cm.s-1 and 4.22 x 10(-5) cm.s-1, respectively. CONCLUSION: Timolol penetrated corneal membrane mainly as free base by intracellular pathway, and corneal epithelium was the rate-limiting barrier.

Animals↗

PubMed1992

Drug induced systemic lupus erythematosus due to ophthalmic timolol.

We report a case of systemic lupus erythematosus (SLE) apparently induced by topical use of ophthalmic timolol maleate, a beta adrenergic blocking agent. The patient developed fever, malaise, pleurisy and recurrent sterile pleural effusions while taking no medication other than timolol. Antinuclear antibodies in a homogenous pattern, and markedly elevated histone antibodies (IgG anti-(H2A-H2B)-DNA) were present while antibodies to native DNA were absent. After discontinuation of the timolol, his symptoms improved promptly and the pleural effusions resolved. To our knowledge, this is the first report of timolol induced SLE.

Administration, Oral↗

PubMed1992

[Effects of timolol and carteolol on ocular pulsatile blood flow].

Effects of timolol (0.5%) and carteolol (2%) on ocular pulsatile blood flow (PBF) were studied in healthy adult volunteers. PBF was measured with the BFA system, analyzing the ocular pressure waves. Each drug was instilled in one eye and PBF was measured in both eyes before and fifteen minutes after the instillation. In each drug, the PBF change between the two measurements was evaluated with a control study, which was performed in the same manner with physiological saline solution. In the non-instilled eyes, both timolol (n = 6) and carteolol (n = 9) had no significant change on PBF. In the instilled eyes, timolol (n = 6) caused no significant change, whereas carteolol (n = 9) increased PBF significantly. The range of the BFA system measurement error was within 4.7 +/- 2.4 microliters/min (P = 95%). Taking the error into account in each instilled eye, timolol (n = 6) increased PBF in 3 eyes and decreased it in 3 eyes, while carteolol (n = 9) increased PBF in 7 eyes, did not change it in one eye and decreased it in one eye. It is thought the effect of carteolol to increase PBF may be explained by endothelium-dependent relaxing factor (EDRF).

Adult↗

PubMed1992

Color Doppler ultrasound of orbital and optic nerve blood flow: effects of posture and timolol 0.5%.

Color Doppler ultrasound allows simultaneous imaging with real-time ultrasound and superimposed color-coded vascular flow, allowing visualization of vessels previously beyond the resolution of conventional imaging, such as those in the orbit. With this technique, 20 healthy volunteers were studied. Three regional vessels named 1, 2, and 3 were identified. No significant difference in maximum or minimum blood velocity or resistive index was detected between vessels 1 and 2, although significant differences were noted between both these vessels and vessel 3 (P less than 0.01 and P less than 0.001, respectively). These regional variations are unaffected by small but significant rises in pulse (P less than 0.05) and diastolic blood pressure (P less than 0.01) induced by postural change. No significant change within each vessel was recorded in response to posture, reflecting autoregulation within these vessels. Using a similar technique, 10 healthy volunteers were studied at baseline and at 2 hr and 3 d following the unilateral instillation of 0.5% timolol eye drops. A fall in resistive index was recorded in vessel 3 for both eyes (P less than 0.05, timolol administered eye; P less than 0.01 timolol-free eye). This effect was independent of any simultaneous fall in intraocular pressure that occurred only in the eye receiving timolol drops (P less than 0.01). These results support the presence of B receptors in the vessels at the optic nerve head (vessel 3). A fall in resistive index should not compromise the blood supply in this region, and may even increase it.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

PubMed1978

[A new beta-blocking agent in the treatment of chronic open-angle glaucoma: timolol maleate. Effect of instillation of 1 drop on the intraocular pressure].

A total of 45 patients with chronic open-angle glaucoma were divided randomly into three groups of fifteen. Each patient in each group was given one drop into one eye (the other eye serving as a control), of either placebo, timolol 0,5%, or timolol 1,5%. The patients were observed for a period of seven hours, and results showed that timolol was effective in reducing ocular tension when compared to placebo. It was also rapid in action (one to two hours after instillation), and no side-effects were noted. Timolol 0,5% appears to be as equally effective as the 1,5% strength.

Adolescent↗

PubMed1991

[Intraocular pressure changes after Nd:YAG laser capsulotomy with preoperative use of timolol].

Sixty-four eyes undergoing Nd:YAG laser posterior capsulotomy were randomly assigned to pretreatment with 5 mg/ml (0.5%) timolol maleate in 32 eyes, and no drugs was given in the other 32 eyes as comparison. The result showed that the mean rise in intraocular pressure was significantly less in the timolol-pretreated group than that in the comparison group within 4 hours after laser procedure and the intraocular pressure was the lowest 2 hours after capsulotomy. The mean rise in intraocular pressure in pretreated group was less than that in the comparison group 24 or 48 hours after capsulotomy, but the difference was not significant. It is suggested that pretreatment with 5 mg/ml (0.5%) timolol could blunted the immediate post-capsulotomy pressure rise though delayed pressure increases could not be prevented. Therefore, it is recommended that timolol should be administrated before the YAG laser capsulotomy in order to reduce side effects caused by higher immediate post-capsulotomy pressure rise.

Adolescent↗

PubMed1991

Effects of topical dihydroergocristine on intraocular pressure, aqueous humor dynamics and pupil diameter in conscious rabbits. A comparative study with timolol and pilocarpine.

This work comparatively studies the effects of dihydroergocristine, timolol and pilocarpine on intraocular pressure and pupil diameter in conscious rabbits. Intraocular pressure was measured by applanation tonometry and the pupil diameter by a photographic technique. In anesthetized rabbits, changes in tonographic facility of aqueous humor outflow and rate of aqueous humor formation were evaluated. Dihydroergocristine reduced the intraocular pressure more than timolol and much more than pilocarpine. The ocular hypotensive effect of dihydroergocristine was accomplished by a great reduction in aqueous humor formation, which surpasses the decrease in aqueous humor outflow, while timolol mainly reduced aqueous humor formation and pilocarpine increased aqueous humor outflow. Pupil diameter remained unchanged on dihydroergocristine, whereas timolol induced a slight mydriasis and pilocarpine provoked a clear myosis. Effects of dihydroergocristine might result in blockade of alpha-adrenoceptors in ciliary body, although available data about pretreatment with either metoclopramide or domperidone suggest that dopamine DA2-receptors might participate in ocular hypotensive effect of ergot derivatives.

Administration, Topical↗

PubMed1990

Apraclonidine hydrochloride: an evaluation of plasma concentrations, and a comparison of its intraocular pressure lowering and cardiovascular effects to timolol maleate.

We performed a prospective, placebo-controlled, cross-over study in 20 young healthy female volunteers. We evaluated both the cardiovascular and IOP effects of both timolol maleate and apraclonidine hydrochloride. In addition, we evaluated the plasma levels of various apraclonidine concentrations. We utilized 0.5% timolol and both the 0.25% and 0.50% concentrations of apraclonidine. Both timolol and apraclonidine lowered IOP comparably. Timolol lowered the resting pulse rate and blunted exercise-induced tachycardia. Apraclonidine did not affect blood pressure or heart rate any differently than placebo. We detected plasma levels of apraclonidine in many individuals for up to 8 hours. These serum levels were variable and did not appear to relate to the quantity of IOP lowering.

Adrenergic alpha-Agonists↗

PubMed1991

Aqueous humor pilocarpine and timolol levels after instillation of the single drug or in combination.

Aqueous humor levels of pilocarpine and timolol in rabbits after administration of either 2% pilocarpine or 0.5% timolol in single-drug solutions were compared with the concentrations found after instillation of a fixed combination of 0.5% timolol and 2% pilocarpine drops. Time intervals considered were 15 min, 30 min, 1 hr, 4 hr, and 8 hr after application. Drug concentrations were analyzed in individual aqueous samples by high-performance liquid chromatography. No statistically significant differences in either pilocarpine or timolol concentrations in aqueous humor were found at any time tested between the single-drug preparations and the combination.

Administration, Topical↗

PubMed1991

Effects of topical administration of timolol maleate on intraocular pressure and pupil size in dogs.

Effects of topical administration of a single dose of timolol maleate on intraocular pressure (IOP) and pupil diameter were evaluated in normotensive eyes of 11 clinically normal dogs over 12 hours (7:00 AM to 7:00 PM). Mean (+/- SEM) normal IOP was 15.5 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the morning. Mean normal pupil diameter was 8.5 (+/- 0.3) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in the treated and nontreated eyes. Mean reduction of IOP in the treated eye was 2.5 mm of Hg, a reduction of 16.1%, with maximal reduction of 3.7 mm of Hg. Mean reduction of IOP in the nontreated eye was 1.4 mm of Hg, a reduction of 9.0%. The treated eye had reduced pupil diameter at 30 minutes after treatment, which persisted throughout the 12 hours of the study. Mean reduction of pupil diameter in the treated eye was 2.9 mm, a reduction of 34.1%. In addition, a contralateral effect on pupil diameter was seen in the nontreated eye, with mean reduction of 1.2 mm, a reduction of 14.1%. Topical administration of timolol maleate resulted in reduction of IOP and pupil diameter in treated and contralateral eyes, thus supporting the use of timolol for treatment of glaucoma in dogs. Miosis indicates possible beta-adrenergic inhibition or alpha-adrenergic activation of the sphincter muscle. beta-Adrenergic blockade would then result in miosis.

Administration, Topical↗

PubMed1991

Effects of topical administration of timolol maleate on intraocular pressure and pupil size in cats.

Effects of topical administration of a single dose of timolol maleate, a nonselective beta-adrenergic blocking agent, on intraocular pressure (IOP) and pupil diameter were evaluated in the normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was 10.1 (+/- 0.5) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 6 hours after treatment. Mean reduction of IOP was 22.3% in the treated eye and 16.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction of pupil diameter was 38.7%. A contralateral effect on pupil diameter was not seen in the nontreated eye. Topical administration of timolol maleate results in a reduction of IOP in treated and contralateral eyes, which supports the use of timolol for treatment of glaucoma in cats. In addition, the treated eye becomes miotic. This effect may indicate beta-adrenergic inhibition or alpha-adrenergic activation of the iris sphincter muscle. beta-Adrenergic blockade would then result in miosis.

Administration, Topical↗

PubMed1990

Restoring sensitivity to timolol after long-term drift in primary open-angle glaucoma.

In a prospective randomized single-masked study lasting 6 months, 39 eyes with primary open-angle glaucoma showing a long-term drift with 0.5% timolol were put on a "timolol holiday" lasting 30 or 60 days. Twenty-three of them were enrolled with dipivefrin 0.1% twice daily during the holiday. When timolol therapy was restored, the dipivefrin-treated group showed a more pronounced decrease of intraocular pressure (IOP) (8.2 +/- 1.5), whereas the IOP decrease in the nondipivefrin-treated group was lower (3.9 +/- 1.2) and of shorter duration (less than 60 days). Among the dipivefrin-treated group, the response to timolol was more prolonged in the eyes treated for 60 days: the IOP of these eyes was less than 23 mmHg throughout the follow-up.

Aged↗

PubMed1989

Comparative evaluation of the antihypertensive effect of timolol and propranolol in patients with essential hypertension.

Fifty patients with essential hypertension were studied for the antihypertensive effect of timolol and propranolol. In 16 out of 25 patients on timolol therapy (64%) blood pressure could be brought well under control (defined as diastolic blood pressure less than 90 mmHg) while with propranolol 13 out of 25 patients (52%) responded. Side-effects were negligible with timolol as compared to propranolol therapy. This study revealed that timolol is an effective and safe drug in essential hypertension, and is tolerated better than propranolol by the patients.

Adult↗

PubMed1989

Effect of topical timolol maleate on the ophthalmic artery blood pressure.

The effects of topical timolol maleate 0.5% on the ophthalmic artery diastolic (OABPd), systolic (OABPs) and mean blood pressure (OABPm) were investigated in 19 healthy subjects using compression ophthalmodynamometry. In a randomized, double-blind study, one eye of each subject received one drop of timolol maleate 0.5% and the fellow eye received a drop of placebo. Measurements of OABPd and OABPs were performed just prior to instillation of the drops, and then 2 hr later. OABPm was calculated as OABPm = OABPd + 1/3 (OABPs - OABPd). No significant changes in OABPd, OABPs or OABPm were observed following the drops in the timolol-treated eyes or in the placebo-treated eyes. A significant difference (P = 0.0198) was found, however, when the changes in OABPm occurring in the timolol-treated eyes were compared with the changes occurring in the placebo-treated eyes, suggesting that the drug may have an effect upon ophthalmic artery pressure and retinal artery pressure that is expressed differently in each eye.

Administration, Topical↗

PubMed1977

[Antihypertensive therapy with a new beta-blocking agent Timolol. Double blind study and comparison with Alprenolol and Pindolol (author's transl)].

In a double blind study including 24 patients with essential hypertension the beta-blocking agent Timolol showed a mild antihypertensive effect. These patients had been pretreated with hydrochlorothiazid to which they responded already with a significant lowering of their blood pressure before Timolol was added. The effect of Timolol equals the effects of Pindolol and Alprenolol. We also found a suppression of the plasma-renin-activity under Timolol. This effect did not correlate with the degree of blood pressure reduction. There were no side effects noted except for a lowering of the pulse rate about which some of the patients complained and which is typical for beta blocking agents without intrinsic symphaticomimetic activity. According to our results this new beta blocking agent for antihypertensive therapy has very much the same properties as the other beta-blocking drugs already in use.

Adult↗

PubMed1985

Transient ischemic attacks and amaurosis fugax from timolol.

A variety of neurological disturbances may occur in patients receiving ocular administration of timolol. Possible mechanisms include direct effects on neurons of the central nervous system, effects on peripheral vasculature, and cardiac arrhythmias. Interestingly, transient ischemic attacks have not been documented to occur synchronously with timolol-related arrhythmias. We report a case of recurrent dizziness and staggering gait occurring synchronously with timolol related arrhythmias. An attack of amaurosis fugax also occurred. Discontinuing timolol abolished all the symptoms. Pre-existing autonomic dysfunction in our patient may have been an important contributing factor in his symptomatology.

Aged↗