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At least 865 records · Page 48Linked to original sources

PubMed1978

The mechanism of timolol in lowering intraocular pressure. In the normal eye.

A single-drop, double-masked, randomized, placebo-controlled study of the mechanism of the ocular-pressure lowering property of timolol maleate, a beta-adrenergic blocker, was carried out in 23 normal subjects, using fluorophotometry. Timolol suppressed aqueous formation in all subjects. The range of suppression was 13% to 48%, with a mean +/- SD of 34% +/- 9%. The drug had no effect on anterior chamber volume or endothelial permeability to fluorescein and, apparently, had no effect on outflow resistance. No differences were observed between its effect on men and women or between eyes with light and dark irides.

Adult↗

PubMed1980

Evaluation of timolol in chronic open-angle glaucoma. Once a day vs twice a day.

Regimens of once-a-day or twice-a-day 0.25% timolol ophthalmic solution were compared for efficacy and tolerability in a four-week study of 41 patients with chronic open-angle glaucoma and elevated, untreated intraocular pressure. Significant reductions in IOP relative to untreated baseline values were achieved within a range of 18% to 25%. No significant between-group differences were noted, although the twice-a-day group had somewhat lower IOPs at each evaluation point and the once-a-day group had somewhat fewer subjective symptoms of local irritation. A statistically significant decrease from baseline in mean pulse rate was noted in the twice-a-day treatment group after two weeks; no clinically significant or serious adverse reactions occurred in any patient. Both once-daily and twice-daily administrations of 0.25% timolol ophthalmic solution were found to be effective and well tolerated in the population studied.

Adult↗

PubMed1984

Timolol inhibits corneal epithelial wound healing in rabbits and monkeys.

To determine the effect of timolol maleate on corneal epithelial wound closure, 6.4-mm (diameter) epithelial defects were created chemically in five experiments. In rabbits, wound closure was not significantly altered by the administration of 0.5% Timoptic (a commercially prepared timolol maleate solution) every eight hours, but it was inhibited during the first 15 hours of healing when a 4% solution was applied every two hours. Monkeys received a 5% solution every 12 hours and were divided into treated and control groups. Two phases of wound healing were apparent: a rapid initial phase and a slower final phase. Wound closure was inhibited in treated eyes during the initial rapid phase. This experiment repeated on the same monkeys, but with the control and treated animals switched, yielded the same result. Another experiment, with the fellow eye of the monkey used as a control, showed no significant difference in wound closure.

Animals↗

PubMed1985

Levobunolol compared with timolol for the long-term control of elevated intraocular pressure.

Levobunolol hydrochloride (0.5% and 1%) and timolol maleate (0.5%) are being compared in an ongoing, double-masked, randomized study of 141 patients with ocular hypertension or chronic open-angle glaucoma. Baseline intraocular pressure (IOP) in the three treatment groups ranged from 26 to 27 mm Hg. During the first 15 months of the study, the two drugs have not proved to be significantly different in ocular hypotensive efficacy, with overall mean IOP decreases of 6.8 to 7.6 mm Hg. In addition, the two concentrations of levobunolol have been equally effective in controlling IOP. Neither drug has been associated with any significant ocular side effects. Both drugs have produced significant decreases (five to ten beats per minute) in mean heart rate. The effect on mean blood pressure has been less pronounced: overall decreases have been less than 4 mm Hg for both systolic and diastolic blood pressure. The results of this ongoing study suggest that levobunolol is as effective and as safe as timolol for the long-term control of IOP.

Adult↗

PubMed1986

Betaxolol vs timolol. A six-month double-blind comparison.

Betaxolol hydrochloride (0.5%) and timolol maleate (0.5%) were compared in a six-month randomized, double-blind study involving 29 patients with glaucoma. The two drugs were comparable with regard to efficacy in lowering intraocular pressure. Betaxolol effected an average reduction of 7.6 mm Hg (26%); timolol, 8.4 mm Hg (29%). No patient required adjunctive medications during this study. Ocular side effects were mild and similar for both treatments. Neither drug affected corneal sensitivity, visual acuity, basal tear production, or pupil size. Since betaxolol has been shown to have little effect on the cardiopulmonary system, it should be strongly considered for the treatment of glaucoma.

Adult↗

PubMed1990

Topical timolol decreases plasma high-density lipoprotein cholesterol level.

beta-Adrenergic antagonists taken orally adversely alter plasma lipid profiles. This study was designed to determine whether 0.5% topical timolol maleate has a similar effect. Forty volunteers who were not using medications known to alter plasma lipid levels were recruited for an unmasked study in which each subject served as his or her own control. Twelve subjects did not complete the study because of ocular and systemic side effects or extraneous factors. Twenty-eight subjects used topical timolol for an average of 76 days, with two 12-hour fasting plasma specimens obtained at the beginning and end of the period. Mean total cholesterol and low-density lipoprotein cholesterol levels did not change significantly with treatment. Triglyceride values increased 12%; high-density lipoprotein cholesterol levels decreased 9%; and the total cholesterol-high-density lipoprotein cholesterol ratio increased 8%. Higher baseline high-density lipoprotein cholesterol levels were associated with larger reductions in high-density lipoprotein cholesterol levels. Changes in high-density lipoprotein cholesterol levels of this magnitude have been estimated to increase the risk of coronary artery disease by 21%.

Administration, Topical↗

PubMed1991

Apraclonidine and timolol. Combined effects in previously untreated normal subjects.

Twenty healthy subjects were tested for the aqueous-suppressing effects of the alpha 2-adrenergic agonist apraclonidine hydrochloride. Apraclonidine caused a 30% reduction of mean (+/- SD) aqueous flow during the daytime from 2.84 +/- 0.61 microL/min, similar to what has been observed for beta-adrenergic antagonists. Apraclonidine, like acetazolamide and unlike timolol maleate, was able to suppress the aqueous flow of sleeping subjects below the spontaneous nocturnal rate of 1.15 +/- 0.40 microL/min to 0.84 +/- 0.28 microL/min, a 27% change. When apraclonidine and timolol were given together in the daytime, no clinically significant or statistically significant additive effect was observed. The range of flows with either drug alone or the combination of the two measured from 2 to 4 PM was 1.41 to 1.78 microL/min. This result contrasts with studies of the effect of apraclonidine on patients who have received long-term beta-blockers where an additive effect is observed. The lack of an additive effect on flow in previously untreated normal subjects suggests that the two drugs act at least in part via a common pathway.

Administration, Topical↗

PubMed1998

Topical timolol therapy in pregnancy: is it safe for the fetus?

At 21 weeks of gestation, a 37-year-old woman was referred to our hospital. The fetus showed bradycardia and arrhythmia. Because of glaucoma the woman had previously been treated with timolol eye drops. In this paper a possible association between the timolol eye drops and the fetal cardiac arrhythmia is discussed.

Adult↗

PubMedDate not supplied

Estimation of the systemic bioavailability of timolol in man.

The systemic bioavailability of timolol, a beta-adrenergic receptor blocking agent, was calculated from published data in normal volunteers and uremic patients after oral doses. Equations based on the perfusion limited model that account for the biological determinants affecting drug disposition were derived and applied to calculate systemic bioavailability. The means of the fraction of the administered oral dose reaching the systemic circulations intact drug were calculated to be 0.58 and 0.60 for normal volunteers and uremic patients, respectively. Minimal first pass biotransformation during absorption was inferred from these figures for timolol when compared with other analogs such as propranolol and alprenolol, each of which undergoes an extensive first pass effect.

Biological Availability↗

PubMed1977

Amelioration of bendrofluazide-induced hypokalemia by timolol.

The beta adrenergic blocking drug, timolol, tended to correct the hypokalemia of short-term bendrofluazide treatment in 6 healthy male subjects and although the effect was small it was significant. Timolol also reduced the rise in plasma aldosterone and urine potassium excretion following bendrofluazide and increased the urine sodium/potassium ratio. There was no evidence of a shift of potassium from the intracellular to the extracellular space.

Bendroflumethiazide↗

PubMed2002

Effect of Timolol vs. a postural orthotic on hand tremor during microsurgery.

The efficacy of beta blockers to control hand tremor remains equivocal. This study evaluated the effectiveness of Timolol, as well as a postural orthotic, in reducing movement deviation during a laboratory exercise. Eleven volunteers completed three randomized trials involving administration of Timolol, a placebo, or a postural orthotic. Drug administration was blinded. Each trial consisted of a simulated 2-hr clinical procedure, punctuated by video recordings of the subject's hand motion during a standardized pattern of instrument movement. ECRL EMG activity and digital oxygen perfusion were also measured. Recordings were converted into estimates of linear variance at baseline and 1 and 2 hr. A repeated-measures ANOVA, or the Friedman test, were used to assess significant differences. Movement deviation, EMG activity, and oxygen perfusion were unaffected by the duration of exercise or treatment (P > or = 0.454). We conclude that none of the treatments accorded a significant benefit in allaying hand tremor.

Adrenergic beta-Antagonists↗

PubMed1980

Ocular penetration of beta-adrenergic blocking agents. An experimental study with atenolol, metoprolol, timolol and propranolol.

A comparison was made between the ocular penetration of topically applied 14C-atenolol, 14C-timolol, 14C-propranolol and 3H-metoprolol by means of liquid scintillation counting. Only one eye was treated, the fellow eye served as a control. Blood plasma levels were measured as well. We could detect a relationship between the ocular penetration and the degree of lipophilicity of the drugs used, as was to be expected. Drugs with a higher degree of lipophilicity penetrated more readily into the eye, whereas they also achieved higher blood plasma levels. Relatively high concentrations of atenolol were found in the nicitating membrane, thus reflecting its poor ocular penetration. The concentrations detected in the untreated eye were low and probably cannot explain the marked reduction in intraocular pressure observed after unilateral instillation of active beta-adrenergic blocking drugs, as for instance timolol. Our findings suggest that the ocular penetration of beta-adrenergic blocking agents on topical application only plays a minor part in their ocular hypotensive effect.

Adrenergic beta-Antagonists↗

PubMed1980

Once-daily dosing of timolol in hypertension: a controlled study.

Nine previously untreated patients with mild-moderate hypertension were included in a dose-ranging double-blind trial to determine the effectiveness of daily versus thrice daily timolol administration. In 8 patients control of blood pressure was equally effective though with significantly lower heart rate achieved in the once daily group. One patient was not satisfactorily controlled on the daily regimen demostrating that many but not all hypertensives can be controlled with daily administration of timolol.

Administration, Oral↗

PubMed1978

Plasma timolol levels after oral and intravenous administration.

The plasma kinetics of timolol administered orally and intravenously to 5 male subjects were examined. Bioavailability was reduced by 25% when the drug was taken orally. Mean plasma half-life after oral dosing was 4.86 h, and after intravenous administration it was 4.56 h; the difference was not significant. The volume of distribution was 3.5 1/k. It is suggested that timolol is little affected by the 'first pass effect', even though there is marked interindividual variation in availability and peak plasma level.

Administration, Oral↗

PubMed1988

Effects of verapamil and timolol on cellular morphometric changes in cat hearts with regional ischaemia.

In twenty-one anaesthetized open chest cats the left anterior descending coronary artery (LAD) was occluded for three hours. Seven cats were pretreated with a bolus injection of Verapamil, followed by a continuous infusion of Verapamil during the ischaemic period. Seven cats were pretreated with a bolus injection of Timolol to a heart rate reduction of 20 beats/min or more and seven cats were given saline. In the latter two groups the cats received a continuous infusion of saline during the period of coronary occlusion. Biopsies were taken from the mid-myocardium of the normal, border and ischaemic zones, as defined by fluorescein staining, and verified by blood flow measurements with radiolabelled microspheres. Standard point counting techniques were used for calculations of fractional volumes of mitochondria, cytoplasm and myofibrils as well as of mitochondrial surface density and surface to volume ratio. We observed a cytoplasmic oedema in the border and ischaemic zones, that was not altered by medical treatment. In the border zone of the control cats there is greater mitochondrial swelling than in the ischaemic zone. This particular swelling is not seen in the treatment groups. However, in the normal and border zones of the verapamil group the mitochondria are smaller when compared with the respective zones in the two other groups, but increases relatively more in size in the border and ischaemic zones. Furthermore, we measured the water content, sarcomere length and per cent heavily damaged cells. These variables were not altered by Verapamil or Timolol in any zone when compared with the respective zones in the control group.

Animals↗

PubMed1987

[Changes in lung function following administration of eyedrops containing timolol, metipranolol, pindolol and pilocarpine in healthy probands and patients with mild bronchial asthma].

Lung function was studied double blind and randomized in 5 patients with mild asthma bronchiale and 10 normal adults before and 30, 60 and 90 minutes after one drop of 0.5% Timolol, 0.6% Metipranolol or 0.9% NaCl in each eye. In the asthmatics bronchoconstriction was seen after both beta-receptor blocking agents, more pronounced after Timolol than after Metipranolol. There was a decrease in the forced expiratory volume in one second (FEV1.0) of 32, respectively 18%. No changes were observed in the normal subjects. In a separate study no significant changes were seen in the mean values of 10 other asthmatic subjects after 1% Pindolol, 3% Pilocarpin or 0.9% NaCl. However, in two patients FEV1.0 was reduced by 15% and 20% of the control values after applying Pindolol. In summary, not only beta-receptor-blocking agents without ISA produce a bronchoconstriction in asthmatic subjects, but also beta-blocker with ISA in individual cases.

Airway Resistance↗

PubMed1989

The effect of timolol, betaxolol and levobunolol on the surface of rabbit cornea.

Pigmented rabbits were treated with timolol maleate, betaxolol hydrochloride or levobunolol hydrochloride eye drops twice a day for six months. Animals of the same age group and breed were used as controls. There were no differences observed in corneal epithelium with light and transmission electron microscopy. With scanning electron microscopy, in the timolol and betaxolol treated animals the picture of the corneal surface was similar to that of normal rabbit corneas after exposure to air. In scanning electron micrographs of the levobunolol treated animals, the corneal surface resembled the corneas of normal rabbits treated with artificial tears.

Administration, Topical↗

PubMed1982

The influence of long-term treatment with timolol on human tear lysozyme albumin content.

The long-term effect of timolol maleate on lacrimal secretion was tested by investigating the concentration of lysozyme and albumin in tears before the start of treatment and after different follow-up periods. A total of 25 patients (45 eyes) were treated with 0.25% or 0.5% timolol as the only antiglaucomatous therapy over a 7.6 month mean observation period (2-13 months). No significant change was found either in the lysozyme or in the albumin concentration.

Adult↗