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At least 793 records · Page 44Linked to original sources

PubMed1982

The comparative multiple-dose intraocular pressure responses of nadolol and timolol in glaucoma and ocular hypertension.

In a double-masked clinical study the relationship between acute and chronic IOP responses to topical Nadolol 2% solution and Timolol 0.25% solution twice daily was investigated in 10 patients with glaucoma or ocular hypertension. Both drugs were evaluated in an intra-individual comparison over 4 weeks. Nine patients completed the study, one was discontinued because of essential loss of response to both drugs. At the beginning of therapy Timolol as well as Nadolol gave a mean IOP reduction of about 40% relative decrease. During the following visits the Nadolol treated eyes were significantly higher in IOP than the Timolol treated eyes. The maximum IOP effect of the first day of treatment could not be reproduced by either drug at the subsequent checks. There had been no significant changes of blood pressure, pulse rate or pupillary diameter.

Adrenergic beta-Antagonists↗

PubMed1983

Vascular effects of timolol and pilocarpine in the iris. A simultaneous bilateral fluorescein angiographic study.

Simultaneous bilateral fluorescein angiography of the iris vessels (SIFA) was performed on 2 groups of patients. One group comprised previously untreated patients with elevated intraocular pressure who underwent a SIFA both before and after a 3 days' timolol treatment in one eye and pilocarpine treatment in the other eye. The other group consisted of glaucomatous patients treated with timolol for 4 to 24 (mean 11) months before the angiography. Short- or long-term use of timolol neither caused, increased nor decreased leak of the dye from the iris vessels, either at the pupillary border, or in other areas of the iris. Dynamics of the blood flow also remained unaffected. Short-term use of pilocarpine increased extrapupillary focal leakage in one eye.

Adult↗

PubMed1985

Timolol in aqueous humour after topical administration. A pilot study.

The concentration of timolol in aqueous humour after one single drop of timolol ophthalmic solution was studied in 19 patients. Relatively high concentrations were found (mean: 626 ng/ml), but the individual differences were great (range: 0 ng/ml - 2080 ng/ml). Possible explanations are discussed. No detectable levels of timolol were found in plasma (detection level greater than or equal to 1 ng/ml).

Adult↗

PubMed1985

A comparison between iris-ciliary body concentration and receptor affinity of timolol.

Topical unilateral application of timolol reduces the IOP (intraocular pressure) of both the treated and the untreated eye. For this reason, a cental mechanism of action, in addition to the local one, has been suggested for the reduction of IOP by this drug. In this study timolol concentrations in the iris-ciliary body of the treated and untreated rabbit eyes were compared with pharmacologically active in vitro timolol concentrations. The drug concentration in the untreated eye too was found to be high enough to exert a local action.

Animals↗

PubMed1986

Timolol inhibits adenylate cyclase activity in the iris-ciliary body and trabecular meshwork of the eye and blocks activation of the enzyme by salbutamol.

The enzymatic activity of adenylate cyclase in homogenates and membrane-rich fractions prepared from rabbit iris-ciliary bodies and bovine trabecular meshwork was found to be inhibited by timolol. Treatment of iris-ciliary body homogenates with Triton X-305 resulted in abolition of the inhibitory effect of the drug on the activity of the enzyme. The stimulatory effect of salbutamol on the enzyme was also susceptible to blockade by timolol. It is suggested that the hypotensive action of timolol on intraocular pressure results from structural and functional changes induced on the plasma membranes of the iris-ciliary body and trabecular meshwork by the thiadiazole group of the molecule, and, also, from the occupation of the adrenergic receptors of the iris-ciliary body by the tert-butylamino-2-hydroxypropoxy part of the compound.

Adenosine Triphosphate↗

PubMed1992

Recurrent choroidal detachment following timolol therapy in previously filtered eye. Choroidal detachment post filtering surgery.

A 64-year-old patient with open-angle glaucoma was treated with timolol following two unsuccessful filtering procedures. While on timolol therapy, she developed three episodes of choroidal detachment, hypotony and shallow anterior chamber. These findings resolved upon cessation of timolol and reappeared on 3 occasions shortly after reinstitution of the beta blocker therapy.

Choroid Diseases↗

PubMed1993

Intraocular pressure reduction with topically administered pilocarpine, timolol and betaxolol in normal tension glaucoma.

The IOP-lowering effect of topical glaucoma medication has been studied mainly in eyes with ocular hypertension or high tension glaucoma. We tested the IOP-lowering effect of the commonly used topical medications (pilocarpine, timolol and betaxolol) in eyes with normal tension glaucoma. Instillation of 2% pilocarpine hydrochloride three times a day had no statistically significant lowering effect on the IOP level (F test, P = 0.0596, n = 18). 0.5% timolol maleate administered twice a day (n = 16) and 0.5% betaxolol hydrochloride administered twice a day (n = 17) led to statistically significant lowering of the IOP level (F test, P < 0.0001 for timolol and P = 0.0001 for betaxolol). There was no statistically significant difference in IOP-reducing effect whether topical IOP-lowering medication had been used previously or not. The results for 11 eyes participating in all three tests were similar to the results for the other eyes in the three test groups.

Administration, Topical↗

PubMed1988

Levobunolol compared with timolol: a four-year study.

Fifty-one patients with raised intraocular pressure (IOP) were treated for up to four years with one of three ophthalmic solutions: 0.5% levobunolol, 1% levobunolol, or 0.5% timolol. The study was conducted as a double-masked, randomised trial in which medications were administered twice daily to both eyes. Levobunolol and timolol were equally effective in reducing overall mean IOP; reductions were greater than 8.8 mmHg in all three treatment groups. The study showed levobunolol to be as safe and effective as timolol in the long-term control of raised IOP.

Aged↗

PubMed1990

Effects of topical timolol (0.5%) and betaxolol (0.5%) on corneal sensitivity.

There are conflicting reports on the propensity of topical beta blockers to produce corneal anaesthesia. We measured corneal sensitivity thresholds quantitatively for 10 minutes following the administration of one drop of topical timolol maleate (0.5%), betaxolol hydrochloride (0.5%), or saline in 30 eyes of 18 normal subjects in a randomised, double-masked study. Most subjects had insignificant changes in corneal sensitivity thresholds. We identified, however, a subgroup of four subjects (five eyes) that had a marked and prolonged increase of corneal sensitivity threshold (corneal anaesthesia) after timolol (three eyes) and betaxolol (two eyes). The group mean age of these 'responders' (49.0 years) was significantly greater (p less than 0.005) than that of the non-responders (35.0). We recommend periodic measurements of corneal sensitivity in older patients receiving topical timolol or betaxolol, especially when given in higher concentrations, to identify responders, who may be at risk of developing keratitis.

Adult↗

PubMed1998

Randomised, controlled trial of spirometric changes in elderly people receiving timolol or betaxolol as initial treatment for glaucoma.

AIM: To investigate respiratory and cardiovascular side effects in elderly people in the first 12 months after commencing topical beta antagonists. METHODS: 40 patients (mean age 74 years) were recruited to a randomised, masked study. Spirometry, pulse, and blood pressure were recorded before, 1 month, and 12 months after starting topical therapy with either timolol 0.5% twice daily or betaxolol 0.5% twice daily. RESULTS: After 1 month five of 20 patients allocated timolol and three of 20 given betaxolol had discontinued it for respiratory reasons, not always accompanied by symptoms. There were no significant differences in changes in mean values of spirometry, pulse, or blood pressure between groups. No further changes were made in therapy for respiratory reasons in the following year. One patient suffered a hypotensive stroke within 2 days of starting timolol. CONCLUSIONS: By performing spirometry before starting topical beta antagonist therapy and repeating it after 1 month most patients at risk of respiratory impairment can be identified.

Aged↗

PubMed1985

Effect of smoking habits and timolol treatment on mortality and reinfarction in patients surviving acute myocardial infarction.

The Norwegian Multicenter Group Study noted the effect of smoking habits before and after myocardial infarction and their relation to mortality and reinfarction rate after treatment with timolol in patients surviving acute myocardial infarction. The mean follow up period was 17.3 (range 12-33) months. No relation was found between initial smoking habits and risk category after infarction or between initial smoking habits and later outcome. At the time of their first infarct smokers were seven years younger than non-smokers. One moth after infarction nearly 60% of the smokers had stopped smoking completely. A significantly lower incidence of early cardiac death and lower total mortality was found in patients treated with timolol in both those who continued smoking and in the combined non-smoking groups and a significantly lower reinfarction rate among non-smokers. Cessation of smoking alone was associated with a reduced reinfarction rate by 45% but a non-significant reduction in mortality by 26%. It is concluded that treatment with timolol and cessation of smoking have an additive effect in reducing mortality and reinfarction rate after myocardial infarction.

Aged↗

PubMed1982

Cerebrospinal fluid formation in rats and cats during treatment with timolol.

The influence of timolol upon cerebrospinal fluid formation rate has been examined in rats by the measurement of 22Na+ entry into this fluid after 10, 100, or 1000 micrograms x kg-1 i.v. and in cats by the dye-dilution measurement of new fluid formation after 30, or 3000 microgram x kg-1 i.v., or 250 micrograms x mL-1 in ventricular perfusate. In rats no change from control rates occurred. In the cats there appeared to be no effect of intraventricular timolol; however, a significant decrease of approximately 25% in the mean flow rate was seen after 40 min when drug was given i.v. at either dose level. A time study showed that no further decrease occurred within 5 h and that the observed decrease continued for at least 3 h. These findings are of interest in view of the ability of topical, intraocular, and i.v. timolol to reduce aqueous humor formation rate.

Animals↗

PubMedDate not supplied

Comparison of the effects of preserved and unpreserved formulations of timolol on the ocular surface of albino rabbits.

Thirty-six albino rabbits, randomly divided into six groups, were used to study their ocular tolerance to (a) 0.25 and 0.50% Timoptol preserved with 0.01% benzalkonium chloride, (b) 0.25 and 0.50% Timoptol-LP, a gel-forming solution preserved with 0. 012% benzododecinium bromide, and (c) 0.25 and 0.50% Timabak unpreserved in the ABAK eyedrops dispenser. All eyedrops were applied in the right eye for 60 days. A clinical follow-up with slitlamp examination and break-up time evaluation was performed for 2 months. At the end of the experimentation, the animals were sacrificed and their eyes enucleated for histological analyses of the conjunctiva and cornea. There was no significant difference in the clinical examination between each group, except for the break-up time evaluation between Timoptol and Timabak at each concentration which was better with the unpreserved timolol. Histological results showed a significant difference in the corneal stroma edema between preserved and unpreserved timolol. This study confirms that using unpreserved timolol may be beneficial for the long-term treatment of glaucomatous patients as it increases tear film stability and decreases epithelial permeability and stromal aggression of the cornea.

Adrenergic beta-Antagonists↗

PubMed2003

Inhibition of neutrophil migration and oxygen free radical release by metipranolol and timolol.

Propanolol and metoprolol exert adrenoceptor-independent effects including scavenging of free radicals and inhibition of protein kinase C leading to inhibition of leukocyte migration and radical release as a consequence. Whether topically used metipranolol and timolol exert such effects is unknown. Neutrophil chemotaxis was tested using modified Boyden microchemotaxis chambers. Respiratory burst activity of neutrophils was detected fluorometrically. Radical scavenging properties were tested using 2',7'-dichlorofluorescein diacetate. Metipranolol and timolol inhibited neutrophil chemotaxis at doses in the micromolar range, oxygen free radical production triggered with formyl-Met-Leu-Phe was inhibited at higher concentration. Protein kinase C involvement, suggested to trigger free radical production with phorbol myristate acetate, was antagonized. A direct radical scavenging effect of the beta-blockers was also seen. Inhibition of neutrophil chemotaxis and free radical production is a novel mode of action of metipranolol and timolol that may be relevant for beneficial effects in the topical treatment of eye disease.

Adrenergic beta-Antagonists↗

PubMed1989

[Effect of carteolol and timolol eyedrops on the pressure tolerance of the optic nerve head].

In a planned, randomized, double blind study ocular perfusion pressures were measured before and after a 3-day regimen of 2% carteolol hydrochloride or 0.5% timolol maleate. A pressure tolerance test was also carried out. The results of this test revealed the critical pressure: it is the artificially increased intraocular pressure at which the visual function (monitored by visually evoked cortical potentials) is reduced to 20% of its initial value. The ocular perfusion pressures are affected by both drugs. They are more clearly reduced by carteolol than by timolol. The critical pressure is affected by both drugs too. After application of carteolol, the critical pressure is clearly lower than after application of timolol. The difference is statistically significant (p less than 0.05).

Adaptation, Physiological↗

PubMed1990

Pindolol and timolol: short-term influence on angioscotomas and static brightness contrast sensitivity.

In a double-masked, short-term study on 12 healthy elderly volunteers, angioscotomas and contrast sensitivities were measured 2 h after treatment with placebo, pindolol 1% and timolol 0.5%. In perimetry, angioscotomas did neither change in deepness nor in diameter significantly. However, the mean differential light sensitivity was highest with timolol (15.5 dB) and lower with pindolol (15.2 dB p less than 0.018) and placebo (15.0 dB; p less than 0.004). In contrast sensitivity testings, the mean contrast sensitivity was lowest with timolol (15.0 dB) and higher with pindolol (15.3 dB p less than 0.001) and placebo (15.7 dB; p less than 0.001). The differences between pindolol and placebo were not significant in both tests. The contrasting results may be explained by the locations where retinal sensitivity was tested, near or far from retinal vessels i.e. foveally or near the blind spot. Pharmacologically, the main difference between the two medications is the intrinsic sympathomimetic activity of pindolol.

Aged↗

PubMed1985

Systemic side effects associated with the ophthalmic administration of timolol.

Since the introduction of ophthalmic timolol solution in 1978 there have been numerous reports of systemic toxicity associated with its use. The majority of the systemic side effects reported are the same as those associated with oral timolol. Several cases of respiratory distress have been described generally in patients with underlying restrictive airway disease. Cardiovascular effects range from effects on resting pulse rate to the development of overt bradycardia and heart failure. Central nervous system effects reported include fatigue, confusion, depression, and hallucinations. A variety of other systemic effects have also been described. Caution should be used when ophthalmic timolol is administered to elderly patients or those patients with contraindications to systemic beta-blockers.

Absorption↗

PubMedDate not supplied

Effects of antiglaucoma drugs GLC756, a novel dopamine D2 agonist and D1 antagonist, and timolol on endotoxin-induced TNF-alpha release in serum of rats.

PURPOSE: Anti-inflammatory activity of an antiglaucoma drug may be an advantage for long-term treatment of glaucoma since it may reduce the risk of treatment-related inflammatory processes in outer compartments of the eye and probably also prevent or delay progression of glaucomatous retinal neurodegeneration. In this study, the effect of GLC756, a novel mixed dopamine D 2 receptor agonist and dopamine D 1 receptor antagonist, and timolol on endo-toxin-induced cytokine tumor necrosis factor-alpha (TNF-alpha) release in serum was examined. METHODS: For endotoxin-induced TNF-alpha release, 8-week-old Lewis rats were intravenously injected with 160 microg lipopolysaccharide (LPS) from Salmonella typhimurium. GLC756, timolol, or betamethasone were either systemically (1 mg/kg SC for 5 days) or topically (0.4%, 0.5%, and 0.1%, respectively, 20 microL eye drops given 16 times over 48 hours in left and right eye) administered. TNF-alpha was measured in serum 2 and 48 hours after LPS induction. RESULTS: A marked TNF-alpha increase in serum was found 2 hours after LPS induction. Administration of GLC756 and betamethasone, systemically and topically, decreased TNF-alpha release. However, due to large scattering of mean values only the effect of systemically administered GLC756 was statistically significant. In contrast, timolol increased TNF-alpha values stronger than LPS alone. CONCLUSIONS: The significant suppression of LPS-induced TNF-alpha increase by GLC756 suggests an additional anti-inflammatory potential of the dopaminergic compound in the treatment of glaucoma.

Animals↗