Influence Of Timolol Research Articles

Influence of timolol, benzalkonium-preserved timolol, and benzalkonium-preserved brimonidine on oxidative stress biomarkers in the tear film

Purpose The objective of this study was to investigate the influence of topical preservative-free timolol, benzalkonium chloride(BAC)-preserved timolol, BAC-preserved timolol, and BAC-preserved brimonidine on total protein concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response, and Oxidative Stress Index (OSI) in the tear film. Methods The patients were divided into four groups: group C (n = 25)—control group—subjects who did not use topical antiglaucoma medications, group T (n = 17)—patients using topical preservative-free timolol, group T + BAC (n = 24)—patients using topical BAC-preserved timolol, and group BR + BAC (n = 19)—patients using topical BAC-preserved brimonidine. Results The SOD, CAT, and GPx activities as well as AOPP, TOS, and OSI were found to be higher in the tear film of patients treated with BAC-preserved topical timolol or brimonidine in comparison with patients treated with preservative-free timolol or patients who did not use antiglaucoma topical medications. Conclusions This indicates that using BAC-preserved topical medications increases oxidative stress in the tear film and may, in the long-term, contribute to the clinical presentation of dry eye disease.

Does Long-Term Administration of a Beta-Blocker (Timolol) Induce Fibril-Based Cataract Formation In-vivo?

Timolol is a non-selective beta-adrenergic receptor antagonist administered for treating glaucoma, heart attacks and hypertension. In the present study, we set out to determine whether or not timolol can provoke cataract formation, thus the influence of timolol on the amyloid-type aggregation of crystallin was investigated. We then provided experimental evidence of crystallin aggregation and its induction by timolol using different spectroscopic measurements. Turbidimetric measurements as well as ThT fluorescence data indicated that timolol induce extent of crystallin amyloid formation. The kinetic of protein aggregation was also changed in presence of increasing concentrations of the drug suggesting that long-term drug administration may contribute to the development of cataract. Since the consequence of timolol-crystallin interaction has yet to be identified, additional data on it may help us to postpone amyloid cataract formation.

Association between low plasma levels of ophthalmic timolol and haemodynamics in glaucoma patients

The aims of the study were to assess the correlation between the plasma concentration of ophthalmic timolol and cardiovascular parameters, and the influence of timolol on advanced haemodynamic variables, such as stroke (SI), cardiac (CI) and systemic vascular resistance (SVRI) indices and arterial pulse wave velocity (PWV). Twenty-five glaucoma or ocular hypertensive patients were treated with 0.5% aqueous and 0.1% hydrogel formulations of timolol using a randomised, double-masked, crossover, multicentre design. All the patients were subjected to passive head-up tilt, electrocardiography, exercise test and measurement of plasma concentration of timolol. In the analysis, the data on the two treatments were combined, and the Spearman correlation coefficients between the plasma level of timolol and physiological effects were calculated. During the head-up tilt test before rising the bed up, the resting heart rate (HR; R=-0.52, P=0.001) and PWV (R=-0.34, P=0.04) were inversely correlated with timolol level. In the upright position, ophthalmic timolol effectively suppressed the rise in HR (R=-0.36, P=0.03). The SI did not change with timolol concentration, while CI diminished as timolol concentration rose (R=-0.39, P=0.02). The SVRI correlated with timolol concentration (R=0.38, P=0.02). In the exercise test, correlation between HR and plasma level of timolol steadily grew stronger as the load increased, reaching R=-0.60 (P<0.0001) at the maximum load. Systolic and diastolic arterial pressures were not associated with the timolol concentration. The plasma concentration of ophthalmic timolol correlates with several haemodynamic effects. As HR decreases, SVRI increases and blood pressure is kept unchanged.

The β-adrenoceptor antagonists metipranolol and timolol are retinal neuroprotectants: comparison with betaxolol

β-adrenoceptor antagonists are used clinically to reduce elevated intraocular pressure in glaucoma which is characterised by a loss of retinal ganglion cells. Previous studies have shown that the β 1-selective adrenoceptor antagonist, betaxolol, is additionally able to protect retinal neurones in vitro and ganglion cells in vivo from the detrimental effects of either ischemia-reperfusion or from excitotoxicity, after topical application. The neuroprotective effect of betaxolol is thought not to be elicited through an interaction with β-adrenoceptors, but by its ability to reduce influx of sodium and calcium through voltage-sensitive calcium and sodium channels. In the present study it is shown that the non-selective β-adrenoceptor antagonists, metipranolol and timolol behave like betaxolol. When topically applied they all attenuate the detrimental effect of ischemia-reperfusion. Protection of the retina was determined by evaluating changes in the electroretinogram and by assessing the loss of mRNA for Thy-1, which is expressed in retinal ganglion cells. In addition, studies conducted on neurones in mixed retinal cultures demonstrated that metipranolol, betaxolol and timolol were all able to partially counteract anoxia-induced cell loss and viability reduction. The influence of timolol was, however, not significant. Within the confines of these investigations, an order of neuroprotective efficacy was delineated for the three β-adrenoceptor antagonists: betaxolol>metipranolol>timolol. The ability of the β-adrenoceptor antagonists to attenuate ligand-induced stimulation of calcium and sodium entry into neuronal preparations showed a similar order of effectiveness. In conclusion, the ability to confer neuroprotection to retinal neurones is a common feature of three ophthalmic β-adrenoceptor antagonists (betaxolol, metipranolol and timolol). A comparison of the effectiveness of the individual compounds in protecting retinal cells in vivo was not possible in these studies. However, in vitro studies show that the capacity of the individual β-adrenoceptor antagonists to act as neuroprotectants appears to relate to their capacity to attenuate neuronal calcium and sodium influx.

Timolol and cornea

The influence of timolol on the corneal epithelium and endothelium was studied in organ culture. The cell morphology was not influenced by drug concentrations less than or equal to 690 micrograms/ml. Cell death was observed at 6900 micrograms/ml. Endothelial cell proliferation after an experimental injury was slowed down at a drug concentration of 690 micrograms/ml. Injurious effects were not observed at the drug concentrations found in the aqueous humour by use of ophthalmic eye solution in eyes with a normal cornea. However, it may be indicated to use eye drops with reduced concentration of timolol in conditions facilitating the resorbtion of the drug.