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Ceska a Slovenska Oftalmologie :... 2020The paper presents the up-to-date overview of pathogenesis, functional and structural changes in normotensive glaucoma (NTG) and its differences from hypertensive... (Review)
Review
The paper presents the up-to-date overview of pathogenesis, functional and structural changes in normotensive glaucoma (NTG) and its differences from hypertensive glaucoma (HTG). The autors point out new facts that distinguish both diagnostic groups. In the first place are the results of OCT angiography, which verify the pathology of NTG to the anterior part of optic nerve. Our findings confirmed that vascular component (VD) is more involved in changes of visual field than in perfusion parameters, especially in arteria ophtalmica (AO). Perfusion in arteria centralis retinae (ACR) does not play a significant role in NTG changes in the visual field. VD has very little effect on changes in visual field in HTG. Similarly, the retinal nerve fiber layer (RNFL) for changes in the visual field. Howerver, VD is moderately influenced by changes in RNFL. It should be emphasized that we compared the sum of sensitivity in the central part of the visual field (0-22 degrees) with RNFL and VD. In NTG, the anterior part of the optic nerve is altered. Mainly VD contributes to visual filed changes in NTG. It is also important to note that when the intraocular pressure (IOP) increased above 20 mm Hg, the macular and papillary VD was significantly reduced. Antiglaucomatous treatment with prostaglandins and beta-blockers is essential for the reduction of IOP in HTG. This reduction shoud be bellow 20 mm Hg, in eyes with thinner cornea the decrease in IOP should be more pronounced. It does not matter which antiglaucoma treatment was used. However, it should be noted that prostaglandins have a greater effect on disease progression, but the greater protective effect on the visual field have beta-blockers. Neuroprotectives should be recommended systemically in patients with HTG. When treating NTG, it is important to maintain blood flow of the posterior pole of the eye, but mainly of the anterior part of the optic nerve. Prostaglandins are not suitable in NTG patients, although their effect on IOL reduction is high. Beta-blockers (betaxolol and carteol) and brimonidine are most suitable. Corneal thickness has no effect on disease progression.
Topics: Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Optic Disk; Tomography, Optical Coherence; Visual Field Tests
PubMed: 33499643
DOI: 10.31348/2020/31 -
Ceska a Slovenska Oftalmologie :... 2020The purpose of the study was to evaluate influence of betaxolol, brimonidine and carteolol in the progression of the visual field defects during time at patients with...
PURPOSE
The purpose of the study was to evaluate influence of betaxolol, brimonidine and carteolol in the progression of the visual field defects during time at patients with normotensive glaucoma (NTG).
MATERIALS AND METHODS
This study included (60 eyes of) 30 patients with NTG. First group consisted of 20 eyes of 10 patients of the average age of 58.5 years, who were treated by betaxolol. Second group also consisted of 20 eyes of 10 patients of the average age of 62.6 years and they were treated by brimonidine. Third group had the same count of the eyes and patients, the average age was 61.1 years and these patients were treated by carteolol. Diagnose of NTG was based on the comprehensive ophthalmological examination including electroretinography and visual evoked potentials. Visual fields were examined by fast threshold glaucoma test using Medmont M700 device. We compared pattern defect (PD) in the visual field for 3 years. The including criteria were: similar visual field findings at the beginning of the study, stable eye therapy (treatment was not changed during the study), uncorrected or best corrected (up to +-3 D) visual acuity of 1,0 of ETDRS, intraocular pressure between 10-15 mm Hg, if present, then compensated cardiovascular disease, no other internal or neurological disorders.
RESULTS
We didnt notice any statistically important difference of PD. The study revealed that brimonidin (p=0,99) and betaxolol (p = 0,81) had the best effect.
CONCLUSION
Local therapy of betaxolol, brimonidine and carteolol has an essential clinical value in normotensive glaucoma. All the mentioned treatments had a protective effect on the visual field. However, local side-effects of brimonidinu are a question.
Topics: Betaxolol; Carteolol; Evoked Potentials, Visual; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Middle Aged
PubMed: 33126804
DOI: 10.31348/2020/17 -
Cardiology Journal 2020Early detection and management of elevated blood pressure is crucial in reducing the burden of cardiovascular disease (CVD). The importance of an absolute risk... (Review)
Review
Early detection and management of elevated blood pressure is crucial in reducing the burden of cardiovascular disease (CVD). The importance of an absolute risk assessment and patient risk stratification has been highlighted in the European hypertension guidelines since 2003. Amongst numerous risk factors influencing patient prognosis, elevated heart rate (HR) has been indicated as important predictor of future risk of hypertension, coronary heart disease, sudden cardiac death, heart failure, CVD, stroke, total cancer and mortality. Given that resting HR can be easily determined in clinical practice and modified by lifestyle changes as well as beta-blocker therapy, it seems reasonable that lowering resting HR should be a potential target to reduce disease burden and premature mortality. However, there is a lack of outcome studies of HR lowering in tachycardia-related hypertension. This review outlines the underlying mechanisms of early course hypertension pathophysiology with the critical role of the sympathetic nervous system activation, the prognostic significance of fast HR and the mechanistic rationale for the use of non-pharmacological approaches and/or highly long-acting cardioselective beta-blockers with some consideration given to betaxolol properties.
Topics: Cardiovascular Diseases; Heart Disease Risk Factors; Humans; Hypertension; Risk Factors; Tachycardia
PubMed: 30799548
DOI: 10.5603/CJ.a2019.0021 -
Experimental Eye Research Nov 2021Our study aims to determine whether the beta-adrenergic system is involved in the regulation of lymphatic drainage from the eye. For this purpose, we assessed the effect...
Our study aims to determine whether the beta-adrenergic system is involved in the regulation of lymphatic drainage from the eye. For this purpose, we assessed the effect of 2 topical beta-adrenergic blockers, timolol and betaxolol, commonly used as glaucoma drugs, on lymphatic clearance of albumin from the aqueous humor to neck lymph nodes. Adult mice were treated with either topical timolol, a non-selective β-blocker, 0.5% (n = 8), or topical betaxolol, a selective β-adrenergic blocker, 0.5% (n = 6) twice daily for 14 days and compared to respective control groups (n = 5 and n = 7). Changes in lymphatic clearance from the eye were assessed using a quantitative in vivo photoacoustic imaging approach. In all subjects, right eye and neck lymph nodes were longitudinally assessed by sequential photoacoustic imaging just prior to near-infrared dye injection into the anterior chamber of the eye, and 20 min, 2 and 4 h after injection. Repeat measurements of mean pixel intensities (MPIs) of right eyes and nodes were performed at all timepoints. The areas under the curves (AUC) were calculated and the AUC of the treated-group was compared to that of controls using the Mann-Whitney U test. The slopes of MPI of each region of interest over time were compared using the linear mixed model after adjusting for IOP decrease after treatment and other parameters such as sex and body weight. In the timolol-treated group, right neck nodes showed significant decrease in AUC signal intensity compared with controls (P = 0.003), and significant decrease in slope of MPI compared with controls (P = 0.0025). In the betaxolol-treated group, right neck nodes showed significant decrease in AUC signal intensity compared with controls (P = 0.02), and significant decrease in slope of MPI compared with controls (P = 0.0069). Topical treatment with timolol and betaxolol reduced lymphatic clearance of albumin from the aqueous humor to the neck lymph nodes. This finding may be relevant for the management of secondary glaucomas and inflammatory eye disease in which the clearance of accumulated proteins and antigen from the eye is important to disease recovery and sight protection. This study suggests that the beta-adrenergic system plays a role in the regulation of lymphatic clearance from the eye.
Topics: Administration, Topical; Adrenergic beta-Antagonists; Animals; Aqueous Humor; Disease Models, Animal; Female; Glaucoma; Intraocular Pressure; Lymphatic Vessels; Male; Mice; Photoacoustic Techniques; Timolol
PubMed: 34599970
DOI: 10.1016/j.exer.2021.108775 -
Molecular Pharmaceutics Feb 2020The mechanisms of drug clearance from the aqueous humor are poorly defined. In this study, a cocktail approach was used to simultaneously determine the pharmacokinetics...
The mechanisms of drug clearance from the aqueous humor are poorly defined. In this study, a cocktail approach was used to simultaneously determine the pharmacokinetics of three β-blocker agents after intracameral (ic) injection into the rabbit eyes. Aqueous humor samples were collected and analyzed using LC-MS/MS to determine drug concentrations. Pharmacokinetic parameters were obtained using a compartmental fitting approach, and the estimated clearance, volume of distribution, and half-life values were the following: atenolol (6.44 μL/min, 687 μL, and 73.87 min), timolol (19.30 μL/min, 937 μL, and 33.64 min), and betaxolol (32.20 μL/min, 1421 μL, and 30.58 min). Increased compound lipophilicity (atenolol < timolol < betaxolol) resulted in higher clearance and volume of distributions in the aqueous humor. Clearance of timolol and betaxolol is about 10 times higher than the aqueous humor outflow, demonstrating the importance of other elimination routes (e.g., uptake to iris and ciliary body and subsequent elimination via blood flow).
Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Aqueous Humor; Atenolol; Betaxolol; Chromatography, Liquid; Drug Combinations; Half-Life; Injections, Intraocular; Intraocular Pressure; Male; Metabolic Clearance Rate; Rabbits; Tandem Mass Spectrometry; Timolol; Tissue Distribution
PubMed: 31794668
DOI: 10.1021/acs.molpharmaceut.9b01024 -
European Journal of Pharmaceutics and... Sep 2021Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in...
Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in silico models to be developed. To this end, a topical cocktail of betaxolol, timolol and atenolol was instilled on albino rabbit eyes. Tear fluid, corneal epithelium, corneal stroma with endothelium, bulbar conjunctiva, anterior sclera, iris-ciliary body, lens and vitreous samples were collected and analysed using LC-MS/MS. Iris-ciliary body was also analysed after intracameral cocktail injection. Non-compartmental analysis was utilized to estimate the pharmacokinetics parameters. The most lipophilic drug, betaxolol, presented the highest exposure in all tissues except for tear fluid after topical administration, followed by timolol and atenolol. For all drugs, iris-ciliary body concentrations were higher than that of the aqueous humor. After topical instillation the most hydrophilic drug, atenolol, had 3.7 times higher AUC than AUC, whereas the difference was 1.4 and 1.6 times for timolol and betaxolol, respectively. This suggests that the non-corneal route (conjunctival-scleral) was dominating the absorption of atenolol, while the corneal route was more important for timolol and betaxolol. The presented data increase understanding of ocular pharmacokinetics of a cocktail of drugs and provide data that can be used for quantitative modeling and simulation.
Topics: Administration, Ophthalmic; Animals; Aqueous Humor; Atenolol; Betaxolol; Biological Availability; Drug Combinations; Ophthalmic Solutions; Outcome Assessment, Health Care; Rabbits; Solubility; Tears; Timolol; Tissue Distribution
PubMed: 34139290
DOI: 10.1016/j.ejpb.2021.06.003 -
European Journal of Pharmaceutical... Dec 2020Ocular bioavailability after eye drops administration is an important, but rarely determined, pharmacokinetic parameter. In this study, we measured the pharmacokinetics...
Ocular bioavailability after eye drops administration is an important, but rarely determined, pharmacokinetic parameter. In this study, we measured the pharmacokinetics of a cocktail of three beta blockers after their topical administration into the albino rabbit eye. Samples from aqueous humour were analysed with LC-MS/MS. The pharmacokinetic parameters were estimated using compartmental and non-compartmental analyses. The ocular bioavailability was covering broad range of values: atenolol (0.07 %), timolol (1.22%, 1.51%) and betaxolol (3.82%, 4.31%). Absolute ocular bioavailability presented a positive trend with lipophilicity and the values showed approximately 60-fold range. The generated data enhances our understanding for ocular pharmacokinetics of drugs and may be utilized in pharmacokinetic model building in ophthalmic drug development.
Topics: Administration, Topical; Adrenergic beta-Antagonists; Animals; Atenolol; Betaxolol; Biological Availability; Chromatography, Liquid; Ophthalmic Solutions; Rabbits; Tandem Mass Spectrometry; Timolol
PubMed: 32946960
DOI: 10.1016/j.ejps.2020.105553