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      Effects of Latanoprost and Betaxolol on Cardiovascular and Respiratory Status of Newly Diagnosed Glaucoma Patients

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          Aims: To investigate the cardiovascular and respiratory effects of topical latanoprost 0.005% and topical betaxolol 0.25% monotherapy in newly diagnosed glaucoma patients. Methods: Fortynewly diagnosed glaucoma patients were enrolled in this prospective, observer-masked, randomized, parallel study. Patients received either latanoprost 0.005% or betaxolol 0.25% for a duration of 3 months. Baseline evaluation included intraocular pressure (IOP) measurement and cardiorespiratory examinations including pulse rate, systolic and diastolic blood pressure measurements and spirometry. These measurements were repeated after 3 months. Results: Both latanoprost and betaxolol reduced IOP significantly (p = 0.001). After 3 months of therapy, the mean pulse rate, systolic and diastolic blood pressure values of the betaxolol group were reduced (p = 0.027, p = 0.07 and p = 0.016, respectively). No significant changes occurred in the cardiovascular measurements of the latanoprost group (p > 0.05). There were no significant changes in any of the spirometric measurements tested for both groups (p > 0.05). Conclusion: Both latanoprost and betaxolol are safe concerning respiratory functions. Betaxolol may cause small changes in the cardiovascular system, suggesting that blood pressure and pulse rates should be checked before and in regular intervals after prescribing it for the elderly. Latanoprost seems to be a safe medication in view of absence of systemic cardiovascular and respiratory side effects.

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          Most cited references 17

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          Ocular and systemic pharmacokinetics of latanoprost in humans.

          The ocular pharmacokinetics of latanoprost (13,14-dihydro-17-phenyl-18, 19,20-trinor-PGF(2alpha)-isopropyl ester; Xalatan [Pharmacia-Upjohn, Peapack, NJ]) was studied in patients undergoing cataract surgery using radio-immunoassay, and the systemic pharmacokinetics of latanoprost was studied in healthy human volunteers with 3H-latanoprost as well as radioimmunoassay. After topical application, latanoprost was rapidly hydrolysed in the cornea and blood. The maximum concentration of the active drug, latanoprost acid, was detected in the aqueous humor 1-2 hours after topical administration of the clinical dose and amounted to 15-30 ng/ml. The half-life of latanoprost acid in the aqueous humor was 2-3 hours. In the systemic circulation the peak concentration of latanoprost acid appeared 5 minutes after topical application and reached a level of 53 pg/ml with an elimination half-life of 17 minutes. In patients that had been on the drug continuously for more than 1 year, 5 out of 10 had plasma levels of latanoprost acid below the limit of detection (<30 pg/ml). The mean plasma clearance was 0.40 +/- 0.04 l/h. kg, and the volume of distribution was 0.16 +/- 0.02 l/kg after intravenous administration. The corresponding figures after ocular administration were 0.88 l/h. kg, and 0.36 l/kg. The majority of the radioactivity was recovered in urine (88%) and the rest was found in feces. In the eye the main metabolism of latanoprost was the ester hydrolysis. The only prominent chromatographic peak in plasma corresponded to latanoprost acid. In urine no latanoprost or latanoprost acid was detected. Before excretion latanoprost acid was beta oxidized to 1,2-dinor and 1,2,3,4-tetranor latanoprost acid. These metabolites accounted for approximately 66% of the radioactivity in urine. In conclusion, latanoprost is rapidly hydrolyzed in the eye and blood to latanoprost acid. Minimal further metabolism occurs in the eye, but latanoprost acid undergoes beta oxidation and other metabolism outside the eye. After topical application the peak concentration in aqueous humor was approximately 10(-7) M, whereas that in plasma was about 10(-10) M or less.
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            Reduced subjective awareness of bronchoconstriction provoked by methacholine in elderly asthmatic and normal subjects as measured on a simple awareness scale.

            Asthma death rates are rising, with the greatest rise and highest death rates in old age. A reduced cardiovascular response in the elderly may lead to the underestimation by physicians of the severity of acute asthma attacks. This would be compounded if elderly patients had reduced awareness of bronchoconstriction. Methacholine provoked bronchoconstriction was compared in 34 elderly (17 asthmatic, 17 normal; age 60-83, mean 68 years) and 33 young subjects (16 asthmatic, 17 normal; 20-46, mean 30 years). None were smokers. All underwent inhaled methacholine challenge by the Newcastle dosimeter method, monitored by maximal expiratory flow-volume loops (MEFVL). The endpoints were a 35% fall in forced expiratory flow at 50% vital capacity or cumulative inhalation of 6.4 mg methacholine. The one second forced expiratory volume (FEV1) was derived from MEFVL. After challenge and before bronchodilatation subjects graded awareness of respiratory discomfort from 1 (no symptoms) to 4 (pronounced symptoms needing immediate treatment). Despite a greater fall in FEV1 in elderly asthmatic patients (mean (SE) 27.4% (2.2%)) than in young asthmatic patients (21.5% (1.7%)) elderly patients were less aware of bronchoconstriction (awareness score 2.00 (SE 0.15) than young patients (3.06 (0.11)). Similar differences in awareness score were seen between elderly normal subjects (1.53 (0.17)) and young normal subjects (2.76 (0.22)), despite no difference in degree of bronchoconstriction. Reduced awareness of moderate acute bronchoconstriction in old age may delay self referral in acute asthma and contribute to higher asthma mortality in the elderly.
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              Effects of glaucoma medications on the cardiorespiratory and intraocular pressure status of newly diagnosed glaucoma patients.

              To evaluate the short term cardiovascular, respiratory, and intraocular pressure (IOP) effects of four glaucoma medications in newly diagnosed glaucoma patients. 141 newly diagnosed glaucoma patients were recruited and underwent a full ocular, cardiovascular, and respiratory examination, including an electrocardiogram (ECG) and spirometry. They were prescribed one of four topical glaucoma medications and reviewed 3 months later. One eye of each patient was randomly chosen for analysis, performed using analysis of variance and the chi(2) test. Latanoprost had the greatest mean IOP lowering effect in both the primary open angle glaucoma (POAG) (p = 0.005) and the "presumed" normal tension glaucoma (NTG) groups (p = 0.33), reducing the IOP by 8.9 mm Hg and 4.1 mm Hg respectively. Timolol was associated with lowered pulse rates and reductions in the spirometry measurements. 41% of patients using brimonidine complained of systemic side effects and over 55% of patients using betaxolol complained of ocular irritation. 28% of patients required an alteration in their glaucoma management. Latanoprost appears to be a useful primary treatment for glaucoma patients, in view of superior IOP control and a low incidence of local and systemic side effects. Timolol causes a reduction in measurements of respiratory function, a concern in view of the potential subclinical reversible airways disease in the elderly glaucoma population. Brimonidine is associated with substantial, unpredictable systemic side effects and betaxolol causes ocular irritation and weak IOP control. Spirometry is advised in all patients receiving topical beta blocker therapy to control their glaucoma.

                Author and article information

                S. Karger AG
                September 2006
                07 September 2006
                : 220
                : 5
                : 332-337
                aDepartment of Ophthalmology, and bDepartment of Chest Diseases, Celal Bayar University School of Medicine, Manisa, Turkey
                94625 Ophthalmologica 2006;220:332–337
                © 2006 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 4, References: 24, Pages: 6
                Original Paper


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