Wirkmechanismen, klinisches Profil und Stellenwert von Betablockern in der antiglaukomatösen Therapie

Zusammenfassung

Die Beta(rezeptoren)blocker sind eine der wichtigsten Substanzklassen in der medikamentösen Glaukomtherapie. Ihre Vorteile liegen in einer guten Wirksamkeit bei primären und sekundären Glaukomen, Abstufungen in der Dosierung, jahrzehntelanger klinischer Erfahrung, guter Kombinierbarkeit mit anderen Substanzen, und geringen Kosten. Timolol ist das am häufigsten in fixen Kombinationspräparaten verwendete Glaukommittel. Topisch eingesetzte Betablocker dürften auf der anderen Seite die Glaukommittel mit der potenziell höchsten systemischen Nebenwirkungsrate sein und gehen auch nicht selten Wechselwirkungen mit anderen systemisch eingesetzten Arzneimitteln ein.

Abstract

Beta-blockers are among the most important groups of drugs for glaucoma therapy. The advantages of beta-blockers are a good efficacy in primary and secondary types of glaucoma, different dosages, clinical experiences over decades, easy use in combination with all other glaucoma drugs, and low costs. Timolol is the most frequently used drug in fixed glaucoma medications. In comparison with other glaucoma drugs, beta-blockers have the most severe systemic side effects and may interact with other systemic medication.

Schlüsselwörter

Glaukom - Pharmakologie - Biochemie

Key words

glaucoma - pharmacology - biochemistry

• Literatur

• 1 Goel M, Picciani RG, Lee RK et al. Aqueous humor dynamics: A review. Open Ophthalmol J 2010; 4: 52-59
• 2 Yamaguchi Y, Watanabe T, Hirakata A et al. Localisation and ontogeny of aquaporin-1 and -4 expression in iris and ciliary epithelial cells in rats. Cell Tissue Res 2006; 325: 101-109
• 3 Taniguchi T, Kitazawa Y. The potential systemic effect of topically applied beta-blockers in glaucoma therapy. Curr Opin Ophthalmol 1997; 8: 55-58
• 4 Volotinen M, Hakkola J, Pelkonen O et al. Metabolism of ophthalmic timolol: new aspects of an old drug. Basic Clin Pharmacol Toxicol 2011; 108: 297-303
• 5 Van der Valck R, Webers CA, Schouten JS et al. Intraocular lowering-effects of all commonly used glaucoma drugs. A meta-analysis of randomized clinical trials. Ophthalmology 2005; 112: 1177-1185
• 6 Cheng J-W, Cai J-P, Wie R-L. Meta-analysis of medical intervention for normal tension glaucoma. Ophthalmology 2009; 116: 1243-1249
• 7 Hejl A, Strahlman E, Sverrisson T et al. A comparison of dorzolamide and timolol in patients with pseudoexfoliation and glaucoma or ocular hypertension. Ophthalmology 1997; 104: 137-142
• 8 Konstas AG, Maltezos A, Bufidis T et al. Twenty-four hour control of intraocular pressure with dorzolamide and timolol maleate in exfoliation and primary open-angle glaucoma. Eye (Lond) 2000; 14: 73-77
• 9 Konstas AG, Mantziris DA, Cate EA et al. Effect of timolol on the diurnal intraocular pressure in exfoliation and primary open-angle glaucoma. Arch Ophthalmol 1997; 115: 975-979
• 10 Konstas AG, Mylopoulos N, Karabatsas CH et al. Diurnal intraocular pressure reduction with latanoprost 0.005 % compared to timolol maleate 0.5 % as monotherapy in subjects with exfoliation glaucoma. Eye (Lond) 2004; 18: 893-899
• 11 Hatanaka M, Grigera DE, Barbosa WL et al. An eight-week, multicentric, randomized, interventional, open-label, phase 4, parallel comparison of the efficacy and tolerability of the fixed combination of timolol maleate 0.5 %/brimonidine tartate 0.2 % versus fixed combination of timolol maleate 0.5 %/dorzolamide 2 % in patients with elevated intraocular pressure. J Glaucoma 2008; 17: 674-679
• 12 Yüksel N, Gök M, Altintas O et al. Diurnal intraocular pressure efficacy of the timolol-brimonidine fixed combination and the timolol-dorzolamide fixed combination as a first choice of therapy in patients with pseudoexfoliation glaucoma. Curr Eye Res 2011; 36: 804-808
• 13 Aptel F, Cucherat M, Denis P. Efficacy and tolerability of prostaglandin-timolol fixed combinations: a metaanalysis of randomized clinical trials. Eur J Ophthalmol 2012; 22: 5-18
• 14 Webers CA, Beckers HJ, Zeegers MP et al. The intraocular pressure-lowering effect of prostaglandin analogs combined with topical β-blocker therapy: a systematic review and meta-analysis. Ophthalmology 2010; 117: 2067-2074
• 15 Inoue K, Okayama R, Higa R et al. Ocular hypotensive effects and safety over 3 months of switching from an unfixed combination to latanoprost 0.005 %/timolol maleate 0.5 % fixed combination. J Ocul Pharmacol Ther 2011; 27: 581-587
• 16 Inoue K, Okayama R, Higa R et al. Assessment of ocular hypotensive effect and safety 12 months after changing from an unfixed combination to a latanoprost 0.005 % + timolol maleate 0.5 % fixed combination. Clin Ophthalmol 2012; 6: 607-612
• 17 Salim S, Shields MB. Glaucoma and systemic diseases. Surv Ophthalmol 2010; 55: 64-77
• 18 Schuman JS. Effects of systemic beta-blocker therapy on the efficacy and safety of topical brimonidine and timolol. Brimonidine Study Group 1 and 2. Ophthalmology 2000; 107: 1171-1177
• 19 Tattersall C, Vernon S, Singh R. Resting pulse rates in a glaucoma clinic: the effect of topical and systemic betablocker usage. Eye 2006; 20: 221-225
• 20 Mielke J. Intraokularer Druck. In: Schlote T, Kellner U. Unerwünschte Arzneimittelwirkungen in der Augenheilkunde. Stuttgart: Thieme Verlag; 2011: 83
• 21 Beckers HJ, Schouten JS, Webers CA et al. Side effects of commonly used glaucoma medications: comparison of tolerability, chance of discontinuation, and patient satisfaction. Graefes Arch Clin Exp Ophthalmol 2008; 246: 1485-1490
• 22 Erb C, Gast U, Schremmer D. German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin Exp Ophthalmol 2008; 246: 1593-1601
• 23 Baudouin C, Liang H, Hamard P et al. The ocular surface of glaucoma patients treated over the long term expresses inflammatory markers related to both T-Helper 1 and T-Helper 2 pathways. Ophthalmology 2008; 115: 109-115
• 24 Berstein LP, Henkind P. Additional information on adverse reactions to timolol. Am J Ophthalmol 1981; 92: 295-296
• 25 Höh H. Lokalanästhetische Wirkung und subjektive Verträglichkeit von Carteolol 2 % und Metipranolol 0,6 % bei Augengesunden. Klin Monatsbl Augenheilkd 1989; 194: 241-248
• 26 Akingbehin T, Villada J. Metipranolol-associated granulomatous anterior uveitis. Br J Ophthalmol 1991; 75: 519-523
• 27 Thorne J, Anhalt GJ, Jabs DA. Mucous membrane pemphigoid and pseudopemphigoid. Ophthalmology 2004; 111: 45-52
• 28 Lama PJ. Systemic adverse effects of beta-adrenergic blockers: an evidence-based assessment. Am J Ophthalmol 2002; 134: 749-760
• 29 Vander Zanden JA, Valuck RJ, Bunch CL et al. Systemic adverse effects of ophthalmic beta-blockers. Ann Pharmacother 2001; 35: 1633-1637
• 30 Ramdas WD, van der Velde N, van der Cammen TF et al. Evaluation of risk of falls and orthostatic hypotension in older long-term topical beta-blocker users. Graefes Arch Clin Exp Ophthalmol 2009; 247: 1235-1241
• 31 Müskens RP, Wolfs RC, Witteman JC et al. Topical beta-blockers and mortality. Ophthalmology 2008; 115: 2037-2043
• 32 Silverstone BZ, Marcus T. Hypoglycemia due to ophthalmic timolol in a diabetic. Harefuah 1990; 118: 693-694
• 33 Gerber SL, Cantor LB. Systemic side effects and interactions of glaucoma medications. In: Albert DM, Jakobiec FA, eds. Principles and practice of ophthalmology. 2nd ed. Philadelphia, PA: WB Saunders; 2000: 2916-2930
• 34 Gottfredsdottir MS, Allingham R, Shields MB. Physiciansʼ guide to interactions between glaucoma and systemic medications. J Glaucoma 1997; 6: 377-383
• 35 Lazarov A, Amichai B. Skin reactions due to eye drops: report of two cases. Cutis 1996; 58: 363-364