Download PDF
Klin Monbl Augenheilkd 2013; 230(2): 146-149
DOI: 10.1055/s-0032-1328163
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

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

Mode of Action, Clinical Profile and Relevance of Carbonic Anhydrase Inhibitors in Glaucoma Therapy
M. Eichhorn
Institut für Anatomie – LS II, Universität Erlangen-Nürnberg
› Author Affiliations
Further Information

Publication History

eingereicht 10 December 2012

akzeptiert 20 December 2012

Publication Date:
21 February 2013 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die lokalen Carboanhydrasehemmer (CAH) Dorzolamid und Brinzolamid haben sich seit ihrer Einführung fest in der medikamentösen Therapie des Glaukoms etabliert. Ihre drucksenkende Wirkung beruht auf der spezifischen Hemmung der Carboanhydrase im Ziliarepithel und der damit einhergehenden Reduktion der Kammerwasserbildung. Ihre Wirkung ist mit der von Betablockern vergleichbar, aber geringer als die von Prostaglandinanaloga. Aufgrund ihres spezifischen Wirkmechanismus erzielen sie mit allen anderen Klassen von Glaukommedikationen einen additiven drucksenkenden Effekt und eignen sich daher besonders gut für Kombinationstherapien. Zusätzlich gibt es Hinweise, dass CAH die Durchblutung im hinteren Auge verbessern. Erste Befunde an Glaukompatienten, dass Dorzolamid die Perfusion verbessert und damit das Progressionsrisiko senkt, bedürfen einer weiteren Bestätigung.

Abstract

Since their introduction the local carbonic anhydrase inhibitors (CAH) dorzolamide and brinzolamide have become well established in the drug therapy of glaucoma. They lower intraocular pressure (IOP) by blocking specifically carbonic anhydrase in the ciliary epithelium and thereby the secretion of aqueous humor. The IOP lowering effect is comparable with that of beta-blockers, but less than that of prostaglandin agonists. Because of their specific mode of action they produce an additive pressure lowering effect with any other glaucoma drug. Therefore they are ideal for being combined with other drugs. In addition, CAH may improve perfusion of the posterior eye. Preliminary results in glaucoma patients under dorzolamide therapy suggesting a reduction in the risk of progression due to enhanced blood flow need further confirmation.

Schlüsselwörter

Glaukom - Pharmakologie - Carboanhydrase - Dorzolamid - Brinzolamid

Key words

glaucoma - pharmacology - carbonic anhydrase - dorzolamide - brinzolamide
 

  • Literatur

  • 1 Becker B. Decrease in intraocular pressure in man by a carbonic anhydrase inhibitor, diamox; a preliminary report. Am J Ophthalmol 1954; 37: 13-15
    PubMedSearch in Google Scholar
  • 2 Pfeiffer N. Dorzolamide: development and clinical application of a topical carbonic anhydrase inhibitor. Surv Ophthalmol 1997; 42: 137-151
    CrossrefPubMedSearch in Google Scholar
  • 3 Talluto DM, Wyse TB, Krupin T. Topical carbonic anhydrase inhibitors. Curr Opin Ophthalmol 1997; 8: 2-6
    PubMedSearch in Google Scholar
  • 4 Herkel U, Pfeiffer N. Update on topical carbonic anhydrase inhibitors. Curr Opin Ophthalmol 2001; 12: 88-93
    CrossrefPubMedSearch in Google Scholar
  • 5 Lütjen-Drecoll E, Lönnerholm G, Eichhorn M. Carbonic anhydrase distribution in the human and monkey eye by light and electron microscopy. Graefes Arch Clin Exp Ophthalmol 1983; 220: 285-291
    CrossrefPubMedSearch in Google Scholar
  • 6 Eichhorn M, Lütjen-Drecoll E. Vorkommen und funktionelle Bedeutung der Carboanhydrase in den Gefäßendothelien. Med Welt 1985; 36: 679-702
    PubMedSearch in Google Scholar
  • 7 Ingram CJ, Brubaker RF. Effect of brinzolamide and dorzolamide on aqueous humor flow in human eyes. Am J Ophthalmol 1999; 128: 292-296
    CrossrefPubMedSearch in Google Scholar
  • 8 Wayman L, Larsson LI, Maus T et al. Comparison of dorzolamide and timolol as suppressors of aqueous humor flow in humans. Arch Ophthalmol 1997; 115: 1368-1371
    CrossrefPubMedSearch in Google Scholar
  • 9 Matsui H, Murakami M, Wynns GC et al. Membrane carbonic anhydrase (IV) and ciliary epithelium. Carbonic anhydrase activity is present in the basolateral membranes of the non-pigmented ciliary epithelium of rabbit eyes. Exp Eye Res 1996; 62: 409-417
    CrossrefPubMedSearch in Google Scholar
  • 10 Helbig H, Korbmacher C, Erb C et al. Coupling of 22Na and 36Cl uptake in cultured pigmented ciliary epithelial cells: a proposed role for the isoenzymes of carbonic anhydrase. Curr Eye Res 1989; 8: 1111-1119
    CrossrefPubMedSearch in Google Scholar
  • 11 Sugrue MF, Waheed A, Sly WS. A study of the in-vitro inhibition of human carbonic anhydrase inhibitor isoenzymes I, II and IV. Invest Ophthalmol 1993; 34: 930
    PubMedSearch in Google Scholar
  • 12 Martens-Lobenhoffer J, Banditt P. Clinical pharmacokinetics of dorzolamide. Clin Pharmacokinet 2002; 41: 197-205
    CrossrefPubMedSearch in Google Scholar
  • 13 Sugrue MF. The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor. J Ocul Pharmacol Ther 1996; 12: 363-376
    CrossrefPubMedSearch in Google Scholar
  • 14 Stefansson E, Jensen PK, Eysteinsson T et al. Optic nerve oxygen tension in pigs and the effect of carbonic anhydrase inhibitors. Invest Ophthalmol Vis Sci 1999; 40: 2756-2761
    PubMedSearch in Google Scholar
  • 15 Rassam SM, Patel V, Kohner EM. The effect of acetazolamide on the retinal circulation. Eye 1993; 7: 697-702
    CrossrefPubMedSearch in Google Scholar
  • 16 Kiss B, Dallinger S, Findl O et al. Acetazolamide-induced cerebral and ocular vasodilation in humans is independent of nitric oxide. Am J Physiol 1999; 276: R1661-R1667
    PubMedSearch in Google Scholar
  • 17 Reber F, Gersch U, Funk RW. Blockers of carbonic anhydrase can cause increase of retinal capillary diameter, decrease of extracellular and increase of intracellular pH in rat retinal organ culture. Graefes Arch Clin Exp Ophthalmol 2003; 241: 140-148
    CrossrefPubMedSearch in Google Scholar
  • 18 Torring MS, Holmgaard K, Hessellund A et al. The vasodilating effect of acetazolamide and dorzolamide involves mechanisms other than carbonic anhydrase inhibition. Invest Ophthalmol Vis Sci 2009; 50: 345-351
    PubMedSearch in Google Scholar
  • 19 Sugrue MF. Pharmacological and ocular hypotensive properties of topical carbonic anhydrase inhibitors. Prog Retin Eye Res 2000; 19: 87-112
    CrossrefPubMedSearch in Google Scholar
  • 20 Boyle JE, Ghosh K, Gieser DK et al. A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide. Dorzolamide-Timolol Study Group. Ophthalmology 1998; 105: 1945-1951
    CrossrefPubMedSearch in Google Scholar
  • 21 Clineschmidt CM, Williams RD, Snyder E et al. A randomized trial in patients inadequately controlled with timolol alone comparing the dorzolamide-timolol combination to monotherapy with timolol or dorzolamide. Dorzolamide-Timolol Combination Study Group. Ophthalmology 1998; 105: 1952-1959
    CrossrefPubMedSearch in Google Scholar
  • 22 Francis BA, Du LT, Berke S et al. Comparing the fixed combination dorzolamide-timolol (Cosopt) to concomitant administration of 2 % dorzolamide (Trusopt) and 0.5 % timolol – a randomized controlled trial and a replacement study. J Clin Pharm Ther 2004; 29: 375-380
    CrossrefPubMedSearch in Google Scholar
  • 23 Bell NP, Ramos JL, Feldman RM. Safety, tolerability, and efficacy of fixed combination therapy with dorzolamide hydrochloride 2 % and timolol maleate 0.5 % in glaucoma and ocular hypertension. Clin Ophthalmol 2010; 4: 1331-1346
    PubMedSearch in Google Scholar
  • 24 Ichhpujani P, Katz LJ. Efficacy, safety and tolerability of combination therapy with timolol and dorzolamide in glaucoma and ocular hypertension. Drug Healthc Patient Saf 2010; 2: 73-83
    PubMedSearch in Google Scholar
  • 25 Siesky B, Harris A, Sines D et al. A comparative analysis of the effects of the fixed combination of timolol and dorzolamide versus latanoprost plus timolol on ocular hemodynamics and visual function in patients with primary open-angle glaucoma. J Ocul Pharmacol Ther 2006; 22: 353-361
    CrossrefPubMedSearch in Google Scholar
  • 26 Martínez A, Sánchez-Salorio M. A comparison of the long-term effects of dorzolamide 2 % and brinzolamide 1 %, each added to timolol 0.5 %, on retrobulbar hemodynamics and intraocular pressure in open-angle glaucoma patients. J Ocul Pharmacol Ther 2009; 25: 239-248
    CrossrefPubMedSearch in Google Scholar
  • 27 Harris A, Arend O, Chung HS et al. A comparative study of betaxolol and dorzolamide effect on ocular circulation in normal-tension glaucoma patients. Ophthalmology 2000; 107: 430-434
    CrossrefPubMedSearch in Google Scholar
  • 28 Januleviciene I, Harris A, Kagemann L et al. A comparison of the effects of dorzolamide/timolol fixed combination versus latanoprost on intraocular pressure and pulsatile ocular blood flow in primary open-angle glaucoma patients. Acta Ophthalmol Scand 2004; 82: 730-737
    CrossrefPubMedSearch in Google Scholar
  • 29 Martinez A, Sanchez M. A comparison of the effects of 0.005 % latanoprost and fixed combination dorzolamide/timolol on retrobulbar haemodynamics in previously untreated glaucoma patients. Curr Med Res Opin 2006; 22: 67-73
    CrossrefPubMedSearch in Google Scholar
  • 30 Siesky B, Harris A, Brizendine E et al. Literature review and meta-analysis of topical carbonic anhydrase inhibitors and ocular blood flow. Surv Ophthalmol 2009; 54: 33-46
    CrossrefPubMedSearch in Google Scholar
  • 31 Martínez A, Sanchez-Salorio M. Predictors for visual field progression and the effects of treatment with dorzolamide 2 % or brinzolamide 1 % each added to timolol 0.5 % in primary open-angle glaucoma. Acta Ophthalmologica 2010; 88: 541-552
    PubMedSearch in Google Scholar
  • 32 Mundorf TK, Rauchman SH, Williams RD et al. A patient preference comparison of Azarga (brinzolamide/timolol fixed combination) vs. Cosopt (dorzolamide/timolol fixed combination) in patients with open-angle glaucoma or ocular hypertension. Clin Ophthalmol 2008; 2: 623-628
    PubMedSearch in Google Scholar