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Medical Therapy for Glaucoma
Published in Neil T. Choplin, Carlo E. Traverso, Atlas of Glaucoma, 2014
Jennifer E. Williamson, Janet B. Serle
Clinical use of the orally administered CAIs, especially for a long duration, is limited by the potential systemic side effects. Frequently encountered side effects include anorexia; weight loss; fatigue and drowsiness; general malaise; tingling and numbness in the hands and feet; metallic taste in the mouth after ingestion of carbonated beverages; gastrointestinal upset, including diarrhea and nausea; potassium loss with the attendant complications of hypokalemia, which could be fatal in patients taking digitalis; kidney stones (less common with methazolamide); systemic acidosis; and shortness of breath. Idiosyncratic reactions may result in fatal aplastic anemia, estimated to occur in 1 in 18,000 patient-years. Because all CAIs are sulfa derivatives, they must be used with caution, if at all, in patients with sulfa allergies. Indications for oral CAIs include short-term adjunctive therapy, particularly for acute pressure elevations or to temporize prior to planned surgical intervention, and, if necessary, for chronic use in patients who are unwilling or unable to administer topical medications or are unable to undergo glaucoma surgery.
Transscleral Drug Delivery to the Retina and Choroid
Published in Glenn J. Jaffe, Paul Ashton, P. Andrew Pearson, Intraocular Drug Delivery, 2006
The diffusion of small molecules across the sclera has been well characterized. Various sulfonamides diffuse across rabbit sclera (40,41). In patients undergoing cataract surgery, methazolamide, a hydrophilic compound, penetrated the sclera much faster than the cornea, but ethoxzolamide, which is lipophilic, had similar diffusion across the sclera and cornea (40). Other studies also have found greater scleral permeability to hydrophilic molecules than lipophilic ones (42,43).
5-(Sulfamoyl)thien-2-yl 1,3-oxazole inhibitors of carbonic anhydrase II with hydrophilic periphery
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Stanislav Kalinin, Alexander Kovalenko, Annika Valtari, Alessio Nocentini, Maxim Gureev, Arto Urtti, Mikhail Korsakov, Claudiu T. Supuran, Mikhail Krasavin
Glaucoma-related high intraocular pressure can be alleviated by the use of eye drops of prostaglandin analogues, beta blocking agents and carbonic anhydrase inhibitors (CAIs)1. The recent approval of rho kinase inhibitors and NO donors significantly expands the range of treatment options2,3. The clinically used topical CAIs for glaucoma treatment include dorzolamide (1) and brinzolamide (2), compounds that are (a) relatively lipophilic and (b) non-selective as inhibitors of a particular carbonic anhydrase isoform4. Acetazolamide (3) and methazolamide (4) are also used as anti-glaucoma agents (Figure 1), but they are oral medications which frequently cause adverse drug reactions5. Potent and selective inhibition of carbonic anhydrase II isoform (hCA II) is an important mechanism of action due to the critical importance of this enzyme in reduction of glaucoma-related intraocular pressure6.
Antibacterial carbonic anhydrase inhibitors: an update on the recent literature
Published in Expert Opinion on Therapeutic Patents, 2020
Claudiu T. Supuran, Clemente Capasso
The best VchCAβ inhibitors were deacetylated acetazolamide and methazolamide and hydrochlorothiazide (Figure 1), which showed inhibition constants of 68.2–87.0 nM. Other compounds with medium potency against VchCAβ were sulfanilamide, metanilamide, sulthiame, and saccharin with KIs in the range of 275–463 nM. The clinically used agents such as acetazolamide, methazolamide, ethoxzolamide, dorzolamide, zonisamide and celecoxib were micromolar inhibitors (KIs in the range of 4.51–8.57 mM) [11]. Selenides bearing benzenesulfonamide moieties were excellent and selective inhibitors of VchCAβ over the two human isoforms hCA I and hCA II [120]. A series of 1,2,3-triazole-bearing benzenesulfonamides characterized by a spacer between benzenesulfonamide and triazole preferentially inhibited VchCAβ with KIs in the range 54.8–102.4 nM, being more effective than the clinically used AAZ [122].
Advances in ophthalmic preparation: the role of drug nanocrystals and lipid-based nanosystems
Published in Journal of Drug Targeting, 2020
Maria Christina Camasmie Peters, Edson dos Santos Neto, Lis Marie Monteiro, Megumi Nishitani Yukuyama, Marcella Gabrielle Mendes Machado, Isabela Fernandes de Oliveira, Maria Helena Ambrosio Zanin, Raimar Löbenberg, Nádia Bou-Chacra
The SLN to treat glaucoma also presented higher activity in vivo tests. The pharmacodynamic performance revealed that 3–4 h after methazolamide (MZA) SLN instillation in rabbit eyes. The mean maximum percentage of IOP decreased, and the drug action continued over 8 h. These results showed a sustained drug release property slightly better compared with the commercial product (Azopt®) which decreased the IOP 2 h after instillation, and the effect lasted no more than 8 h. This study compared two different drug substances, methazolamide and brinzolamide prepared using nano-based technology and as a conventional suspension, respectively [63]. Another study, comparing MZA-SLN and the free MZA presented intraocular pressure reduction of 8.30 mmHg and 4.85 mmHg within 3 h, respectively, and the pressure reduction was sustained for 12 h and 5 h, respectively [64]. Additional MZA-SLN formulation, coated with chitosan, presented IOP percentage decrease versus time profiles 1.5-fold higher for this SLN than Azopt and 5-fold higher than methazolamide solution [64].