Therapeutic Use of Carbonic Anhydrase Inhibitors and Their Multiple Drug Interactions

Carbonic anhydrases, also known as carbonate dehydratases, are ubiquitous metalloenzymes present throughout most living organisms prokaryotes and eukaryotes. The systemic carbonic anhydrase inhibitor, acetazolamide, was initially discovered as a diuretic agent and introduced in 1954 into ophthalmology as a treatment for glaucoma and, since then, has been widely used for this purpose. The ability of salicylate to inhibit significantly the renal tubular secretion of the acetazolamide is well known and an important cause of severe toxicity in glaucoma patients receiving these drugs concomitantly. Sulthiame has been used since the early 1960s as an effective anticonvulsant agent in combination with other antiepileptic drugs for major epilepsy. Celecoxib is the first selective cycloxigenase-2 inhibitor to be approved for clinical practice in the treatment of patients with rheumatoid arthritis, osteoarthritis and for management of the pain of these conditions. Topiramate was licensed for clinical use in 1995 as adjunctive treatment of partial seizures and primary generalized tonic-clonic seizures.