Carbonic anhydrase inhibitors (CAIs) are nonbacteriostatic sulfonamides that reduce the formation of hydrogen and bicarbonate ions from carbon dioxide and water. In the kidneys, this causes a decrease in hydrogen ion secretion and an increase in sodium, potassium, bicarbonate and water excretion at the proximal tubules resulting in an alkaline diuresis. Inhibition of carbonic anhydrase in the ciliary process of the eye results in a decrease in production of bicarbonate and aqueous humor, thus reducing intraocular pressure in patients with glaucoma. It is suggested that the anticonvulsant effects of CAIs are due to carbonic anhydrase inhibition in the CNS which retards abnormal, paroxysmal and excessive discharge from neurons.

CAIs are used in the adjunctive treatment of chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. Acetazolamide is also used to prevent symptoms of high-altitude sickness, as an adjunct in the treatment of absence seizures and in the treatment of edema, hydrocephalus and periodic paralysis.

Currently, oral CAIs are rarely used in the treatment of glaucoma because of their serious adverse effects. Therapy has shifted toward the use of topical CAIs which are better tolerated and have fewer side effects. The role of acetazolamide as a diuretic or an anticonvulsant is also limited because tolerance to CAIs develop quickly. Intermittent use is more effective than long-term use.

CAIs are contraindicated in patients with liver disease or dysfunction. Administration of CAIs to patients with cirrhosis can cause hepatic encephalopathy. Acetazolamide should be avoided in patients with creatinine clearance of less than 10 mL/min. Methazolamide is contraindicated in patients with renal insufficiency. CAIs should not be given to patients with low serum potassium or sodium levels, suprarenal gland failure or hyperchloremic acidosis. Long-term use of CAIs for the treatment of noncongestive angle-closure glaucoma is contraindicated since decreased intraocular pressure may mask worsening glaucoma.

It is recommended that a complete blood count be performed at baseline and at regular intervals (at least once every 6 months) during CAI therapy. If there are any significant changes, the drug should be discontinued. Regular monitoring of electrolytes is also recommended. The dose of acetazolamide should be adjusted in patients with renal impairment. Patients with previous sulfonamide sensitivity should take CAIs with caution since cross-sensitivity between antibacterial and other diuretic sulfonamides have been reported. CAIs should be used with caution in patients with respiratory acidosis or those with severe loss of respiratory capacity since they can precipitate or aggravate acidosis. Diabetics should be advised that blood or urine glucose levels may increase. Patients taking CAIs should avoid tasks that require mental alertness or physical coordination until they know how the drug will affect them.