VA Class:OP105

ATC Class:S01EC03

AHFS Class:

• Carbonic Anhydrase Inhibitors 52:40.12

Associated Monographs

• Acetazolamide

• Brinzolamide

• Dorzolamide

• Methazolamide

Carbonic anhydrase inhibitors decrease the formation of aqueous humor and also may exhibit diuretic activity.

Glaucoma

In the treatment of chronic open-angle glaucoma, oral carbonic anhydrase inhibitors (i.e., acetazolamide, dichlorphenamide, methazolamide) are used principally in situations involving acute intraocular pressure (IOP) elevation or chronically elevated IOP that is refractory to maximal topical ocular hypotensive therapy prior to a more definitive procedure to reduce IOP.136 Although oral carbonic anhydrase inhibitors are effective in reducing elevated IOP, systemic adverse effects limit their long-term use.134,136 Orally or parenterally administered carbonic anhydrase inhibitors may also be used for short-term administration with topical miotics, other topical ocular hypotensive agents (e.g., β-adrenergic blocking agents, α-adrenergic agonists), and/or oral or IV osmotic agents such as glycerin, mannitol, or urea to lower IOP prior to appropriate laser or incisional surgery for the correction of acute angle-closure (obstructive, narrow-angle) glaucoma, infantile glaucoma, or glaucoma secondary to intumescent cataract or phacolysis. The drugs should not be used for long-term administration in patients with chronic noncongestive angle-closure glaucoma, because further closure of the angle may occur while worsening of the glaucoma is masked by lowered IOP.

Oral carbonic anhydrase inhibitors are also used as adjuncts in the short-term treatment of self-limiting secondary glaucomas which may result from anterior uveitis, trauma, iritis, herpes zoster infections, or the glaucomatocyclitic crisis syndrome. Prolonged therapy with oral carbonic anhydrase inhibitors may be of value in the treatment of some chronic secondary glaucomas.

Topical carbonic anhydrase inhibitors (e.g., brinzolamide, dorzolamide) are used topically to reduce elevated IOP in patients with open-angle glaucoma or ocular hypertension. Selection of an initial ocular hypotensive agent is influenced by the extent of the required reduction in IOP, coexisting medical conditions, and the characteristics of the individual drugs (e.g., dosing frequency, adverse effect profile, cost).130,132 With single-agent regimens, the reduction in IOP is approximately 25-33% with topical prostaglandin analogs; 20-25% with topical β-adrenergic blocking agents, α-adrenergic agonists, or miotic (parasympathomimetic) agents; 20-30% with oral carbonic anhydrase inhibitors; 18% with topical rho kinase inhibitors; and 15-20% with topical carbonic anhydrase inhibitors.130,131 For additional information on the use of topical carbonic anhydrase inhibitors in the treatment of glaucoma, see Uses: Ocular Hypertension and Glaucoma, in Brinzolamide 52:40.12 and in Dorzolamide Hydrochloride 52:40.12.

Tolerance may develop in patients receiving therapy with a carbonic anhydrase inhibitor for glaucoma; in such cases one of the other drugs in this group may be effective.

Edema

Acetazolamide may be used in the management of edema secondary to congestive heart failure or drug therapy. However, carbonic anhydrase inhibitors are much less potent diuretics than are the thiazide diuretics and metabolic acidosis resulting in loss of diuretic effect occurs after 2-4 days of continuous therapy with carbonic anhydrase inhibitors. For these reasons, carbonic anhydrase inhibitors have largely been supplanted by the thiazides.

Seizure Disorders

Acetazolamide is used as an adjunct to other anticonvulsants in the management of centrencephalic epilepsies (e.g., petit mal, unlocalized seizures). Tolerance to the anticonvulsant effects of carbonic anhydrase inhibitors develops quickly, and they may be ineffective for prolonged therapy. Although acetazolamide may be useful in partial, myoclonic, absence, and primary generalized seizures that have not responded adequately to other anticonvulsants, acetazolamide has not been evaluated in controlled clinical studies in specific seizure types and guidelines for appropriate use of the drug are not available.

Acute High-Altitude Sickness

Acetazolamide is used to increase altitude tolerance in the prevention or amelioration of symptoms associated with acute high-altitude sickness (mountain sickness) in climbers attempting rapid ascent and in those who are very susceptible to the condition despite gradual ascent. Acetazolamide has been designated an orphan drug by the US Food and Drug Administration for this use. It should be remembered, however, that whenever possible, gradual ascent and adequate acclimatization (e.g., spending 24 hours at an intermediate altitude, minimizing exertion during the initial 24-48 hours at high altitude) are desirable to prevent acute high-altitude sickness. In controlled studies, prophylactic administration of 250 mg of acetazolamide every 8-12 hours as conventional tablets or 500 mg once daily as extended-release capsules before and during rapid ascent to high altitudes decreased the frequency and/or ameliorated the severity of symptoms of acute high-altitude sickness, including headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue. Pulmonary function (e.g., minute ventilation, expired vital capacity, peak flow) was better in acetazolamide-treated patients, including symptomatic and asymptomatic patients, than in those receiving placebo. Climbers treated with acetazolamide also had less difficulty sleeping. The drug decreases periodic breathing and apnea during sleep and diminishes sleep hypoxemia.

About 50% of untreated, nonacclimatized individuals who rapidly ascend to an altitude of 10,000 feet or higher develop symptoms of acute high-altitude sickness within 6-8 hours. Some individuals develop severe symptoms even with gradual ascent. The syndrome usually responds to rest and supplemental oxygen at night and subsides after 3-4 days, but severe forms of acute altitude sickness (e.g., high-altitude pulmonary and/or cerebral edema) requiring prompt descent and appropriate therapy occasionally occur. The number of individuals at risk of developing acute altitude sickness is increasing as rapid ascents and air travel to areas of high altitude by tourists, without periods of adequate acclimatization, increase. Acetazolamide therapy can hasten acclimatization and may prevent or ameliorate the symptoms of acute altitude sickness in these individuals. Use of acetazolamide does not obviate prompt descent in patients with severe forms of acute altitude sickness. The drug does not prevent acute altitude sickness, but rather shortens the time of acclimatization and has little, if any, effect after symptoms of altitude sickness occur.

Other Uses

Acetazolamide has been used in the treatment of both hyperkalemic and hypokalemic forms of periodic paralysis†, and it may be the drug of choice in the hypokalemic form of this condition.

Acetazolamide has been used with good results in the prevention or treatment of alkalosis following open-heart surgery†. Correction of the blood pH and diminished respiratory and cardiac distress were reported to occur within 30 minutes after the drug was administered.

Acetazolamide has been used to increase excretion of phenobarbital, lithium carbonate, or salicylates in acute intoxication caused by these drugs†. However, because metabolic acidosis results both from salicylate intoxication and acetazolamide administration, use of acetazolamide in the treatment of salicylate intoxication is dangerous and can lead to severe complications; if it is used at all, acetazolamide should probably be used only in adults with respiratory alkalosis and only under the supervision of clinicians experienced in the use of the drug in salicylate overdosage.

Although intracranial pressure may be lowered in some hydrocephalic patients† receiving oral acetazolamide or methazolamide, the drugs have not been consistently effective in the treatment of this condition.

In one controlled randomized study in preterm infants with posthemorrhagic ventricular dilatation, infants who received acetazolamide (100 mg/kg daily) and furosemide (1 mg/kg daily) in addition to standard therapy (intermittent removal of CSF) experienced a higher rate of shunt placement and increased neurologic morbidity compared with infants who received standard therapy alone.

Because acetazolamide may inhibit the formation of gastric and pancreatic secretions, it has been used in the treatment of acute pancreatitis† and peptic ulcer†. Beneficial effects of the drug in these conditions have not been proven.

Administration

Carbonic anhydrase inhibitors are usually administered orally. For parenteral therapy, acetazolamide sodium is preferably administered IV; IM administration may be used but is painful. Brinzolamide is applied topically to the eye as an ophthalmic suspension. Dorzolamide hydrochloride is applied topically to the eye as an ophthalmic solution.

Dosage

Dosage of carbonic anhydrase inhibitors should be adjusted according to the patient's requirements and response. When acetazolamide is used as a diuretic, the drug should be given intermittently. In the treatment of glaucoma, epilepsy, or other conditions in which the effectiveness of the carbonic anhydrase inhibitors is independent of their diuretic effects, administration of the drugs is continuous. When acetazolamide is used in the prophylactic management of epilepsy, it should be kept in mind that adding, withdrawing, or replacing one anticonvulsant with another should be accomplished gradually. In addition, anticonvulsants should be discontinued very gradually because sudden withdrawal can precipitate status epilepticus.

The incidence and severity of many adverse reactions to carbonic anhydrase inhibitors are dose related and usually respond to a lowering of dosage or withdrawal of the drug. Because all adverse effects do not occur with the same frequency and/or severity with all of these drugs, many patients unable to tolerate one carbonic anhydrase inhibitor may be able to tolerate another. Serious adverse effects are infrequent, especially during short-term therapy.

While systemic absorption of brinzolamide or dorzolamide occurs following topical administration to the eye, the risk of systemic effects attributable to carbonic anhydrase inhibition following topical application to the eye in usual dosages is low.

GI Effects

GI disturbances including anorexia, nausea, vomiting, diarrhea, weight loss, altered taste and smell, constipation, dryness of the mouth, excessive thirst, and abdominal distention may occur during therapy with systemically administered carbonic anhydrase inhibitors.

Nervous System Effects

CNS disturbances such as drowsiness, sedation, headache, confusion, depression, fatigue, lassitude, malaise, irritability, nervousness, excitement, dizziness, vertigo, and seizures have been reported with systemically administered carbonic anhydrase inhibitors. Paresthesia, characterized as numbness and a tingling sensation, may occur in the extremities, tongue, and/or the mucocutaneous junctions of the lips or the anus. Muscular weakness, ataxia, tremor, and flaccid paralysis have been reported in patients receiving these drugs.

Hypersensitivity Reactions

Hypersensitivity reactions common to all sulfonamide derivatives occur rarely in patients receiving carbonic anhydrase inhibitors. One patient died of cholestatic jaundice after taking 13 g of acetazolamide in 26 days. The jaundice was attributed to drug-induced hypersensitivity and hepatitis. Other hypersensitivity reactions which may occur include fever, rash and skin eruptions including exfoliative dermatitis and urticaria, and pruritus.

Hematologic Effects

Bone marrow depression manifested by aplastic anemia, thrombocytopenia or thrombocytopenic purpura, leukopenia, agranulocytosis, and hemolytic anemia has been reported with systemically administered carbonic anhydrase inhibitors. Fatalities resulting from aplastic anemia have been reported following therapy with acetazolamide or methazolamide. In one patient, fatal bone marrow depression with leukopenia, thrombocytopenia, and anemia occurred after therapy with 500 mg of acetazolamide twice daily for 14 weeks.

Renal and Metabolic Effects

Dysuria, crystalluria, renal colic, and sulfonamide-like renal lesions have been reported during therapy with systemically administered carbonic anhydrase inhibitors. Renal calculi have also occurred, possibly because of reduced excretion of citrate combined with unchanged or increased calcium excretion. Renal calculi may occur more frequently in patients with hypercalciuria. Phosphaturia also has been reported. One clinician has suggested that 24-hour urinary calcium determinations be performed before initiating therapy with a carbonic anhydrase inhibitor and that patients with hypercalciuria who must be treated with one of these drugs should be cautioned to reduce dietary intake of calcium and increase fluid intake.

One case of renal failure (anuria) occurred in a patient after taking 500 mg of acetazolamide twice daily for 2 weeks. The patient recovered after treatment with sodium bicarbonate (4 g orally initially, followed by 2 g every 6 hours) and forced fluids.

Rarely, hypokalemia may occur, especially in patients taking dichlorphenamide, and is especially likely if brisk diuresis occurs or in patients with hepatic cirrhosis or who are receiving other drugs that increase potassium excretion. Ingestion of potassium-rich foods may reduce or prevent potassium depletion; however, administration of a potassium supplement may be necessary in patients whose serum potassium concentrations are below about 3 mEq/L or who are receiving digitalis glycosides. When selecting a potassium supplement for a patient receiving a carbonic anhydrase inhibitor, the fact that plasma chloride concentrations may be elevated should be kept in mind.

Elevation of blood glucose, possibly caused by hypokalemia, and glycosuria have been reported rarely in diabetics and prediabetics receiving acetazolamide.

Uric acid excretion is decreased during therapy with systemically administered carbonic anhydrase inhibitors, and gout may be exacerbated. Elevated serum uric acid concentrations return to pretreatment levels when the drugs are discontinued. The possibility of hyponatremia should also be considered.

Reduced plasma bicarbonate concentrations and, in some instances, elevated plasma chloride concentrations may result in metabolic acidosis during long-term therapy with systemically administered carbonic anhydrase inhibitors. However, severe acidosis occurs rarely, if at all, with dosages of the drugs used to lower intraocular pressure. If necessary, acidosis may be corrected by administration of sodium bicarbonate.

In patients with hepatic cirrhosis, hypokalemia and/or elevations in blood ammonia concentrations caused by systemically administered carbonic anhydrase inhibitors may precipitate hepatic coma or precoma. Disorientation occurs in patients with cirrhosis receiving carbonic anhydrase inhibitors, possibly because of elevations of blood ammonia or increased cerebral carbon dioxide tension and decreased oxygen consumption.

Other Adverse Effects

Myopia has been reported in patients receiving carbonic anhydrase inhibitors; this effect is transient and subsides when dosage is reduced or the drug withdrawn.

Acetazolamide has been implicated in hirsutism which occurred in a 30-month old child after 1 year of treatment with 5 mg/kg daily. The excessive growth of hair on the back and legs was reported to be diminishing 1 year after acetazolamide was discontinued.

Other adverse effects which may occur in patients receiving carbonic anhydrase inhibitors are hepatic insufficiency, melena, hematuria, hearing dysfunction or tinnitus, globus hystericus, polyuria or increased urinary frequency, hyperpnea, cyanosis, and elevations in serum bilirubin concentrations.

Precautions and Contraindications

Electrolyte balance should be monitored in patients receiving systemically administered carbonic anhydrase inhibitors. (See Cautions: Renal and Metabolic Effects.) Systemically administered carbonic anhydrase inhibitors should be used with caution in patients with respiratory acidosis or those with severe loss of respiratory capacity caused by pulmonary infection, obstruction, emphysema, or advanced pulmonary disease. One manufacturer states that dichlorphenamide is contraindicated in patients with severe pulmonary obstruction. Respiratory acidosis may be precipitated or increased in these patients. Administration of these drugs may be especially hazardous in patients with elevated pCO₂ values or those in whom blood pH is below 7.2.

Periodic hematologic determinations should be performed in patients receiving systemically administered carbonic anhydrase inhibitors. If blood dyscrasias occur, the drug should be discontinued and appropriate therapy instituted.

Since systemically administered carbonic anhydrase inhibitors may cause hyperglycemia and glycosuria in patients with diabetes mellitus, the drugs should be used with caution in these patients.

Use of acetazolamide for the prevention of acute high-altitude sickness (mountain sickness) in climbers attempting a rapid ascent does not obviate the need for prompt descent if severe forms of acute altitude sickness such as high-altitude pulmonary or cerebral edema occur.

Systemically administered carbonic anhydrase inhibitors are contraindicated in patients with hepatic disease or insufficiency, especially those with cirrhosis because of the risk of developing hepatic encephalopathy. Systemically administered carbonic anhydrase inhibitors are also contraindicated in patients with depressed serum concentrations of sodium and/or potassium and in patients with adrenocortical insufficiency, hyperchloremic acidosis, or severe renal disease or dysfunction.

Patients receiving oral or parenterally administered carbonic anhydrase inhibitors should be warned that the ability to perform tasks requiring mental alertness and/or physical coordination may be impaired.

Pregnancy, Fertility, and Lactation

Pregnancy

Teratogenic and embryocidal effects have been demonstrated in rats and mice receiving carbonic anhydrase inhibitors in doses 10 times those recommended in humans. Acetazolamide can cause fetal toxicity when administered to pregnant women. Acetazolamide, administered orally or IV, has been shown to be teratogenic (defects of the limbs) in mice, rats, hamsters, and rabbits, and premature delivery and congenital anomalies have been reported in neonates born to women receiving the drug. If acetazolamide is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the possible hazard to the fetus.

Fertility

Acetazolamide had no effect on fertility in male or female rats receiving the drug orally at up to 4 times the maximum recommended daily human dose (1 g in a 50-kg patient).

Lactation

Because of the potential for serious adverse effects in nursing infants, the manufacturer states that a decision should be made whether to discontinue nursing or therapy with the drug, taking into account the importance of the drug to the woman.

Systemically administered carbonic anhydrase inhibitors increase excretion of lithium, and patients receiving lithium should be observed for impairment of responsiveness to that drug whenever a carbonic anhydrase inhibitor is administered.

Alkalinization of the urine produced by systemically administered carbonic anhydrase inhibitors may decrease the rate of excretion of some drugs such as amphetamines, procainamide, quinidine, or possibly tricyclic antidepressants and the effects of the drugs may be enhanced and/or prolonged. Since the rate of excretion of weak acids, including phenobarbital and salicylates, is increased when the urine is alkaline, the effectiveness of these drugs may be reduced during therapy with carbonic anhydrase inhibitors. In addition, metabolic acidosis induced by systemically administered carbonic anhydrase inhibitors may potentiate salicylate toxicity, and some evidence suggests that toxicity observed in some patients receiving concomitant therapy may result from either the carbonic anhydrase inhibitor or salicylate or from both drugs. (See Drug Interactions: Acidifying and Alkalinizing Agents, in the Salicylates General Statement 28:08.04.24.) Methenamine compounds, such as methenamine, methenamine hippurate, and methenamine mandelate require an acid urine in order to be effective and may be inactive in the alkaline urine produced by the carbonic anhydrase inhibitors.

Carbonic anhydrase inhibitors may augment the effects of other diuretics such as the thiazides. Results of one study indicate that acetazolamide competes with and displaces chlorthalidone from erythrocyte binding sites. Although it appears that this effect may alter the response to chlorthalidone, the clinical importance has not been determined.

Rarely, systemically administered carbonic anhydrase inhibitors may interfere with the hypoglycemic response to insulin or oral antidiabetic agents, possibly by causing hypokalemia. In patients receiving digitalis glycosides, hypokalemia may predispose the patient to digitalis toxicity and possibly fatal cardiac arrhythmias may result. Other drugs, including most diuretics, corticosteroids, corticotropin, and amphotericin B also cause increased excretion of potassium, and patients receiving one of these drugs concurrently with a systemically administered carbonic anhydrase inhibitor may experience severe hypokalemia.

Severe osteomalacia has been reported in 2 patients receiving acetazolamide and phenytoin or primidone. It has been postulated that acetazolamide hastens bone demineralization and accentuates the deleterious effects of phenytoin and related drugs on calcium metabolism.

Laboratory Test Interferences

Systemically administered carbonic anhydrase inhibitors, by alkalinizing the urine, may cause false-positive results in determination of urinary protein with bromophenol blue reagent (Albustix^®, Albutest^®, and the protein test area of Labstix^®). False-positive results may also occur when laboratory determinations of urinary protein are performed by the sulfosalicylic acid (Bumintest^®, Exton's Test Reagent), heat and acetic acid, or nitric acid ring test methods.

In patients with hyperthyroidism or normal thyroid function, but not those with hypothyroidism, systemically administered carbonic anhydrase inhibitors may depress iodine uptake by the thyroid.

In vitro, acetazolamide interferes with urinary steroid determinations. Whether this interference occurs when the drug is administered to patients has not been determined.

Pharmacology

Carbonic anhydrase inhibitors reduce the formation of hydrogen and bicarbonate ions from carbon dioxide and water by noncompetitive, reversible inhibition of the enzyme carbonic anhydrase, thereby reducing the availability of these ions for active transport into secretions. Most of the studies performed with this group of drugs have utilized acetazolamide. Although the pharmacologic effects are presumably shared to some degree by the other carbonic anhydrase inhibitors, the drugs may differ in the dosage required to produce an effect in various tissues.

Ocular Effects

Orally, parenterally, or topically administered carbonic anhydrase inhibitors decrease the formation of aqueous humor, thereby lowering intraocular pressure in both normal and glaucomatous eyes. The ocular effects of these drugs are independent of their diuretic effect and persist in the presence of metabolic acidosis. Carbonic anhydrase inhibitors do not increase the facility of aqueous outflow.

Renal and Metabolic Effects

Inhibition of carbonic anhydrase and the subsequent reduction in hydrogen ion concentration in the renal tubules result in increased excretion of bicarbonate and, to a lesser extent, sodium and potassium. Potassium loss is greatest during acute administration of oral or parenteral carbonic anhydrase inhibitors. Although potassium loss with these drugs is greater than that caused by mercurial diuretics, with chronic administration it is less than that produced by the thiazides. Reabsorption of water is decreased, urine volume is increased, and the urine becomes alkaline in patients receiving oral or parenteral carbonic anhydrase inhibitors. Urinary excretion of ammonia and titratable acidity are decreased. Excretion of chloride is increased in patients receiving dichlorphenamide and may be increased, slightly decreased, or unchanged in patients receiving any of the other carbonic anhydrase inhibitors (i.e., acetazolamide, methazolamide). Calcium excretion may also be increased, slightly decreased, or unchanged. Excretion of citrate and uric acid is decreased and excretion of lithium is increased. The drugs have little effect on excretion of magnesium or phosphate.

In patients receiving acetazolamide as a diuretic, plasma bicarbonate concentrations are reduced and plasma chloride concentrations may be elevated, possibly resulting in metabolic acidosis. In the presence of acidosis, hydrogen ion concentration in the renal tubule increases, sodium and potassium excretion decreases, and the diuretic effect ceases. The diuretic response to the drug is enhanced in patients with metabolic alkalosis. Plasma ammonia concentrations may also be elevated in patients receiving carbonic anhydrase inhibitors. In dosage used to lower intraocular pressure, dichlorphenamide and methazolamide have minimal renal effects and are unlikely to cause acidosis with prolonged therapy. Long-term administration of topical brinzolamide or dorzolamide is unlikely to cause acid-base or electrolyte disturbances.

Anticonvulsant Effects

Acetazolamide has anticonvulsant activity which is independent of its diuretic effect. Dichlorphenamide appears to have less anticonvulsant effect than does acetazolamide. Methazolamide has been demonstrated to be more potent than acetazolamide in protecting rats and mice against electroshock seizures, but the manufacturer states that the drug is not an effective anticonvulsant in humans. It has been theorized that the anticonvulsant effect may be caused by production of metabolic acidosis. However, it has also been postulated that a direct effect on carbonic anhydrase in the brain may result in increased carbon dioxide tension, which has been demonstrated to retard neuronal conduction; an adrenergic mechanism may also be involved. Orally or parenterally administered carbonic anhydrase inhibitors may also decrease CSF formation.

Other Effects

Rarely, acetazolamide has caused elevations of blood glucose and glycosuria in diabetic and prediabetic patients, possibly due to hypokalemia.

Systemically administered carbonic anhydrase inhibitors depress iodine uptake by the thyroid gland in patients with hyperthyroidism or normal thyroid function but not in those with hypothyroidism; however, the drugs are not useful as antithyroid agents.

Systemically administered carbonic anhydrase inhibitors may increase carbon dioxide tension in tissues and decrease carbon dioxide tension in the pulmonary alveoli. A transient decrease in the rate of carbon dioxide elimination may result, but in most patients this is rapidly overcome by compensatory mechanisms. Respiratory and metabolic acidosis caused by carbonic anhydrase inhibitors may increase oxygenation during hypoxia by increasing ventilation, cerebral flood flow, and/or dissociation of oxygen from oxyhemoglobin.

In patients with hyperkalemic or hypokalemic periodic paralysis, acetazolamide terminates attacks of paralysis, decreases muscle weakness, and, when given prophylactically, prevents recurrence of paralytic attacks. The drug appears to act by stabilizing muscle membranes, thereby preventing abnormal fluxes of potassium ions.

Acetazolamide has been reported to reduce the formation of gastric and pancreatic secretions and to reduce acidity of gastric secretions.

Pharmacokinetics

Absorption

After oral administration, acetazolamide, dichlorphenamide, and methazolamide are absorbed from the GI tract. The approximate onset, peak, and duration of action in lowering intraocular pressure following a single dose of the carbonic anhydrase inhibitors are as follows:

Some systemic absorption of brinzolamide or dorzolamide occurs following topical application to the eye.

Distribution

Carbonic anhydrase inhibitors are distributed throughout the body in those tissues containing high concentrations of carbonic anhydrase especially the erythrocytes and renal cortex. The drugs also enter the aqueous humor of the eye.

For information on the pharmacokinetics of specific carbonic anhydrase inhibitors, see the individual monographs in 52:10.

Chemistry

The carbonic anhydrase inhibitors (acetazolamide, brinzolamide, dichlorphenamide, dorzolamide, and methazolamide) are nonbacteriostatic sulfonamide derivatives containing an unsubstituted sulfamyl (-SO₂NH₂) group. Substitution on the sulfamyl nitrogen causes loss of the inhibitory effect on carbonic anhydrase.

Only references cited for selected revisions after 1984 are available electronically.

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