CARBONIC ANHYDRASE INHIBITORS These sulfonamide derivatives, though originally developed a

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CARBONIC ANHYDRASE INHIBITORS These sulfonamide derivatives, though originally developed as diuretics, are now used primarily for glaucoma and high altitude sickness. Mechanisms * The carbonic anhydrase inhibitors selectively inhibit this ubiquitous enzyme, with major effects in the kidney, the eye, and perhaps the lung. The major renal effect is in the proximal tubule, where secre- tion of hydrogen ion by the tubule cells is important for the reabsorp- tion of bicarbonate. By reducing bicarbonate reabsorption, the drugs increase excretion of sodium bicarbonate. Much of the sodium is sub- sequently reabsorbed downstream and replaced by potassium, with result- ing potassium wasting. The diuretic effect is short-lived because bicarbonate is rapidly depleted from the body, a metabolic acidosis follows, and the filtered load of bicarbonate is reduced. (PgDn key for more text) Major indications * Glaucoma: open-angle glaucoma and secondary glaucoma; preoperatively in acute angle-closure glaucoma. See Chapter 22. * Epilepsy: petit mal epilepsy (absence seizures). See Chapter 16. * Mountain (high altitude) sickness: used prophylactically. * Edema due to congestive failure: acetazolamide in patients who are resistant to loop agents and thiazides. * Alkalinization of the urine, eg, to increase solubility of uric acid (unlabeled): acetazolamide. Pharmacokinetics * Absorption: well absorbed from the gut. * Elimination: primarily by renal excretion. Contraindications and Warnings * Renal failure, adrenal insufficiency, hyperchloremic acidosis. * Hypersensitivity to these agents or other sulfonamides (thiazides, loop agents, sulfa antimicrobials). * Long-term use is contraindicated in angle-closure glaucoma. (PgDn key for more text) Adverse Reactions * Neurologic: paresthesias, tremor, drowsiness, confusion, ataxia. * GI: nausea, vomiting. Hepatic insufficiency in patients with liver dis- ease. * Electrolyte: hyperchloremic acidosis; hypokalemia. * Immunologic: fever, rash, Stevens-Johnson syndrome, blood dyscrasias. Toxicity and Overdosage * Extensions of adverse effects. Treat by removing drug and monitor and correct electrolyte abnormalities. Interactions * Aspirin: potentiation of salicylate toxicity by shifting salicylate into the intracellular space. * Amine drugs that are excreted in the urine: may have reduced clearance as a result of urine alkalinization by the carbonic anhydrase in- hibitors. Examples include amphetamine, quinidine, and ephedrine. * Lithium: clearance may be reduced. Significance not established. (Home key to return to top of file)


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