CARBONIC ANHYDRASE INHIBITORS These sulfonamide derivatives, though originally developed a
CARBONIC ANHYDRASE INHIBITORS
These sulfonamide derivatives, though originally developed as
diuretics, are now used primarily for glaucoma and high altitude
* 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.
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* 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
* 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.
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* Neurologic: paresthesias, tremor, drowsiness, confusion, ataxia.
* GI: nausea, vomiting. Hepatic insufficiency in patients with liver dis-
* 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.
* 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.
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E-Mail Fredric L. Rice / The Skeptic Tank