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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.
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- 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.
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- (PgDn key for more text)
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- 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.
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- Pharmacokinetics <tab6-3>
- * Absorption: well absorbed from the gut.
- * Elimination: primarily by renal excretion.
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- 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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- (PgDn key for more text)
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- 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.
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- Toxicity and Overdosage
- * Extensions of adverse effects. Treat by removing drug and monitor and
- correct electrolyte abnormalities.
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- 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.
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