carbonic anhydrase inhibitors
Summary
Carbonic anhydrase inhibitors are diuretics that block the enzyme carbonic anhydrase, primarily in the proximal tubule of the kidney. They cause mild diuresis, metabolic acidosis, and are mainly used for glaucoma, altitude sickness, and certain seizure disorders rather than as primary diuretics.
Detail
Carbonic anhydrase inhibitors (primarily acetazolamide) work by blocking carbonic anhydrase throughout the body, but their primary therapeutic effects occur in the kidney and eye. In the proximal tubule, carbonic anhydrase normally facilitates H+ secretion and HCO3- reabsorption by converting CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-. When inhibited, this leads to: (1) Decreased Na+ and HCO3- reabsorption, causing mild diuresis and metabolic acidosis; (2) Self-limiting diuretic effect due to metabolic acidosis. In the eye, they reduce aqueous humor production by ciliary body epithelium, decreasing intraocular pressure. Clinical uses include: open-angle glaucoma (primary use), acute mountain sickness prevention/treatment (reduces CSF production), epilepsy (particularly absence seizures), and idiopathic intracranial hypertension. Side effects include metabolic acidosis, hypokalemia, kidney stones (calcium phosphate), paresthesias, and contraindication in sulfa allergy. The diuretic effect is weak and self-limiting, making them unsuitable as primary diuretics for heart failure or hypertension.
Sources
- Katzung's Basic & Clinical Pharmacology
- Goodman & Gilman's Pharmacological Basis of Therapeutics
- First Aid for the USMLE Step 1
- Pharmacology by Lippincott
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