Learning Objective

Describe the mechanism of action, clinical uses, and adverse effects of carbonic anhydrase inhibitors (CAIs), and explain how they influence renal handling of bicarbonate, sodium, and hydrogen ions.

Drugs

• Acetazolamide
• Other –zolamides

Mechanism of Action (Site: Proximal Convoluted Tubule)

Inhibition of carbonic anhydrase →

• ↓ H⁺ formation inside the PCT cell
• ↓ Na⁺/H⁺ antiporter activity
• ↑ Na⁺ and HCO₃⁻ in lumen → bicarbonate-rich diuresis
• ↑ Urine pH
• Metabolic acidosis (from HCO₃⁻ loss)

Clinical Uses

• Glaucoma (↓ aqueous humor formation)
• Acute mountain sickness
• Metabolic alkalosis
• Pseudotumor cerebri (bonus high-yield)

Side Effects

• Bicarbonaturia → metabolic acidosis
• Hypokalemia
• Hyperchloremia (hyperchloremic metabolic acidosis)
• Paresthesias
• Renal stones (from Ca²⁺ phosphate stones in alkaline urine)
• Sulfonamide hypersensitivity

Activity