Acetazolamide is administered to a glaucoma patient. Given that this drug inhibits carbonic anhydrase in the renal proximal tubule, which of the following substances will be excreted at a lower rate?
The primary effect of carbonic anhydrase inhibitors such as acetazolamide is to inhibit both H+ secretion and NaHCO3 reabsorption, making the urine alkaline. NH4+ excretion is reduced as a result of the diminished H+ secretion. Carbonic anhydrase inhibitors restrict H+ secretion by inhibiting the intracellular hydration of CO2, a primary source of intracellular H+. The decline in H+ secretion inhibits the Na+-H+ exchange at the luminal membrane of the proximal tubule, which is the primary site of NaHCO3 diuresis. Carbonic anhydrase inhibitors also block the dehydration of H2CO3 formed in the tubular lumen. Chronic doses of such drugs can lead to hyperchloremic acidosis (metabolic acidosis). Ref: McNamara J.O. (2011). Chapter 21. Pharmacotherapy of the Epilepsies. In L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds), Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e.
Na+
H2O
HCO3-
NH4