Review Question - QID 101002

Acetazolamide, a carbonic anhydrase inhibitor, is used clinically to treat glaucoma. Acetazolamide blocks reabsorption of bicarbonate in the proximal tubule.

Within the proximal tubule, filtered bicarbonate combines with hydrogen ions to form H2CO3. Carbonic anhydrase catalyzes the dissociation of H2CO3 into H2O and CO2. CO2 then rapidly leaves the tubules by diffusing across cell membranes. Acetazolamide acts by inhibiting carbonic anhydrase, which results in bicarbonate accumulating in the urinary lumen. This decreased reabsorption of bicarbonate leads to the production of alkaline urine, occasionally leading to metabolic acidosis.

O'Brien and Chennubhotla discuss the site and mechanism of action of diuretics in the treatment of edema. Carbonic anhydrase inhibitors and phosphodiesterase inhibitors act on the proximal tubule. Loop diuretics block the sodium-potassium chloride transporter in the ascending loop of Henle. Thiazide diuretics block the sodium chloride transporter in the distal convoluted tubule. Amiloride and triamterene block apical sodium channels in the cortical collecting tubule.

Pokhrel and Loftus note that acute angle-closure glaucoma is an emergency and presents with acute onset of severe pain, blurred vision, frontal headache, halos around lights, increased intraocular pressure (IOP), and red eye/conjunctiva. Slit lamp shows a mid-dilated and sluggish pupil with a normal or hazy cornea. Treatment consists of lowering IOP with acetazolamide 500 mg orally once, and one drop each of 0.5% timolol, 1% apraclonidine, and 2% pilocarpine one minute apart and repeated three times at five-minute intervals.

Illustration A shows various diuretics and their associated sites of action in the nephron.

Incorrect answers:
Answer 1: Loop diuretics such as furosemide block the sodium-potassium chloride transporter in the ascending loop of Henle.
Answer 2: Thiazide diuretics block the sodium chloride transporter in the distal convoluted tubule.
Answer 3: Aldosterone stimulates H+/K+ ATPase in alpha-intercalated cells, which secretes H+ actively into tubular fluid. This causes acidification of urine.
Answer 5: Bicarbonate is secreted and not reabsorbed in the beta-intercalated cells.