Question

Which of the following diuretics decreases the renal clearance of lithium?

• A. Acetazolamide
• B. Hydrochlorothiazide
• C. Furosemide
• D. Spironolactone

Hint:

Thiazide diuretics cause proximal tubular reabsorption of lithium to rise, lowering its renal clearance and raising blood levels. This is a classic, well tested drug interaction.

Answer 1

The Correct Option is B

Step 1: Recall how lithium is handled by the kidney.
Lithium is filtered freely at the glomerulus and then reabsorbed mainly in the proximal convoluted tubule, alongside sodium and water, using the same transporters. A smaller amount is also reabsorbed later in the collecting duct through sodium channels.

Step 2: Think about how thiazide diuretics change this.
Thiazide diuretics such as hydrochlorothiazide block sodium reabsorption in the distal convoluted tubule. This causes mild volume depletion, and the kidney responds by increasing sodium (and, along with it, lithium) reabsorption in the proximal tubule to conserve fluid. Since more lithium is pulled back into the blood, its renal clearance falls and its blood level can rise toward toxic levels. This drug-lithium interaction is one of the most important and frequently tested in pharmacology.

Step 3: Check the other diuretics.
Acetazolamide acts on the proximal tubule directly by blocking carbonic anhydrase; it actually increases lithium excretion rather than decreasing it. Furosemide, a loop diuretic, acts on the thick ascending limb of the loop of Henle; because its natriuretic mechanism is different from a thiazide's, it produces much less compensatory proximal reabsorption, so it has only a weak, clinically less significant effect on lithium clearance and is generally considered safer to combine with lithium than a thiazide. Spironolactone works on the collecting duct by blocking aldosterone; it is not the classic drug linked to lithium toxicity.

Step 4: Final answer.
Hydrochlorothiazide is the diuretic that most significantly decreases renal lithium clearance and raises serum lithium levels, making regular monitoring necessary when the two are combined.
\[ \boxed{\text{Hydrochlorothiazide}} \]

Note on the source answer key:
The original printed key for this paper marks furosemide as the answer. The well documented pharmacology, and the reason lithium levels are monitored closely in practice, points to thiazide diuretics, not loop diuretics, as the ones that reduce lithium clearance. This entry has been corrected to hydrochlorothiazide.