In the lithium toxicity scenario, which of the following interactions increases the risk of toxicity?

• A. Cystic fibrosis with inhaled saline
• B. Acetazolamide use
• C. Hydrochlorothiazide use
• D. Excessive caffeine consumption

Answer: (C)

Lithium is cleared by the kidneys and behaves similarly to sodium. Drugs that reduce kidney sodium reabsorption or cause volume depletion push the kidney to reabsorb more sodium—and with that, more lithium as well. A thiazide diuretic does exactly that: it causes natriuresis and volume loss, which leads to increased proximal tubule reabsorption of lithium and higher serum levels. That rise in lithium concentration raises the risk of toxicity, making hydrochlorothiazide use the interaction most likely to increase toxicity.

The other options don’t have the same, well-established impact on lithium levels: inhaled saline for cystic fibrosis isn’t a known toxicity-raising interaction; acetazolamide can affect fluids and acid-base balance but isn’t as reliably linked to significant lithium elevation; caffeine can cause diuresis but isn’t a classic lithium toxicity risk.