Which factor is least likely to contribute to lithium toxicity?

• A. Thiazide diuretics
• B. Dehydration
• C. NSAIDs
• D. Constipation

Answer: (D)

Lithium is cleared mainly by the kidneys, and its therapeutic window is narrow. Anything that reduces renal lithium clearance or increases its reabsorption in the tubules raises the risk of toxicity. Dehydration lowers circulating volume, which tells the kidneys to reabsorb more sodium and lithium in the proximal tubule, boosting lithium levels. Thiazide diuretics promote sodium loss and volume depletion, triggering more lithium reabsorption to compensate, again raising levels. NSAIDs reduce renal perfusion by inhibiting prostaglandins, which can decrease GFR and increase lithium reabsorption, lifting serum concentrations.

Constipation, however, does not directly affect renal lithium handling or clearance. It’s not a known driver of increased lithium levels, so it’s the least likely contributor to lithium toxicity.