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The concurrent use of NSAIDs (nonsteroidal anti-inflammatory drugs) or diuretics is an important precipitant of lithium toxicity because both of these medication categories can affect the renal clearance of lithium. Lithium is primarily excreted by the kidneys, and any factors that alter renal function or fluid balance can lead to an increase in lithium levels in the bloodstream.

NSAIDs can lead to elevated lithium levels by inhibiting renal prostaglandins, which play a role in the renal processing of lithium. When prostaglandin synthesis is inhibited, there is reduced clearance of lithium, resulting in higher serum concentrations, even at doses that were previously therapeutic. Similarly, diuretics, especially thiazide diuretics, can cause dehydration or electrolyte imbalances that also impact lithium levels.

This interaction underscores the importance of monitoring renal function and lithium levels when a patient is on lithium therapy, especially if they need treatment with NSAIDs or diuretics. Adjustments in lithium dosing may be crucial in these situations to prevent toxicity and maintain safe therapeutic levels.