Lithium has a narrow therapeutic window (0.6–1.2 mEq/L). Which ion transport mechanism explains why NSAIDs increase lithium toxicity?
- A NSAIDs inhibit CYP3A4, reducing lithium metabolism and raising plasma levels
- B Lithium is reabsorbed in the proximal tubule via the Na+/H+ exchanger as a Na+ substitute; NSAIDs reduce renal prostaglandin synthesis, causing Na+ and Li+ retention, raising plasma lithium levels ✓
- C NSAIDs cause acute tubular necrosis, reducing GFR and impairing lithium filtration
- D NSAIDs inhibit aldosterone, promoting Na+ and Li+ retention in the collecting duct
Correct answer: B. Lithium is reabsorbed in the proximal tubule via the Na+/H+ exchanger as a Na+ substitute; NSAIDs reduce renal prostaglandin synthesis, causing Na+ and Li+ retention, raising plasma lithium levels
Explanation
Lithium is not protein-bound and is freely filtered at the glomerulus. Approximately 80% is reabsorbed proximally by the Na+/H+ exchanger, as the proximal tubule cannot distinguish Li+ from Na+. Prostaglandins normally inhibit proximal tubular Na+ (and Li+) reabsorption. NSAIDs reduce renal prostaglandin synthesis (PGE2 inhibition), increasing proximal Na+ and Li+ reabsorption and raising plasma lithium to toxic levels. Thiazides cause the same effect by volume contraction increasing proximal reabsorption.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.