Which drug interaction can increase lithium toxicity?

• A. NSAIDs
• B. Acetaminophen
• C. Cough Syrup With Dextromethorphan
• D. Antibiotics Like Penicillin

Answer: (A)

Lithium is cleared by the kidneys, so any drug that affects renal function or sodium handling can raise lithium levels and increase toxicity risk. Nonsteroidal anti-inflammatory drugs reduce prostaglandin production, which decreases renal blood flow and the glomerular filtration rate. With lower GFR, the kidneys reabsorb more lithium in the proximal tubule, similar to how they reabsorb more sodium when volume status is low. That extra reabsorption elevates serum lithium and raises the chance of toxicity, manifesting as tremors, confusion, ataxia, nausea, vomiting, and other CNS or GI symptoms.

Acetaminophen doesn’t significantly affect renal prostaglandins in a way that would raise lithium levels, so it’s not associated with the same risk. Cough syrup containing dextromethorphan or penicillin-type antibiotics don’t have a well-established, consistent impact on lithium clearance, so they’re not generally linked to increased lithium toxicity. If NSAIDs must be used, monitoring for signs of toxicity and possibly checking lithium levels or choosing alternative analgesics is prudent.