Which two classes of medications are explicitly listed as increasing lithium toxicity risk when used concurrently with lithium?

• A. NSAIDs and ACE inhibitors
• B. Calcium channel blockers and NSAIDs
• C. ACE inhibitors and calcium channel blockers
• D. NSAIDs and calcium channel blockers

Answer: (A)

Lithium has a very narrow therapeutic window and is cleared by the kidneys, so anything that alters renal perfusion or sodium handling can push lithium levels higher. Nonsteroidal anti-inflammatory drugs reduce renal prostaglandin production, which lowers renal blood flow and glomerular filtration rate, decreasing lithium clearance and raising the risk of toxicity. ACE inhibitors, by dilating the efferent arteriole and affecting sodium balance, also reduce renal clearance and can increase proximal tubule reabsorption of lithium, leading to higher serum levels. Calcium channel blockers don’t have a clearly documented, consistent effect that raises lithium toxicity risk, so they are not the combination most explicitly associated with this problem. Therefore, the pairing of NSAIDs and ACE inhibitors is the one most clearly linked to increased lithium toxicity risk; if both are used together, monitor lithium levels and renal function closely and consider alternatives when possible.