Question

A patient on lithium therapy developed hypertension and was started on a thiazide diuretic. After a few days, he developed coarse tremors and other features suggestive of lithium toxicity. What is the probable mechanism of this interaction?

• A. Thiazide increases the tubular reabsorption of lithium
• B. Thiazide inhibits the metabolism of lithium
• C. Thiazide acts as an add-on drug to lithium
• D. All of the above

Hint:

Lithium is not metabolised; think how sodium loss changes its tubular handling.

Answer 1

The Correct Option is A

Rule out and reason: First kill the wrong options. Lithium undergoes no hepatic metabolism, so thiazide cannot inhibit its metabolism, option B falls. Thiazide is not simply an additive mood agent, so option C is meaningless. That makes All of the above wrong too.
Now the real mechanism: lithium mimics sodium in the nephron. Thiazides block distal sodium reabsorption, causing natriuresis and mild volume depletion. The proximal tubule reacts by avidly reabsorbing sodium, and lithium rides along the same path, so its reabsorption climbs and plasma lithium rises into the toxic range, producing coarse tremor and other toxicity.
So option A, increased tubular reabsorption of lithium, is correct.
Pearl: any sodium-depleting state (thiazide, low-salt diet, dehydration) raises lithium; manage by lowering the lithium dose and checking levels.
Ref: K. D. Tripathi, 7th Edition, lithium.