Lithium toxicity
Lithium is cleared by the kidney alongside sodium, so volume depletion, renal impairment or a drug that blocks its elimination turns an unchanged dose into rising concentrations and neurotoxicity.
Definition
Lithium toxicity is the clinical syndrome produced by lithium accumulation, usually because renal clearance has fallen rather than because the dose has changed. It is diagnosed from the combination of exposure, the clinical features and a serum concentration read against the time of the last dose. Severity is graded on symptoms, because UK sources set the concentration threshold differently and toxicity occurs within the reported therapeutic range.
First principles
Lithium follows sodium through the kidney
Lithium is filtered and then reabsorbed in the proximal tubule alongside sodium. Deplete volume or sodium and the tubule reabsorbs more of both, so clearance falls and the level climbs on an unchanged dose. Vomiting, diarrhoea, fever, sweating, hot weather, a sudden drop in dietary salt and acute kidney injury all do this. Dehydration and low-sodium diets are therefore BNF contra-indications to lithium, not cautions. Drugs that reduce renal elimination do the same: NSAIDs, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), thiazide and thiazide-like diuretics, loop diuretics, spironolactone, metronidazole and tetracyclines. Thiazides can raise the level fast. Theophylline, acetazolamide, products containing sodium bicarbonate and sodium-glucose co-transporter 2 (SGLT-2) inhibitors such as dapagliflozin lower it instead. A third group raises neurotoxicity risk without necessarily raising the level: antipsychotics, verapamil, diltiazem, carbamazepine, selective serotonin reuptake inhibitors (SSRIs) and triptans.
This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.