Pathophysiology
Clinical meaning
Lithium is a monovalent cation used as a first-line mood stabilizer for bipolar disorder, with a uniquely narrow therapeutic index (therapeutic range 0.6-1.2 mEq/L; toxicity begins at 1.5 mEq/L). Understanding lithium's pharmacokinetics is essential for preventing and managing toxicity. Lithium is absorbed completely from the GI tract, is not protein-bound, is not metabolized by the liver, and is eliminated almost exclusively by renal excretion. It is freely filtered by the glomerulus and approximately 80% is reabsorbed in the proximal tubule via the sodium-lithium counter-transporter. This reabsorption parallels sodium reabsorption -- any condition that increases proximal tubular sodium reabsorption (dehydration, volume depletion, sodium restriction) will simultaneously increase lithium reabsorption, raising serum lithium levels. Three patterns of lithium toxicity exist. Acute toxicity (overdose in lithium-naive patient): GI symptoms predominate, CNS toxicity may be delayed. Acute-on-chronic toxicity (overdose in patient on chronic lithium): most dangerous because both tissue stores and serum levels are elevated. Chronic toxicity (most common): a stable patient develops toxicity from a precipitating factor (dehydration, renal impairment, drug interaction). Chronic toxicity is particularly dangerous because lithium has equilibrated into brain...