• Understand the PK and toxicological profile of lithium.
  1. Monovalent cation
  1. Functions by inhibiting IP3 and GSK-3, which is a multifunctional protein kinase.
  2. Overall acts to reduce α-adrenergic and muscarinic transmission.
  3. Also inhibits adenylyl cyclase and second messenger systems, therefore causing hypothyroidism and Nephrogenic DI.
  1. PO
    • Absorption is virtually complete in 6-8 hours.
  1. Initially distributed in TBW, with Vd ~0.5L/kg, rising to 0.7 to 0.9L/kg.
  2. No protein binding, but some sequestration in bone.
  1. Nil
  1. Virtually entirely in urine. Clearance is ~20% of creatinine clearance.
  2. Long T ½ – about 20 hours.
  1. Bipolar affective disorder (especially manic phase)
  2. Depressive disorders
  3. Schizophrenia
Special precautions
  1. Pregnancy – renal clearance increases during pregnancy and clearance decreases post-partum.
  1. Thiazide diuretics reduce clearance of lithium by 25%.
  2. Clearance also reduced by NSAIDs.
  3. Use of anti-psychotics may produce more severe extrapyramidal symptoms with lithium.
Adverse events
  1. Neurological
    • Very common. Tremor, ataxia and dysarthria are common. May also cause new psychiatric disturbances (mental confusion)
  2. Endocrinology
    • Hypothyroidism
  3. Renal
    • Nephrogenic DI à causes polyuria and polydipsia
  4. Cardiac
    • Depresses SA node (CI in SSS and tachy-brady syndrome)
  5. Pregnancy and post-partum
    • Lithium causes Ebstein’s anomaly
    • May also cross breast milk – results in lethargy, poor suck and poor reflexes.
  6. Idiosyncratic
    • Acne, leukocytosis.
  1. Therapeutic ODs are more common than intentional/accidental OD, due to changes in the patient’s status (that is ,decreased serum Na, increased diuretic use or fluctuating renal function)
    • Treatment is dialysis or supportive care.
Withdrawal syndrome
Special notes