Lithium

1
Lithium

• Widely used very effective drug in the treatment
  of bipolar and other psychiatric d/o
• Buthas a narrow therapeutic index (0.6-1.2 mEq/L
  for control 1.0-1.5 for acute mania and gt1.5 is
  toxic)
• Likelihood of toxicity is increased when
  excretion is impaired.
• --renal insufficiency
• --volume depletion
• --acute decline in GFR ACEI or NSAID use
• --elderly pts
• --polyuria due to nephrogenic DI

2
Lithium

• Forms lithium carbonate or lithium citrate
  sustained release formulas
• Peak plasma levels 2-4 hours no protein or
  tissue binding
• Almost completely excreted by the kidneys
• Most reabsorped in the proximal tubule the
  remaining 20 excreted
• Reabsorption follows that of sodium

3
Lithium

• Can induce chronic renal injury chronic
  interstitial nephritis renal tubular acidosis
  nephrotic syndrome
• Can produce a nephrogenic DI
• Cause of hypothyroidism
• Can cause hypercalcemia
• Can cause permanent neurologic sequelae (tremor
  ataxia)

4
Clinical manifestationsof Lithium toxicity

• Mild (1.5-2.5) to Moderate (2.5-3.5)
  neuromuscular excitabilty with twitching fine
  tremor motor agitation ataxia muscular
  weakness delirium N/V diarrhea
• Severe (gt3.5) seizures stupor coma
• Labs leukocytosis electrolyte disturbance
  reduced anion gap

5
Treatment

• Fluid repletion is essential
• Monitor sodium in pts who may have underlying DI
• Diuretics not useful FELI does not change
  consistently
• Hemodialysis the most dialyzable toxin known.
  Vd similar to that of water.
• Rebound effect may occur intracellular Li
  diffuses out or there is continued absorption
  from GI tract.

6
Indications to Dialyze

• Plasma Li above 4
• Plasma Li above 2.5 in a pt who is markedly
  symptomatic or has ongoing condition that limits
  urinary excretion
• Li level 2.5-4.0 in an asymptomatic pt who cannot
  reduce to lt0.6 within 36 hours. Can plot 3 or
  more Li at 2 hour intervals on a log-linear scale
  vs. time.