Pharm 101: Lithium

Class

Mood stabiliser

Pharmacodynamics
  • Mechanism of action uncertain
  • Suppresses inositol signalling and inhibits glycogen synthase kinase-3 (GSK-3), a multifunctional protein kinase
  • No significant antagonistic actions on CNS or autonomic nervous system receptors
Pharmacokinetics
  • Bioavailability 100%
  • Complete absorption within 6-8 hours, peak plasma levels 30-120 minutes
  • Volume of distribution initially 0.5L/kg, rising to 0.7-0.9L/kg (distributes in total body water)
  • No protein binding
  • No metabolism
  • Half life 20 hours
  • Renal excretion
    • Clearance is 20% of creatinine
    • Lithium excretion is reduced by proximal tubular reabsorption
    • Drugs such as thiazide diuretics increase activity of this resorptive mechanism and can precipitate lithium toxicity
    • NSAIDs and ACE-inhibitors also increase plasma levels
Clinical uses
  • Bipolar Affective Disorder
  • Recurrent depression with a cyclic pattern
  • Can be used in combination with other therapies to treat acute major depression and schizoaffective disorder
  • Requires serum monitoring:
    • Therapeutic concentration 0.6-1.4 mmol/L
    • Initial levels or levels following dosage adjustments should be taken 5 days after initiation of treatment
    • Levels should be measured 10-12 hours after last dose
    • Treatment of toxicity is supportive and haemodialysis
Adverse effects
  • Neurological:
    • Tremor
    • Ataxia
    • Psychiatric disturbances at toxic concentrations
  • Endocrine:
    • Hypothyroidism
    • Diabetes insipidus
  • Renal dysfunction
  • Edema
  • Cardiac adverse events:
    • Sick sinus syndrome is a contraindication to use because Lithium further depresses the sinus node
    • T-wave flattening is often seen on ECG with Lithium use but is of uncertain signicance
  • Pregnancy:
    • Ebstein’s anomaly (further research required to establish certainty regarding this)
    • Increased clearance during pregnancy
    • Passage in breast milk can predispose newborns to Lithium toxicity
Further Reading
Pharm 101 700

Pharmacology 101

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MBBS CCPU (RCE, Biliary, DVT, E-FAST, AAA) Rob is an Emergency Medicine Advanced Trainee based in Melbourne, Australia. He has special interests in medical education, ECG interpretation, and the use of diagnostic and procedural ultrasound in the undifferentiated and unwell patient.

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