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

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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