Chapter 158 – Lithium
Therapeutic Physiology and Pathophysiology
Mechanism of action is unclear
 Antimania:
◦ ↓ inosotol monophosphate metobolism
◦ ↑ DA and NE activity
◦ ↑ GABA activity
 Antidepressant:
◦ ↑ synthesis and ↓ breakdown of 5HT
Pharmacology
 Absorption: Rapidly absorbed (1-2 hrs) with peak levels in 2-4 hrs in immediate release preparations. ↑
peak in SR preparations and overdose
 Distribution: Not protein bound. Distributes quickly into the kidneys and liver, follow by a slow
redistribution in to the CNS. Redistribution out of the brain is also slow, and can lead to rebound ↑ in
serum levels following dialysis of serum lithium
 Metabolism/Elimination: Renal elimination.
Pathophysiology
 CNS: Spectrum of symptoms from fine tremors, ↑ reflexes, confusion, ↓ LOC, seizures
 GU:
Renal concentration deficit (↓ ADH activity, ↓ aquaporin fn) often leading to diabete insipidus
 Metab: Hypothyroidism (↓ iodine uptake, ↓ TSH sensitivity, ↓ thyroid hormone release, ↓ conversion of
T3 → T4)
 Serontonin syndrome: Li → ↑ rls and ↓ reuptake of 5HT which may precipitate serotonin syndrome when
combined with other serotonergic agents (MAOi, SSRIs, tryptans, etc)
Clinical Presentation
System
Acute Toxicity
GI
Renal
Neurologic
CVS
Endocrine
Chronic Toxicity
Nausea and vomiting
Minimal
Concentrating deficits
Nephrogenic DI, AIN, ARF
Mild: weakness, fine tremor
Mild: weakness, fine tremor
Moderate: twitching, ↑ reflexes, slurred
Moderate: twitching, ↑ reflexes, slurred speech,
speech, drowsiness
drowsiness
Severe: psychosis, memory deficits,
Severe: confusion, clonus, ↓ LOC, seizures
Parkinsons disease
↑ QTc, non-specific ST & T wave changes
Myocarditis
Hypothyroidism
Hypothyroidism
Hematologic ↑ WBCs
Aplastic anemia
Risk Factors for Chronic Toxicity
 Drug related: High dose treatment, interaction with other medications (SSRIs, antipsychotics, CBZ)
 Renal elimination related: Volume contraction, hyponatremia, drugs which affect renal function (NSAIDs,
diuretics, ACEi)
Diagnosis
 Lithium levels: Serial levels are useful to assess for both chronic and acute toxcity. Repeat in 2 hrs for
acute toxicity and 6 hrs for chronic toxicity. Repeat levels immediately post-dialysis & 6 hrs later b/c of
redistribution from brain/bone/muscle into vascular space.
 Diagnosis is largely symtomatic as levels may be therapeutic in pts who are toxic, particularly those with
chronic toxicity
Management
 ABCs: Normal ACLS Protocol
 Decontamination: AC and gastric lavage not useful. Consider WBI if protected airway, particularly for
long acting preparations. Sodium resins bind Li in the GI tract and ↓ absorption
 Enhanced Elimination
◦ Hydration with NS at 2x's maintenance to correct hypovolemia and other electrolyte problems, and
optimize urinary clearance.
◦ Hemodialysis (hemofiltration) should be considered if:
▪ Li level > 4 mmol/L (acute) or > 2.5 mmol/L (chronic)
▪ Elevated Li level + symptoms
▪ Renal failure
▪ Inability to tolerate hydration