Lithium is used to treat mania and gout. Its exact mechanism of action is unclear but it affects intracellular signaling pathways related to mood stabilization and energy metabolism. It is rapidly absorbed orally and excreted by the kidneys. Toxicity symptoms vary depending on lithium levels and can include nausea, arrhythmias, neurological effects, and renal issues. Diagnosis is based on history, exam, and serum lithium concentration. Treatment involves hydration, gastrointestinal decontamination, and hemodialysis in severe cases.

1. “Religion is regarded by the common people as true, by the wise as false, and by the
rulers as useful.”
― Richard Dawkin
INTRODUCTION
Late 1800s to treat mania and gout
Serum monitoring important
narrow therapeutic index
PHARMACOLOGY AND CELLULAR TOXICOLOGY
● Exact mechanism of action is not clearly understood
● Similar to sodium
● Affects two intracellular signaling pathways
○ Decreases intracellular inositol, which may be a mechanism for mood
stabilization.
○ Inhibits glycogen synthase kinase-3 - involved in energy metabolism,
neuroprotection, and neuroplasticity.
PHARMACOKINETICS
Rapid and complete GI absorption after oral administration
Small ion (74 Daltons) with no protein or tissue binding
Freely distributed throughout total body water
Excreted almost entirely by the kidneys
EPIDEMIOLOGY
● -Increasing being used in psychiatry
● M=F
● Any age group
● Elderly - at high risk
○ Lower Volume of distribution
○ Lower GFR
● Usually accidental, may be suicidal
● Urban > rural
Non nobis solum nati sumus
(​Not for ourselves alone are we born​)
-Dr. Eashan Srivastava

2. “Religion is regarded by the common people as true, by the wise as false, and by the
rulers as useful.”
― Richard Dawkin
CLINICAL PRESENTATION
May be
● Acute
● Acute-on-chronic
● Chronic
The symptoms and signs of toxicity ddepend on
● Total body burden of lithium
● Rate of onset of toxicity.
Acute and acute-on-chronic poisoning
● D​etermine the formulation of the drug (eg, standard formulation or sustained release),
● Amount ingested
● Timing (eg, acute or chronic)
● Ask about dehydration, medications, and coingestants
● Gastrointestinal
○ Nausea
○ Vomiting
○ Diarrhea
● Cardiac
○ Arrhythmias
○ Prolonged QTc
○ Bradycardia
● Neurologic
○ Develop late because time is required for the drug to be absorbed and to
penetrate the CNS
○ Sluggishness
○ Ataxia
○ Confusion or agitation
○ Neuromuscular excitability=irregular coarse tremors, fasciculations, or myoclonic
jerks
○ Seizures
○ Encephalopathy
Non nobis solum nati sumus
(​Not for ourselves alone are we born​)
-Dr. Eashan Srivastava

3. “Religion is regarded by the common people as true, by the wise as false, and by the
rulers as useful.”
― Richard Dawkin
● Long-term neurologic sequelae
○ Neurologic complications persist in some
○ Syndrome of irreversible lithium effectuated neurotoxicity (SILENT)
■ Cerebellar dysfunction
■ Extrapyramidal symptoms
■ Brainstem dysfunction
■ Dementia
■ Nystagmus
■ Choreoathetoid movements
■ Myopathy
■ Blindness
■ Can continue for months - years
Chronic toxicity
● Concentrating deficit in the kidneys- polyuria and polydipsia
● Neurologic​ - often present with neurologic findings
○ Identical to those seen with acute
○ At risk for SILENT
● Cardiac​ same as acute
● Renal
○ Nephrogenic diabetes insipidus
○ Hypernatremia.
● Both hypothyroidism and hyperthyroidism
LABORATORY TESTING
● Lithium concentration
● complete blood count - lithium alone elevates the white blood cell count
● basic electrolytes (particularly serum sodium concentration)
● BUN and creatinine
● Electrocardiogram, - QTc intervals
● TFT
Non nobis solum nati sumus
(​Not for ourselves alone are we born​)
-Dr. Eashan Srivastava

4. “Religion is regarded by the common people as true, by the wise as false, and by the
rulers as useful.”
― Richard Dawkin
Serum lithium concentration
● F​or determining the severity + establish diagnosis
● Recommended therapeutic concentration = 0.8 - 1.2 mEq/L
● Must be measured in a lithium free tube
● Repeated every two to four hours initially to determine the adequacy of therapy (IV
hydration or hemodialysis)
Correlation with clinical toxicity
● Poor in acute
● Probably due to slow absorption into the central nervous system
● Correlate more closely with clinical signs in patients with chronic toxicity
● 1.5 to 2.5 = tremor, slurred speech, and mild lethargy
● 2.5 to 3.5 = worsening lethargy, coarse tremors, and clonus
● > 3.5 = seizures, encephalopathy
DIAGNOSIS
On the basis of
History
Suggestive examination
Serum lithium concentration
A single normal concentration does not rule out the diagnosis
TREATMENT
Non nobis solum nati sumus
(​Not for ourselves alone are we born​)
-Dr. Eashan Srivastava

5. “Religion is regarded by the common people as true, by the wise as false, and by the
rulers as useful.”
― Richard Dawkin
● ABCs and supportive care
● Hydration
○ IV hydration with isotonic saline
● Gastrointestinal decontamination
○ Activated charcoal (AC) does ​not​ prevent the absorption
○ Whole bowel irrigation with polyethylene glycol (PEG) solution can be effective in
acute ingestions
○ Sodium polystyrene sulfonate (Kayexalate) has been shown to reduce ​lithium
concentrations (Potential for hypokalemia )
● Hemodialysis
○ Readily dialyzable
○ Indications
■ Serum lithium > 5
■ Serum lithium > 4 with renal impairment
■ Decreased level of consciousness, seizure, or life-threatening
complications, irrespective of the serum ​lithium​concentration.
○ Rebound increase after the cessation of hemodialysis, as intracellular lithium
diffuses into the extracellular space
○ 1 session of hemodialysis is usually sufficient.
● Psychiatric evaluation
Non nobis solum nati sumus
(​Not for ourselves alone are we born​)
-Dr. Eashan Srivastava