Lithium is an effective and approved drug for the treatment of bipolar disorder and
acute episodes of mania.1 Unapproved uses for lithium
include augmentation of the action of other antidepressant drugs
and treatment of aggression, post-traumatic stress disorder, and
pediatric conduct disorders. Lithium toxicity most often results
from accidental or intentional overdose or from an alteration in
lithium clearance secondary to impaired renal function.
It has been estimated that up to 75% to 90% of
patients who are treated with lithium over the long term develop
toxicity at some time during their therapy.2 During
2008, the American Association of Poison Control Centers received
reports of 6492 potential toxic exposures to lithium with four reported
Lithium has several known pharmacologic effects, but which ones
are responsible for the therapeutic benefit in treating bipolar
disorder and mania is unknown.4 As would be expected,
lithium competes with other similar cations, including sodium, potassium,
magnesium, and calcium, displacing them from both intracellular
and extracellular sites. Interference with sodium ions at the sodium
channel and the sodium-potassium pump located on the cell membrane
is responsible for the adverse effect that lithium has on myocardial
electrical activity. Lithium inhibits arginine vasopressin, an effect
that is responsible for a common adverse effect seen during lithium
therapy. Some of the toxic effects of lithium may be due to inhibition
of 3-glycogen synthase kinase, which is present in high quantities
in the brain.4
Lithium inhibits inositol monophosphatase and reduces the concentration
of inositol in the cytoplasm.5 Intracellular inositol
depletion is one of the proposed mechanisms for the therapeutic
effect of lithium in bipolar disorders. Lithium inhibits adenylate
cyclase, decreasing intracellular cyclic adenosine monophosphate
and possibly cyclic guanosine monophosphate. Lithium is also thought
to interfere with the release and reuptake of the neurotransmitter
norepinephrine at the nerve terminal site. Lithium may enhance serotonin
release, particularly from the hippocampus, and has been implicated
in serotonin syndrome when combined with other medications that
alter serotonin metabolism.
Risk of lithium toxicity increases when it is combined with other
medications. Most often toxicity involves a drug–drug interaction
with lithium (Table 175-1). Although patients
are routinely cautioned about pharmacologic interactions, they may not understand that nonprescription herbal
diuretics may also potentiate toxicity.6 An
important potential interaction relevant to the emergency physician
is that neuromuscular blocking agents such as succinylcholine, vecuronium,
and pancuronium may result in a prolonged neuromuscular blockade
when given to patients receiving long-term lithium therapy.7
Table 175-1 Drugs
That Interact with Lithium
| Favorite Table
Table 175-1 Drugs
That Interact with Lithium
|Angiotensin-converting enzyme inhibitors|
|Angiotensin II receptor blockers|
|Calcium channel blockers|
|Loop and potassium-sparing diuretics|
|Monoamine oxidase inhibitors|
|Neuromuscular blocking agents|
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