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LITHIUM
CLINICAL RESPONSE
Patients presenting
with mania generally show
at least partial response to
lithium within the first 2
weeks of therapy
For patients presenting
with depression, the
timeframe is considerably
longer. It would be 4-6 weeks
to see the response.
INDICATION
MOA
1. Effects on
neurotransmitters
Inhibit NE release and
accelerate its metabolism
May increase presynaptic
re-uptake of NE and 5-HT
2. Effect on second
messengers and G
proteins:
Inhibits conversion of IP to
inositol
leads to depletion of PIP2
PIP2 IP3 and DAG
For both a-adrenergic and
muscarinic transmission
Effect on G-proteins
involved in receptor
desensitization, in
modulating membrane
structure events, in
regulating transcription, in
mediating immune
responses, in regulating cell
growth, and in learning,
mood and memory
Bipolar Disorder:
Mild Mania:
Lithium alone is effective
Carbamazepine is useful
when manic episodes are not
controlled by lithium alone
Severe mania
Always add clonazepam /
lorazepam and often give one
of the anti-psychotic drugs
Depression
Requires concurrent use of
antidepressants
ADVERSE EFFECTS
Neurologic and Psychiatric
Tremor
Choreoathetosis, ataxia,
dysarthria, motor
hyperactivity, aphasia
Psychiatric disturbances
(confusion)
Thyroid function
Decreased thyroid activity
(hypothyroidism)
DRUG-DRUG INTERACTIONS
Decrease Lithium conc:
Methylxanthines
Osmotic Diuretics
Pregnancy (3rd trimester)
Urine alkalinizers
Increase Lithium conc:
ACE inhibitor
NSAIDs
Thiazides
Dehydration
Postpartum
Renal
Polyuria, polydipsia
reversible
Lithium-induced diabetes
insipidus
Treatment: amiloride
Long term renal dysfunction:
Chronic interstitial nephritis
Minimal change
glomerulopathy
Pregnancy
Lithium is transferred to
nursing infants through
breastmilk
Lithium toxicity in newborn:
lethargy, cyanosis, poor suck,
hepatomegaly
Increase in frequency of
cardiac anomalies (Ebsteins
anomaly)
Miscellaneous:
Acneiform eruptions
Folliculitis
Leukocytosis
OVERDOSE
Therapeutic overdose is
more common than
accidental ingestion due to
accumulation of lithium (eg.
use of diuretics , NSAIDs)
Any value over 2 mEq/L
must be considered as
indicating potential toxicity.
Normal Lithium serum
concentration:
0.6 1.4mEq/L
VALPROIC ACID
An anticonvulsant that is
Mechanism is unknown
DOSE-RELATED SIDE