Review of Pharmacology - 9E (2015)

Central Nervous System
Anti Manic Drugs
Lithium
It is a small monovalent cation that does not produce any acute effect but on prolonged use, acts
as a mood stabilizer. It has no psychotropic effect in normal persons. It acts by inhibiting the
hydrolysis of inositol-1-phosphate (required for the regeneration of IP 3
and DAG).
• It has narrow margin of safety (low therapeutic index) and therapeutic drug
monitoring (TDM) is essential.
• It takes 1-2 weeks to exert its maximum effect. It is the drug of choice for the
prophylaxis of bipolar disorder. Its t 1/2
is 24 hours.
• It can be used in acute mania but benzodiazepines like lorazepam must be added
(due to slow action of Li). In patients not controlled by BZDs, antipsychotics like
olanzapine may be added.
• Plasma concentration of lithium should be 0.5-0.8 mEq/L for maintenance therapy
of bipolar disorder and 0.8-1.2 mEq/L for acute mania. Toxic symptoms are seen if
plasma concentration exceeds 1.5mEq/L.
• Diuretics (particularly thiazides) decrease the renal excretion of lithium and thus
may result in toxicity. This is due to increased reabsorption of Na + and lithium ions
(as a compensatory response to excessive loss of Na + )
Half-life of lithium is 24 hours
Other effects of lithium are
L – Leucocytes are Useful in the treatment of cancer chemotherapy induced leucopenia
I – Increased
T – Tremors (Most common side effect)
H – Hypothyroidism
I – Increased Nephrogenic diabetes insipidus, can be used for the treatment of SIADH.
U – Urine Amiloride is DOC for lithium induced DI.
M should be avoided in expectant Mothers as it causes Ebstein’s anomaly
• Acne and weight gain (due to Na + and water retention) are the other adverse effects.
• It can cause benign and reversible elevation of T waves in ECG.
Alternatives to Lithium
• Carbamazepine and valproate are useful in manic depressive psychosis (bipolar
disorder). These can also be used for acute mania. Valproic acid is the drug of
choice for treatment of rapid cyclers (> 4 cycles/year).
• Benzodiazepines like lorazepam are the drugs of choice for acute mania when
combined with lithium. Olanzapine and other atypical antipsychotics show
efficacy in bipolar disorder as well as acute mania.
• Lamotrigine is specifically useful for depressive phase of bipolar disorder. It is
the first agent to be approved by FDA for bipolar disorder without an indication for
acute mania.
L – Leucocytes
I – Increased
T – Tremors
H – Hypothyroidism
I – Increased
Polyuria
U – Urine
M
should be avoided in
expectant mothers
General Central Nervous Pharmacology System
Lithium Toxicity
• Acute intoxication is characterized by vomiting, diarrhea, coarse tremor (fine tremor
in mild intoxication), ataxia, coma and convulsions.
• More serious effects involve mental confusion, hyperreflexia, dysarthria, seizures,
and cranial and focal neurological signs progressing to coma and death.
• Other toxic effects are cardiac arrhythmias, hypotension and albuminuria.
• There is no specific antidote for lithium. Dialysis is most effective means of removing
Li from body. It is indicated at serum Li levels of > 4m Eq/L in acute overdose or >
1.5 mEq/L in chronic overdose.
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