DRUG NAME : SODIUM VALPROATE ( Depakote, Epilim, Episenta)

Mechanism of action

Sodium valproate is a weak blocker of sodium ion channels; it is also a weak

inhibitor of enzymes that deactivate GABA such as GABA transaminase. It
may also stimulate the synthesis of GABA, but the direct mechanism is not
known. Because of its many mechanisms of action, sodium valproate has
efficacy in all partial and generalised seizures including absence seizures.

What is GABA ?

GABA is a chemical messenger that is widely distributed in the brain.GABA's

natural function is to reduce the activity of the neurons to which it binds.
Some researchers believe that one of the purposes that GABAserves is to
control the fear or anxiety experienced when neurons are overexcited.

gamma-Aminobutyric acid

SODIUM VALPROATE USES

(INDICATIONS)

Sodium valproate is used to treat all types of epilepsy in adults and

children.

It is an anti-epileptic drug also know as an anti-convulsant.

It is used to calm or stabilise the electrical activity in the brain of patients

with epilepsy.

In general this drug is used to control or stabilize the rapid electrical activity
that occurs in the brain if you suffer from epilepsy. This activity or over
stimulation of the brain can trigger seizures (fits). By reducing this
activity,sodium valproate can prevent the seizures from occurring.

Benefits of being on this drug can include preventing seizures caused by

epilepsy, and for some patients the control of seizures may be good enough
to allow them to hold a driving licence.

Listed below are the typical uses of sodium valproate.

Control of all types of epilepsy (generalised, partial or other epilepsy)

Treatment of manic episodes in bipolar disorder

The intravenous form of sodium valproate may be given for the treatment of
epileptic patients who temporarily cannot take oral medication.

Contraindications

Hypersensitivity to valproate sodium; thrombocytopenia, patient with

bleeding disorders or liver dysfunction or disease; cirrhosis, pancreatitis;
congenital metabolic disorders, those with severe seizures, or on multiple
anticonvulsant drugs; AIDS; pregnancy (category D), lactation; child <2 y;
children <18 y for treatment of mania.

Drug-Drug Interactions

As above, valproic acid is highly protein bound and extensively metabolized

by the liver, and, therefore, toxicity can be precipitated by administration
with other highly protein-bound and/or hepatically metabolized drugs. For
example, aspirin, which is also highly protein bound, can displace valproate
from its protein-binding sites and precipitate toxicity. Serum levels of
valproate can be decreased drastically in the presence of hepatic-inducing
agents. Fluoxetine can increase valproic acid concentrations by inhibiting
liver metabolism. Valproate can drastically increase serum levels of
lamotrigine and increase the risk of life-threatening rash when administered
concomitantly with lamotrigine. Risk of hepatic failure may be increased
when valproic acid is administered with other anti-epileptic drugs.

Side Effects

The symptomatic adverse reactions produced by Sodium Valproate are

more or less tolerable and if they become severe, they can be treated
symptomatically, these include Weight gain, Tremor, Hair loss, GI disorders,
Hematological disorder, Leucopenia, bone marrow depression, nocturnal
enuresis, curly hair development.

Like lithium, valproic acid and related compounds carry a black box
warning. The potentially lethal side effects include hepatic failure,
teratogenic effects, acute hemorrhagic pancreatitis, and very rarely
agranulocytosis and thrombocytopenia. Unlike lithium, these rare and
sudden adverse events appear not to be dose related, so routine blood
monitoring does not necessarily decrease their risk. It is nonetheless
recommended that hepatic and hematologic parameters be monitored
every 612 months, to check for transaminase elevation, pancreatitis, and
the very rare risk of agranulocytosis/thrombocytopenia.

Acute valproate toxicity is characterized primarily by sedation and cognitive

dulling. Unlike lithium, there is no specific valproate serum concentration
that is associated with toxicity, but clinical consensus is to target levels
<150 mg/L. Vaproate is a strongly protein-bound anticonvulsant, and in
patients with conditions which may impact the level of valproate-albumin
binding, it is strongly recommended that free serum valproate levels, as
oppose to total serum valproate, be measured. For example, patients with
chronic liver disease and patients with hypoalbuminemia (burn patients,
elderly, pregnancy, AIDS, etc.) should have free drug monitoring.13

Common dose-related side effects include gastrointestinal (GI) symptoms,

sedation, hair loss, and weight gain.3 A pooled analysis by Smith and
colleagues14 showed improved tolerability with enteric-coated divalproex
sodium. There were significant reductions of weight gain, tremor, hair loss,
and GI symptoms.14 GI side effects can further be targeted with divalproex
sprinkle capsules on food. In general, a lower dose is associated with fewer
side

effects

and

better

safety

profile.

Valproic

acid,

like

all

anticonvulsants, should be discontinued with a slow taper, as abrupt

discontinuation can result in a seizure, even in the absence of an underlying
seizure disorder.

SODIUM VALPROATE PRECAUTIONS

This medication should not be used if you have certain medical conditions.
Before using this medicine, consult your doctor or pharmacist if you have:
porphyria (a rare inherited blood disorder), acute or severe liver problems,

or a family history of liver problems. Children under 3 years old should not
use aspirin (or other salicylate medications) while on sodium valproate
because there is an increased risk of liver problems. Additionally, aspiring
and other salicylates should not be used in children under 16 years old due
to the risk of developing the rare but serious Reyes syndrome

What is Reye's syndrome?

Reye's Syndrome, a deadly disease, strikes swiftly and can attack any child,
teen, or adult without warning. All body organs are affected with the liver
and brain suffering most seriously. While the cause and cure remain
unknown, research has established a link between Reye's Syndrome and the
use of aspirin and other salicylate containing medications, over the counter
products, and topical use products.

Dosage

Valproic acid is FDA approved for the treatment of acute mania, and first
became available for use in the US in 1978. Although it has no maintenance
indication in bipolar disorder, it is a first-line agent for maintenance
treatment as well.11 Numerous placebo-controlled trials demonstrate the
efficacy of valproate in the treatment of acute mania, with therapeutic
effect occurring several days after achieving serum concentrations of
a50mg/L. Optimal dosing usually begins at 15 mg/kg/day, which typically
corresponds to 5001,000 mg/day in two to four divided doses. Valproate
should be increased for efficacy and tolerability by 250500 mg/day
every 13 days, targeting serum concentrations of 50150 mg/L.3

The evidence suggests that only 30% of individuals will achieve goal serum
concentration (50 mg/L) in 3 days using the standard titrations schedule:
250 mg TID times 2 days, followed by standard dose titration of increasing
weekly by 510 mg/kg/day.12 For a more rapid response in patients with
acute mania, valproate can be orally loaded starting at 2030 mg/kg/day.
Eighty percent of individuals will achieve the goal concentration in 3 days
by using a loading dose, ie, 30 mg/kg/day on days 1 and 2, followed by 20
mg/kg/day.

Nursing Implications

Assessment & Drug Effects

Monitor for therapeutic effectiveness achieved with serum levels of valproic

acid at 50100 mcg/mL.

Monitor patient alertness especially with multiple drug therapy for seizure
control.

Evaluate

plasma

levels

of

the

adjunctive

anticonvulsants

periodically as indicators for possible neurologic toxicity.

Monitor patient carefully during dose adjustments and promptly report

presence of adverse effects. Increased dosage is associated with frequency
of adverse effects.

Lab tests: Perform baseline platelet counts, bleeding time, and serum
ammonia, then repeat at least q2mo, especially during the first 6 mo of
therapy.

Multiple drugs for seizure control increase the risk of hyperammonemia,

marked by lethargy, anorexia, asterixis, increased seizure frequency, and
vomiting. Report such symptoms promptly to physician. If they persist with
decreased dosage, the drug will be discontinued.

What is hyperammonaemia? hyperammonaemia is a metabolic disturbance

characterised by an excess of ammonia in the blood. It is a dangerous
condition that may lead to encephalopathy and death. It may be primary or
secondary.

CITATION

http://primarypsychiatry.com/optimal-dosing-of-lithium-valproic-acid-andlamotrigine-in-the-treatment-of-mood-disorders/

http://drugs.webmd.boots.com/drugs/drug-437-Sodium-Valproate.aspx

http://en.wikipedia.org/wiki/Mood_stabilizer

http://www.druginfosys.com/Drug.aspx?
drugCode=669&drugName=&type=1

http://www.reyessyndrome.org/

http://en.wikipedia.org/wiki/Hyperammonemia