drug study of sodium valproate

1.  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

2.  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

3. 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 6–12 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 a 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

4. serious Reye’s 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.11Â
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 a‰50mg/L. Optimal dosing usually begins at 15
mg/kg/day, which typically corresponds to 500≉1,000 mg/day in two to four
divided doses. Valproate should be increased for efficacy and tolerability by
250≉500 mg/day every 1≉3 days, targeting serum concentrations of
50≉150 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
5≉10 mg/kg/day.12 For a more rapid response in patients with acute mania,
valproate can be orally loaded starting at 20≉30 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
50≉100 mcg/mL.
 Monitor patient alertness especially with multiple drug therapy for seizure control.
Evaluate plasma levels of the adjunctive anticonvulsants periodically as indicators

5. 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.
 SITATION
 http://primarypsychiatry.com/optimal-dosing-of-lithium-valproic-acid-and-lamotrigine-
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

6. 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.
 SITATION
 http://primarypsychiatry.com/optimal-dosing-of-lithium-valproic-acid-and-lamotrigine-
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