(Valproate) use as anti-epileptic drug

Valproate

Anti-epileptic drug

What to learn?

·    Drug Class & Brand Name

·    Clinical uses

·    Mechanism of Action

·    Key side effect

·    Pregnancy risk

·    Summary

Drug class

·    Anticonvulsant                       

Brand Name      

·    Depakote

·    Depakene

·    Depacon

·    Divalproex

Clinical uses

·    Seizures prophylaxis

·    Absence seizures

·    Partial seizures

·    Generalized seizures

·    Status epilepticus (off-label uses)

·    Given in IV, with benzodiazepine

·    Bipolar disorder

·    Migraine prevention

 Mechanism of action

1.      Increase availability of gamma-aminobutyric acid (GABA)

2.      Enhance the action of GABA in the brain neurons

3.      GABA is an inhibitory neurotransmitter, which is believe to lead to anticonvulsant effects of the drug.

4.      It also blocks voltage-dependent sodium channels, which suppress high-frequency repetitive neuronal firing, and help with anticonvulsant effect.

Key side effects (1)

·    CNS depression

·    Dizziness and Drowsiness

·    MOA: decrease neuronal excitation in the CNS by enhancing GABA.

·    Hepatotoxicity

·    onset of hepatotoxicity is most common in the first 6 months.

·    May progress even discontinuation.

          Key side effects (1)

·    Coagulopathy

·    May cause thrombocytopenia and decrease platelet aggregation.

·    MOA: direct bone marrow toxicity.

·    Pancreatitis

·    Cases of pancreatitis have been reported in both children and adults receiving valproate.

·    Recurrence after rechallenge with valproate has also been documented.

 Pregnancy risk

·    Valproate can cause major congenital malformations.

·    Decrease IQ scores

·    Neurodevelopmental disorders

·    Neural tube defects (NTD)

·    Valproate is contraindicated in pregnancy

·    Unless there is no other alternatives in controlling seizures during pregnancy, which may causes life-threatening event.

 Summary

·    Valproate is an anticonvulsant that is used for seizures prophylaxis, bipolar disorder and migraine prevention.

·    It works by increasing the availability of GABA within the CNS.

·    Some key side effects to watch out for include CNS depression, hepatotoxicity, coagulopathy and pancreatitis.

·    It can cause major congenital malformations and is C/I in pregnancy.

valproate