Valproic acid (Sodium Valproate)

Lithium, Semi Sodium Valproate (Depakote) and Carbamazepine are used in prophylaxis of Bipolar disorder.

Lithium is the drug of choice but it will require frequent blood level montoring due to it’s narrow therapeutic index.

Sodium valproate cannot be used in women of child bearing age due to possible teratogenicity to the foetus.

All mood stabilisers work by preventing manic episodes.

They have very little effcet on the depression. However, if mania is controlled the episodes of depression are likely to be insignificant. Chlorpromazine is an old generation anti-psychotic.

Ans. is a i.e Sodium valproate causes open neural tube defect

Sodium valproate “used during pregnancy. has produced neural tube defects in the offspring; therefore should be avoided”.

Therefore option “a” is correct

“The risk of recurrence of anencephaly is 5% after one affected child and 13% after two affected children.°

Therefore option “b” is incorrect.

Diagnostic protocol in case of patients who have had a child with neural tube defect :

In such patients At 16 weeks of gestation –                                                                        

• Level II ultrasound
• Maternal serum alpha feto protein (MSAFP).

Based on the results of these two investigations : the need for amniocentesis is decided.

Neural tube defect

A i.e. LiCO₃; B i.e. Na valproate; C i.e. Phenytoin

Ans. is ‘a’ i.e., Sodium valproate

Ans. is ‘c’ i.e., Sodium valproate

GABA level is increased by

1. Valproate and vigabatrine        —> by inhibiting GABA transaminase
2. Gabapentin                            —> by increasing synaptic vesicle release of GABA.

Ans. is ‘b’ i.e., Carnitine

• Valprate is a hepatotoxic drug.
• Valproate is metabolized by CYP450 enzymes in to a minor metabolite 2-propy1-4-pentenoic acid (4-ene-VPA) which is hepatotoxic.
• Enzyme inducers like carbamazepine, phenytoin and phenobarbital can induce the microsomal enzymes and increase production of this metabolite. This increases the risk of hepatotoxicity if carbamazepine is used along with valproate.
• Valprate hepatotoxicity is more common in persons with mitochondrial enzyme deficiency and may be ameliorated by administration of Carnitine, which valproate therapy can deplete.

Ans. ‘B’ i.e., Sodium valproate

• Most of the anticonvulsants are enzyme inducers except valproate which is an inhibitor.
• Note: Valproate is an enzyme inhibitor overall but it induces the metabolism of carbamazepine: “Valproate and carbamazepine induce each other’s metabolism”

Ans. is ‘d’ i.e., Sodium valproate

Petit mal seizures are synonymous with Absence seizure

Now DOC for absence seizure is valproate (previously it was Ethosuxamide).

Answer is D (Lymphadenopathy):

Lymphadenopathy ‘Pseudolymphoma’ is a complication associated with use of phenytoin and is not seen with valproate.

Drugs causing Lymphadenopathy –Harrison

• Phenytoin^Q
• Primidone^Q

Ans. is ‘b’ i.e., Continue the drug in same dose

Valproic acid has the risk of fetal malformations during the first trimester of pregnancy.

This patient has normal level II scan at 5 months of pregnancy so the risk period of valproate is already over and valproate is the drug of choice in juvenile myoclonic epilepsy.

Thus the drug shoud be continued in the same doses.

Ans. is ‘a’ i.e., Fulminant hepatits

Valproate

• Valproate acts by multiple mechanism :

1. Prolongation of inactivated Na* channel.
2. Inhibition of T type Ca’ current.
3. Inhibition of degradation of GABA by GABA transminase → facilitation of GABA mediated Cl- channel opening.

• Its most serious adverse effect is fulminant hepatitis especially in children below 3 years.
• Used during pregnancy, it has produced spina bifida and other neural tube defects.
• Uses (other than epilepsy) –> mania & bipolar illness, prophylaxis of migraine, trigeminal neuralgia, tardive dyskinesia.

Adverse effect of Valproate

• Neurological – Ataxia, sedation,tremor
• Systemic- Hepatotoxicity, thromobocytopenia,GI irritation, weight gain, transient alopecia, hyperammonemia, pancreatitis,coagulation disorder.