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Valproic acid (Valproate level)

February 25, 2025Chemical pathologyLab Tests

Table of Contents

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  • Valproic acid
        • What sample is needed for Valproic acid estimation?
        • What are the Indications for Valproic acid?
        • What are the complications of Valproic acid (antiepileptic drug)?
        • What is the pathophysiology of Valproic acid (Valproate)?
        • What is the mechanism of valproic acid (Valproate level)?
        • What are the complications of Valproic acid?
      • Questions and answers:

Valproic acid

What sample is needed for Valproic acid estimation?

  1. This is done on the serum of patients (mostly epileptics).
  2. The best time is before the second dose.
  3. The other best time is early in the morning.

What are the Indications for Valproic acid?

  1. This is done on patients who are on Valproic acid drug treatment.
  2. This monitors the dose and prevents toxic levels.
  3. This is done in the patient with Epilepsy.

What are the complications of Valproic acid (antiepileptic drug)?

  1. Valproate level (Valproic acid) may cause serious or life-threatening damage to the liver.
  2. Anticonvulsant drugs like phenobarbital were used for epilepsy, and this may lead to:
    1. Drowsiness.
    2. Fatigue.
    3. Depression.
    4. Decreased mental capacity.
  3. Valproic acid (Valproate level)  has a great risk in children under the age of 2 years.

What is the pathophysiology of Valproic acid (Valproate)?

  1. Valproic acid absorption from GIT is rapid and complete.
  2. It is eliminated by liver metabolism.
  3. Circulating valproic acid is highly protein-bound, almost 93%.
  4. The percentage of protein-bound decreases in:
    1. Renal failure.
    2. In late liver diseases.
    3. Drugs that compete for their binding sites.
  5. Valproic acid is used to control tonic-clonic and partial seizures.
  6. Avoid other medications when the patient is taking valproic acid.

What is the mechanism of valproic acid (Valproate level)?

  1. It inhibits GABA transaminase, resulting in an increase in the concentration of  GABA in the brain.
  2. GABA is a potent inhibitor of presynaptic and postsynaptic discharge in the brain.
Valproic acid: Mechanism of Valproic acid

Valproic acid: Mechanism of Valproic acid

  1. This acid modulates the synaptic sodium by prolonging inactivation, decreasing the neurons’ ability to respond at high frequency.
  2. Valproic acid is rapidly absorbed from the GIT after oral intake.
    1. The peak level is 1 to 4 hours after the oral dose.
    2. The half-life is 16 hours but decreases to 12 hours after the therapy.
    3. In the case of long-term therapy, it decreases in 8 hours.
Valproic acid metabolism in the body and dose adjustment

Valproic acid metabolism in the body and dose adjustment

What are the complications of Valproic acid?

  1. Valproic acid dose >100 µg /mL is hepatotoxic and leads to acute hepatic encephalopathy.
    1. The dose should be adjusted from 40 µg /mL to 100 µg /mL.
    2. The best time to get a blood sample is before the next dose.
  2. The patient may develop complications:
    1. Excessive tiredness,
    2. There is a lack of energy.
    3. The patient may develop weakness.
    4. There is stomach pain.
    5. There is a loss of appetite, nausea, vomiting, or swelling of the face.
    6. This may cause damage to the pancreas.
  3. Level >200 µg/mL may show:
    1. Pancreatitis.
    2. Hallucination.
    3. Raised ammonia level (Hyperammonemia).
  4. Hepatic dysfunction may happen even at a therapeutic level. So, regularly check the liver function tests.
    1. Initially, liver functions should be checked frequently in the first 6 months of therapy.
  5. Valproic acid can cause birth defects in pregnant women.
  6. The goal of epilepsy treatment is:
    1. Seizure control.
    2. Epilepsy control.
    3. Ultimately, the reversal of the disease.
  7. Evaluation of the free or nonbound fraction is a more reliable index of a therapeutic or toxic dose.

Another source 2

Toxic level = >100 µg/mL.

Questions and answers:

Question 1: What is the peak level of valproic acid?
Show answer
The peak level is after 4 hours of oral intake.
Question 2: What is the indication of valproic acid?
Show answer
It is advised in epilepsy.

Possible References Used
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