Medicine & USMLE

Valproate

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Antiepileptics (New)
  1. Ethosuximide
  2. Levetiracetam
  3. Gabapentinoids
  4. Valproate
  5. Benzodiazepine Drug Names
  6. Benzodiazepine Clinical Uses
  7. Benzodiazepine Mechanisms and Side Effects
  8. Topiramate
  9. Lamotrigine

Summary

Valproate is a medication with several mechanisms of action. It blocks GABA transaminase, blocks sodium channels, and also blocks voltage-dependent calcium channels.

Clinically, valproate is used as an antiepileptic drug to treat seizures. It has broad spectrum effects, meaning it can treat both generalized seizures affecting the entire body, as well as focal seizures affecting a single part of the body. Valproate is also used as a mood stabilizer in the treatment of bipolar disorder. It can also be used prophylactically to treat migraine headaches.

Valproate has several potential side effects. By suppressing brain activity, it can lead to sedation and dizziness. It can cause thrombocytopenia, leading to bleeding as well as easy bruising. Gastrointestinal side effects include hepatotoxicity, pancreatitis, and vomiting. Metabolically, valproate can lead to weight gain, and as a CYP450 inhibitor, it can cause many different drug interactions. It is also a teratogen and may lead to hair loss in patients.

Key Points

  • Valproic acid (valproate)
    • Mechanism
      • Blocks Sodium (Na+) channels
        • Prolongs inactivation, preventing firing of next action potential
      • Blocks GABA transaminase
        • This enzyme normally breaks down GABA; blocking it results in an increase in GABA concentrations
      • Blocks Calcium (Ca2+) channels
        • Blocks T-type voltage-dependent calcium channels in the brain
    • Clinical Use
      • Treats seizures (antiepileptic)
        • Broad spectrum effects
          • Treats generalized (tonic-clonic) seizures
            • Used first line
          • Treats focal (partial) seizures
            • Used first line for myoclonic seizures
            • Used second line for absence seizures (after ethosuximide)
      • Treats bipolar disorder
        • Mood stabilizer
      • Treats migraine headache (prophylaxis)
      • Also used for migraine prophylaxis and trigeminal neuralgia
    • Side Effects
      • Hepatotoxicity
        • Rare but fatal; monitor liver function tests
      • Pancreatitis
        • Can monitor serum amylase and lipase levels
      • Teratogen
        • Most commonly associated with neural tube defects
      • CYP450 Inhibitor
        • May lead to drug interactions
      • Sedation
      • Dizziness
      • Vomiting
      • Weight gain
      • Nausea/vomiting
      • Hair loss
      • Thrombocytopenia
        • Easy bruising