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Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat migraine headaches and schizophrenia. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, juvenile myoclonic epilepsy and the seizures associated with Lennox-Gastaut syndrome. It is also used in treatment of myoclonus. In some countries, parenteral (administered intravenously) preparations of valproate are used also as second-line treatment of status epilepticus, alternatively to phenytoin. Related drugs include the sodium salts sodium valproate, used as an anticonvulsant, and a combined formulation, valproate semisodium, used as a mood stabilizer and additionally in US also as an anticonvulsant. Valproate is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain, making it an alternative to lithium salts in treatment of bipolar disorder. Valproic acid is an inhibitor of the enzyme histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection. This may one day lead to a cure for HIV and AIDS. Another potential indication may be leukemia in juvenile patients. Studies conducted by several European centres are ongoing. Although it is too early to make a definitive statement, preliminary results are encouraging.
History Pierre Eymard serendipitously discovered valproic acid's anticonvulsant properties while using it as a vehicle for a number of other compounds. Side effects Common side effects are dyspepsia and/or weight gain. Less common are dysphoria, fatigue, dizziness, drowsiness, hair loss, headaches, nausea, sedation and tremors. Valproic Acid also causes Hyperammonemia. Rarely, valproic acid can cause blood dyscrasia, impaired liver function, jaundice, thrombocytopenia, and prolonged coagulation times. In about 5% of pregnant users, valproic acid will cross the placenta and cause congenital anomalies. Due to these side effects, most doctors will ask for blood tests, initially as often as once a week and then once every 2 months. Temporary liver enzyme increase has been reported in 20% of cases during the first few months of taking the drug. Inflammation of the liver (hepatitis), the first symptom of which is jaundice, is found in rare cases. There have also been rare reports of cognitive dysfunction, Parkinson's disease, and even pseudoatrophic brain changes in long-term treatment with valproic acid. Contraindications Valproate is relatively contraindicated in pregnancy due to its teratogenicity; women who become pregnant whilst taking valproate should be counselled as to its risks, take high dose folic acid and be offered antenatal screening (alpha-fetoprotein and second trimester ultrasound scans).. It is a known folate antagonist, which can cause neural tube defects. Thus, folic acid supplements may alleviate the teratogenic problems. Valproate is contraindicated in overweight patients because it causes weight gain as outlined above. Preexisting liver damage, bone marrow depression, and coagulation disorders are additional contraindications. Formulations Branded products include Depakene (Abbott Laboratories in US & Canada),Valpro (Alphapharm in Australia), Epilim (Sanofi-Aventis in the UK), Convulex (Pfizer in the UK and Byk Madaus in South Africa), Depakine and MicropakineLP by Sanofi-Aventis and Orfiril by Desitin Arzneimittel GmbH in Europe. | ||||||||
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