valproát

Valproát, in Czech commonly referring to valproate, is the salt or ester of valproic acid used as an anticonvulsant and mood stabilizer. It exists as sodium valproate, valproic acid, or valproate semisodium and is prescribed for a range of conditions.

Mechanism of action and effects: valproát increases brain gamma-aminobutyric acid (GABA) levels by inhibiting GABA-transaminase and succinate semialdehyde dehydrogenase, which helps dampen neuronal activity. It also modulates voltage-gated sodium channels and T-type calcium channels, contributing to its stabilizing effects on neurons. This combination underlies its use in epilepsy, bipolar disorder, and migraine prevention in some settings.

Indications: it is used for various seizure types, including generalized and focal seizures, as well as for mood stabilization in bipolar disorder and for migraine prophylaxis in select patients. It may be used off-label for other conditions, depending on local guidelines.

Pharmacokinetics and interactions: valproát is well absorbed orally and has high protein binding. It is extensively metabolized in the liver by glucuronidation and beta-oxidation and is excreted in the urine. It is a relatively strong inhibitor of certain hepatic enzymes (UGTs), which can raise levels of other drugs such as lamotrigine and increase the risk of interactions.

Safety and cautions: valproát carries a risk of serious adverse effects, including hepatotoxicity, pancreatitis, thrombocytopenia, weight gain and hair changes. It is teratogenic and associated with neural tube defects and potential developmental issues; it should be avoided in pregnancy unless no suitable alternatives exist, and women of childbearing potential require counseling, contraception, and usually the lowest effective dose with monitoring. Caution is advised in patients with liver disease or mitochondrial disorders, such as POLG mutations. Regular monitoring of liver function, blood counts, and clinical status is recommended.

Dosing and discontinuation: dosing is individualized; abrupt withdrawal can trigger seizure recurrence. Therapy should be managed by a clinician with appropriate monitoring.