Pharmacological action
Convulex® — an antiepileptic drug that also has a central muscle relaxant and sedative effect. The mechanism of action is primarily due to inhibition of the enzyme GABA-transferase and an increase in the content GABA in < span title="central nervous system">CNS. GABA inhibits pre- and postsynaptic discharges and, thereby, prevents the spread of seizure activity in CNS.
In addition, in the mechanism of action of the drug, a significant role belongs to the effect of valproic acid on the receptors GABAA, as well as the effect on voltage-dependent sodium channels. According to another hypothesis, it acts on the sites of postsynaptic receptors, simulating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in potassium conductance. Improves the mental state and mood of patients, has antiarrhythmic activity.
Pharmacokinetics
Equilibrium concentration when in/in is achieved within a few minutes and can be maintained with a slow infusion. The therapeutic concentration of the drug in blood plasma ranges from 50 to 150 mg/l. Valproic acid is bound to plasma proteins by 90–95% — at a concentration in blood plasma of up to 50 mg/l and by 80–85% — at a concentration of 50–100 mg/l; with uremia, hypoproteinemia and cirrhosis, protein binding is reduced.
Concentration levels in cerebrospinal fluid correlate with the non-protein bound fraction of the drug, being approximately 10% of serum levels.
Valproic acid penetrates the placental barrier and is excreted in breast milk. The concentration in breast milk is 1–10% of the concentration in the mother’s blood plasma.
The drug undergoes glucuronidation and oxidation in the liver, metabolites and unchanged valproic acid (1-3% of the dose) are excreted by the kidneys, small amounts are excreted in feces and exhaled air. T< sub>1/2of the drug is in healthy subjects and with monotherapy from 8 to 20 hours; when combined with other Drug,T1/2 can be 6– 8 hours due to induction of metabolic enzymes; in patients with impaired liver function and elderly patients — may be significantly longer.
Indications
Status epilepticus; treatment of epileptic seizures (generalized — absences, myoclonic seizures, tonic-clonic, atonic, mixed; partial — simple, complex, secondary generalized seizures; specific syndromes (West, Lennox-Gastaut).
Contraindications
- hypersensitivity to valproic acid;
- severe dysfunction of the liver and/or pancreas;
- porphyria;
- hemorrhagic diathesis;
- severe thrombocytopenia.
With caution:
- in children when treated with several antiepileptic drugs;
- in children and adolescents with multiple comorbidities and severe forms of seizures;
- for renal dysfunction;
- in patients with anamnestic data on diseases of the liver and pancreas;
- in case of suppression of bone marrow hematopoiesis: leukopenia, anemia, thrombocytopenia;
- for congenital enzymopathies;
- for organic brain lesions;
- with hypoproteinemia.
