With proven high clinical efficacy, the mechanism of action of VC is not completely understood. The main areas of influence of VC on epileptic activity are the following:
- One of the main mechanisms of epileptogenesis is depolarization associated with the activation of Na channels, which is accompanied by sustained volleys of action potentials. It is proved that valproaty inhibit excitatory synapses, reducing the activity of sodium channels.
- Valproates activate the presynaptic destruction of the excitatory transmitter glutamate.
- Valproates potentiate postsynaptic GABA-ergic inhibition, blocking GABA transaminase.
- Valproic acid preparations inhibit postsynaptic membrane low-threshold calcium currents of the thalamic neurons that underlie absences.
Pharmacokinetics
When used inside drugs VC quickly and almost completely absorbed. Peak plasma concentrations are reached after 1-2 hours when taken on an empty stomach and 4-5 hours when taken during or after a meal.
Valproate binding to plasma proteins is more than 90%. VK preparations are metabolized mainly in the liver and a very small amount (1-3%) is excreted unchanged. VK is an inhibitor of liver microsomal enzymes, therefore it causes an increase in the blood of other AEDs (phenobarbital, lamotrigine, the active metabolite of carbamazepine).
The pharmacokinetic curve after a single dose of VC approaches linear with absorption. With regular admission, a stable concentration is reached in 2-4 days after the start of therapy. Therapeutic concentration of valproate in serum is 50-100 mg / ml.
Indications for use of valproate
VK and its derivatives have a wide spectrum of anticonvulcate activity. Therefore, if the doctor is confident that the patient has epilepsy, but is not sure of the exactness of the nosological form, treatment should begin with valproate.
VK preparations are the means of the first choice in case of:
primary generalized seizures (generalized tocicoeliconics, absences, myoclonic);
partial seizures with secondary generalization;
In recent years, the high efficacy of valproates in the treatment of partial epilepsy (rolandic, temporal, etc., Brodie M. et al., 1999) has been confirmed;
in cases where the patient has difficult to classify attacks, valproate is also the drug of choice;
The positive effect of VC, in contrast to other AEDs, on the cognitive sphere contributes to the fact that these drugs are used for epilepsy in violation of higher mental functions. For example, with Landau-Kleffner syndrome or epileptic aphasia.
Valproates effectively suppress neuronal activity, which is a major factor in mental and behavioral disorders in epilepsy. The treatment is accompanied by an improvement in memory and mood, an ability for operational activities, a decrease or complete elimination of psychotic manifestations. An improvement in psychosocial adaptation is noted. Therefore, in epilepsy with psycho-communicative disorders, valproate is the drug of choice.
The presence of the parietal theta rhythm on the EEG of a patient with epilepsy is an indication for the use of valproates, as the ineffectiveness of the drugs of the carbamazepine group is proved with a similar EEG pattern.
Along with the anticonvulsant effect, valproates have an anxiolytic, thymoleptic, anti-migraine, and antinociceptive effects, which are associated with effects on the GABAergic system, as well as on the noradrenaline and serotonin transmission.
In this regard, some literature data indicate the use of VC in clinical practice for:
1) prevention of severe migraine attacks occurring with neurological symptoms;
2) behavior correction in case of organic brain lesions, secondary prevention of the development of manic or depressive stages; mixed affective or affective-delusional states within the framework of cyclotymy; TIR (Guzeva, 2002).
Contraindications to the use of valproate are abnormal liver function, including the presence in the family history of cases of liver disease, porphyria, hemorrhagic diathesis.
Treatment tactics
The beginning of treatment, as with any pharmacotherapy, is preceded by a general examination of the patient, including laboratory tests.
In the case of valproat, particular attention should be paid to blood clotting and liver function tests.
In the absence of contraindications, treatment begins (with the exception of cases of severe and frequent — daily seizures) with a gradual increase in doses, based on the minimum per weight of the body. The rate of growth is optimally U * single dose every 3 days.
The first dose should be done at night, then the morning dose is added. Increase the dose should also be, starting with the evening.
The recommended daily doses of 20-30 mg / kg / day for adults and 30-40 mg / kg / day for children. The frequency of taking the usual forms 3 times a day, prolonged – 1-2 times a day.
Poboch e actions. Dose-dependent: weight gain, hair loss, dyspepsia, nausea, vomiting. According to the mechanism of idiosyncrasy: hepatotoxicity, thrombocytopenia, encephalopathy.