What medications are prescribed for epilepsy. Anticonvulsant (antiepileptic) drugs Taking antiepileptic drugs

The modern arsenal of medicines is quite large, but insufficient for the treatment of all forms of epilepsy. Bromides (potassium bromide) were the first anticonvulsants introduced into the pharmacotherapy of epilepsy as early as 1857 by Charles Lockock. In 1938, phenytoin (difenin), a derivative of hydantoin, was synthesized structurally close to barbiturates. Since then, numerous antiepileptic drugs have been developed, but phenytoin remains the drug of choice for epilepsy with grand mal seizures. The history of the emergence of valproates as anticonvulsants dates back to 1962, when R. Eymard accidentally discovered anticonvulsant properties in these compounds. However, as a chemical compound, valproic acid was synthesized 80 years earlier - in 1882 it will melt. This compound has been used for many years in laboratory biochemical and pharmacological research work as a lipophilic agent for dissolving water insoluble compounds. To the surprise of researchers, valproic acid itself (W. Gosher) also had anticonvulsant properties. Currently, valproates remain one of the groups of anticonvulsants that are in great demand (the target for valproates is primary generalized seizures - convulsive absences and idiopathic form of epilepsy) and are used as basic drugs for monotherapy in patients with epilepsy. In recent years, new, fairly safe drugs, such as lamotrigine, topiramate, have been obtained and found their use, which are often used alongside drugs synthesized earlier, very often as a combination therapy.

Antiepileptic drugs - these are drugs of various origins used to prevent or reduce (in intensity and frequency) by the court, their equivalents (loss or impairment of consciousness, behavioral and autonomic disorders, etc.), which are observed during recurrent seizures of various forms of epilepsy.

Epilepsy is a consequence of the occurrence in the cerebral cortex or subcortical brain centers (substance nigra, tonsils, etc.) of foci of excitation that is transmitted to the nervous and muscular systems, which leads to the development of epileptic seizures or an epileptic state. The cause of epilepsy is not clear, so the main drugs are aimed at eliminating the seizure or preventing it.

The main clinical sign of epilepsy is a sudden onset of clonic or tetanic seizures with loss of consciousness. Clonic convulsions are characterized by periodic contraction and relaxation of muscles, and tonic or tetanic convulsions are characterized by simultaneous contraction of the flexor and extensor muscles, which is accompanied by a tense posture with the head thrown back, the release of bloody saliva due to biting the tongue. Such convulsions are classified as major attacks (grand mal). During small seizures (petit mal) consciousness is lost for a very short time, sometimes even the sick person herself does not have time to notice it. Very frequent seizures sometimes turn into an epileptic state. As a rule, this pathology is confirmed by characteristic epileptic waves-peaks (discharges) on the electroencephalogram (EEG), which makes it possible to accurately determine the localization of the focus of excitation. During a convulsive seizure, drugs are administered to the patient, and after it ends, an individual anti-relapse pharmacotherapy is selected.

Classification of antiepileptic drugs

By chemical structure:

I. barbiturates and their derivatives: phenobarbital (bafetal) benzobarbital (benzonal).

II. Hydantoin derivatives phenytoin (difenin).

III. Carboxamide derivatives: carbamazepine (tegretol, finlepsin).

IV. Benzodiazepine derivatives: phenazepam; clonazepam; Diazepam (Sibazon, Relium) Nitrazepam (Radedorm) Midazolam (Fulsed).

V. Fatty acid derivatives:

5.1) valproic acid (Enkorat, Enkorat-chrono, convulex)

5.2) sodium valproate (depakin, depakin-Enteric)

5.3) combined (valproic acid and sodium valproate) depakine-chrono.

VI. Various anticonvulsants and antispastic drugs: lamotrigine (lamiktal), topiramate (topamax), gabapeptin (Neuralgin).

According to the mechanism of action

1. Means that suppress sodium channels: phenytoin; carbamazepine; valproic acid; sodium valproate; topiramate; lamotrigine.

2. Means that suppress calcium channels (T and L type): trimetin; sodium valproate; gabapentin.

3. Means that activate the GABAergic system:

3.1) postsynaptic action benzodiazepines; barbiturates; gabapentin;

3.2) presynaptic action sodium valproate; tiagabine;

4. Means that suppress the glutamatergic system.

4.1) postsynaptic action barbiturates; topiramate;

4.2) presynaptic action of lamotrigine.

According to clinical indications, antiepileptic drugs can be divided into the following groups:

1. Means used in partial seizures (psychomotor seizures): carbamazepine; sodium valproate; lamotrigine; gabapentin; phenobarbital; clonazepam; diphenin.

2. Means used in generalized seizures:

2.1) grand mal seizures ( grandmat): sodium valproate; carbamazepine; phenobarbital; diphenin; lamotrigine;

2.2) small seizures of epilepsy - absence (petite mat): sodium valproate; lamotrigine; clonazepam.

3. Means used in status epilepticus: diazepam; lorazepam; clonazepam; drugs for anesthesia (sodium oxybutyrate, sodium thiopental).

Types of action of antiepileptic drugs on the body (pharmacological effects):

Anticonvulsant;

Sedative (phenobarbital, magnesium sulfate)

Sleeping pills (phenobarbital, benzobarbital, diazepam) (Fig. 3.12);

Tranquilizing (derivatives of valproic acid, diazepam) (Fig. 3.13);

Muscle relaxant (phenytoin, clonazepam, diazepam) (Fig. 3.14);

Cerebroprotective;

Analgesic (Fig. 3.15).

Action mechanism algorithm antiepileptic drugs can be summarized in two main points:

1) inhibition of pathological hyperactivity of nerve cells in the epileptogenic bonfire;

2) inhibition of the spread of hyperactivity from the epileptogenic focus to other neurons, prevents generalization of excitation and the occurrence of seizures.

In a generalized form, it is customary to distinguish 3 main mechanisms antiepilepticactions drugs, in particular:

1) facilitation of GABA and glycine-depleted (inhibitory) transmission;

2) suppression of excitatory (glutamate and aspartatergic) transmission;

3) change in ion currents (primarily blockade of sodium channels).

Indications: epilepsy: large, focal, mixed (including large and focal) epileptic seizures. In addition, the pain syndrome is predominantly of neurogenic origin, incl. essential trigeminal neuralgia, trigeminal neuralgia in multiple sclerosis, essential glossopharyngeal neuralgia. Diabetic neuropathy with pain syndrome. Prevention of seizures in alcohol withdrawal syndrome. Affective and schizoaffective psychoses (as a means of prevention). Diabetes insipidus of central origin, polyuria and polydipsia of a neurohormonal nature.

Status epilepticus, somnambulism, various forms of muscle hypertonicity, sleep disturbances, psychomotor agitation. Convulsive syndrome when editing, eclampsia, poisoning with convulsive poisons.

Rice. 3.12. Mechanism of hypnotic action

Figure 3.13. Mechanism of tranquilizing action

Rice. 3.14. Mechanism of muscle relaxant action

Rice. 3.15. Mechanism of analgesic action

For emergency treatment of acute seizures; when editing. As a sedative to reduce anxiety, tension, fear. Hyperbilirubinemia. Behavioral disorders associated with epilepsy. Febrile convulsions in children, children's tick. West syndrome.

Side effects of antiepileptic drugs their group affiliation is determined by the mechanism of action. Thus, drugs that increase GABAergic inhibition more often than others cause disturbances in behavioral reactions in patients. Skin reactions in the form of a rash are more characteristic of drugs that affect the sodium channels of cell membranes. In addition, adverse reactions can be determined by the pharmacological variability of the organism - idiosyncrasy. Idiosyncratic side effects include liver failure, which can develop when using phenytoin, carbamazepine, valproic acid salts; pancreatitis can occur when taking valproate; agranulocytosis - as a result of treatment with phenytoin, phenobarbital, carbamazepine, valproate; aplastic anemia sometimes complicates treatment with phenytoin, phenobarbital, carbamazepine; Stevens-Johnson syndrome may occur during treatment with phenytoin, phenobarbital, carbamazepine, lamotrigine; allergic dermatitis and serum sickness occur with the use of any of the antiepileptic drugs; lupus-like syndrome is more common when using phenytoin, carbamazepine. These reactions are dose-independent and may occur at any stage of therapy.

Dose-dependent side effects of anticonvulsants can be divided into 3 large groups:

1) from the side of the central nervous system (phenobarbital, phenytoin, carbamazepine, benzodiazepines, topiramate)

2) hematological (valproates, carbamazepine, phenytoin, phenobarbital)

3) leading to impaired reproductive health (valproates).

Dose-dependent side effects from the central nervous system are of great clinical importance. Phenytoin and carbamazepine can cause brainstem and cerebellar dysfunction, with ataxia, dysarthria, nystagmus, and sometimes diplopia. Tremor may be a dose-dependent stigmatizing consequence of valproate use. Paradoxical psychomotor agitation is possible in children taking benzodiazepines and barbiturates. Serum benzodiazepine concentrations greater than 20 µg/mL can lead to marked brainstem dysfunction and stupor. Already after the start of the patient's recovery from stupor, a second wave of this complication is possible, due to the formation of a large amount of toxic 10,11-epoxy metabolites. Cognitive side effects can be observed during topiramate therapy, mainly during the titration period, with a rapid increase in the dose of the drug.

Complications from the hematopoietic organs when using anticonvulsants can be clinically manifested by leukopenia, neutropenia, thrombocytopenia, as well as complex - aplastic anemia, agranulocytosis and megaloblastic anemia. Megaloblastic anemia may occur with long-term use of phenytoin. Treatment with phenytoin, carbamazepine may be complicated by agranulocytosis. Thrombocytopenia is characteristic of phenytoin, carbamazepine, and especially valproic acid, which has an inhibitory effect on platelet aggregation and depletes fibrinogen stores, which can lead to increased bleeding. Valproates cause hyperandrogenism in girls, dangerous during puberty.

Some adverse reactions to anticonvulsant zysobs are associated with their inducing effect on liver enzymes. This effect is most pronounced in phenobarbital, carbamazepine, and phenytoin. Enzyme inducers may increase the elimination of concomitant medications, especially anticonvulsants (such as lamotrigine), corticosteroids, anticoagulants, and some antibiotics. Serious problems can arise if the metabolism of endogenous substances, for example, cholecalciferol (vitamin D3), is increased, which leads to the development of rickets in children; metabolic disorders of steroid and thyroid hormones; an increase in the level of α1-acid glycoprotein, sex hormone-binding globulin, γ-glutamyl transferase and alkaline phosphatase, the ability to exacerbate porphyria.

Contraindications to the appointment of antiepileptic drugs: impaired liver and pancreas function, hemorrhagic diathesis, acute and chronic hepatitis AV blockade, myelodepression, history of intermittent porphyria, simultaneous use of MAO inhibitors and lithium preparations; myasthenia gravis; acute poisoning with drugs that have a depressing effect on the central nervous system, and alcohol; drug addiction, drug addiction; chronic alcoholism; acute pulmonary insufficiency, respiratory depression. Adams-Stokes syndrome, heart failure, cachexia; diseases of the hematopoietic system; pregnancy, lactation.

sodium valproate- sodium salt of valproic (dipropylacetic) acid.

Pharmacokinetics. After taking before meals, it is quickly and almost completely (70-100%) absorbed in the stomach and small intestine. In case of preliminary dissolution, bioavailability increases by 10-15%. But you should not dissolve the tablet in mineral water, as valproic acid may form, and the solution will become cloudy, although its activity does not decrease. After 1-3 hours, the maximum concentration in the blood plasma is reached, where sodium valproate is 90% protein-bound, and 10% of it is in an ionized form. It accumulates mainly in the structures of the central nervous system, where there is a large amount of GABA transaminase (cerebellum, etc.). It penetrates poorly to other body fluids and tissues: in the CSF - 12%; saliva - 0.4-4.5 %; nursing milk - 5-10%.

The main part of sodium valproate is metabolized in the liver to inactive derivatives, which are excreted through the kidneys and intestines. T1 / 2 about 10 hours. Only about 3% leaves the body in the form of propionic acid, which can lead to false positive results for ketonuria, as well as for urine glucose.

Pharmacodynamics. The mechanism is quite complex, not fully understood, does not fully explain the whole variety of clinical effects, since this drug has a wide spectrum of action and is indicated for almost all types of seizures. The main mechanism of action of valproates is the ability to increase the content of GABA (Fig. 3.16) in the central nervous system, which is due to:

a) inhibitory effect on the breakdown of GABA, due to the suppression of GABA transaminases;

b) increased release of GABA into the synaptic cleft;

c) an indirect effect on the synthesis and breakdown of GABA.

Gamma-aminobutyric transaminase (GABA-T) provides the conversion of GABA to succinate (succinate, succinic) semialdehyde in the GABA cycle, is closely related to the Krebs cycle. Due to the inhibition of this enzyme, a large amount of the inhibitory mediator GABA accumulates, which leads to a decrease in the activity of overly excited nerve cells in the epileptic focus. Sodium valproate does not reduce, but also increases a person's vigilance, while barbiturates significantly suppress it. In patients prone to depressive reactions, sodium valproate improves mood, improves mental state, reduces fears without causing a hypnogenic effect.

In addition, valproate exhibits a moderately pronounced n-anticholinergic effect, as evidenced by the prevention of nicotine-induced tonic convulsions by valproate.

Indications: epilepsy, especially in children.

Rice. 3.16. Neurotransmitter action profiles of sodium valproate.

Note: "+" - activation; "-" - Inhibition, Sir - serotonin, N-xp - n-cholinergic receptor, DA - dopamine, HA - noradrenshn, GABA - γ-shobutyric acid, GABA-T GABA-transaminshch MPC - glutamate decarboxylase, BD-site - benzodiazepine site, Glu - glutamate

Contraindications: pregnancy, lactation, liver disease, pancreas, hemorrhagic diathesis, hypersensitivity to the drug, alcohol consumption; drivers and other persons whose work requires increased attention should not be taken.

Side effects: loss of appetite, nausea, abdominal pain, vomiting, diarrhea, sometimes impaired liver function, pancreas (more often 2-12 weeks after the start of the drug does not require discontinuation of treatment, but requires careful monitoring of the patient's condition); hair loss (0.5%); weight gain; acute hepatoencephalopathy (only children under 2 years of age in terms of polytherapy) hemorrhagic-necrotic pancreatitis (extremely rare).

Interaction. Sodium valproate in combination with diphenine and phenobarbital displaces both drugs from their association with proteins and significantly increases the content of their free fractions in the blood. In some cases, the drug against the background of another antiepileptic drug can lead to excitation of the body.

Difenin (phenytoin) according to the chemical structure, it is a derivative of hydantoin (a mixture of 5,5-diphenylhydantoin and sodium bicarbonate). The main mechanism of action of difenin is the suppression of not one epileptic focus in the cerebral cortex or in subcortical structures, but a decrease in the irradiation of epileptic discharges to other brain centers and through the efferent nerves to the muscular system. Along with this, the drug reduces the excitability of nerve cells and increases the threshold for secondary trace discharges, which determine the maintenance of epileptic activity in the focus. Probably, this effect is due to the inhibition of NADH-dehydrogenase activity in the mitochondria of nerve cells, a significant decrease in oxygen consumption in them, and, consequently, insufficient energy supply for epileptic discharges. Equally important is the reduced penetration of calcium into nerve cells and its ionization in cells that produce mediators and hormones that can provoke the development of epileptic discharges.

Difenin effectively suppresses the spread of epileptic impulses without changing the normal function of nerve cells. The drug significantly weakens, and in the case of long-term use, it can completely prevent the development of major seizures in patients with focal or focal epilepsy.

Indications: epilepsy of various forms (generalized tonic-clonic, simple and complex partial psychomotor seizures); prevention by court after injuries and neurosurgical operations on the brain.

Contraindications: peptic ulcer of the stomach and duodenum, severe violations of the liver, kidneys, decompensation of cardiac activity, diseases of the hematopoietic system.

Side effect triad of symptoms (nystagmus, diplopia, ataxia), gingival hyperplasia.

Carbamazepine, unlike difenin, which suppresses the spread of epileptic discharges in the brain, it acts mainly on the nerve cells of the spinal cord and medulla oblongata. Its anticonvulsant activity is almost 3 times less than difenin. Carbamazepine normalizes metabolism, activates the choline and adrenergic mediator systems, and has a high antidepressant effect. It significantly inhibits the activity of Na +, K + -ATPase, reduces the elevated level of cAMP, which is considered as the main mechanism of its antiepileptic effect. After taking it, patients have increased motivation for treatment, increased mood, interest in the environment, decreased depression, fear, hypochondria.

Indications: all forms of epilepsy, especially the "temporal" form with aura, myoclonic and tonic-clonic spasms of the muscles of the face.

Contraindications: pregnancy, bronchial asthma, blood diseases, disorders of the liver, kidneys.

Side effect. Of course, adverse reactions appear in the first week after the start of treatment, more often in the elderly in the form of nausea, anorexia, vomiting, dizziness, ataxia, and allergic reactions. Sometimes there is also an increase in seizures, especially in children. Rarely - jaundice, changes in the blood picture (thrombocytopenia, agranulocytosis, aplastic anemia, etc.), peripheral neuritis.

Interaction. When combining carbamazepine with diphenine, the level of the latter in the blood plasma may increase due to a delay in its metabolism. Difenin and phenobarbital reduce the level of carbamazepine in blood plasma by accelerating its biotransformation.

Recently, a group of new generation drugs has appeared, in particular, lamotrigine, tiagabine, etc. They have a different mechanism of action, but the final effect is to reduce the level of excitatory (glutamic acid) or accumulation of inhibitory mediators (GABA, glycine) in the CNS. Tiagabin(gabitril) is, in contrast to the irreversible GABA blocker, its functional blocker.

Lamotrigine blocks long-term high-frequency discharge of neurons in the same way as depakine and carbamazepine. It is assumed that this effect is mediated by a suppressive effect on the voltage-gated sodium channels of neurons and a prolongation of the refractory period of the cell. Lamotrigine inhibits the release of excitatory glutamic acid, indicating a possible neuroprotective effect of this drug. Lamotrigine is well absorbed when taken orally (both when taken with and without food). Bioavailability close to 100 %. Serum concentration is reached 2-3 hours after taking the drug. Lamotrigine is metabolized in the liver, mainly by conjugation with glucuronic acid. Its main metabolite, 2-N-glucuronic acid conjugate, is excreted in the urine.

Indications: forms of epileptic seizures resistant to other drugs, primarily partial, primary and secondary generalizations, absences, atonic, Lennox-Gastaut syndrome.

Side effect allergic reactions in the form of skin rashes, angioedema, diplopia, blurred vision, dizziness, drowsiness, headache, when combined with valproates - squamous dermatitis.

Interaction diphenin, phenobarbital and carbamazepine reduce the concentration of lamotrigine. Valproate increases (up to 2 or more times) the concentration of lamotrigine, given the potentiating effect of the interaction of lamotrigine and valproate, it is recommended to prescribe a dose of lamotrigine not higher than 250 mg / day to prevent the development of side effects.

Topiramate well absorbed after oral administration (both with and without food). The maximum plasma concentration is reached 2-4 hours after ingestion. Approximately 15% of the drug binds to plasma proteins. Only a small amount of topiramate is metabolized in the liver, while approximately 80 % The drug is excreted unchanged in the urine.

Pharmacodynamics Topiramate blocks voltage-dependent sodium channels of the membrane, potentiates GABA activity at non-benzodiazepine sites of GABA receptors. It blocks the corresponding types of glutamate receptors in the postsynaptic membrane.

Indications: epilepsy (great tonic-clonic seizures, astatic (falls) in Lennox-Gastaut syndrome as an additional drug in cases resistant to other drugs).

Side effect ataxia, decreased concentration, confusion, dizziness, fatigue, drowsiness, paresthesia, thought disorders.

Epilepsy is a chronic brain disease characterized by a tendency to form a pathological focus of synchronous discharge of neurons and is manifested by large, small seizures and epileptic equivalents.

In the treatment of epilepsy, the principle of monotherapy is used - a life-long intake of one specific drug. Bi- and tritherapy are sometimes used when the patient takes two or more medications. Polytherapy is used when monotherapy with one drug does not work.

Basic Approach

Antiepileptic drugs are a group of drugs that prevent the development of seizures and stop an acute epileptic seizure.

For the first time in clinical practice, bromides were used. Despite their low efficiency, they were prescribed from the middle of the 18th to the beginning of the 20th centuries. In 1912, the drug phenobarbital was first synthesized, but the drug had a wide range of side effects. Only in the middle of the 20th century did researchers synthesize phenytoin, trimethadione, and benzobarbital, which had fewer side effects.

In the course of development, doctors and researchers drew up principles that modern drugs for the treatment of epilepsy should comply with:

• high activity;
• duration of action;
• good absorption in the digestive organs;
• low toxicity;
• influence on most pathological mechanisms of epilepsy;
• lack of dependence;
• no side effects in the long term use.

The goal of any pharmacological therapy is to completely eliminate seizures. But this is achieved only in 60% of patients. The rest of the patients acquire drug intolerance or persistent resistance to antiepileptic drugs.

The disease is based on a pathological process in which a large group of neurons are synchronously excited in the brain, due to which the brain issues uncontrolled and inadequate commands to the body. The clinical picture of symptoms depends on the localization of the pathological focus. The task of drugs for the treatment of epilepsy is to stabilize the membrane potential of the nerve cell and reduce their excitability.

Anticonvulsants for epilepsy have not been well studied. However, their fundamental principle mechanism of action is known - inhibition of excitation of brain neurons.

Excitation is based on the action of glutamic acid, the main excitatory neurotransmitter of the nervous system. Drugs, such as phenobarbital, block the reception of glutamate in the cell, due to which the electrolytes Na and Ca do not enter the membrane and the action potential of the neuron does not change.

Other agents, such as valproic acid, are glutamine receptor antagonists. They prevent glutamate from interacting with the brain cell.

In the nervous system, in addition to excitatory neurotransmitters, there are inhibitory neurotransmitters. They directly suppress cell excitation. A typical representative of inhibitory neurotransmitters is gamma-aminobutyric acid (GABA). Drugs of the benzodiazepine group bind to GABA receptors and act on them, causing inhibition in the central nervous system.

In the synaptic clefts - in the place where two neurons come into contact - there are enzymes that utilize certain neurotransmitters. For example, after the processes of inhibition, small residues of gamma-aminobutyric acid remained in the synaptic cleft. Normally, these residues are utilized by enzymes and subsequently destroyed. So, for example, the drug Tiagabine prevents the utilization of the remaining gamma-aminobutyric acid. This means that the concentration of the inhibitory neurotransmitter does not decrease after its exposure, and it further inhibits excitation in the postsynaptic membrane of the neighboring neuron.

The inhibitory neurotransmitter gamma-aminobutyric acid is produced by the breakdown of the excitatory neurotransmitter glutamate by the enzyme glutamate decarboxylase. For example, the drug Gebapantin accelerates the utilization of glutamate to produce more gamma-aminobutyric acid.

All of the above drugs affect indirectly. However, there are drugs (carbamazepine, phenytoin or valproate) that directly affect cell physiology. The neuron membrane has channels through which positively and negatively charged ions enter and exit. Their ratio in the cell and around it determines it, the cell, the membrane potential and the possibility of subsequent inhibition or excitation. Carbamazepine blocks voltage-gated channels and prevents them from opening, as a result of which ions do not enter the cell and the neuron is not excited.

From the list of drugs it is clear that the doctor has a modern arsenal of antiepileptic drugs of different groups that affect many mechanisms of excitation and inhibition of the cell.

Classification

Antiepileptic drugs are classified according to the principle of influence on the mediator and ionic systems:

1. Drugs that enhance the activity of inhibitory neurons by stimulating and increasing the amount of gamma-aminobutyric acid in the synaptic cleft.
2. Drugs that inhibit the excitation of neurons by inhibiting glutamic acid receptors.
3. Drugs that directly affect the membrane potential by acting on voltage-gated ion channels of nerve cells.

New generation drugs

There are three generations of antiepileptic drugs. The third generation is the most modern and studied means in the treatment of the disease.

Antiepileptic drugs of the new generation:

• Brivaracetam.
• Valrocemide.
• Ganaxolone.
• Caraberset.
• Karisbamat.
• Lacosamide.
• Losigamon.
• Pregabalin.
• Retigabalin.
• Rufinamide.
• Safinamide.
• Seletracetam.
• Serotolid.
• Stiripentol.
• Talampanel.
• Fluorofelbamate.
• Phosphenition.
• DP-valproic acid.
• Eslicarbamazepine.

13 of these drugs are already being tested in laboratories and clinical trials. In addition, these drugs are being studied not only as an effective treatment for epilepsy, but also for other psychiatric disorders. The most studied and already studied drugs are Pregabalin and Lacosamide.

Possible side effects

Most antiepileptic drugs suppress the activity of neurons, causing inhibition in them. This means that the most common effect is central nervous system sedation and relaxation. Means reduce the concentration of attention and the speed of psychophysiological processes. These are non-specific adverse reactions that are characteristic of all antiepileptic drugs.

Some of the remedies have specific side effects. For example, phenytoin and phenobarbital in some cases provoke blood cancers and softening of bone tissue. Preparations based on valproic acid cause trembling of the extremities and dyspeptic symptoms. When taking Carbamazepine, visual acuity decreases, double vision and swelling of the face appear.

Many drugs, in particular drugs based on valproic acid, increase the risk of defective fetal development, so these drugs are not recommended for pregnant women.

Many have heard about epilepsy, but not everyone understands what kind of disease it is, why it occurs and how it proceeds. In most cases, we imagine an epileptic seizure, when a person is convulsing and foaming at the mouth. However, such phenomena are just a small part of the possible options for the development of the disease, because there are many manifestations of such a pathological condition. Many patients can live without seizures at all, provided they take their epilepsy medication on time and have regular check-ups.

This disease has been known for a long time. Epilepsy, perhaps, is one of the oldest forms of brain ailments, which was recognized and tried to be treated with folk methods hundreds of years ago. Since ancient times, people suffering from such a pathology preferred to hide their diagnosis. This often happens today.

What it is

Epilepsy has been known to people for a long time: even ancient Greek healers associated epileptic seizures with the world of the gods and believed that this ailment was sent to them for an unworthy image of their being. In 400 BC, the prominent ancient Greek physician and philosopher Hippocrates described this phenomenon. He believed that the cause of epileptic seizures was natural conditions that could provoke liquefaction of the brain.

In the Middle Ages, this disease was feared, believing that it was transmitted from the patient during an epileptic seizure. Meanwhile, they trembled before her, since many saints and prophets suffered from such an affliction.

Modern medicine has proven that epilepsy is a chronic brain disease, an indicator of which is regularly recurring seizures. This is a very common disease that affects about 50 million people worldwide, which is approximately 1% of the total population of the planet.

How the disease appears

Many patients think about what was the beginning of the disease, because this is a dangerous condition and requires mandatory medical supervision. Medicine distinguishes three main groups of factors that can lead to the development of the disease:

• Idiopathic (genetic predisposition). Even after tens of generations, the disease can be transmitted. In this case, there are no organic defects and damages in the brain, but there is a certain reaction of neurons. With this form of pathology, an epileptic seizure can begin without a reason.
• Symptomatic. The disease can appear after trauma, intoxication or tumor processes in the brain. This form of epilepsy occurs spontaneously, and seizures can occur unpredictably.
• Cryptogenic. A little-studied factor, the exact cause of which has not yet been established. A seizure can happen due to any psycho-emotional stimulus.

The disease can manifest itself at any age, however, according to statistics, small children, adolescents and adults over 60 are more likely to have epilepsy. To date, medicine has identified about 40 different types of epilepsy. Therefore, the attending physician must conduct an accurate diagnosis in order to establish the form of the disease and determine the nature of the seizures. The effectiveness of the results in certain cases depends entirely on the adequacy of the choice of an antiepileptic drug and the appointment of a treatment regimen. With untimely or inadequate treatment, the patient may die. Therefore, a complete examination of the patient and an accurate diagnosis of the disease are necessary.

A spontaneous attack can occur with hormonal changes in the body, alcohol intoxication, or the appearance of flickering and flashing pictures while driving a car.

Examinations and treatment

If epilepsy is suspected, the patient is comprehensively examined. First of all, the patient is examined by a neurologist and studies the anamnesis of the course of the disease, including family history. The patient is assigned research:

• blood;
• fundus;
• x-ray of the cranium;
• Doppler study of the cerebral arteries.

It is mandatory to visualize the structure, functions and biochemical characteristics of the brain using X-ray, computed or magnetic resonance imaging (MRI). Electroencephalography (EEG) is of great importance in the diagnosis of the disease.

Such laboratory studies are aimed at determining the true causes of the disease and the exclusion of pathologies that can cause seizures, but are not associated with brain diseases.

The main effect on epilepsy is medications. The result of medical care in the treatment of pathology depends both on the correct selection of drugs, and on the implementation of all the doctor's recommendations by the patient. The principle of medical intervention is an individual approach to each patient, continuity and duration of treatment. Antiepileptic therapy will be effective for:

• early onset of exposure to the manifestation of characteristic symptoms with antiepileptic drugs;
• striving for monotherapy;
• the right choice of medication for epilepsy, depending on the uniformity of seizures of a particular patient;
• if necessary, the introduction of a rational combination of polytherapy (if there is no effect from the use of one agent);
• the appointment of suitable medications in dosages that provide complete therapy;
• taking into account the pharmacokinetic and pharmacodynamic properties of prescribed drugs;
• monitoring the presence of antiepileptic drugs in the patient's body.

Epilepsy medications cannot be stopped at the same time. They should be taken until complete relief from pathological manifestations is obtained. Only in cases of individual intolerance to the components of the drug, allergies, or in case of manifestations of side effects, a gradual withdrawal of the drug is necessary. Doses of drugs for the treatment of epilepsy are gradually reduced. If the doctor decides that the therapy does not bring the desired result, then new drugs are also gradually introduced.

It has been proven that almost all patients who are first diagnosed with epilepsy can fully control the occurrence of seizures with the help of antiepileptic drugs. After 2-5 years of full treatment, most patients can stop treatment without risk of relapse.

Drug groups

Achieving optimal results in the treatment of epilepsy is largely determined by the correct calculation of the dose and duration of treatment. Depending on the symptomatic manifestations, the names of the recommended drugs may belong to different groups of drugs:

• Anticonvulsants. Drugs belonging to this group of drugs help to relax muscle tissue. They are often recommended for the treatment of various epileptic forms. Similar drugs can be prescribed to both an adult and a child in the presence of tonic-clonic and myoclonic seizures.
• Tranquilizers. The purpose of this group of drugs is the removal or suppression of nervous excitability. They help in the fight against the manifestations of small seizures. However, such drugs are used with caution, since at the beginning of the reception they can aggravate the severity of the course of the disease.
• Sedatives. Not all epileptic seizures end well. Often before, immediately before or after a seizure, the patient falls into severe depressive states, becomes irritable or aggressive. Sedatives in combination with a visit to a psychotherapist can calm and relieve such symptoms.
• Injections. Used in twilight states and affective disorders. Injections of nootropic drugs (actovegin, cerebrolysin, etc.) have proven themselves as a means of alleviating and localizing some symptoms of neurological disorders

The action of medications

It is known that if you regularly and timely take anticonvulsants for epilepsy, you can completely control the appearance of epileptic seizures. Modern medicines allow:

• block the system of excitability of neurons of the epileptic focus;
• stimulate the activity of the inhibitory complex of gamma-aminobutyric acid receptors;
• act on ion channels and stabilize neuronal membranes.

The prescribed pills for epilepsy can have both one of these mechanisms of action, and their complex. Modern antiepileptic drugs are conditionally divided into drugs of the 1st line (basic category) and 2nd line (latest generation drugs). Depending on the symptoms shown, the doctor recommends taking certain drugs.

Basic category of antiepileptic drugs

In our country, basic therapy preparations are used as the main direction in the treatment of signs of epilepsy. The list of these drugs includes drugs that have been tested for many years and have good results in treatment. These include:

• Phenobarbital (Luminal);
• Primidone (Hexamidin);
• Benzobarbital (Benzene);
• Lamotrigine;
• Phenytoin (Difenin, Epanutin);
• Carbamazepine (Tegretol, Finlepsin);
• Valproic acid and its salts (Convulex, Depakine);
• Ethosuximide (Petnidan, Suxilep, Zarontin);
• Levetiracetam (Keppra, Levetinol, etc.).

This is not the whole list of drugs that are recommended for epileptics to drink. The choice of this or that medicine depends on the form of the disease, the nature of the attacks, the age and sex of the patient.

2nd line preparations

Means belonging to the second category of antiepileptic drugs do not have the same spectrum of action or have a larger list of contraindications than the basic ones. Luminal, Diakarb, Lamictal, Sabril, Frizium or Seduxen have a good therapeutic effect and they are also often recommended as effective epilepsy pills, but for a short time.

The list of drugs for the treatment of epilepsy is very large. Epilepsy should be treated by a doctor. Self-selection of drugs and inadequate self-medication can lead to death.

Migraine and depression are constant companions of epilepsy. It has been proven that in patients suffering from migraine, manifestations of epilepsy occur much more often. At the same time, it turned out that depressive states in people with controlled seizures occur 20% less often than in people with uncontrolled seizures.

Polytherapy: combined treatment regimen

In the treatment of this pathology, the doctor seeks to come to monotherapy. This allows you to choose the right drug, the optimal dosage and the appropriate treatment regimen, as well as achieve high clinical efficacy. In addition, monotherapy minimizes the side effects of treatment.

However, in some situations it is more appropriate to choose a combined regimen for the use of drugs. This is how they do it:

• In the form of a pathological process, which combines several types of seizures at once and there is no possibility of full-fledged monotherapy;
• In conditions accompanied by the same type of epileptic seizures, but not treatable by any of the medications.

In these cases, medications with different mechanisms of action are used in therapy regimens. However, the chosen treatment tactics should be rational and combine drugs that do not counteract each other. For example, a prohibited combination is the simultaneous use of phenobarbital with primidone and benzobarbital or phenytoin with lamotrigine.

When using a combined treatment method, a slight decrease in the therapeutic effect is possible. Often, patients experience signs of intoxication when using one of the drugs that was previously well tolerated. Therefore, at the initial stages of polytherapy, control of the level of the drugs used in the blood plasma is necessary.

Duration of treatment

Termination or reduction of epileptic seizures, reduction of their duration, relief and improvement of the psycho-emotional state of the patient is already considered a positive trend in treatment. The use of the latest methods of pharmacotherapy allows to achieve complete relief or significant minimization of seizures.

The duration of drug therapy is determined by the type of attacks and the form of the disease, the age and individual characteristics of the patient. Practical recovery can occur with idiopathic forms of epilepsy. A small percentage of relapses occur in idiopathic forms with absences occurring in childhood or adolescence. Cancellation of treatment for low recurrence epilepsy is possible after two years of remission. In other cases, the question of stopping therapy can only be raised after five years of remission. At the same time, the EEG should show a complete absence of pathological activity.

Anticonvulsant drugs are used as a means to eliminate pain symptoms and muscle spasms, to prevent the transition from a state of pain attacks to convulsive and.

The activation of a nerve impulse simultaneously by a group of certain neurons is similar to the signal given by motor-type neurons in the cerebral cortex. In the event of a lesion of this type, the nerve endings do not appear in tics or convulsions, but cause bouts of pain.

The purpose of the use of anticonvulsants is to eliminate pain or muscle spasms without provoking oppression of the central nervous system. Depending on the complexity of the disease, these drugs can be used from several years to lifelong use in severe chronic or genetic forms of the disease.

Attacks of convulsive activity are associated with an increase in the degree of excitation of nerve endings in the brain, usually localized in certain areas of its structure and diagnosed upon the onset of a condition characteristic of the onset.

The cause of seizures can be a deficiency in the body of essential chemical elements, such as magnesium or potassium, pinching of a muscle nerve in the canal, or a sharp prolonged exposure to cold. Deficiency of potassium, calcium or magnesium provokes failures in the transmission of signals to the muscles from the brain, as evidenced by the occurrence of spasms.

In the initial stage, the manifestation of the development of a neurological type of disease consists in local pain sensations emanating from the area of ​​\u200b\u200bthe affected nerve cells and manifested by bouts of pain of varying strength and nature of manifestation. With the course of the disease due to the development of inflammatory processes or muscle spasms in the area of ​​pinched nerve endings, the strength of the attacks increases.

In the case of an early appeal to a specialist, a complex of drugs is used for therapy, eliminating the causes and signs of damage to the nerve endings. Self-diagnosis and treatment does not allow choosing from a wide range of anticonvulsant drugs the most suitable for relieving pain symptoms and eliminating the cause of discomfort.

Most of the drugs used in the treatment of seizures have combined effects and have many contraindications, on the basis of which, the unauthorized prescription and use of these drugs can pose a danger to the patient's health.

When observed by a specialist, he evaluates the work of the prescribed drug by its effectiveness and diagnoses the absence of pathological changes after taking it according to the results of blood tests.

Fundamentals of anticonvulsant therapy

The composition of complex treatment for convulsive manifestations includes groups of drugs of various principles of action, including:

Some of the prescribed drugs have the effect of inhibiting the development or preventing the occurrence of allergic-type reactions.

The main groups of anticonvulsants

Anticonvulsants are divided into several groups, a list of which is offered below.

Iminostilbenes

Iminostilbenes are characterized by an anticonvulsant effect, after their use, pain symptoms are eliminated and mood is improved. The drugs in this group include:

• Tegretol;
• Amizepine;
• Zeptol.

Sodium valproate and derivatives

Valproates, used as anticonvulsants and as iminostilbenes, help to improve the emotional background of the patient.

In addition, when using these drugs, tranquilizing, sedative and muscle relaxant effects are noted. The drugs in this group include:

• Acediprol;
• sodium valproate;
• Valparin;
• Convulex;
• Epilim;
• Apilepsin;
• Diplexil.

Barbiturates

Barbiturates are characterized by a sedative effect, help lower blood pressure and have hypnotic effect. Among these drugs, the most commonly used are:

• Benzobamyl;
• Benzamyl;
• Benzoylbarbamyl;
• Benzoal.

Benzodiazepines

Anticonvulsants based on benzodiazepine have a pronounced effect, they are used in the event of the appearance of convulsive conditions in epilepsy and prolonged attacks of neuralgic disorders.

These drugs are characterized by sedative and muscle relaxant effects, with their use, normalization of sleep is noted.

Among these drugs:

• Antilepsin;
• Klonopin;
• Ictoril;
• Ravatril;
• Ravotril;
• Rivotril;
• Ictorivil.

Succiminides

Anticonvulsants of this group are used to eliminate spasms of the muscles of individual organs with neuralgia. When using drugs in this group, sleep disturbances or nausea are possible.

Among the most used means are known:

• Pufemid;
• Suxilep;
• Succimal;
• Ronton;
• Etimal;
• Ethosuximide;
• Pycnolepsin.

Anticonvulsants used for leg cramps:

• Valparin;
• Xanax;
• Difenin;
• Antinerval;

Hitting the nine convulsive "gates"

The main anticonvulsants that are most often used for epilepsy, convulsive seizures and neuralgia of various origins:

Practical experience of consumers

What is the situation with anticonvulsant therapy in practice? This can be judged by the reviews of patients and doctors.

I take Carbamazepine as a replacement for Finlepsin, since the foreign analogue is more expensive, and the domestic drug is excellent for therapy with my illness.

Since I tried both drugs, I can say that both drugs are highly effective, but a significant difference in cost is a significant disadvantage of a foreign remedy.

Ivan

After several years of taking Finlepsin, on the advice of a doctor, I changed it to Retard, since the specialist believes that this drug is more suitable for me. I had no complaints while taking Finlepsin, however, in addition to a similar action, Retard has a sedative effect.

In addition, the drug is characterized by great ease of use, since, compared with analogues, it must be taken not three times a day, but once.

Victor

The drug Voltaren helps with pain syndromes of moderate severity. It is good to use it as an addition to the main treatment.

Luba

Time to collect stones

A distinctive feature of anticonvulsants is the impossibility of a quick end of their intake. With a noticeable effect from the action of the drug, the term for canceling its use is up to six months, during which there is a gradual decrease in the rate of taking the drug.

According to the popular opinion of doctors, the most effective drug for the treatment of seizure activity is Carbamazepine.

Less effective are such drugs as Lorazepam, Phenytoin, Seduxen, Clonazepam, Dormicum and valporic acid, arranged in order of decreasing their therapeutic effect.

It remains to be added that it is impossible to obtain anticonvulsants without prescriptions, which is good, since it is very dangerous to take them irresponsibly.

Antiepileptic drugs prevent and reduce the frequency and intensity of seizures and their equivalents in epilepsy. This disease is characterized by unprovoked, recurrent (two or more) seizures or progressive neurological deficits that correlate with persistent focal or secondarily generalized epileptic activity on the EEG. Epilepsy affects 0.5 - 1% of the adult population and 1 - 2% of children (100 million people). The debut of epilepsy in 70% of cases falls on the age of up to 12 years. The number of new cases in 1 year reaches 100 per 100,000 population.
The pathogenesis of epilepsy is due to the functioning of the epileptogenic focus in the brain. It consists of 103 - 105 neurons with pathologically altered membranes that have increased permeability to sodium and calcium ions. These neurons, spontaneously generating high-frequency action potentials, form a hypersynchronous discharge. In the center of the epileptogenic focus are constantly "epileptically" functioning neurons, "dormant" neurons are localized along the periphery. Their inclusion in the pulsed activity increases the power of the hypersynchronous discharge. Most often, an epileptogenic focus is formed in structures with a low threshold of excitation - the mediobasal regions of the cerebral cortex, the hippocampus, amygdala, thalamus, and the reticular formation of the midbrain.
The next step in the progression of epileptogenesis is the formation of the epileptic system - the excitation of the conduction systems and centers of the brain. With right hemispheric foci, epileptic activity first spreads to the subcortical structures of the left hemisphere, with left hemisphere foci, the centers of their own hemisphere are excited first of all. With the progressive course of epilepsy, total epileptization of neurons develops (“epileptic brain”).
The antiepileptic defense system consists of structures with a well-functioning system of GABAergic inhibition - the fronto-orbital cortex, the striatum, the cerebellum, and the pontine reticular formation. They generate slow waves that suppress epileptic discharges.
The reasons for the high incidence of epilepsy in childhood are the morphological and functional features of the brain of children - significant hydration, incomplete myelination, long duration of action potentials, slow activation of potassium channels during repolarization, the predominance of excitatory glutamatergic synapses, and the excitatory effect of GABA. Epileptic discharges cause a delay in the psychomotor and psychoverbal development of the child.
There are generalized and partial (focal) forms of epilepsy (Table 32). For a long time, generalized epilepsy accounts for 5-6% of cases, partial epilepsy - 83%.
Generalized tonic-clonic epileptic seizures occur as a result of frequent action potentials caused by the entry of sodium ions into neurons. During the resting potential, sodium channels are closed (external activation and intracellular inactivation gates are closed); when depolarized, the channels open (both types of gates are open); during the period of repolarization, sodium channels are in an inactivated state (activation gates are open, inactivation gates are closed).
Antiepileptic drugs that have a therapeutic effect in tonic-clonic seizures (difenin, carbamazepine, valproates, lamotrigine, topiramate) prolong the inactivated state of sodium channels and slow down repolarization. This delays the onset of the next action potential and leads to a more rare generation of discharges in neurons.
With absences, the focus of convulsive activity is localized in the thalamus. Thalamic neurons generate action potentials at a frequency of three per 1 s as a result of the entry of calcium ions through T-type channels (English transient - transient, short-term). Thalamic impulses excite the cerebral cortex. Calcium ions, having a neurotoxic effect, create the danger of a progressive mental disorder.

Drugs effective for absence seizures (ethosuximide, valproates) block G-channels, suppress calcium-type action potentials in the thalamus, eliminate their excitatory effect on the cortex, and have a neuroprotective effect.
In epilepsy, the function of inhibitory GABAergic synapses is impaired, the function of synapses that release excitatory amino acids, glutamine and aspartic, increases. A decrease in the work of inhibitory synapses by only 20% is accompanied by the development of convulsive seizures.
Table 32. Forms of epilepsy and means for their therapy

Phenobarbital, hexamidine, benzonal, clonazepam and topiramate potentiate GABAergic inhibition caused by GABA receptors. These receptors, opening the chloride channels of neurons, increase the entry of chloride ions, which is accompanied by hyperpolarization.
Valproates activate an enzyme that catalyzes the formation of GABA from glutamic acid,

• glutamate decarboxylase, and also inhibit the GABA inactivation enzyme - GABA transaminase. Vigabatrin irreversibly blocks GABA transaminase. Gabapentin triples the release of GABA from presynaptic terminals. As a result, valproate, vigabatrin and gabapentin cause a significant accumulation of GABA in the brain. Lamotrigine, blocking the sodium channels of the presynaptic membrane, reduces the release of glutamic acid. Topiramate is an excitatory kainate glutamic acid receptor antagonist.

Recently, epileptic encephalopathy has been distinguished in the classification of epilepsy. It combines those forms of epileptic syndromes in which epileptic activity during the interictal period causes severe brain dysfunction in the form of progressive neurological, neuropsychological and psychiatric symptoms. Of great importance in the formation of mental disorders is the degeneration of neurons that carry receptors for excitatory amino acids. Changes in the psyche in patients with epilepsy are nonspecific and depend on the localization of the epileptogenic focus and the direction of propagation of its discharges. The left hemispheric lesions are characterized by verbal memory disorders, cognitive dysfunction in the speech sphere, ignoring details, depression and anxiety, while the right hemisphere lesions cause visual memory impairment, pronounced verbal and spatial disorders, emotional instability, and euphoria. Only in chronic patients who have been in psychiatric hospitals for years, classical symptoms of an epileptic nature are observed - concreteness of thinking, mental viscosity, excessive pedantry, affective explosiveness, touchiness, pettiness, stubbornness. Many antiepileptic drugs improve the psyche of patients.
In the ХIХv. bromides in high doses were the main means of treatment for epilepsy. In 1912, phenobarbital was used to treat epilepsy. Its hypnotic influence prompted the search
drugs with selective anticonvulsant effect. Difenin, discovered in 1938 during the screening of many compounds in a model of tonic-clonic epileptic seizure (maximum electric shock), became such a drug. Until 1965, trimetin and ethosuximide, the treatment of absences, entered medical practice; after 1965, carbamazepine, valproates, lamotrigine, and gabapentin were created.
PRINCIPLES OF TREATMENT OF EPILEPSY
Patients with epilepsy are treated by family physicians and general practitioners, unless resistance to therapy and associated severe disorders do not require specialized help from a neurologist, psychiatrist or epileptologist. The goal of pharmacotherapy is the complete cessation of seizures without neuropsychiatric and somatic side effects, improving the quality of life and ensuring the pedagogical, professional and social adaptation of patients. It is impossible to achieve the elimination of seizures at any cost. "Price", i.e. side effects of antiepileptic drugs should not exceed the benefit received by the patient from positive treatment.
Drugs are prescribed for a long time to prevent seizures (starting from the second). Epileptic seizures, with the exception of status epilepticus, do not stop. Treatment may not be required for rare seizures during sleep, seizures with a frequency of one in 2 to 3 years, seizures due to the abuse of alcohol and psychotropic drugs, seizures in the acute period of traumatic brain injury, simple febrile seizures.
The ideal antiepileptic drug should be potentially effective in all types of seizures and at the same time have its target - the types and forms of seizures in which its action is most pronounced. About 35% of patients receive valproates, 25% - carbamazepine, each of the drugs of the other groups accounts for no more than 10-15%. The principles of pharmacotherapy for epilepsy are as follows:

• if possible, monotherapy is carried out taking into account the form of epilepsy, the type of seizures, individual tolerability of the drug, liver and kidney function; the combination of anticonvulsants does not always increase the effectiveness of treatment (there is an induction of biotransformation of xenobiotics);
• with polymorphic and asynchronous seizures, duotherapy is necessary, with catastrophic epilepsy, polytherapy is immediately resorted to;
• the effectiveness of therapy is assessed only after a few weeks of continuous use of drugs, effective drugs reduce the number of seizures by at least 50-75% (selection of an effective dose of drugs is facilitated with frequent seizures); therapeutic doses of antiepileptic drugs are set, focusing on the clinical effect and EEG parameters, the doses of traditional drugs can be adjusted based on their concentration in the blood;
• phenobarbital, hexamidine, benzonal, valproates, gabapentin are immediately prescribed in an average effective therapeutic dose; the dose of carbamazepine, lamotrigine, topiramate is titrated slowly; replacement of an ineffective agent with another is carried out smoothly, increasing the dose of an alternative drug without canceling the main one; if the drug of the second choice gave a therapeutic effect, the first drug is canceled with a return to monotherapy;
• pharmacotherapy is carried out continuously (when the drugs are stopped, remission failure and even status epilepticus occur);
• take into account that antiepileptic drugs can provoke the development of other types of seizures (with ethosuximide therapy, there is a danger of tonic-clonic and myoclonic seizures, barbiturates contribute to the aggravation of absence seizures, carbamazepine and gabapentin - absence seizures and myoclonic attacks); if this happens, it is necessary to reconsider the diagnosis and correct the therapy;
• in women in the pubertal period, the doses of antiepileptic drugs are increased by 1/4 - 1/3 (estrogens contribute to the development of seizures, progesterone has an anticonvulsant effect); during pregnancy, monotherapy is carried out in the minimum effective individual dose,
  practice frequent divided doses or prescribe drugs with controlled release, in the first 12 weeks. take folic acid (difenin causes congenital malformations in 9% of cases, phenobarbital - in 5%, carbamazepine - in 6%, valproates - in 11%);
• in elderly patients, doses of antiepileptic drugs (drugs of choice - valproates) are reduced by 1/3 - 1/2 depending on age, taking into account the presence of neurological, mental and somatic diseases.

Table 34. Characteristics of remissions in epilepsy

In 60 - 90% of patients in a hospital setting and in 33% of patients receiving outpatient care, it is possible to control all types of epileptic seizures. Controlled epilepsy, or remission of seizures, is a complex compensatory process, accompanied not only by a persistent long-term absence of all types of seizures, the disappearance of paroxysmal changes in the EEG, the regression of a mental defect, but also by the restoration of physiological defense mechanisms (Table 34).
CHARACTERISTICS OF ANTIEPILEPTIC DRUGS Drugs effective in tonic-clonic and partial seizures
DIFENIN (PHENYTOIN, DILANTIN) - a derivative of hydantoin, is effective in tonic-clonic and partial (simple, psychomotor) seizures.
Difenin prolongs the inactivated state of neuronal sodium channels, which reduces the frequency of action potential generation. Does not have a sedative and hypnotic effect. In doses 5-10 times greater than therapeutic doses, it potentiates GABAergic inhibition.
The drug is a weak acid with pKa = 8.3, poorly soluble in water. After oral administration or injection into the muscles, it is absorbed slowly and incompletely. The peak concentration is reached after 3-12 hours, 90% of the dose is associated with blood albumin. It penetrates well into the central nervous system. It is converted with the participation of cytochrome P-450 of the liver into oxidized metabolites.
Difenin has neurotoxicity and hepatotoxicity. When taken in a toxic dose, it disrupts the functions of the cerebellum and the vestibular system with the development of ataxia (uncertain unsteady gait), dizziness, dysarthria, diplopia, nystagmus, and even convulsions. Other symptoms of an undesirable effect of difenin on the central nervous system are dilated pupils, accommodation paralysis, drowsiness or agitation, hallucinations. In 30% of patients taking difenin, peripheral neuropathy occurs, the activity of liver enzymes increases in the blood, in 5% gum hyperplasia occurs due to a violation of collagen metabolism (careful oral hygiene is necessary).

Difenin can cause dyspeptic disorders, hypersecretion of vasopressin (antidiuretic hormone) and insulin. As an inducer of cytochrome P-450, it accelerates the metabolism of xenobiotics, as well as vitamins D, K, and folic acid. With long-term therapy with difenin, there is a risk of rickets-like osteopathy, bleeding, and macrocytic anemia. Allergic reactions to diphenin are manifested by skin rash, leukopenia to agranulocytosis, thrombocytopenia, bone marrow aplasia, lymphadenopathy, malignant lymphoma, systemic lupus erythematosus-type syndrome.
PHENOBARBITAL (LUMINAL) - a barbiturate with a pronounced hypnotic effect, enhances GABAergic inhibition by acting on barbiturate receptors in the macromolecular GABA-receptor complex; reduces the release of excitatory amino acids, blocks AMPA receptors for glutamic acid. Used in subhypnotic doses for tonic-clonic and partial seizures. The hypnotic effect of phenobarbital develops addiction while maintaining anticonvulsant activity. The drug provides protection of the central nervous system from hemodynamic and hypoxic disorders, promotes the redistribution of blood in favor of ischemic zones, reduces the brain's need for oxygen and intracranial pressure, inhibits lipid peroxidation in neurons, prevents membrane damage, inactivation of Na +, K + pump, development of edema.
Phenobarbital (a weak acid with pKa = 7.3) is completely but slowly absorbed from the intestine. Creates a maximum concentration in the blood after a few hours. 40 - 60% of the dose is associated with blood albumin. Eliminated by the kidneys - 25% of the dose unchanged, the rest in the form of oxidized metabolites conjugated with glucuronic acid.
Side effects of phenobarbital - sedative, hypnotic effects, impaired cognitive and vestibular functions, allergic reactions (skin rash, exfoliative dermatitis), effects of cytochrome P-450 induction, mental and physical dependence.
HEXAMIDINE (PRIMIDONE) - deoxybarbiturate, turns into phenobarbital (25%) and phenylethylmalonamide, which have an anticonvulsant effect. In epilepsy, hexamidine is three times less active than phenobarbital. It has weak hypnotic properties.
The toxic effects of hexamidine are the same as those of phenobarbital (sedation, dizziness, ataxia, diplopia, nystagmus, vomiting, skin rash, leukopenia, thrombocytopenia, lymphadenopathy, acceleration of vitamin inactivation). In patients with partial epilepsy, hexamidine can cause acute psychosis.
The benzoyl derivative of phenobarbital Benzonal (Benzobarbital) is used to treat convulsive forms of epilepsy of various origins, including cases with partial seizures. In combination with hexamidine and carbamazepine, it is indicated for the treatment of non-convulsive and polymorphic seizures. Benzonal does not disrupt the function of the wakefulness system - the reticular formation of the midbrain and does not cause a hypnotic effect; suppresses the thalamo-cortical synchronizing system, which prevents hypersynchronous discharges in cortical neurons and the development of seizures.
In patients with epilepsy, benzonal, in addition to preventing seizures, reduces the viscosity of thinking, malice, aggression, and improves mood.
CARBAMAZEPIN (MAZEPIN, STAZEPIN, TEGRETOL, FINLEPSIN, EPIAL) is a tricyclic derivative of iminostilbene, used since 1974 for the treatment of tonic-clonic, simple and psychomotor epileptic seizures. Carbamazepine increases the duration of the inactivated state of sodium channels in neurons, inhibits the release of glutamic acid. It has the properties of a tricyclic antidepressant, smoothes the symptoms of an epileptic nature - the viscosity of thinking, depression and aggressiveness.
Carbamazepine is the main analgesic for trigeminal and glossopharyngeal neuralgia. The analgesic effect is due to the blockade of sodium channels of the afferent pathways, the nuclei of the trigeminal and glossopharyngeal nerves and the thalamus. The drug eliminates pain in 60 - 80% of patients with trigeminal neuralgia within 3 - 4 hours (difenin, valproates, clonazepam are also used).
Carbamazepine and other anticonvulsants are prescribed for patients with chronic neuropathic pain. Neuropathic pain is pain caused by damage to the peripheral or
central somatosensory system - from the peripheral nerve to the cerebral cortex. Anticonvulsants together with antidepressants are indicated for peripheral nerve neuropathy, radicular lesions, spinal cord pathology, phantom pain, atypical facial and post-stroke pain.
Carbamazepine is slowly absorbed from the intestine, creating a peak blood concentration after 4 - 8
h, after taking a large dose - after 24 hours. 75% of the dose is associated with blood proteins. The concentration of the drug in the cerebrospinal fluid is the same as in the blood. It is oxidized by cytochrome P-450 of the liver into a toxic metabolite - 10, 11-epoxide, which is neutralized in the glucuronidation reaction. The glucuronides of carbamazepine and its metabolites are eliminated by the kidneys. The elimination half-life of carbamazepine is 10-20 hours, as the induction of cytochrome P-450 develops, it is shortened to 9-10 hours.
Side effects of carbamazepine are close to the undesirable effect of diphenin (drowsiness, dizziness, ataxia, diplopia, impaired liver function, dyspepsia, moderate leukopenia, thrombocytopenia, sensitization). In patients taking carbamazepine for a long time, bradycardia, arrhythmia, aplastic anemia, a hormone-like antidiuretic effect with the appearance of edema are possible, in women there is a risk of polycystic ovaries. In experiments on rats, the carcinogenic effect of carbamazepine was established, but it is not recorded in the clinic.
OXCARBAMAZEPINE (TRILEPTAL) is a 10-oxo derivative of carbamazepine. Used for the same indications. It does not have the properties of an inducer of cytochrome P-450 and does not turn into a toxic epoxide.
Medicines effective for absence seizures
ETOSUKSIMIDE (SUKSILEP) - a derivative of succinimide, has a selective therapeutic effect in absence seizures. Blocks T-type calcium channels in epileptogenic foci of the thalamus, reduces the effects of aspartic acid.
Ethosuximide is completely absorbed after oral administration, well penetrates the blood-brain barrier. The maximum concentration in the blood occurs after 3 hours. Little binds to blood proteins. 25% of the dose is excreted in the urine unchanged, the rest is subjected to oxidation and glucuronidation in the liver. The elimination half-life in adults is 40-50 hours, in children - 30 hours.
Long-term therapy with ethosuximide reduces the threshold for the development of tonic-clonic and myoclonic seizures, which can transfer the course of epilepsy from absences to these types of seizures. To prevent this complication, ethosuximide is taken together with difenin or carbamazepine. Ethosuximide causes drowsiness, lethargy, dizziness, headache, hiccups, parkinsonism, photophobia, eosinophilia, neutropenia, thrombocytopenia, aplastic anemia, pancytopenia in some patients.
Drugs with a broad antiepileptic spectrum
Valproates SODIUM VALPROATE (ACEDIPROL, DEPAKINE, ORFIRIL), VALPROIC ACID (DIPROMAL, CONVULEX) and combined preparations of sodium valproate and valproic acid (DEPAKIN CHRONO) are derivatives of 2-propylvaleric acid (branched-chain carboxylic acid). Initially, valproic acid was proposed as a solvent for anticonvulsants. In the mid 1970s. valproates have been shown to have independent anticonvulsant activity.
Valproates, dissociating into ions, disrupt the conductivity of sodium channels similarly to difenin and block calcium channels by the type of action of ethosuximide; activate potassium channels. They also contribute to the accumulation of GABA in the synapses of the brain. Indicated for the treatment of tonic-clonic seizures, absences, myoclonus epilepsy, partial epilepsy, epileptic encephalopathy. The advantage of prolonged dosage forms of valproate is the possibility of taking it once a day at night. Valproates are less likely than other antiepileptic drugs to cause paradoxical aggravation of seizures.
Valproates are completely and rapidly absorbed from the intestine, creating the highest concentration in the blood after 1 to 4 hours. 90% of the dose is associated with proteins. They penetrate the blood-brain barrier with the help of carrier proteins. In the liver, they undergo a- and P-oxidation, conjugate with

glucuronic acid. Elimination period - 15 - 17h.
In 40% of patients, valproates increase the activity of liver enzymes in the blood, in one patient out of 50,000, a pathology such as Reye's syndrome occurs with severe encephalopathy and liver failure. Cases of pancreatitis are also known. Therapy with valproate may be accompanied by a sedative effect, ataxia, tremor, increased appetite, dyspeptic disorders, allergies, polycystic ovaries.
CLONAZEPAM (ANTELEPSIN, RIVOTRIL) is a benzodiazepine derivative that has not only anticonvulsant, but also anti-anxiety and antidepressant effects. Potentiates GABA-ergic inhibition in the central nervous system, as it acts on the benzodiazepine receptors of the GABA-complex. In high concentrations, it prolongs the inactivation of sodium channels. Clonazepam is indicated for all forms of epilepsy with the exception of tonic-clonic seizures. It is prescribed for a short time (10 - 30 days) during periods of increasing frequency of seizures. The drug is also injected into a vein to relieve status epilepticus.
Clonazepam is well absorbed from the intestines, creating a peak concentration in the blood after 1 to 4 hours. After injection into a vein, it is distributed in the body as a lipophilic substance. Quickly penetrates into the brain, but then redistributed to other organs. 85% of the dose is bound to blood proteins. In the liver, the nitro group of clonazepam is reduced to an amino group. Half-life - 24
h.
The toxic effect of clonazepam is drowsiness (in half of the patients), lethargy, anterograde amnesia, muscle weakness, ataxia, dizziness, dysarthria. Possible behavioral disorders - aggression, irritability, inability to concentrate, anorexia or increased appetite. Long-term therapy with clonazepam is accompanied by mental, physical dependence and addiction, as with the use of tranquilizers of the benzodiazepine group. Infusion of the drug into a vein sometimes leads to respiratory depression, bradycardia, arterial hypotension. Sudden withdrawal of clonazepam is dangerous by worsening the course of epilepsy up to status epilepticus.
New antiepileptic drugs
New antiepileptic drugs have a complex of mechanisms of action, between which synergism is observed. This increases their therapeutic effect in drug-resistant forms of epilepsy and reduces the risk of seizure aggravation. Most drugs are characterized by linear pharmacokinetics, which eliminates the need to determine the concentration in the blood. New anticonvulsants are licensed for the complex pharmacotherapy of epilepsy, and information about their independent use is accumulating.
VIGABATRIN (SABRIL) is a selective, irreversible GABA transaminase inhibitor that significantly increases the content of GABA in the brain. The effectiveness of vigabatrin depends on the rate of GABA transaminase resynthesis.
Vigabatrin is indicated for the treatment of the most severe forms of epilepsy when other antiepileptic drugs have failed. The drug is rapidly and well absorbed from the intestine, its bioavailability does not depend on food intake. It does not bind to plasma proteins and does not participate in oxidation reactions catalyzed by cytochrome P-450. 70% of the dose is excreted by the kidneys in 24 hours, the elimination half-life is 5-8 hours.
The side effect of vigabatrin is due to the significant accumulation of GABA in the brain. The drug can cause depression, fatigue, weakness, attention disorders, headache, narrowing of visual fields. In rare cases, retinal atrophy and optic neuritis occur, the frequency of epileptic seizures increases, and even status epilepticus develops. During treatment with vigabatrin, an ophthalmologist's consultation is required every 6 months.
GABAPENTIN (NEIRONTIN) is a GABA molecule covalently linked to a lipophilic cyclohexane ring. Stimulates the release of GABA from the presynaptic endings of the central nervous system. Interacts with gabapentin-binding protein in calcium channels, which reduces the flow of Ca2+ into presynaptic endings, followed by a decrease in the release of excitatory neurotransmitters. Indicated for the treatment of partial epilepsy, contraindicated in tonic-clonic seizures.

Gabapentin is completely absorbed from the intestine, does not bind to plasma proteins, and is excreted by the kidneys unchanged (drug
choice for partial epilepsy in patients with hepatitis). Elimination half-life - 5 - 7 hours.
Gabapentin was well tolerated by 86% of patients. In rare cases, nervousness or drowsiness, vestibular disorders, headache, amnesia, loss of vision, dyspepsia, rhinitis, pharyngitis, cough, myalgia occur.
LAMOTRIGIN (LAMICTAL) - a derivative of phenyltriazine, blocks the sodium channels of neurons, inhibits the release of glutamic acid and eliminates its neurotoxic effects. It is used to treat tonic-clonic seizures, absences and partial epilepsy. It is not recommended for the treatment of myclonus epilepsy due to the risk of seizure aggravation.
Lamotrigine is completely absorbed when taken orally. It is excreted by the kidneys in the form of glucuronides. The elimination half-life is 24 hours. Biotransformation inducers - difenin, phenobarbital, hexamidine and carbamazepine shorten this figure to 15 hours, metabolic inhibitors - valproates double. Lamotrigine reduces the concentration of valproate in the blood by 25% after several weeks of combined use; promotes the conversion of carbamazepine into a toxic metabolite - 10,11-epoxide.
Lamotrigine is considered to be a safe antiepileptic drug. Only in isolated cases does it cause dizziness, ataxia, maculopapular skin rash. The drug does not affect the profile of female sex hormones and does not cause polycystic ovaries.
TOPIRAMATE (TOPAMAX) in terms of chemical structure is an unusual compound for antiepileptic drugs - it is a sulfamate-substituted derivative of D-fructose. drug, bl