Anticonvulsants for epilepsy: a review of the means

Anticonvulsants are medicines for controlling seizures, as with the main manifestation of epilepsy. The term "antiepileptic" drugs is considered more correct, because they are used to combat epileptic attacks, which are not always accompanied by the development of seizures.

Anticonvulsant drugs, to date, are represented by a fairly large group of funds, but the search and development of new drugs continue. This is due to the variety of clinical manifestations of epilepsy. After all, there are many types of seizures with different mechanisms of development. The search for innovative drugs is also conditioned by the resistance of epileptic seizures to some already existing drugs, the presence of side effects, which complicate the life of the patient and some other aspects. From this article you will get information about the main antiepileptic drugs and the features of their application.

Some principles of pharmacotherapy of epilepsy

The main goal of treating epilepsy is to preserve and improve the patient's quality of life. This is attempted with the complete elimination of epileptic seizures. But thus the developed side effects from constant reception of medical products should not exceed negative influence of seizures. That is, one can not achieve the elimination of seizures "at any cost". It is necessary to find a "golden mean" between manifestations of the disease and adverse effects of exposure antiepileptic drugs: so that the number of seizures decreases, and the side effects are minimal.

The choice of an antiepileptic agent is determined by several parameters:

• clinical form of attack;
• type of epilepsy (symptomatic, idiopathic, cryptogenic);
• age, sex, weight of the patient;
• presence of concomitant diseases;
• way of life.

Before the attending physician there is a difficult task: from all the abundance of antiepileptic agents to pick up (and, well, at the first attempt) an effective remedy. Moreover, monotherapy of epilepsy, that is, the use of a single drug, is desirable. Only in cases where several drugs in turn are not able to cope with seizures, resort to the simultaneous intake of two or even three drugs. The recommendations on the use of individual drugs based on their effectiveness in this or that form of epilepsy and types of seizures have been developed. In this regard, there are preparations of the first and second line of choice, that is, those from which it is necessary to begin treatment (and the probability of their effectiveness is higher), and those to which should be resorted in case of ineffectiveness of the drugs of the first line.

The complexity of the selection of the drug largely depends on the availability of its individual (!) Effective dose and tolerability. That is, for two patients with the same types of seizures, same sex, weight, and approximately the same age, and even same co-morbidities, a different dose of the same drug may be required to control disease.

It must also be taken into account that the drug should be used for a long time without interruption: after the control of seizures is established for another 2-5 years! Unfortunately, sometimes it is necessary to take into account the material possibilities of the patient.

How does anticonvulsant work?

The occurrence of seizures in epilepsy is the result of abnormal electrical activity in the cortex: an epileptic focus. Reduction of excitability of neurons of epileptic focus, stabilization of membrane potentials of these cells lead to a reduction in the number of spontaneous discharges and, accordingly, to a decrease in the number seizures. Here in this direction and "work" antiepileptic drugs.

There are three main mechanisms of action of anticonvulsants:

• stimulation of GABA-receptors. GABA - gamma-aminobutyric acid - is the inhibitory mediator of the nervous system. Stimulation of its receptors leads to inhibition of neuronal activity;
• blockade of ion channels in the neuron membrane. The appearance of an electric discharge is associated with a change in the action potential of the cell membrane, and The latter occurs at a certain ratio of sodium, calcium, potassium ions on both sides of membrane. The change in the ratio of ions leads to a decrease in epiactivity;
• decrease in the amount of glutamate or blockade of its receptors in the synaptic cleft (at the place of transfer of an electrical discharge from one neuron to another). Glutamate is a neurotransmitter with an exciting type of action. Elimination of its effects allows you to localize the focus of excitation, not allowing it to spread to the entire brain.

Each anticonvulsant drug can have one or more mechanisms of action. Side effects from the use of antiepileptic drugs are also associated with these mechanisms of action, because they realize their capabilities not selectively, but, in fact, in the entire nervous system (and sometimes not only in it).

Basic anticonvulsants

Epilepsy is treated with various medications since the XIX century. The choice of these or other preparations varies with time in connection with the appearance of new data on their use. A number of drugs have sunk into the past, and some still retain their positions to this day. Currently, among the anticonvulsants the most common and often used are the following drugs:

• Valproate sodium and other valproate;
• Carbamazepine;
• Oxcarbazepine;
• Lamotrigine;
• Ethosuximide;
• Topiramate;
• Gabapentin;
• Pregabalin;
• Phenytoin;
• Phenobarbital;
• Levetiracetam.

Naturally, this is not the whole list of existing anticonvulsants. Only in Russia, today, more than 30 drugs have been registered and approved for use.

Separately, it should be noted that in the treatment of epilepsy, this fact is of great importance: an original (brand) drug or generic (generic) is used. The original drug is a drug that was created for the first time, tested and patented. Generic is a drug with the same active substance, but produced already repeatedly, by another firm and at the expiry of the term of the brand patent. The excipients and manufacturing technology of the generic may differ from the original. So, in case of treatment of epilepsy, the use of brand or generic plays a big role, as it is noticed that when transferring the patient from the original drug to generic (usually due to financial difficulties, since branded drugs are very expensive), a dose adjustment of the latter (more often aside increase). Also, with the use of generics, the frequency of side effects usually increases. As you can see, the equivalence of drugs in this case can not be said. Therefore, in the treatment of epilepsy, one can not change one drug to another with a similar active substance without consulting a doctor.

Valproate sodium and other valproate

The original drug from this group is Depakin. Depakin is available in the form of various medicinal forms: tablets, syrup, tablets and granules of prolonged action, enteric-soluble tablets, and also as a lyophilizate for the preparation of a solution for intravenous introduction. Generics with a similar active substance are many: Convulex, Enkorat, Convulsofin, Acediprol, Valparin, Valproate sodium, Valproate calcium, Valproic acid, Valprokom, Apilepsin.

Depakin is a first-line drug for treating virtually all existing epileptic seizures, both partial and generalized. Therefore, quite often it is with him that the treatment of epilepsy begins. A positive feature of Depakin is the absence of negative influence on any species epileptic seizures, that is, it does not cause more frequent seizures, even if it proves ineffective. The drug works through the GABA-ergic system. The average therapeutic dosage is 15-20 mg / kg / day.

Receiving Depakin has an adverse effect on the liver, so it is necessary to control the level of liver enzymes in the blood. Of the most common side effects, the following should be noted:

• weight gain (obesity);
• decrease in the number of platelets in the blood (which leads to violations of the blood coagulation system);
• nausea, vomiting, abdominal pain, upset of the stool (diarrhea) at the very beginning of treatment. In a few days these phenomena pass;
• slight trembling of limbs and drowsiness. These phenomena are in some cases dose-dependent;
• increased concentration of ammonia in the blood;
• hair loss (may be a transient or dose-dependent phenomenon).

The drug is contraindicated in acute and chronic hepatitis, hemorrhagic diathesis, simultaneous intake of St. John's wort, in children under 6 years.

Carbamazepine

Original preparation with an active ingredient, such as Finlepsin. Generics: Carbamezepine, Tegretol, Mazetol, Zeptol, Carbapine, Zagreton, Actinerval, Stazepin, Storilat, Epial.

First of all, the treatment of partial and secondarily generalized seizures begins with it. Finlepsin can not be used for absences and myoclonic seizures, because in this case it is certainly an ineffective drug. The average daily dosage is 10-20 mg / kg. Finlepsin requires a titration dose, that is, the initial dose is gradually increased to achieve the optimal effect.

In addition to the anticonvulsant effect, it also has an antipsychotic effect, which allows "to kill two rabbits "with the help of one drug in the presence of the patient accompanying changes in mental sphere.

The drug is allowed to children from year to year.

The most common side effects are:

• dizziness, unsteadiness in walking, drowsiness, headache;
• allergic reactions in the form of rash (urticaria);
• a decrease in the content of leukocytes, platelets, an increase in the content of eosinophils;
• nausea, vomiting, dry mouth, increased alkaline phosphatase activity;
• fluid retention in the body and, as a consequence, swelling and weight gain.

You can not use Finlexin in patients with acute intermittent porphyria, atrioventricular heart block, with disturbance of bone marrow hematopoiesis (anemia, decrease in the number of leukocytes), simultaneously with lithium preparations and inhibitors of MAO.

Oxcarbazepine (Trileptal)

This is the second-generation drug of carbamazepine. It is also used, like carbamazepine, for partial and generalized seizures. Compared with carbamazepine has several advantages:

• the absence of toxic metabolic products, that is, his stay in the body is accompanied by the development of a much smaller number of side effects. The most common side effects of taking Oxcarbazepine are headache and general weakness, dizziness;
• better tolerated by patients;
• less often causes allergic reactions;
• does not require dose adjustment;
• less interacts with other drugs, so it is preferable to use if you need to simultaneously take with other medicines;
• is approved for use in children from the first month.

Lamotrigine

Original preparation: Lamykal. The generics are Lamitor, Convulsant, Lamotriks, Trigineth, Seizar, Lamolep.

Used in the treatment of generalized tonic-clonic seizures, absences, partial seizures.

The average therapeutic dose is 1-4 mg / kg / day. Requires a gradual increase in dose. In addition to anticonvulsant, it has antidepressant effect and normalizes mood. It is allowed for use in children starting from the age of 3 years.

The drug is fairly well tolerated. To frequent side effects on the part of Lamotrigine include:

• rash on the skin;
• aggressiveness and irritability;
• headache, sleep disturbances (insomnia or drowsiness), dizziness, trembling of limbs;
• nausea, vomiting, diarrhea;
• fast fatigue.

Another plus of this drug is a small number of obvious contraindications to use. This is an intolerance (allergic reactions) of lamotrigine and the first 3 months of pregnancy. When breastfeeding, up to 60% of the dose of the drug contained in the blood can enter the baby.

Ethosuximide

Ethosuximide, or Suxilep, refers to less commonly used medications. It is used only to treat absences as a first-line drug. The effective dosage is 15-20 mg / kg / day. It is often used in the treatment of epilepsy in children.

The main side effects:

• dizziness, headache;
• skin rash;
• photophobia;
• the phenomena of parkinsonism;
• gastrointestinal disorders;
• reduction in the number of any blood cells.

Do not use in renal or hepatic insufficiency, blood, porphyria, pregnancy and breastfeeding.

Topiramate

The original drug is known as Topamax, generics - Topaleptsin, Topsaver, Maxitopyr, Epitope, Toreal, Epimax.

It can be used in generalized tonic-clonic, secondary generalized and partial seizures, myoclonias as a means of the first line. The effective dose is 200-400 mg / kg / day.

Often causes drowsiness, dizziness, the appearance of paresthesias (a feeling of crawling, chills, numbness in any part of the body), memory impairment, attention, thinking, lack of appetite and even anorexia, muscle aches, double vision, blurred vision, pain and ringing in the ears, nosebleeds, hair loss, skin rash, provokes the formation of sand and kidney stones, leads to the development of anemia. And although absolute contraindications include only hypersensitivity to the drug and children age up to 2 years, nevertheless, a large number of side effects require a deliberate appointment Topiramate. That is why in most cases this drug is in the second row among others, that is, it is used only in case of inefficiency of such drugs as Depakin, Lamotrigine, Finplepsin.

Gabapentin and Pregabalin

These active substances are analogues of gamma-aminobutyric acid, on which the mechanism of their action is based. Original drugs are Neuronthin and Lyrics, respectively. Generics of Neurontin: Tebantin, Gapentec, Lepsitin, Gabagamma. Generics Lyric: Algerika, Pregabalin, Prabegin.

Both drugs are classified as second line drugs for epilepsy. It is most expedient to use them for partial and secondarily generalized seizures, in a number of cases - for primary generalized seizures. The required dose of Gabapentin is 10-30 mg / kg / day, Pregabalin - 10-15 mg / kg / day. In addition to epileptic seizures, drugs are well-stopping neuropathic pain (postherpetic neuralgia, diabetic pain, pain in alcoholic polyneuropathy), as well as pain in fibromyalgia.

A feature of the use of drugs is their good tolerability. Among the side effects, the most common are:

• dizziness and drowsiness;
• dry mouth, impaired appetite and stool;
• blurred vision;
• erectile disfunction.

Gabapentin is not used in children under 12 years of age, Pregabalin is banned until 17 years. Do not recommend drugs and pregnant women.

Phenytoin and Phenobarbital

These are "veterans" among therapeutic drugs with epilepsy. To date, they are not drugs of the first line, they are used only in the case of resistance to treatment with other drugs.

Phenytoin (Diphenin, Digidan) can be used for all types of seizures, except for absences. The advantage of the drug is its low price. The effective dose is 5 mg / kg / day. The drug can not be used for problems with the liver and kidneys, heart rhythm disorders in the form of various blockades, porphyria, heart failure. When using Phenytoin, side effects can occur in the form of dizziness, fever, excitation, nausea and vomiting, trembling, excessive hair growth, increased lymph nodes, increased blood glucose, difficulty breathing, allergic rashes.

Phenobarbital (Luminal) has been used as an anticonvulsant since 1911. It is used for the same types of seizures as Phenytoin, in a dose, g / day. The drug "withdrew" to the background in connection with a large number of side effects. Among them, the most common are: the development of insomnia, the emergence of involuntary movements, deterioration cognitive functions, rash, lowering of arterial pressure, impotence, toxic effect on the liver, aggressiveness and depression. The drug is prohibited for myasthenia gravis, alcoholism, drug dependence, severe liver and kidney disease, diabetes, severe anemia, obstructive bronchial diseases, pregnancy.

Levetiracetam

One of the new drugs for the treatment of epilepsy. The original drug is called Keppra, generics - Levitinol, Komviron, Levetiracetam, Epitera. It is used to treat both partial and generalized seizures. The daily dose is, on average, 1000 mg.

The main side effects:

• drowsiness;
• asthenia;
• dizziness;
• abdominal pain, impaired appetite and stool;
• rashes;
• double vision in the eyes;
• increased cough (if there are problems with the respiratory system).

Contraindications only two: individual intolerance, the period of pregnancy and lactation (because the effect of the drug has not been studied under such conditions).

The list of existing preparations for epilepsy can be continued further, since the ideal medicine does not exist yet (there are too many nuances in the treatment of epileptic seizures). Attempts to create a "gold standard" for the treatment of this disease continue.

Summarizing the above, I would like to clarify that any drug from anticonvulsants is not harmless. It should be remembered that the treatment should be done only by a doctor, there can be no question of any independent choice or change of the drug!