Modern standards for the management of patients with epilepsy and the basic principles of treatment
Epilepsy is one of the most common diseases of the nervous system. The incidence of epilepsy is 50 – 70 cases per 100 thousand people, the prevalence of 5 – 10 per 1 thousand people, at least 1 seizure is borne by 5% of the population during life, in 20 – 30% of patients the disease is lifelong. In 1/3 of the cases, the cause of death of patients is associated with a seizure (E.I. Gusev, G.S. Burd, 1994; W. Hauser, 1983, 1995). Compared with the first half of the 20th century, the incidence among the elderly has significantly increased (A.B. Geht et al., 1997; P. Jallon, P. Loiseau, 1995). According to WHO, the lack of adequate information on the epidemiological characteristics of epilepsy in many countries leads to significant shortcomings in the organization of medical care. So, more than 75% of the 40 million patients with epilepsy in the world do not receive adequate treatment.
According to the recommendations of the International Antiepileptic League, epileptology is distinguished – an interdisciplinary science that combines various aspects of neurology, pediatrics, psychiatry, neurosurgery, neurophysiology, neuroradiology, clinical pharmacology, neuropsychology and social medicine. An epileptologist is usually a neurologist, pediatrician or psychiatrist with special knowledge and experience in the diagnosis, research, treatment and management of patients with epilepsy.
The World Health Organization, the International Antiepileptic League and the Bureau of Epilepsy announced the 1997 Out of Shadows – A Global Campain campaign. She is addressed to politicians, legislators, health authorities, medical and non-medical organizations of all countries. Its purpose is to lead patients with epilepsy from the “shadow” of social stigmatization, and the disease itself – from the “shadow” to the “light” of one of the priority areas in healthcare. The objectives of the campaign: increasing the level of knowledge and understanding of epilepsy in society; attracting the attention of health authorities to the problem of epilepsy, its study and prevention; providing all the needs of patients, including education, training, service. In 1998, the European Declaration on Epilepsy was adopted in Heidelberg (Germany).
Modern standards for the management of patients with epilepsy, developed by the World Anti-Epileptic League (Epilepsia, 1997), include the use of the International Classification of Epilepsies and Epileptic Syndromes (1989), as well as the International Classification of Seizures as the basis for diagnosis and choice of treatment tactics for patients. In a clinical examination of patients, special attention should be paid to a thorough history taking with a description of the details of the seizure, the therapy performed, its effectiveness and side effects, the identification of neurological and psychiatric disorders, as well as damage caused by seizures. Particular attention should be paid to the recurrence of seizures, the presence of various types of seizures, chronobiological features (confined to a specific time of day, phase of the menstrual cycle, etc.), the presence of aura, the first objective signs of a seizure, the sequence and variability of symptoms, a change in consciousness during seizure time, patient’s condition after a seizure.
In 1981, the Commission on the Terminology and Classification of the International Antiepileptic League adopted the International Classification of Epileptic Seizures, according to which partial (focal, local) seizures and generalized are distinguished.
I. Partial seizures are divided into simple, complex (occurring with impaired consciousness) and secondarily generalized.
Among simple partial seizures, the following, characterized by the presence of:
– motor signs;
– somatosensory or specific sensory symptoms (sounds, flashes of light or lightning);
– vegetative symptoms or signs (peculiar sensations in the epigastrium, pallor, sweating, redness of the skin, piloeretia, mydriasis);
– mental symptoms.
For complex seizures, one or another degree of impaired consciousness is characteristic. In this case, consciousness may not be completely lost, but the patient only partially understands what is happening around and subsequently cannot reproduce it.
Complex partial seizures are divided into simple seizures, followed by impaired consciousness and impaired consciousness from the onset of the seizure. Often complex partial seizures are due to focus in the temporal or frontal lobe and begin with an aura.
In some cases, with partial seizures, simple or complex, pathological bioelectrical activity, initially focal, spreads throughout the brain – while a secondary-generalized seizure develops.
II. In primary-generalized seizures, both hemispheres of the brain are initially involved in the pathological process. The following types of generalized seizures are distinguished:
1. Absences and atypical absences.
2.Myoclonic.
3. Clonic.
4.Tonic.
5.Tonic-clonic.
6. Atonic.
III. Unclassified seizures
The international classification of epilepsies, epileptic syndromes was adopted in 1989 by the International Antiepileptic League. The classification of epilepsy is based on two principles. The first is to determine if epilepsy is focal or generalized. According to the second principle, idiopathic, symptomatic or cryptogenic epilepsy is isolated.
1. Localization-caused (focal, local, partial) epilepsy:
– idiopathic (primary);
– symptomatic (secondary);
– cryptogenic.
2. Generalized epilepsy:
– idiopathic (including childhood abscess epilepsy and juvenile abscess epilepsy) – see below;
– symptomatic or cryptogenic.
3. Non-deterministic epilepsy.
4. Special syndromes.
Diagnosis of the nature of epilepsy and epileptic syndrome in accordance with the classification is based on the results of clinical, electroencephalographic (EEG) examination taking into account data from other methods (neuropsychology, MRI, etc.).
The leading direction of the examination is EEG. Traditional EEG (surface EEG) should be recorded on at least 12 channels of the encephalograph simultaneously with the location of the electrodes in the “10-20” system; in parallel, other channels can be used to monitor ECG, respiration, myogram, eye movements. Analyzed should be at least 20 minutes of high-quality recording of the “background” EEG. Certain requirements are imposed on carrying out functional loads. Hyperventilation with parallel registration of EEG should be carried out for at least 5 min + 1 min of recording, which is mandatory after the end of hyperventilation; an alternative is to record twice for 3 minutes under hyperventilation and 2 minutes of load again after 10 minutes (in the absence of contraindications). It is also necessary to use photostimulation.
Of great diagnostic importance is prolonged monitoring (LTME: video-EEG, ambulatory EEG), which allows for a long time to monitor EEG in comparison with the clinical picture.
Neuroimaging is one of the main links in the diagnosis. It is aimed at identifying the pathological process, making a syndromic and etiological diagnosis, determining the prognosis, treatment tactics. Neuroimaging methods:
1. CT (currently recognized as adequate only for the detection of tumors, calcifications).
2. MRI (the method of choice is shown to all patients with epilepsy, except for doubtful cases of idiopathic epilepsy).
3. SPECT.
4. PET.
Epilepsy is a disease that requires long-term, long-term (at least 2 years after the cessation of seizures) therapy. This therapy is of fundamental importance to the patient’s health, quality of life; its effect in most cases is obvious (E.I. Gusev et al., 1997; J. Cramer, 1994; O.Devinsky, 1996). Among patients, there are a significant number of children and elderly people, which makes it extremely important to use drugs with a small number of side effects, the absence of toxic effects on other organs and minimal interaction with other drugs. In the contingent of patients, there is also a significant proportion of potentially able-bodied young people for whom the use of a non-toxic highly effective drug for several years with a probability of recovery may be a reasonable alternative to lifelong disability when taking obsolete drugs (A.B.Gecht et al., 1998; S.A. Gromov et al., 1997; J. Cramer, R. Mattson, 1993; S. Ried, 1998).
The goal of the treatment of epilepsy is to prevent the development of seizures with the use of antiepileptic drugs (PEPs) to ensure their constant concentration in the blood (E. Perucca, 1995; S. Shorvon et al., 1996; S. Ried, 1998; P. Wolf, 1994). Patient management should be in accordance with current Standards developed by the International Antiepileptic League (ILAE, 1997).
General principles of drug selection
Partial seizures with or without secondary generalization
Carbamazepine and valproate are the drugs of choice. In recent years, the equal efficacy of these drugs in partial seizures has been shown (Chadwick D. et al., 1997). Phenobarbital and phenytoin are effective, but are not the drugs of choice due to side effects.
New drugs (lamotrigine, tiagabin, etc.) are used for treatment-resistant drugs of choice for epilepsy, as a rule, as adjunctive therapy (in some cases, monotherapy is possible).
Generalized seizures
– tonic-clonic:
drugs of choice – valproates, carbamazepines. In syndromes of generalized epilepsy, valproates are the most effective drugs.
Phenobarbital and diphenin are effective, but are not the drugs of choice due to side effects.
– absences:
drugs of choice are valproates and ethosuximide. If there are only absences in the clinical picture of the disease, these drugs are equally effective, however, when combined with absences with tonic-clonic seizures (with primary generalized epilepsy syndromes), valproates or a combination of these drugs are indicated.
Lamotrigine is also effective and is used for generalized seizures (tonic- clonic, absences) in cases of insufficient effectiveness and / or poor tolerance of the described drugs.
– myoclonic seizures:
the drug of choice is valproate. Clonazepam, lamotrigine are also used.
Atypical absences, atonic and tonic seizures are often resistant to treatment. In individual cases, one of the following drugs may be effective: phenytoin, valproate, lamotrigine, clonazepam, ethosuximide, phenobarbital, acetazolamide and corticosteroids, or a combination thereof.
With undifferentiated seizures, valproates should be used.
It should be emphasized that, according to a multicenter study published in 1995 (A.Heller et al.), In the treatment of newly diagnosed epilepsy with primary generalized or partial seizures, including secondary generalized, phenobarbital, phenytoin are quite effective. , carbamazepine and valproate (during a 3-year follow-up, 12-month remission was achieved in 74%, 72%, 77% and 74% of cases, respectively).
The feasibility of using a particular drug, according to the authors, was due to tolerability and severity of side effects. Thus, the frequency of pronounced side effects requiring drug discontinuation when taking phenobarbital was 22%, which was significantly higher than with phenytoin (3%), carbamazepine (11%), valproate (5%).
The interaction of drugs in most cases is due to the effect on the system of microsomal liver enzymes (induction or inhibition). PEP may also interact with other medications, such as oral contraceptives (P. Patsalos, 1998).
It is important to emphasize that the principle of monotherapy is a leading principle in the treatment of epilepsy. The relief of epileptic seizures should be carried out mainly by one drug. Polytherapy (treatment of 2 PEPs and more) is advisable only if adequate monotherapy is not possible. Polytherapy increases the risk of side effects and drug interactions. Many drugs have mutual antagonism, and their simultaneous use can significantly weaken the effect of each. The use of 3 antiepileptic drugs can be carried out only in isolated cases with resistant forms of epilepsy and should be strictly argued. The simultaneous use of more than 3 anticonvulsants in the treatment of epilepsy is unacceptable (H.Walance et al., 1997; P. Wolf, 1994).
The frequency of administration of an antiepileptic drug is usually determined by its half-life in plasma, and for most antiepileptic drugs (valproate, carbamazepine) is 3 times a day. In general, the time of taking the drug is determined by both the characteristics of the disease (the time of development of seizures, etc.) and the characteristics of the drug (side effects, etc.). So, phenobarbital, which has a long half-life, along with a pronounced sedative effect, can be taken once in the evening. However, in order to avoid sharp fluctuations in the concentration of the drug in the blood, it may be preferable to take this drug twice. Some drugs, especially when prescribing high doses, should be used 3 times a day to avoid side effects. In children, drug metabolism is faster, so in pediatrics it is advisable to take drugs more often and use higher doses (per kg of body weight).
Let us consider in more detail the general principles of the transition from one probe to another. If one of the PEPs is ineffective, alternative monotherapy is used – a gradual transition to monotherapy with another PEP. There are several tactical options for such a transition (S. Ried, 1998).
The first of them is to gradually increase the dose of the second drug while maintaining the dose of the first unchanged. When the desired dose of the second drug is reached (and its concentration in the blood reaches the desired level), the dose of the first drug gradually decreases. Unfortunately, this option may be accompanied by a temporary increase in the frequency and severity of side effects due to the fact that the interaction of drugs can lead to an increase in the concentration of one of them with signs of adverse events. It is necessary to very gradually increase the dose of the second drug until the seizures stop or, conversely, until the increase in the frequency of side effects does not make you refuse to use the second drug.
A so-called counter option is possible, in which the dose of the first drug gradually decreases and the dose of the second increases. This option has its weaknesses. The concentration in the blood of the first drug may decrease below therapeutic values, and the second – not yet reach the required values. This can lead to a temporary increase in the frequency of seizures. To avoid this, it is necessary that the patient carefully follow the doctor’s recommendations according to an individually selected “schedule” of dose changes. Monitoring the concentration of drugs in the blood is extremely important, since many antiepileptic drugs do not have a linear relationship between the dose of the drug and the concentration.
It should be emphasized that the abolition of the first PEP should be done gradually. Replacement of barbiturates and benzodiazepines should be done no faster than within 2 to 4 weeks or more due to the presence of a pronounced withdrawal syndrome.
The determination of the concentration of PEP in the blood is one of the main requirements of the International standards for the management of patients with epilepsy. Monitoring gained great importance in the pharmacotherapy of epilepsy due to the fact that for most anticonvulsants, significant correlations were found between the effect of the drug and its level in the blood of patients.
Epilepsy Medications
We give brief information on the main and some new antiepileptic drugs.
Valproates
Pharmachologic effect. Antiepileptic.
Mechanism of action. The antiepileptic effect is associated with an effect on voltage-dependent sodium channels, inhibition of GABA-transferase, effect on GABA A receptors.
Pharmacokinetics When taken orally, they are well absorbed. Absorption is somewhat slowed when taken after meals (about 75-85% of the drug). Protein binding is about 90%. It is metabolized mainly in the liver (hydroxylation and binding to glucuronide). A small part is oxidized with the participation of microsomal enzymes or in the mitochondria of hepatocytes. It is excreted in the urine in the form of glucuronide. It is an inhibitor of microsomal liver enzymes.
Indications. All forms of epilepsy.
Contraindications Diseases of the liver (in the acute stage). The presence in the family history of cases of severe impaired liver function. Porphyria. Hemorrhagic diathesis.
Drug interaction. Valproates often increase the plasma concentration of active metabolites of carbamazepine and lamotrigine *, primidone, phenobarbital, phenytoin (but they can also decrease), sometimes they increase the plasma concentration of ethosuximide and primidone (with a tendency to a significant increase in phenobarbital levels).
Side effects. Dose-dependent: tremors, weight gain, hair loss, anorexia, dyspepsia, nausea, vomiting, peripheral edema, drowsiness, hyperammonemia.
By the mechanism of idiosyncrasy: acute pancreatitis, hepatotoxicity, thrombocytopenia, encephalopathy, teratogenicity.
Cautions. Cautiously prescribed for impaired liver function (in particular, acute and chronic hepatitis) and kidney, tendency to hemorrhage, before surgery, during pregnancy. The blood picture should be monitored.
Application and doses for epilepsy. For adults – oral administration, starting from 500 mg per day in 2 divided doses, with a gradual increase of 250 mg per week until a maintenance dose of 1000-3000 mg is reached. The maximum dose is 4000 mg per day. Therapeutic plasma concentration of 50-150 mg / ml.
Frequency of administration – 3 times a day, prolonged (“chrono”) forms – 1-2 times a day. A number of works (Bergmann, 1999) show better tolerance and greater efficacy of retard valproate forms.
For children – start with 15-20 mg / kg, a maintenance dose of 30-80 mg / kg per day.
Carbamazepines
Pharmachologic effect. Antiepileptic, analgesic, antidepressant, normotimic.
Mechanism of action. The antiepileptic effect is mainly associated with the effect on voltage-dependent sodium channels.
Pharmacokinetics When taken orally, about 75-85% of the drug is slowly absorbed. Binding to proteins 70-80%. It is metabolized in the liver with the formation of more than 32 metabolites, some of which (especially epoxide) have antiepileptic activity.
The biotransformation of carbamazepines is characterized by self-induction.
Indications. Partial seizures with or without secondary generalization. Primary generalized tonic-clonic seizures (but not other generalized seizures). Trigeminal neuralgia, prevention of manic-depressive disorders that are resistant to lithium treatment.
Contraindications Disorders of atrioventricular conduction, disorders of bone marrow hematopoiesis, porphyria, simultaneous use of MAO inhibitors and lithium salts, absences, myoclonic seizures.
Drug interaction. Carbamazepines often reduce the plasma concentration of clonazepam, lamotrigine, phenytoin (possibly an increase), valproate, and sometimes lower the plasma concentration of ethosuximide and primidone (with a tendency to a corresponding increase in the level of phenobarbital).
Side effects. Dose-dependent: diplopia, dizziness, headaches, nausea, drowsiness, neutropenia, hyponatremia, hypocalcemia, cardiac arrhythmias.
By the mechanism of idiosyncrasy: rash, agranulocytosis, aplastic anemia, hepatotoxicity, photosensitivity, Stevens-Johnson syndrome, thrombocytopenia, teratogenicity.
Cautions. Use with caution in case of impaired liver and kidney function, allergic reactions, glaucoma, pregnancy, driving vehicles. The blood picture should be monitored.
Application and doses for epilepsy. For adults – oral administration, starting from 200 mg per day in 2 divided doses, with a gradual increase of 200 mg per week until a maintenance dose of 600-1200 mg is reached. The maximum dose is 1600 mg per day. The therapeutic plasma concentration of 4-12 mg / ml.
Frequency of admission 3 times a day. It is advisable to use retard forms 1-2 times a day, which allows for greater regularity of drug administration, a stable plasma concentration and, in some cases, better tolerance.
For children, start with 10-15 mg / kg, a maintenance dose of 10-30 mg / kg per day.
Clonazepam
Pharmachologic effect. Antiepileptic, anxiolytic, muscle relaxant and sleeping pills.
Mechanism of action. The antiepileptic effect is mainly associated with the effect on the GABA receptors, as well as the effect on the voltage-dependent sodium channels.
Pharmacokinetics When taken orally, it is well absorbed. Protein binding 47%. Metabolized in the liver with the formation of 5 metabolites; excreted by the kidneys.
Indications. The drug is effective for absences (however, as a rule, it is not a drug of choice due to side effects and possible addiction). It is also indicated as initial or additional therapy for atypical absences, atonic, myoclonic seizures.
Contraindications Respiratory disorders, pulmonary failure, myasthenia gravis.
Drug interaction. Enhances the effect of alcohol, antipsychotics, analgesics, muscle relaxants.
Side effects. Dose-dependent: fatigue, sedation, drowsiness, dizziness, ataxia, irritability, aggressiveness (in children), hyperkinesis (in children), hypersalivation, bronchorrhea, psychosis.
By the mechanism of idiosyncrasy: rash, thrombocytopenia.
Cautions. It is especially carefully prescribed in case of impaired liver and kidney function, respiration, in the elderly, during pregnancy and lactation. With a sharp cancellation, exacerbation of seizures is possible.
Application and doses for epilepsy. For adults, oral administration starting from 1 mg (0.5 mg to the elderly), usually overnight for 4 days, with a gradual increase to a maintenance dose of 2-6 mg for 2 to 4 weeks. The maximum dose is 20 mg per day. The therapeutic plasma concentration of 0.02-0.08 mg / ml. Frequency of admission 3 times a day.
For children under 10 years old – 0.01 – 0.03 mg / kg. At the age of 1 year – start with 0.25 mg and increase to 0.5 – 1 mg, 1 – 5 years – up to 1-3 mg. For children 5-12 years old – start with 0.5 mg – up to 3-6 mg.
Lamotrigine
Pharmachologic effect. Antiepileptic.
Mechanism of action. The antiepileptic effect is due to the fact that lamotrigine is an antagonist of glutamate receptors, and is also associated with the effect on voltage-dependent sodium channels.
Pharmacokinetics When taken orally, it is rapidly and completely absorbed. Protein binding 55%. Metabolized in the liver with the formation of 2-n-glucuronide. The half-life is about 30 hours. At the same time, when administered together with carbamazepine, phenytoin, phenobarbital, it reduces the half-life to 15 hours, and with the simultaneous administration of valproate, the half-life increases to 60 hours.
Indications. Monotherapy and adjunctive therapy for partial and generalized seizures.
Contraindications Liver failure.
Drug interaction. Lamotrigine sometimes increases the plasma concentration of active metabolites of carbamazepine. The drug is susceptible to the action of inducers or inhibitors of microsomal systems of the liver (see also pharmacokinetics).
Side effects. Dose-dependent: drowsiness, diplopia, headache, ataxia, tremor, nausea.
By the mechanism of idiosyncrasy: rash, Stevens-Johnson syndrome.
Cautions. Carefully monitor possible allergic reactions, monitor blood counts and liver function, prevent a sharp withdrawal of the drug (only with the development of side effects). Cautiously prescribed in case of impaired liver and kidney function, allergic reactions, pregnancy.
Application and doses for epilepsy. Dosage substantially depends on concomitant antiepileptic therapy. The dose of lamotrigine should be increased very slowly, no more than 1 time in 2-3 weeks. For those taking drugs – inducers of microsomal liver enzymes in adult patients – start with 50 mg followed by a 50 mg increase until a maintenance dose of 300-500 mg is reached in 2 divided doses. For children under 12 years of age – start with 2 mg / kg per day in 2 divided doses until a maintenance dose of 5-15 mg / kg in 2 divided doses is reached.
For adults taking liver enzyme inhibitors (valproate), start with 25 mg, slowly increasing the dose by 25 mg until a maintenance dose of 100-200 mg is reached. For children – start with 0.2 mg / kg and slowly increase to 1-5 mg / kg.
With monotherapy, start with 25 mg, followed by an increase of 25 mg, then 50 mg to achieve a maintenance dose of 100-200 (rarely up to 500 mg) per day in 2 divided doses.
Phenytoin
Pharmachologic effect. Antiepileptic.
Mechanism of action. The antiepileptic effect is associated with the effect on voltage-dependent sodium channels.
Pharmacokinetics When taken orally, about 85% of the drug is slowly absorbed. Binding to proteins 69-96%. Metabolized in the liver.
The pharmacokinetics of phenytoin is non-linear. A change in the concentration of the drug in the blood occurs faster than a change in the dose of the drug with an increase or decrease in the latter. The time to reach a stable state after a dose change can vary from 5 to 28 days. The concentration of the drug in blood plasma when taking one dose does not allow to predict its value at a different dosage.
Indications. All forms of seizures, with the exception of absences (effective, but not a drug of choice due to side effects).
Contraindications Dysfunction of the liver, kidneys, heart failure, cachexia, porphyria, absences.
Drug interaction. Phenytoin often reduces the plasma concentration of clonazepam, carbamazepine, lamotrigine, topiramate, valproate. Often increases the concentration of phenobarbital. Sometimes it reduces the concentration of ethosuximide and primidone in the blood plasma (in this case, there is a tendency to increase the level of conversion to phenobarbital).
Side effects. Dose-dependent: nystagmus, ataxia, anorexia, dyspepsia, nausea, vomiting, aggression, depression, drowsiness, headaches, paradoxical seizures, megaloblastic anemia, hyperglycemia, hypocalcemia, osteomalacia, neonatal hemorrhages.
By the mechanism of idiosyncrasy: acne, gum hypertrophy, gross facial features, hirsutism, lupus-like syndrome, pseudolymphoma, peripheral nerve neuropathy, rash, Stevens-Johnson syndrome, Dupuytren’s contracture, hepatotoxicity, teratogenicity.
Cautions. Use with caution in case of impaired liver function, pregnancy, lactation, driving a motor vehicle. It should control the picture of blood, liver function.
Application and doses for epilepsy. For adults – oral administration during or after meals (to avoid irritation of the gastric mucosa) 150-300 mg per day in 3 divided doses, with a gradual slow increase of 100 mg per month until a maintenance dose of 300-500 mg is reached. Therapeutic plasma concentration of 10-40 mg / ml.
The frequency of admission is 3 times a day.
For children – start with 5 mg / kg per day in 2 divided doses, a maintenance dose of 4-8 mg / kg per day, maximum 300 mg.
Phenobarbital and other barbiturates
Phenobarbital
Pharmachologic effect. Antiepileptic, sedative, sleeping pills.
Mechanism of action. The antiepileptic effect is mainly associated with the effect on voltage-dependent sodium channels and on GABA A receptors.
Pharmacokinetics When taken orally, about 75-85% of the drug is slowly absorbed. Protein binding is 50% in adults and 30-40% in young children. It penetrates the placenta well. Metabolized in the liver. It is excreted by the kidneys.
Indications. All types of seizures, with the exception of absences.
Phenobarbital is one of the oldest antiepileptic drugs (used since 1911). Gained distribution worldwide due to sufficient efficiency and low cost. At the same time, in developed countries, its use is significantly limited due to side effects.
Contraindications Violation of the functions of the liver, kidneys, myasthenia gravis. alcoholism, drug addiction, absences.
Drug interaction. Often reduces the plasma concentration of carbamazepine, clonazepam, lamotrigine, phenytoin (possibly an increase), valproate, sometimes it reduces the plasma concentration of ethosuximide.
Side effects. Dose-dependent: fatigue, fatigue, depression, insomnia (in children), hyperkinesis (in children), irritability (in children), aggressiveness, memory impairment, impaired libido, impotence, folate deficiency, neonatal bleeding, hypocalcemia, osteomalacia.
By the mechanism of idiosyncrasy: rash, exfoliation, toxic epidermal necrosis, hepatotoxicity, teratogenicity.
Cautions. Use with caution in case of impaired liver and kidney function, breathing, during pregnancy, lactation, in the elderly, children, persons with mental development problems, and driving vehicles. It should control the picture of blood, liver function. Avoid abrupt cessation of the drug.
Application and doses for epilepsy. For adults – oral administration begins with 90 mg in the evening or (to avoid sharp “peak” changes in the concentration of the drug in the blood) 2 times a day. Slowly increase to a maintenance dose of 90-120 mg. Therapeutic plasma concentration of 10-40 mg / ml.
For children – 3-5 mg / kg / day.
Primidone in the liver is partially converted to phenobarbital and phenylethyl malonamide. Both metabolites have antiepileptic activity.
Dosage and administration. Adults – oral administration, usually after meals. Start with 100-125 mg in the evening, then every 3 days the daily dose is increased by 250 mg to a maintenance dose of 750-1000 mg. Therapeutic plasma concentration of 5-12 mg / ml.
Children – 12-25 mg / kg / day (maintenance dose).
Benzobarbital is metabolized to phenobarbital.
Application and doses for epilepsy. For adults – oral administration of 300-600 mg per day in 3 divided doses. For children – 4-6 mg / kg / day, dose – 10-30 mg / kg per day.
Ethosuximide
Pharmachologic effect. Antiepileptic, analgesic, antidepressant, muscle relaxant.
Mechanism of action. The antiepileptic effect is mainly associated with the effect on voltage-dependent calcium channels (T-channels).
Pharmacokinetics When taken orally, it is absorbed rapidly and almost completely. Slightly bound to plasma proteins. Metabolized in the liver; It is excreted mainly in urine. It penetrates well through the blood-brain barrier and the placental barrier.
Indications. Absolute seizures.
Contraindications Hepatic and renal failure. Not recommended during pregnancy. When taking the drug should abandon breastfeeding.
Drug interaction. Ethosuximide sometimes reduces the concentration of phenytoin in the blood plasma.
Side effects. Dose-dependent: nausea, anorexia, vomiting, agitation, drowsiness, headache.
By the mechanism of idiosyncrasy: rash, erythema multiforme, Stevens-Johnson syndrome, lupus-like syndrome, agranulocytosis, aplastic anemia.
Cautions. Use with caution when driving. The blood picture and liver function should be monitored. Not recommended during pregnancy. When taking the drug should abandon breastfeeding.
Dosage and administration. For adults: oral administration, starting from 250-500 mg per day, with a gradual increase of 250 mg per week until a maintenance dose of 1000-1500 mg is reached. The therapeutic plasma concentration of 40-120 mg / ml.
The frequency of administration is 1-3 times a day.
For children under 6 years of age – start with 10-15 mg / kg (not more than 250 mg per day). For children over 6 years of age – start with 250 mg per day. The maintenance dose is 15-30 mg / kg per day.
A number of new highly effective antiepileptic drugs, including tiagabin, are in the process of registration in Russia.
In patients resistant to conservative treatment (not more than 10-15% of all patients), surgical treatment of epilepsy is considered. Surgical treatment of epilepsy is any neurosurgical intervention whose primary goal is to reduce the severity of epilepsy.
Quality of life for patients with epilepsy
The treatment of epilepsy must necessarily include a set of maditsinsky and social measures. In modern epileptology, one of the priority goals is to improve the quality of life and rehabilitation of patients with epilepsy (V.A. Karlov, 1996; S.A. Gromov, 1987, A.B. Geht et al., 1998, Cramer J. et al., 1997). S. Ried (1998) emphasizes that treating epilepsy is always more than pharmacotherapy.
Of great importance is the study of morbidity, prevalence, mortality in various age groups, an analysis of the structure of disability of patients with epilepsy and factors influencing them, as well as the quality of life of patients, aspects of medical and social rehabilitation, including: the adequacy of antiepileptic therapy received by patients; the possibility and methods of eliminating or compensating for the limitations of their livelihoods (training, work, communication, etc.).
According to the standards of the World Antiepileptic League, patients with epilepsy must be provided with:
– services of a regional epileptic service;
– access to a specialized team of professionals, including: a specialist in adult and pediatric epileptology, a nurse, a clinical psychologist, a social worker, a specialist in occupational health and occupational diseases;
– the possibility of inpatient treatment (for example, with epileptic status);
– the possibility of a highly qualified neurophysiological examination;
– access to laboratory examinations and monitoring the level of antiepileptic drugs in the blood;
– access to neuroimaging methods, especially MRI;
– access to epileptic surgery centers;
– the possibility of a comprehensive examination and treatment;
– advice on family planning and pregnancy;
– consultations with a psychologist;
– contact with non-medical organizations;
– accessible written information about seizures, types of epilepsy, examination, treatment.