Posts Tagged Antiepileptic

[ARTICLE] SUPPORTIVE PRINCIPLES IN THE PHARMACOLOGICAL MANAGEMENT OF THE PATIENTS WITH EPILEPSY

Abstract

Background: Pharmacological management of patients with epilepsy is still a very challenging approach for the best outcome of these patients. When considering the appropriate treatment choice for patients it is necessary to take into account several factors that can influence the effectiveness and quality of life. Cancelling or changing treatment suddenly can lead to uncontrolled seizures. After a short period without seizures, many patients are tempted to abandon treatment. Cessation of treatment can be discussed after a seizure-free period for at least two years. Treatment should be discontinued gradually by reducing the dosage and constant supervision of the physician. This paper analyses briefly the general pharmacological and treatment methods in several forms of adult epilepsy.

Conclusions: Management of epilepsy means more than observing the medication prescribed by the specialist. It is also important for the patient to maintain his general health status, monitor the symptoms of epilepsy and response to treatment and take care of his safety. Involvement in the management of one’s own affection can help the patient to control his condition and to continue his routine in usual manner. The objective of antiepileptic treatment is to reduce epileptic seizures to zero without intolerable side effects. New treatments should focus not only on reducing the frequency and intensity of seizures but also improving the quality of life of patients. Key words: patient, epilepsy, therapy and dynamics.

Introduction

The analysis of the specialized literature reveals that many issues regarding differential treatment of epilepsy require subsequent clarification. As far as we are concerned, we have designed and developed therapeutic recommendations, in our opinion, effective, supporting the results of treating epilepsy in its various stages, from premonition to status variants. In this context, the main element in the choice of preparations, besides the trivial clinical signs, was the use of sub-curative monitoring data, including repeated EEG examinations, which fixed the subjective response of patients. Choosing the best possible medicine or an optimal combination of medicines is sometimes difficult. The perfect antiepileptic should be long, nonsedative, well tolerated, very active in various types of convulsive and with non-harmful effects on vital organs and functions. In addition, it must be effective in various forms of active epilepsy and in treating underlying epileptic seizures and capable of restoring the electroencephalogram between seizures to its normal form [5; 9; 10; 18; 23; 24; 27; 31; 38; 40; 41; 43].

It is still debatable whether such a drug will ever be discovered, and especially one that will control all types of epilepsy. The thorough study of pharmacological properties allows us to appreciate which of the existing antiepileptics will meet the current requirements of our patients under study. Due to the fact that patients differ considerably after clinical response to known anticonvulsants and the possibilities of treatment with associated drugs are insufficiently and superficially researched, testing of more efficient substances including new combinations continues. Due to the modern medication, which benefits from a wide and sufficiently efficient range of specific drugs, a large proportion of the recurrent and the disabling sequelae of the disease can be prevented. The adverse effects of drugs are low, so many of the past patients who have been labelled for life by this suffering can now live a productive life. The actual ability to control this disease effectively prevents more of its severe consequences [12; 13; 15; 22; 29; 46; 50].

General principles of pharmacotherapy of epilepsies

In the treatment of psychiatric disorders of our patients with epilepsy we have taken into account the following principles:

Appropriate selection of the remedy, its dosing, routes of administration and possible side effects. And we took into account the following:

  1. The syndrome of psychic state – the gradual expression of the disorders, the relationship between productive and negative alterations and the type of impairment of psychic processes.
  2. The dynamic characteristics of the psychic state – the duration of the disturbances, the changes in the presence of paroxysmal manifestations.
  3. The somatic and neurological condition of the patient with epilepsy. This parameter is important in the context

of the evidence of side effects of favorable and unfavorable preparations. Somatic mood dictates and the route of administration of drugs: parenteral in gastrointestinal disorders, endonasal or transorbital (by electrophoresis) when parenteral administration is not preferred.

Individual features of the patient with epilepsy (age, weight, response to anticonvulsant therapy and others) are also considered. It is often forgotten that lower doses are indicated for children and older people as the exchange of substances in them is slow and standard dose treatment leads to accumulation of preparations and adverse effects [6; 7; 14; 19].

We recommend the gradual increase of the doses, with the preference of the minimal effective doses of the drugs. All the above-described drugs are initially indicated at minimal doses, then the dose gradually increases until the first positive effects are displayed, the subsequent increase of the doses is made after a certain period of time to stabilize the positive effect.

Complex treatment – it is necessary to prescribe unimoment of anticonvulsant remedies from different classes and groups in combination with non-medication methods. Polipharmacologic treatment has certain priorities in comparison with monotherapy because it addresses different links of the pathological process. It is important to avoid the multidimensional effects of many drugs, the doubling of the mechanisms of action and the predilection of some and the same psychological processes.

Continuous therapy. The treatment of productive disorders is done until their complete jugulation (sometimes with the purpose of preventing relapse and longer), of the deficient ones by alternating the cures, with gradual modifications [28; 30; 34; 39; 42].

Principles of medication of psychosomatic syndromes in epilepsy

Criteria for the effectiveness of psychotropic remedies administered in epilepsy are those of improving the knowledge and behavioral processes. More differentiated treatment is based on syndrome of mental disorders.

  1. Deficient disorder (transient dementia, mental-mental diminution, etc.) The treatment is continuously practiced, alternating the belts. It is rational to indicate the preparations of different subgroups. The following criteria are taken into consideration when drawing up the treatment scheme:

a) Main mechanism of action: nootrop, general metabolism, cerebrovascular or actoprotector;

b) Predominant action on mediating processes: GABA (piracetam, fenibut, gamma-aminobutyric acid); cholin-ergic (gliatiline); dopaminergic (nakom); and combined (meclofenoxate, glycine, glutamic acid);

c) With predominant action on the function of the encephalic structures: the cerebral and subcortical (nakom), on the left hemisphere (gliatilline); on the right hemisphere (cortexil);

d) With action on psychomotor activity: major stimulation (piracetam, nakom vinpocetine), mean enhancement (aminalone, gamma-aminobutyric acid, cerebrolizine, nicergoline, tanakan), diminishment (fenibut, glycine, ci-narizine);

e) Route of administration: parenteral, internal, endo-nasal, transorbital (by electrophoresis), mixed. Duration of treatment: from 7 days to 4 months (nakom, fenibut). On the basis of this therapy it is also possible to indicate prophylactic doses of anticonvulsants.

  1. For different types of excitation (chaotic, twilight, delusional, manic, psychopathic, etc.) the support treatment are the sedative neuroleptics. Major tranquilizers, barbiturates and other anticonvulsants, may also be indicated sedative antidepressants.
  • Hallucinatory delusions. More rational are antipsy-chotic neuroleptics. In the case of neuroleptic syndrome with caution are added corrective remedies. That adjuvant preparations use daytime tranquilizers, in depressive or anxious states are used antidepressants.
  • Emotional productive disruptions. In the states of excitation are indicated predominantly sedative neuroleptics and tranquilizers, antidepressants – in depression, tranquilizers and antiepileptics – in dysphoria, in anxiety states -neuroleptics and tranquilizers.

  • Productive districts nearby. Psychoparticular depressions are typically treated with “inor” euroleptics, preferably “behavioral correctors” or low doses of risperidone and tranquilizers; in neurotic manifestations (asthenia, obsessions, hysteria, hypocondria) are used tranquilizers and low doses of antidepressants [1; 2; 3; 4; 8; 11; 25; 26].
    КиберЛенинка: https://cyberleninka.ru/article/n/supportive-principles-in-the-pharmacological-management-of-the-patients-with-epilepsy

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    [WEB SITE] Antiepileptic Drugs – Medscape

    Overview

    Modern treatment of seizures started in 1850 with the introduction of bromides, which was based on the theory that epilepsy was caused by an excessive sex drive. In 1910, phenobarbital (PHB), which then was used to induce sleep, was found to have antiseizure activity and became the drug of choice for many years. A number of medications similar to PHB were developed, including primidone.

    In 1938, Houston Merrit and Tracy Putnam described animal models for screening multiple compounds for antiepileptic activity in the Journal of the American Medical Association. In 1940, phenytoin (PHT) was found to be an effective drug for the treatment of epilepsy, and since then it has become a major first-line antiepileptic drug (AED) in the treatment of partial and secondarily generalized seizures.

    In 1968, carbamazepine (CBZ) was approved, initially for the treatment of trigeminal neuralgia; later, in 1974, it was approved for partial seizures. Ethosuximide has been used since 1958 as a first-choice drug for the treatment of absence seizures without generalized tonic-clonic seizures. Valproate (VPA) was licensed in Europe in 1960 and in the United States in 1978, and now is widely available throughout the world. It became the drug of choice in primary generalized epilepsies and in the mid 1990s was approved for treatment of partial seizures.

    These anticonvulsants were the mainstays of seizure treatment until the 1990s, when newer AEDs with good efficacy, fewer toxic effects, better tolerability, and no need for blood level monitoring were developed. A study of live-born infants in Denmark found that exposure to the newer-generation AEDs lamotrigine, oxcarbazepine, topiramate, gabapentin, and levetiracetam in the first trimester was not associated with an increased risk in major birth defects. [1]

    The new AEDs have been approved in the United States as add-on therapy only, with the exception of topiramate and oxcarbazepine (OXC); lamotrigine (LTG) is approved for conversion to monotherapy. A meta-analysis of 70 randomized clinical trials confirms the clinical impression that efficacy does not significantly differ among AEDs used for refractory partial epilepsy. [2]

    Antiepileptic drugs should be used carefully, with consideration of medication interactions and potential side effects. This is particularly important for special populations, such as patients with HIV/AIDS. [3]

    For more information, see Epilepsy and Seizures.

    Mechanism of Action

    It is important to understand the mechanisms of action and the pharmacokinetics of antiepileptic drugs (AEDs) so that these agents can be used effectively in clinical practice, especially in multidrug regimens (see the image below).

    Pearls of antiepileptic drug use and management.
    Pearls of antiepileptic drug use and management.

    Many structures and processes are involved in the development of a seizure, including neurons, ion channels, receptors, glia, and inhibitory and excitatory synapses. The AEDs are designed to modify these processes so as to favor inhibition over excitation and thereby stop or prevent seizure activity (see the image below).

    Dynamic target of seizure control in management of epilepsy is achieving balance between factors that influence excitatory postsynaptic potential (EPSP) and those that influence inhibitory postsynaptic potential (IPSP).

    The AEDs can be grouped according to their main mechanism of action, although many of them have several actions and others have unknown mechanisms of action. The main groups include sodium channel blockers, calcium current inhibitors, gamma-aminobutyric acid (GABA) enhancers, glutamate blockers, carbonic anhydrase inhibitors, hormones, and drugs with unknown mechanisms of action (see the image below).

    Antiepileptic drugs can be grouped according to th
    Antiepileptic drugs can be grouped according to their major mechanism of action. Some antiepileptic drugs work by acting on combination of channels or through some unknown mechanism of action.

    […]

    For more Visit site —>  Antiepileptic Drugs: Overview, Mechanism of Action, Sodium Channel Blockers

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    [WEB SITE] Antiepileptic Drug Fycompa, Already Approved in US, Launched in Japan

    Antiepileptic Drug Fycompa, Already Approved in US, Launched in Japan

    Eisai recently announced the company will launch its novel antiepileptic drug (AED) Fycompa, which is intended as an adjunctive therapy for people suffering from epilepsy and experiencing partial-onset or primary generalized tonic-clonic seizures despite receiving other AEDs. Eisai’s formulation was approved for marketing and manufacturing in March, and the product was recently included in Japan’s National Health Insurance drug price list.

    Fycompa (perampanel hydrate) was discovered by the company in-house labs, and is suggested as a once-daily oral tablet. Fycompa is a selective and noncompetitive AMPA receptor antagonist which can reduce neuronal hyperexcitation linked to seizures. The drug influences the postsynaptic glutamate activity at AMPA receptors.

    Fycompa was tested in two Phase 3 clinical studies; in a Study 335 of adjunctive therapy in refractory partial-onset seizures, and in a Study 332 of adjunctive therapy in primary generalized tonic-clonic (PGTC) seizures. The studies showed a significant drop in the frequency of seizure occurrence.

    In Study 332, 30.9 percent of people who received Fycompa therapy did not experience PGTC seizures over the 13-week study period. The most frequent adverse events included headache, dizziness, somnolence, irritability, and fatigue.

    About 1 million Japanese people are affected by epilepsy. The disorder is classified by seizure type: partial-onset seizures account for about 60 percent, and generalized seizures account for about 40 percent of cases. PGTC seizures are the most frequent and serious forms of generalized seizures, occurring in 60 percent of generalized seizures and about 20 percent of all epilepsy cases.

    The generalized tonic-clonic seizure is an important risk linked to sudden unexpected death in epilepsy. As about 30 percent of people suffering from epilepsy are not able to manage seizures with current therapeutic approaches, there is a relevant unmet medical need.

    Fycompa is approved in 45 countries and territories, including the U.S. and Europe, as an adjunctive therapy of partial-onset seizures in patients suffering from epilepsy who are 12 or older. Fycompa is also approved in 35 countries and territories, including the Europe and the U.S., for the adjunctive treatment of PGTC seizures in people suffering from epilepsy, who are 12 and older.

    Eisai focuses on neurology as a therapeutic area, and by providing Fycompa as a new therapy in Japan, the company intends to further address the wider needs of people suffering from epilepsy.

    Source: Antiepileptic Drug Fycompa, Already Approved in US, Launched in Japan – Epilepsy News Today

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