Antiepileptic Drug

- Apr 05, 2019-

[Overview]

        Antiepileptic drugs are drugs that inhibit the production or spread of abnormal discharges of brain cells, thereby preventing the occurrence of motor, sensory, conscious or mental disorders, and long-term application can control symptoms.


[main varieties]

        Phenytoin, carbamazepine, sodium valproate


[Mechanism]

        Anti-epileptic drugs can prevent or alleviate seizures in two ways, one of which affects central foci neurons and reduces or prevents them from over-discharging; the second may increase the excitatory threshold of normal brain tissue and attenuate the excitatory spread from the lesion to prevent seizures. . Most of the existing anti-epileptic drugs work by the second method. 5,5-Dimethyloxazolidine-2,4-dione is the main intermediate for antiepileptic drugs.


[Clinical application]

        Different drugs have different curative effects on different types of epilepsy. Improper medication is not only ineffective, but some can aggravate seizures, such as the effect of phenytoin on small episodes. Therefore, rational drug selection is an important principle of clinical treatment. It is generally advocated that phenytoin is the first choice for the treatment of large seizures, which can completely stop the onset of 60 to 65% of patients, and about 20% of patients can be significantly improved. Cases beyond the control of phenytoin, with the addition of phenobarbital or acetophenone (deoxyphenanthridine) or switching to anti-epileptic spirit often can be effective. The preferred drug for small attacks is ethosuxamine, which has a strong effect and low toxicity. For psychomotor episodes, phenytoin or acetophenone may be used, and carbamazepine may also be used. The treatment of status epilepticus (continuous appearance of large episodes, continuous coma of the patient) is preferred for diazepam, intravenous injection. Can also be intramuscularly injected with sodium phenobarbital, or phenytoin plus 25 ~ 50% glucose solution, intravenously intravenously within 6 to 10 minutes. Excessive injection can cause cerebellar dysfunction and severe cardiac suppression. 5,5-Dimethyloxazolidine-2,4-dione

        The dosage should be determined according to the needs of the patient. Starting from a small amount, gradually increase the dosage until the maximum effect is produced without serious adverse reactions. At the beginning of treatment, it is generally recommended to use only one drug, but only when the effect is not good, consider changing the drug or using other drugs. It must be noted that when changing or stopping the drug, the dosage of the original drug must be gradually reduced, and the drug should be gradually replaced. After the drug is applied, the drug should be gradually stopped, and it must not be completely stopped or changed immediately. Another medication that would otherwise cause seizures. Medication time should generally adhere to medication until no seizures for 3 to 4 years, and then gradually discontinue the drug after several months or even 1-2 years.


[Adverse reactions]

        (1) Even can cause subacute cognition or behavioral disorder, but it is difficult to distinguish whether it is caused by drugs or epilepsy or original brain damage. Drugs can impair attention, memory, thinking or speed of movement. Phenobarbital in young children or the elderly can sometimes produce abnormal excitement. Most anti-epileptic drugs can cause dose-related neurological symptoms such as tremors and dyskinesia, but the incidence is low. Poisoning with phenytoin, carbamazepine, valproic acid or phenobarbital can cause symptoms of cerebellar and brainstem dysfunction, such as ataxia, gait instability, difficulty in articulation, and nystagmus. Phenylacetylurea often causes personality changes, psychotic symptoms, and depression.

        (2) Allergic dermatitis usually occurs 10 to 14 days after administration, and even more severe exfoliative dermatitis, systemic lupus erythematosus, dermatomyositis, serum disease or nodular polyarteritis may occur.

        (3) Hydantoin, some barbiturates (such as epilepsy, etc.) can cause megaloblastic anemia, caused by folic acid metabolism disorders. Coagulation defects are seen in neonates born to mothers treated with phenobarbital, epilepsy, or phenytoin, secondary to vitamin K-dependent clotting factor depletion. Anti-epileptic drugs can cause thrombocytopenia, neutropenia, and aplastic anemia.

        (4) visible liver function damage, jaundice, and even fatal liver poisoning, valproic acid and phenylacetylurea drugs are more likely to occur.

        (5) Trimethanthin or metformin may cause renal dysfunction, often invasive development.

        (6) Phenobarbital and phenytoin can lead to a decrease in bone mineral content and an increase in the incidence of rickets, which may be caused by vitamin D metabolism.

        (7) Endocrine system changes are generally subclinical changes, such as decreased thyroid function and decreased function of the anterior pituitary.

        (8) Antiepileptic drugs and antipsychotic drugs generally have no additional side effects, and carbamazepine is not used in combination with clozapine, as both have a tendency to reduce granulocytes.

        (9) The risk of premature birth, low body weight, hypoxia, hemorrhage and congenital malformation increased in infants born to mothers with epilepsy. The risk of seizures generally exceeds the teratogenic risk of antiepileptic drugs. Trimethanthin is a teratogenic drug that causes 80% of pregnant women with pregnancy defects or spontaneous abortion. The use of anti-epileptic drugs by nursing mothers is generally not contraindicated.


[medication principle]

        1. Start with a small dose and gradually adjust to the limit of control;

        2, single medication, only consider the combination when it is invalid, generally no more than 3;

        3, regular medication;

        4, it is not advisable to change the medicine casually. If it is necessary to change the time, the dosage of the original drug should be gradually reduced, and the dose of the new drug should be gradually increased to prevent the onset of attack;

        5, adhere to long-term treatment, can reduce recurrence, generally gradually reduced in 1 to 2 years until the withdrawal;

        6. Adhere to the principle of gradually reducing the amount of withdrawal;

        7, pay attention to adverse reactions, such as rash, dermatitis, etc., regularly check blood, urine and liver function;

        8. If you have symptoms of lethargy during medication, you should add caffeine (0.02 ~ 0.04g / time, 3 times / day), or ephedrine (25mg / time, 3 times / day);

        9, patients should be regular life, avoid alcohol and tobacco, low-salt and low-water diet, do not over-satisfy, avoid excessive tension, avoid intense exercise, avoid high-altitude, waterside and mechanical motor work, so as to avoid danger when the disease.

        10, pregnant women taking drugs may have potential teratogenicity, should pay attention.


[medicine interactions]

        When the antiepileptic drugs are combined, the blood concentration can be lowered, the curative effect can be lowered, and the blood concentration can be increased to cause a toxic reaction, but a reasonable combination can increase the effect. Central inhibitory drugs, such as antihistamines, central alpha agonists, muscle relaxants, opioid analgesics, antidepressants, sedative hypnotics, etc., can aggravate the sedation or neurotoxicity of antiepileptic drugs. 5,5-Dimethyloxazolidine-2,4-dione


[Child medication]

        Two new studies have shown that if the mother takes the antiepileptic drug sodium valproate during pregnancy, it can easily lead to fetal birth defects and low IQ.

        Sodium valproate is a classic antiepileptic drug and the oldest and most widely used antiepileptic drug on the market. The study investigated 144 women who took the drug during pregnancy and found that the child's birth defect rate was 10%, 7 times that of women who did not take the drug, and three times that of women who took other anti-epileptic drugs. The IQ of a child after birth is also significantly lower than that of a child born without a drug.