Epileptic drugs are of special importance. Antiepileptic drugs can eliminate or alleviate seizures in two ways: one is to affect central neurons to prevent or reduce their pathological overdischarge; the other is to increase the excitation threshold of normal brain tissue, attenuate the spread of focal excitation, and prevent seizure recurrence. Generally, the antiepileptic drugs synthesized before the 1960s such as: sodium phenytoin, carbamazepine, ethosuximide and sodium valproate are called old antiepileptic drugs, among which phenobarbital, sodium phenytoin, carbamazepine and sodium valproate are the first-line antiepileptic drugs widely used at present.
I. Introduction of the disease
Epilepsy (epilepsy), commonly known as “goat’s horn” or “goat’s epilepsy”, is a chronic disease in which sudden abnormal discharges of neurons in the brain cause transient brain dysfunction. According to the latest epidemiological data in China, the overall prevalence of epilepsy in China is 7.0‰, the annual incidence rate is 28.8/100,000, and the prevalence of active epilepsy with seizures within one year is 4.6‰. Accordingly, it is estimated that there are about 9 million epilepsy patients in China, of which 5 – 6 million are active epilepsy patients, while about 400,000 new epilepsy patients are added every year. Epilepsy has become the second most common disease after headache in neurology in China.
It can be divided into five categories.
1. grand mal seizures
(Sheep epilepsy): sudden loss of consciousness, screaming, falling to the ground, generalized convulsions (convulsions), foaming at the mouth, pupils dilated, face pale and then turning blue, whistling suspension due to whistling muscle spasm, etc. The convulsions stop after 1 – 3 minutes and consciousness returns or the patient falls into a deep sleep and wakes up after 1 – 2 hours. If a grand mal seizure occurs continuously and the patient is in a coma, it is called persistent status epilepticus, which is very dangerous and must be controlled quickly.
2.Small seizures
(1) Minor seizures with loss of consciousness.
The main manifestation is a brief loss of consciousness, suddenly stop activity, staring straight at the epileptic patient, holding objects in the hands to the ground, but no convulsions, lasting a few seconds and then quickly return to normal, a day can be dozens of seizures, mostly seen in children.
(2) Myoclonic petit mal seizures.
The performance of short (1 – 2 seconds) bilateral muscle clonus, mostly seen in the neck, upper limbs, trunk flexors, and occasionally the whole body, leading to tilting and falling.
3. Atypical petit mal seizures
It is a secondary manifestation of epilepsy, mostly diffuse encephalopathy, often accompanied by impaired intellectual development. It is very much like an aphasic petit mal seizure, but shorter in duration and with shorter impairment of consciousness.
4.Limited seizures
They are caused by pathological stimulation of localized nerve cell populations in the cerebral cortex. In restricted motor seizures, local muscle convulsions start from the corners of the mouth, fingers or toes on one side and later spread to the ipsilateral half of the body, and mild paralysis may occur after the convulsions stop; the other is restricted sensory epilepsy, in which abnormal sensation occurs on one side of the body.
5. Psychomotor seizures
The main manifestation is paroxysmal confusion and unconscious movements (tongue sticking out, lip smacking, swallowing, touching clothes buttons, etc.), and some manifestations are mental disorders (noise, singing, running away, fear, depression, hallucinations, etc.), each seizure lasts from several minutes to several days.
II. Commonly used drugs
Commonly used for grand mal seizures and limited seizures
1.Phenytoin sodium
Features: strong effect; high efficacy; preferred for grand mal seizures, second to psychomotor seizures, also has good efficacy for limited seizures, but ineffective or even worse for petit mal seizures; no drowsiness; large safety range; slow action, oral generally takes 3 – 4 days to show effect, used for seizure prevention and maintenance treatment; and symptom control is based on Phenobarbital is the mainstay of symptom control. Sodium phenytoin inhibits Na+ inward flow, which increases the negative resting potential, increases the distance from the threshold potential, raises the excitation threshold of brain cells, stabilizes the membrane potential, and thus prevents the spread of focal discharges. It also increases the level of the inhibitory transmitter γ-aminobutyric acid in the brain, which is also related to its antiepileptic effect. Phenytoin sodium has analgesic effects on trigeminal neuralgia, sciatica and glossopharyngeal neuralgia, which may be related to the stabilization of nerve cell membrane electrical antiepileptic drug potentials. The efficacy of ventricular arrhythmias due to digitalis poisoning is better.
2.Phenobarbital
Features:Inhibits the motor area of the cerebral cortex, raises the threshold of convulsion, directly inhibits the focal discharge, but also can limit the spread of discharge, so that the grand mal EEG returns to normal. Fast action, long duration (6hr), low toxicity, greater safety, can be preferred for grand mal seizure control; poor efficacy for petit mal seizures and psychomotor seizures. It is not possible to stop the drug suddenly, long-term application can lead to addiction, silly, quite dangerous, use other drugs instead, (such as lamotrigine, levetiracetam, topiramate, oxcarbazepine, etc.) not only clinical efficacy, and small side effects, the patient easily tolerated.
3.Promidone
Features:It is converted to phenobarbital and phenethylmalonamide (PEMA) in the body, and has better efficacy for grand mal, psychomotor and limited seizures, but not as good as phenytoin sodium. It is tolerated by children, so the dosage is larger; elimination in vivo is slow, and long-term application has accumulation; it should not be stopped suddenly.
Commonly used in status epilepticus
1. Valium
It is the first choice for persistent status, but has poor effect on grand mal seizures. In the acute phase of status epilepticus, the combined effect of diazepam and lorazepam lasts longer. The first of these is the use of the newest version of the newest version of the newest version.
2.Chloronitro Valium
The anticonvulsant effect is 5 times stronger than Valium, with a wide antiepileptic spectrum, stable efficacy, fast action and long duration of maintenance. It is not to be stopped suddenly and can be tolerated for six months.
Commonly used for petit mal seizures
1. Ethosuximide: It is the first choice for petit mal seizures. However, it can aggravate grand mal seizures and should be combined with phenobarbital or phenytoin sodium. Do not stop suddenly.
2.Phensuximide,Milontin: similar to ethosuximide, used for petit mal seizures and psychomotor seizures.
Trimethadione, Tridione: It reduces the excitability of cerebral cortex and mesencephalon, shortens its firing activity, and is effective in petit mal seizures, but the effect is slow (2–4 days before it becomes effective), only for prevention. It is easy to accumulate after a long time; it is toxic, and the gastrointestinal reaction is the precursor of serious reaction.
4, vanillin (vanillin) Vanillin: for asparagus extract components, can counteract the convulsions caused by pentazocine and its induced epileptiform EEG, effective for all types of epilepsy, especially petit mal seizures. Adverse effects are mild.
5.Acetazolamide (Acetazolamide), Diamox: It is a carbonic anhydrase inhibitor, which increases Na+, K+ and HCO3- excretion in urine, artificially causes acidemia and hypokalemia, increases the production of inhibitory transmitter g-aminobutyric acid and membrane potential hyperpolarization in brain, decreases neuromuscular excitability, and also reduces cerebral edema. It is effective in petit mal seizures, and also has significant effect on grand mal and psychomotor seizures. It has cross-allergic reactions with sulfonamide and is contraindicated in such patients.
Commonly used for psychomotor seizures
Sulthiame, Ospolt: It is a strong carbonic anhydrase inhibitor with strong effects. Used for psychomotor seizures.
2. Carbamazepine, Tegretol: most effective for psychomotor seizures; similar to phenytoin sodium for grand mal seizures and mixed epilepsy; better than phenytoin sodium for trigeminal neuralgia; with antidiuretic effect, probably to promote the secretion of antidiuretic hormone, can be used for uremia.