What Are Anti-Epileptics?

Antiepileptic drugs have special significance in the treatment of seizures. Antiepileptic drugs can eliminate or reduce seizures in two ways. One is to affect central neurons to prevent or reduce their pathological over-discharge; the other is to increase the excitement threshold of normal brain tissue and reduce the spread of excitement of the lesion. Prevent recurrence of epilepsy. Generally, antiepileptic drugs synthesized before the 1960s, such as phenytoin, carbamazepine, ethosuximide, and sodium valproate, are called old antiepileptic drugs, of which phenobarbital, phenytoin, carbamazepine, and valproate Sodium is a widely used first-line antiepileptic drug.

Antiepileptic drugs have special significance in the treatment of seizures. Antiepileptic drugs can eliminate or reduce seizures in two ways. One is to affect central neurons to prevent or reduce their pathological over-discharge; the other is to increase the excitement threshold of normal brain tissue and reduce the spread of excitement of the lesion. Prevent recurrence of epilepsy. Generally, antiepileptic drugs synthesized before the 1960s, such as phenytoin, carbamazepine, ethosuximide, and sodium valproate, are called old antiepileptic drugs, of which phenobarbital, phenytoin, carbamazepine, and valproate Sodium is a widely used first-line antiepileptic drug.

Drug Name

Antiepileptic drugs

Main indications

Sheep crazy, lamb crazy, epilepsy

Dosage

Follow the doctor's order

Main medication contraindications

Do not change at will

Athletes use with caution

Use with caution

Whether to include health insurance

Incorporate

Introduction to Antiepileptic Drugs

Epilepsy (epilepsy), commonly known as "sheep horn wind" or "sheep epilepsy", is a syndrome of abnormal high-frequency discharge of local neurons in brain tissue caused by various causes and spreads to surrounding tissues, resulting in transient dysfunction of the brain. In addition to genetic factors, almost all neurological diseases can induce seizures, such as infections, nerve tumors, and brain damage. The main clinical manifestations of seizures are: sudden attack, transient motor sensory function or mental abnormality, accompanied by abnormal EEG, often recurrent.

According to the latest epidemiological data in China, the overall prevalence of epilepsy in China is 7.0 , the annual incidence is 28.8 / 100,000, and the prevalence of active epilepsy with seizures within 1 year is 4.6 . According to this estimate, there are about 9 million epilepsy patients in China, of which 5-6 million are active epilepsy patients. At the same time, about 400,000 new epilepsy patients are added every year. In China, epilepsy has become the second most common after neurology in China. disease. Drug therapy is currently the main means of controlling seizures, with the aim of reducing or preventing them.

Epilepsy is divided into localized seizures and systemic seizures according to different seizures.

Clinical classification and its therapeutic drugs ^[1]

Antiepileptic drugs

1. Simple localized seizures: A variety of clinical manifestations are related to the cortical sites that are activated during seizures. The main feature is that it does not affect consciousness, and each episode lasts 20-60s. Therapeutic drugs: carbamazepine, phenytoin sodium, phenobarbital, primidone, sodium valproate, antiepileptic.

2. Complex localized seizures (temporal lobe, psychomotor): affects consciousness during seizures, and is often accompanied by unconscious activities, such as lip twitching and moving head lights. Each episode lasted 30s-2min. Therapeutic drugs: carbamazepine, phenytoin sodium, phenobarbital, primidone, sodium valproate.

3. Localized seizures secondary to generalized tonic-clonic seizures: The above two types of localized seizures may be accompanied by loss of consciousness-tonic-clastic seizures and systemic muscles in tonic contraction, and then enter contraction-relaxation (clonic) State, can last 1-2min. Therapeutic drugs: carbamazepine, phenytoin sodium, phenobarbital, primidone, sodium valproate.

Antiepileptic drugs

1. Absence of seizures (small episodes): A sudden loss of consciousness. Often accompanied by symmetrical clonic activity. EEG is a synchronous spike with a high amplitude of about 3 Hz / s, and each attack lasts about 30 s. Therapeutic drugs: Ethylsuccinamide, clonazepam, sodium valproate, and trimethionone.

2. Atypical absence episodes: Compared with typical absence episodes, the onset and cessation processes are slower, and EEG is more diverse. Therapeutic drugs: Ethylsuccinamide, clonazepam, sodium valproate, and trimethionone.

3. Myoclonic seizures: A brief (about 1 s) shock-like twitch occurs in part of the muscle groups of the unilateral limbs. EEG is accompanied by transient spikes. Therapeutic drugs: sodium valproate, lamotrigine.

4. Infant clonic seizures: Occurred in young children, with rhythmic contractures of muscles throughout the body, loss of consciousness, and obvious symptoms of autonomic disorders. Therapeutic drugs: glucocorticoids, valproate, clonazepam.

5. Tonic-clonic seizures (major seizures): Sudden loss of consciousness accompanied by severe tonic spasticity changes to clonic seizures, followed by central depression for a longer period of time. Therapeutic drugs: carbamazepine, phenytoin sodium, phenobarbital, primidone, antiepileptic, sodium valproate.

6. Sustained status of epilepsy: refers to the sustained state of major seizures, repeated convulsions, continued coma, and failure to save life-threatening in time. Therapeutic drugs: diazepam, olazepam, phenytoin, phenobarbital.

History of antiepileptic drugs

Research on antiepileptic drugs has progressed slowly, and bromide, the first drug to be found effective against epilepsy, has now been phased out. The use of phenobarbital to treat epilepsy in 1912 can effectively control the symptoms of patients who are resistant to bromide. Until the discovery of phenytoin sodium in 1938, the structure had similarities with barbiturates, and these two drugs have been used to this day. It was discovered in 1964 that sodium valproate could be used to treat epilepsy. In recent years, a number of drugs with good curative effect, few adverse reactions, and broad antiepileptic spectrum have been synthesized. Although there are many drugs for epilepsy, people are still looking for drugs with better efficacy and fewer side effects.

Antiepileptic drug classification

1 Antiepileptic drugs 1. According to the mechanism of action of antiepileptic drugs:

(1) Sodium channel regulators: such drugs include phenytoin sodium, carbamazepine, lamotrigine, zonisamide, rallitorin, remazine, flunarizine, riluzole, pentamyl Sodium and topiramate, oxcarbazepine, dendrol, naphthone, etc. These drugs can selectively act on sodium channels, block the rapid release of sodium ion-dependent action potentials, and regulate voltage-dependent sodium ion channels, however, it does not affect hyperpolarized membrane voltage. In addition, these drugs can also block calcium channels and regulate NA + -K + -ATP converting enzyme activity, thereby achieving anticonvulsant effects.

(2) -aminobutyric acid regulator: -aminobutyric acid (GABA) regulator is an inhibitory transmitter of the central nervous system, which can promote the inflow of chloride ions into cells and make the hyperpolarization of the cell membrane more stable. Those who can increase GABA content or prolong the effect or increase sensitivity have anti-epileptic effects. Therefore, antiepileptic drugs can work through the following ways: enhance GABA synthesis, there is no such drug. Valproic acid can enhance GABA synthetase and glutamate dehydrogenase activity; GABA agonists or precursors, such as benzodiazepines, are GABA agonists; GABA metabolism inhibitors, such as aminohexene acid; GABA receptors Body enhancers, such as topiramate.

(3) Excitatory amino acid receptor antagonists and modulators of excitatory amino acid release, such as lamotrigine, block the release of glutamic acid by regulating sodium channels; AMPA receptor antagonists, such as topiramate.

(4) Antiseizure-related drugs related to ethosunamide; for example, trimethyldiketone is a selective T-type calcium ion channel blocker.

(5) The mechanism of action of felamine, gabapentin, and levetiracetam are not completely clear. ^[2]

2 Antiepileptic drugs 2, classified by chemical structure

(1) Hydantoins: Sodium phenytoin, mephenytoin, ethylphenytoin, etc.

(2) Astigmine: Carbamazepine

(3) Barbiturates: phenobarbital, primidone, isoprene barbitur, etc.

(4) Succinimides: such as ethosuccin, mesuccinine, phenylsuccinimide, etc.

(5) Diketones: such as trimethyldiketone, methyl ethyl ketone;

(6) side chain fatty acids, such as sodium valproate;

(7) acetylureas: such as phenylacetylurea, phenylbutyryl urea

(8) Benzodiazepines: such as diazepam, clonazepam, nitrazepam

(9) Sulfonamides: such as acetazolamide, sulbutide

(10) Hormones: such as adrenocorticotropic hormone, dexamethasone, prednisone

(11) Others: such as paraaldehyde, chloral hydrate, lidocaine, caffeine, bromide, miparine hydrochloride ^[2]

Antiepileptic drugs commonly used drugs

Antiepileptic drugs are commonly used for major and localized episodes

Phenytoin sodium

(Dalun Ding) Dilantin, Phynetoin Sodium: Features: Strong effect; High curative effect; First choice for major episodes, followed by psychomotor episodes, and better efficacy for localized episodes, but ineffective or even worse for minor episodes; None Drowsiness effect; large safety range; slow effect. It usually takes 3 to 4 days for oral administration to be effective. It is used for prevention of seizures and maintenance treatment. Phenobarbital is mainly used to control symptoms. Phenytoin inhibits Na + influx, thereby increasing the negative value of cell resting potential, increasing the distance from the threshold potential, increasing the excitability threshold of brain cells, and stabilizing membrane potential, thereby preventing the spread of lesion discharge. It can also increase the content of the inhibitory transmitter -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 potential. It has better curative effect on ventricular arrhythmia caused by digitalis poisoning.

Phenobarbital

Phenobarbital, Luminal: Inhibit the cerebral cortex motor area, increase the convulsive threshold, directly suppress the discharge of the lesion, and limit the spread of the discharge, so that the large-scale EEG returns to normal. It has fast action, long duration (6hr), low toxicity and great safety. It can be used as the first choice for controlling large-scale attacks; the curative effect on small-scale and psychomotor attacks is poor. Do not stop the drug abruptly. Long-term use can cause addiction, sillyness, and danger. Use other drugs instead (such as lamotrigine, levetiracetam, topiramate, and oxcarbazepine). Not only is the clinical effect positive, The side effects are small and easily tolerated by patients.

3, primidone (deoxyphenobarbital, ecstatic ketone) Primidone, Mysoline: In the body into phenobarbital and phenethyl malonamide (PEMA), for major attacks, psychomotor episodes and local

Antiepileptic drugs

Localized attacks have better efficacy, but not as good as phenytoin sodium. Children are tolerant to it, so the dosage is large; elimination in the body is slow, and long-term application is accumulative; do not stop the drug suddenly.

Antiepileptic drugs are commonly used for status epilepticus

stable

(Benzodiazepine, Diazepam) Diazepam, Valium: Intravenous injection is significantly faster and safer than other drugs. It is the first choice for sustained status and has a poor effect on large episodes. In the acute phase of epilepsy, the combined effects of diazepam and laurazepam last longer. Fewer adverse reactions, prolonged sudden arrest can cause convulsions; infants, glaucoma, myasthenia gravis are contraindicated.

Clonazepam

Clomazepam, Clomapin: anticonvulsant effect is 5 times stronger than diazepam, broad antiepileptic spectrum, stable effect, fast effect, long duration. Do not stop abruptly, even for half a year can produce tolerance.

Antiepileptic drugs are often used in small episodes

1. Ethosuximide: the first choice for a small episode of absence. However, severe episodes can be aggravated, and authors with large hair should use phenobarbital or phenytoin sodium. Do not stop suddenly.

2. Phensuximide, Milontin: It is similar to ethylsuccinimide, and is used for small episodes of absence and psychomotor episodes.

3. Trimethadione, Tridione: Reduces cerebral cortex and mesencephalic excitability, shortens the subsequent discharge activity, has a significant effect on small episodes, but the effect is slow (only effective for 2 to 4 days), and is only used for prevention . Jiufu is easy to accumulate; it is relatively toxic, and gastrointestinal reactions are a precursor to serious reactions.

4, Vanillin (vanillin) Vanillin: Extracted from Gastrodia elata, it can fight convulsions caused by pentylenetetrazol and its epilepsy-like EEG, which is effective for all types of epilepsy, especially small episodes. Adverse reactions were mild.

5. Acetazolamide, Diamox: It is a carbonic anhydrase inhibitor, which increases the excretion of Na +, K +, and HCO3- in the urine, causing artificial acidemia and hypokalemia, and inhibiting the neurotransmitter g in the brain. -Increased aminobutyric acid production and membrane potential hyperpolarization reduce neuromuscular excitability and reduce brain edema. It has a good effect on small episodes, and also has obvious effects on large episodes and psychomotor episodes. This product has a cross-allergic reaction with sulfa. Such patients are contraindicated.

Commonly used in psychomotor episodes

1. Sulthiame, Ospolt: It is a strong carbonic anhydrase inhibitor and has a strong effect. For psychomotor seizures.

2. Carbamazepine, Tegretol: most effective for psychomotor seizures; similar to phenytoin for major seizures and mixed epilepsy; efficacy for trigeminal neuralgia is better than phenytoin Sodium is good; it has anti-diuretic effect, may promote the secretion of anti-diuretic hormone, and can be used for diabetes insipidus.

Broad-spectrum antiepileptic drugs

1. Sodium valproate (anti-epileptic, sodium dipropyl acetate) Sodium 2-Propylvalerate, Sodium Valproate, DPA: Does not inhibit epilepsy focus discharge, but prevents the spread of abnormal discharge. It is effective for all types of epilepsy, especially better than esuccinate for small episodes; it is worse than phenytoin and phenobarbital for large episodes, but it is still effective for patients who are ineffective with these two drugs; for small episodes Drug of choice. Low long-term toxicity and few adverse reactions. Possible mechanism of action: Activate glutamate decarboxylase and inhibit g-aminobutyric acid transaminase, promote the synthesis of g-aminobutyric acid, prevent the decomposition of g-aminobutyric acid, and make the content of inhibitory transmitter g-aminobutyric acid in the brain Increased by 30 to 50%, neuromuscular excitability decreases, and has an effect.

Antiepileptic drug principle

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

2. A single medication is considered only when it is ineffective, generally no more than 3;

3. Take medication regularly;

4. It is not advisable to change the medicine casually. When it is really necessary to change medicine, the dose of the new medicine should be gradually reduced while gradually increasing the dose of the new medicine to prevent induced seizures.

5. Insist on long-term treatment, which can reduce recurrence. Generally, it is gradually reduced until the drug is discontinued within 1 to 2 years.

6. Adhere to the principle of gradual reduction and withdrawal;

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

8. If you have drowsiness when taking the drug, you should take caffeine (0.02 0.04g / time, 3 times / day), or ephedrine (25mg / time, 3 times / day);

9, patients should regularize their lives, avoid alcohol and tobacco, low salt and water diet, do not overeat, avoid excessive tension, avoid intense exercise, avoid working at high altitude, waterside and mechanical motors, so as to avoid danger when the disease occurs.

10. Pregnant women may have potential for teratogenicity when taking medicine, so you should pay attention to it.

Antiepileptic drug precautions

1. If there are 1-2 occasions in 1 year, it is generally not necessary to prevent medication;

2. For a simple type of epilepsy, you can choose an effective medicine. Start with a small dose and gradually increase it until you get the desired effect. Maintain the treatment. If a single drug is difficult to achieve results, or mixed epilepsy often requires a combination of drugs.

3. It is not advisable to change the drug randomly during the treatment process. When necessary, a transitional drug method can be adopted, that is, a new drug is added to the original drug, and the original drug is gradually reduced after the effect is exerted. Even after the symptoms are completely controlled, you still need to maintain the medicine for 2-3 years and then gradually stop the medicine, otherwise it will cause relapse.

4. For patients who have been using antiepileptic drugs for a long time, pay attention to toxic and side effects, and conduct related inspections closely and regularly. ^[1]

Clinical application of antiepileptic drugs

(1) Partial epilepsy: carbamazepine, sodium valproate, phenytoin, clonazepam, lamotrigine, and levetiracetam

(2) Tonic-clonic seizures: carbamazepine, sodium valproate, phenytoin, lamotrigine, topiramate

(3) Absence of seizures: esuccinate, clonazepam, sodium valproate, lamotrigine, aminohexene acid

(4) Status of epilepsy: diazepam (iv), phenytoin sodium

(5) Local seizures and secondary generalized seizures: non-urethane

Harm of antiepileptic drugs

The side effects of antiepileptic drugs are a concern for everyone with epilepsy. The severity of side effects varies greatly from individual to individual. So what are the side effects of antiepileptic drugs?

Dose-related adverse reactions

Refers to adverse reactions such as headache, dizziness, unstable walking, anorexia, nausea, vomiting, fatigue, drowsiness, distracted attention, hyperactivity, decreased memory, and mood changes. Etc., generally not heavy, can be improved or disappeared quickly after adjusting the drug dose;

Idiopathic adverse reactions

Refers to an adverse reaction caused by an individual's oversensitivity to a certain component of the drug, such as rash, peripheral neuropathy, liver damage, leukocyte or thrombocytopenia, liver toxicity (especially in children under 2 years old), etc. This reaction is fierce, Unpredictable, the harm is more serious, it mostly occurs in the early stage of medication, and the incidence is less;

Long-term adverse reactions

One: Antiepileptic drugs have an impact on people's memory and exercise speed. The higher the blood concentration, the more obvious the effect. Many experts through clinical trials have also shown that phenytoin affects patients' operating skills, visual spatial ability, and attention, and also affects exercise and reaction speed. Some therapeutic drugs can affect the patient's instant memory and concentration, and also affect the speed of speech. Some drugs are generally considered to have no significant effect on intelligence, but others believe that they may have a certain effect on fine movement.

Two: The harm of anti-epileptic drugs to the body is the cerebral nervous system. The symptoms are dizziness, headache, nervousness, mental disorders, apathy, mental disorders, depression, impulse, stiffness, ataxia, tremor, Speech disorders, diplopia, drowsiness, affecting thinking, work and children with limited intellectual development, children may experience excitement and anxiety. These symptoms have serious adverse effects on the normal life of the patient. In addition, antiepileptic drugs also have some effects on the patient's upper gastrointestinal system, such as nausea, vomiting, anorexia, upper abdominal pain, gastritis, and loss of appetite. The effects on the blood and lymphatic system are generally manifested as aplastic anemia, megaloblastic anemia, lymphadenopathy, increased blood sugar, leukopenia, and hypotension. Adverse reactions to antiepileptic drugs can cause liver and kidney dysfunction and hematopoietic dysfunction in severe cases. Therefore, liver and kidney insufficiency should be used with caution or disabled.

Three: Damage to systemic organs caused by long-term intake of drugs by the human body, such as acne, gingival hyperplasia, rough face, hairy, osteoporosis, atrophy of the cerebellum and brainstem (long-term heavy use), lack of libido, weight change, hair loss, Menstrual disorders or amenorrhea.

Teratogenic effect

It refers to the abnormal development of offspring caused by antiepileptic drugs, and the new type of antiepileptic drugs has significantly reduced this possibility.

Antiepileptic drugs

(Phennytoin sodium) Antiepileptic drug phenytoin sodium

I. Pharmacological action mechanism

1. Stabilize the membrane of excitable cells and reduce their excitability. Use-dependent block Na + channels to reduce Na + influx. It has obvious blocking effect on the Na + channels of high-frequency abnormal discharge neurons, inhibiting high-frequency repeated discharges without affecting normal low-frequency discharges.

2. Phenytoin sodium inhibits Ca2 + influx in fast-inactivating (T-type) Ca2 + channels of neurons; larger concentrations can also inhibit K + outflow, prolonging the action potential duration and refractory period.

3. High concentration of phenytoin can inhibit the uptake of GABA by nerve endings, induce GABA receptor proliferation, indirectly enhance the action of GABA, increase Cl-influx and hyperpolarization, and inhibit the occurrence and diffusion of abnormal high-frequency discharge.

1. Membrane stabilization

1) Block voltage-dependent Na + channels and inhibit Na + influx

2) Blocking of voltage-dependent Ca2 + channels

3) Combined with inactivated Na + channels to prolong its refractory period

2. Enhance central GABA function

Benzodiazepines

Diazepam: one of the drugs of choice for controlling the status of epilepsy. Intravenous injection is effective and safe. Should be injected slowly.

Nitrazepam: It has a good effect on myoclonic epilepsy, atypical microseizures and infantile spasms.

Clonazepam: It is effective for all types of epilepsy, especially for small episodes of absence, myoclonic seizures and atypical small episodes.

Note: Benzodiazepines have significant central inhibitory effects and even ataxia. Prolonged use produces tolerance and dependence.

Antiepileptic drugs phenobarbital and primidone

Phenobarbital, Luminal (-)

Features: 1 Effective for major attacks and persistent states, poor for minor attacks.

2 Faster action than phenytoin sodium. Not as the first choice.

Primidone:

It is better than phenobarbital for partial and major attacks, but less effective than carbamazepine and phenytoin for complex partial attacks.

Adverse effects of both: sedation, drowsiness, dizziness and ataxia.

Esuccinate

Only effective for small episodes of absence, less effective than clonazepam, but with fewer side effects. It is still a commonly used medicine for treating small episodes.

Valproate:

It has different degrees of efficacy for various epilepsy. It is not as effective as phenobarbital and phenytoin sodium for large episodes. It is worse than ethosuccinide for small episodes. It is similar to amimidazine in psychomotor episodes .

Mechanism of action: Increase glutamate decarboxylase activity, thereby increasing GABA concentration in the brain.

Adverse reactions: mild, nausea and vomiting, loss of appetite.