The main reason for the failure of antiepileptic drugs is to ignore the pharmacokinetic factors

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Department of Neurology, Changzheng Hospital Affiliated to Second Military Medical University, Zhao Zhongxin, Zhang Lin,The mechanism of ant


Department of Neurology, Changzheng Hospital Affiliated to Second Military Medical University, Zhao Zhongxin, Zhang Lin,

The mechanism of antiepileptic drugs is to inhibit the abnormal discharge of neurons, and to prevent the expansion of abnormal discharges in the brain. After regular drug treatment, nearly 80% of patients with seizures can be controlled, and ultimately make the full withdrawal of the 50% patients. But because of various reasons, many epilepsy patients failed to get the right medication, seriously affect the normal activities of the patient, repeated attacks can also affect the intelligence or cause injury, if the status epilepticus is likely to cause death. Therefore, it is of great significance to control the seizure, reduce the secondary brain damage and improve the quality of life of patients. The effects of medication or reason is in many aspects, we will ignore the pharmacokinetic factors are often an important reason for antiepileptic drug treatment failure or become part of the patient "permanently", this article discusses the following points.

1 abnormal discharge of cerebral neurons in epileptic patients is random. Epilepsy is a kind of transient brain dysfunction caused by abnormal cerebral neurons and over synchronous discharge. Its characteristic is sudden and transient symptoms, except in special circumstances (such as provocation test with periodic attacks or some tendency of epilepsy), abnormal discharge of neurons was not predictable, is completely random. This important feature requires during drug treatment, drug dose to be used in the "right", which not only can always achieve the effective concentration control of abnormal discharge "(" there are individual differences in relatively large), and can be avoided because of low concentration cannot play a role in treatment, or high concentration of lead the adverse reaction. To achieve this, need to antiepileptic drug pharmacokinetics according to each patient use, arrange daily times of medication and medication time, ensure the anti epileptic drugs always reach stable blood concentration. It is not difficult to understand why patients with poor compliance with medication or sometimes forget to take the medication, there is likely to be a clinical phenomenon of epilepsy.

2 all the antiepileptic drugs had their pharmacokinetic characteristics. Each kind of anti epilepsy drugs have a half-life (T 1/2), such as phenobarbital for 96 - 12 hours, while in the infant period is 47 hours, and sodium valproate for 8-10 hours, 8-12 hours of C Masi Bing, between topamax (topiramate) for 20-30 hours (children 15-20 hours). Half life can help to estimate the time to stabilize the blood concentration of antiepileptic drugs, generally after giving an effective dose of about 5~7 half life, you can achieve steady state plasma concentration. Such as sodium valproate, C Masi Bing takes about 3 days time to reach the stable blood concentration of phenobarbital, and takes about 20 days to achieve stable blood concentration. Only stable blood concentration of antiepileptic drugs can play a stable therapeutic effect. Some patients with epilepsy in the clinical use of antiepileptic drugs has not yet reached a stable blood concentration, because the onset of seizures that this drug is invalid, and stop medication or dressing is inappropriate.

3 according to the pharmacokinetic characteristics, reasonable arrangements for the number of daily medication. In principle, the arrangement of the number of medication should make the blood concentration of drugs in 24 hours to achieve steady state. The time of administration should not exceed the 1 half life of the drug. According to the different drug half-life can calculate the number of daily should take medicine, such as C Masi Bing and sodium valproate tablets had better 3 times a day, only 1 times a day phenobarbital. In recent years, the advent of many new antiepileptic drugs, due to the relatively long half-life, only need 2 times a day. If it is a controlled release dosage form of traditional medicine, it should be based on its release rate to determine the number of daily medication. Very unfortunately, often see examples of daily administration times due to unreasonable clinical "permanently" in clinical practice, such as arranging tablets or valproate Carbamazepine Tablets only take the medicine 1 times a day, or arrange to take the medicine 2 times a day at the same time dose is obviously insufficient etc.. In such cases, the duration of the clinical onset of the patient is often the end of the half-life of the drug.

4 arrange and guide the patient's specific medication time. Because different antiepileptic drugs have different pharmacokinetic characteristics, even if the same antiepileptic drugs still exist. Therefore, it is an important method to ensure the stability of the blood concentration of antiepileptic drugs and to play a stabilizing role. But because of the traditional habits and each time is different, in clinical patients in China, 3 times daily medication will usually be patient arrange within 12 hours (7 -12 -19) executed, which may lead to early time blood concentration is too low; some patients often forget at noon this time the medication may cause PM blood concentration is too low. As a result, these patients often describe seizures in the morning or afternoon. In this regard, if clinicians can ask specific patient time of each episode carefully, and analyze its relationship with the time of taking medicine, it is easy to find and correct the treatment medication time resulting from improper failure.

5 joint use of antiepileptic drugs, attention should be paid to the interaction between antiepileptic drugs. These include pharmacodynamic interactions and pharmacokinetic interactions. The former refers to two drugs with similar or opposite pharmacological mechanism, while the plasma concentration of drugs or / and their metabolites has not changed. The latter refers to a drug that interferes with the process of another drug, including absorption, distribution, metabolism, and excretion, and changes the concentration of the drug at the site of action. Pharmacokinetic interactions in clinical significance, such as C Masi Bing could be expected to decrease in the concentration of sodium valproate, phenytoin, primidone, lamotrigine and ethosuximide and felbamate, but may increase the expected concentration of Phenobarbital; concentration of sodium valproate may increase expected card Ma Xiping epoxides, primidone and phenobarbital, lamotrigine and ethosuximide; C Masi Bing, may reduce the expected concentration of phenytoin sodium valproate, felbamate, lamotrigine and ethosuximide, but may increase the expected concentration of Phenobarbital; expected concentration of phenobarbital may reduce C Masi Bing, sodium valproate, felbamate, lamotrigine and ethosuximide; the expected concentration of primidone may reduce C Masi Bing, sodium valproate, felbamate, lamotrigine and ethosuximide; vigabatrin may reduce phenytoin The expected concentration of sodium, phenobarbital and primidone; expected concentration of lamotrigine may increase the concentration of carbamazepine epoxide; expected ethosuximide may increase phenytoin; felbamate elevated phenytoin and carbamazepine, valproate and phenobarbital expected epoxide concentration. Therefore, when the new antiepileptic drugs reduced the original concentration of antiepileptic drugs, it may worsen the phenomenon of epilepsy, especially in the original antiepileptic drug dose at the lowest effective dose is more likely to occur. The effect of antiepileptic drug therapy is poor in epilepsy patients, adding another anti epileptic drugs, should pay close attention to changes in drug concentration monitoring, observation of clinical seizures and pay attention to the occurrence of adverse drug reactions, according to the specific circumstances of timely adjustment of drug dosage.

6 special patients need special treatment. Very few patients with epilepsy seizures have certain rules, as usual in sleep ormenstruationperiod epilepsy patients. For these often occur in a specific time of epilepsy patients, should try to reach the peak concentration of drug absorption can just cover this time period. For patients who are prone to an increased number of episodes at a particular stage, such as menstrual periods, an appropriate dose of antiepileptic drugs should be considered during this period.

7 should be monitored when the blood concentration. Blood concentration monitoring can accurately reflect the patient for individual antiepileptic drug metabolism, the clinical commonly used antiepileptic drugs to blood concentration monitoring provides an important means for the comprehensive evaluation of the efficacy of antiepileptic drugs, especially for the treatment of refractory epilepsy in guidance. The changes of serum concentration should be analyzed comprehensively, including age, half-life of drugs, medication compliance, diet, gastrointestinal and liver and kidney function, and the interaction of drugs. According to the changes of serum concentration and clinical attack, we can adjust the dosage of antiepileptic drugs, the times of administration and the time of administration. For those who have reached the "effective" plasma concentration, but still can not control the clinical onset of the patient, should be careful analysis of the reasons, if necessary, can be considered to replace antiepileptic drugs. It should be noted that there is a significant difference in the plasma concentration of the individual when the attack has been ideal. The treatment is easy to control the type of seizure and seizure frequency comparison before treatment in patients with low blood concentration is relatively low, you can control the attack, at this time, when the patient's clinical seizure has been completely controlled, even if the lower limit of the serum concentration is lower than the so-called "treatment", there is no need to increase the anti epilepsy drug dose. On the other hand, sometimes treating the upper limit of the range is not absolute, because some patients need the high concentration range to achieve the ideal control purposes, such as some patients serum concentration of valproic acid reached 120ug/ml can completely control the clinical seizures. Therefore, as long as there is no adverse reaction, the treatment of the upper limit of the concentration of the patient's "effective" blood concentration.

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