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Chapter 17 Drugs effective in the Therapy of Epilepsies. Epilepsy is a chronic disorder characterized by recurrent seizures.

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Chapter 17 Drugs effective in the Therapy of Epilepsies


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    1. Chapter 17 Drugs effective in the Therapy of Epilepsies • Epilepsy is a chronic disorder characterized by recurrent seizures. • Seizures are resulted from abnormal discharge of cerebral neurons. The causes of seizures are many and include the full range of neurological disease, from infection to neoplasm and head injury. In a few subgroups, heredity has proved to be a major contributing factor.

    2. Classification of seizures types • Partial seizures Simple partial seizures(单纯性局限性发作) Complex partial seizures (复杂性局限性发作) • Generalized seizures Generalized tonic-clonic seizures(强直阵挛性大发作) Status epilepticus(癫痫持续状态) Absence seizures(失神小发作) Myoclonic seizures(肌阵挛性发作) Infantile spasms(婴儿痉挛)

    3. Mechanism of action of antiepileptic drugs • Enhanncement of GABA-mediated inhibition can be produced in many different ways, involving either direct action on the GABA receptor-chloride channel complex or actions on the reuptake or metabolism of GABA. • Inhibit NDMA receptors • Prolong inactive state of ion channels by mutation突变.

    4. Phenytoin (dilantin)苯妥英钠 • Phenytoin is the oldest nonsedative antiepileptic drug, introduced in 1938 • [Mechanism of Action] • (1) Phenytoin blocks sodium channels,and thereby prevents post-tetanic potentiation(强直后增强),limits development of maximal seizure activity,and reduces the spread of seizures(sustained high-frequency repetitive firing of action potentials). • (2) Phenytoin inhibits calcium influx ,thereby inhibiting neurotransmission at the level of the synapse.

    5. [Clinical Use] • 1. Antiepilepsy: Phenytoin is one of the most effective drug against generalized seizures and partial seizures. • 2. Used in cardiac arrhythmias.

    6. [Adverse effects and toxicity] • Nausea and vomiting • Rash • Blood dyscrasias • Hormonal dyfunction • Bone marrow hypoplasia • Gingival Hyperplasia(齿龈增生)occur to some degree in most patient.

    7. Carbamazepine(卡马西平) • The mechanism of action of carbamazepine appears to be similar to that of Phenytoin. • Carbamazepine is considered the drug of choice for partial seizures and many physicians also use it first for generalized tonic-clonic seizures. It can be used with Phenytoin in many patients who are difficult to control.

    8. Phenobarbital[苯巴比妥] • Phenobarbital may selectively suppress abnormal neurons, inhibiting the spread and suppressing firing from the foci. • Like Phenytoin , phenobarbital suppresses high frequency repetitive firing through an action on ion channel. • Phenobarbital is useful in the treatment of partial seizures and generalized seizures,and is a fist-line grug for treatment of status epilepticus.

    9. Primidone(扑痫酮) • Primidone was metabolized to phenobarbital. • It can be used for partial onset and secondarily generalized seizures.

    10. Ethosuximide (乙琥胺) • Ethosuximide is particularly effective against absence seizures(失神小发作) The most common dose-related adverse effect of ethosuximide is gastric distress, including pain,nausea,and vomiting.

    11. Sodium Valproate(丙戊酸钠) • Valproate is very effective against absence seizures, although ethosuximide is the drug of first choice when absence seizures occur alone. • Valproate is preferred if the patient has concomitant(伴随的) generalized tonic-clonic attacks. The reason for preferring ethosuximide for uncomplicated absence seizures is valproate’s hepatotoxicity.

    12. Benzodiazepines • Diazepam given intravenously(i.v.) is highly effective for stopping continuous seizures activity, especially status epilepticus.