Transcript Chapter 15 Antiepileptic Drugs

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.
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）
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.
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.
[Clinical Use]
• 1. Antiepilepsy: Phenytoin is one of the most
effective drug against generalized seizures and
partial seizures.
• 2. Used in cardiac arrhythmias.
[Adverse effects and toxicity]
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Nausea and vomiting
Rash
Blood dyscrasias
Hormonal dyfunction
Bone marrow hypoplasia
Gingival Hyperplasia(齿龈增生）occur to
some degree in most patient.
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.
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.
Primidone(扑痫酮）
• Primidone was metabolized to phenobarbital.
• It can be used for partial onset and secondarily
generalized seizures.
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.
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.
Benzodiazepines
• Diazepam given intravenously(i.v.) is highly
effective for stopping continuous seizures
activity, especially status epilepticus.