Tài liệu CLINICAL PHARMACOLOGY 2003 (PART 22) pdf

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Epilepsy, parkinsonism and allied

conditions

SYNOPSIS

• Antiepilepsy drugs: principles of

management; withdrawal of therapy;

pregnancy; teratogenic effects; epilepsy in

children; status epilepticus

• Individual drugs: carbamazepine, phenytoin,

sodium valproate, lamotrigine, vigabatrin,

gabapentin, clonazepam, topiramate,

levetiracetam.

• Parkinsonism

Objectives of therapy

Drug therapy; problems of long-term

treatment

• Other disorders of movement

• Tetanus

cortical neurons simultaneously (primary generalised

seizure).

Bromide (1857) was the first drug to be used for

the treatment of epilepsy, but it is now obsolete.

Phenobarbital, introduced in 1912, controlled

patients resistant to bromides. The next success was

the discovery in 1938 of phenytoin (a hydantoin)

which is structurally related to the barbiturates.

Since then many other drugs have been discovered,

but phenytoin still remains a drug of choice in the

treatment of major epilepsy. Over the past ten years

there has been a dramatic increase in the number of

new anticonvulsant drugs (vigabatrin, gabapentin,

lamotrigine, topiramate, oxcarbazepine, levetira￾cetam), but none has been shown to be superior

to the major standard anticonvulsants (phenytoin,

carbamazepine and sodium valproate).

Antiepilepsy drugs

Epilepsy affects 5-10 per 1000 of the general

population.1

It is due to sudden, excessive depolar￾isation of some or all cerebral neurons. This may

remain localised (focal seizure) or may spread to

cause a secondary generalised seizure, or affect all

1

Some people with epilepsy make pilgrimages to Terni

(Italy) to seek intercession from Saint Valentine to relieve

their condition. There was more than one Saint Valentine and

it is unclear if he was also the patron saint of lovers.

MODE OF ACTION

Antiepilepsy (anticonvulsant) drugs inhibit the

neuronal discharge or its spread, and do so in one

or more of three ways:

1. Reducing cell membrane permeability to ions,

particularly the voltage-dependent sodium

channels which are responsible for the inward

current that generates an action potential. Cells

that are firing repetitively at high frequency are

blocked preferentially, which permits

discrimination between epileptic and

physiological activity.

2. Enhancing the activity of gamma-aminobutyric

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