CLINICAL PHARMACOLOGY 2003 (PART 22)

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 • Tetanuscortical 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...
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CLINICAL PHARMACOLOGY 2003 (PART 22) 20 Epilepsy, parkinsonism and allied conditions SYNOPSIS cortical neurons simultaneously (primary generalised seizure). • Antiepilepsy drugs: principles of Bromide (1857) was the first drug to be used for management; withdrawal of therapy; the treatment of epilepsy, but it is now obsolete. pregnancy; teratogenic effects; epilepsy in Phenobarbital, introduced in 1912, controlled children; status epilepticus patients resistant to bromides. The next success was • Individual drugs: carbamazepine, phenytoin, the discovery in 1938 of phenytoin (a hydantoin) sodium valproate, lamotrigine, vigabatrin, which is structurally related to the barbiturates. gabapentin, clonazepam, topiramate, Since then many other drugs have been discovered, levetiracetam. but phenytoin still remains a drug of choice in the • Parkinsonism treatment of major epilepsy. Over the past ten years Objectives of therapy there has been a dramatic increase in the number of Drug therapy; problems of long-term new anticonvulsant drugs (vigabatrin, gabapentin, treatment lamotrigine, topiramate, oxcarbazepine, levetira- • Other disorders of movement cetam), but none has been shown to be superior • Tetanus to the major standard anticonvulsants (phenytoin, carbamazepine and sodium valproate). MODE OF ACTIONAntiepilepsy drugs Antiepilepsy (anticonvulsant) drugs inhibit the neuronal discharge or its spread, and do so in oneEpilepsy affects 5-10 per 1000 of the general or more of three ways:population.1 It is due to sudden, excessive depolar- 1. Reducing cell membrane permeability to ions,isation of some or all cerebral neurons. This may particularly the voltage-dependent sodiumremain localised (focal seizure) or may spread to channels which are responsible for the inwardcause a secondary generalised seizure, or affect all current that generates an action potential. Cells that are firing repetitively at high frequency are1 blocked preferentially, which permits Some people with epilepsy make pilgrimages to Terni(Italy) to seek intercession from Saint Valentine to relieve discrimination between epileptic andtheir condition. There was more than one Saint Valentine and physiological activity.it is unclear if he was also the patron saint of lovers. 2. Enhancing the activity of gamma-aminobutyric 413 20 EPILEPSY, PARKINSONISM AND ALLIED CONDITIONS acid (GABA) the principal inhibitory transmitter appropriate to the type of seizure disorder. of the brain; the result is increased membrane Although some drugs have a wide spectrum of permeability to chloride ion, which reduces cell action against different seizure types, some are excitability. more specific and may even aggravate certain3. Inhibiting excitatory neurotransmitters, e.g. seizure types. Carbamazepine is a drug of first glutamate. choice for focal and secondary generalised epilepsy but aggravates myoclonic and absence seizures. Sodium valproate and lamotrigineCLASSIFICATION OF EPILEPSIES have a wide spectrum of action and are activeA generally accepted classification is given in Table against both primary and secondary generalised20.2 (p. 418), together with drugs of choice for the epilepsy.various seizur ...