Dimensiones de los Estilos de Liderazgo

ETH Corticotrophin VPA

CZP Steroids CZP VPA VPA NZP CZP NZP PHB CZP VPA PHB CBZ PHT VPA CZP CBZ PHT PHB CZP VPA Sulthiame Source: Eadie and Tyrer, 1989

2.5.b.iii Phenytoin

This drug, one of the hydantoin group of drugs, was first synthesised by Blitz in 1908, although its anticonvulsant properties were only recognised in 1938 by Merritt and Putman (Eadie and Tyrer, 1989) . It is a drug of first choice for the treatment of tonic-clonic and partial (simple and complex) seizures. Tonic and atonic seizures may also respond to treatment with PHT (Browne and Pinus, 1983) . In addition,

intravenous PHT therapy is effective in status epilepticus (Engel, 1989). Common dose-related toxic side-effects include ataxia, dizziness, nystagmus, diplopia and tremor.

2.5.b.iv Primidone

This drug was synthesised in 1949 and came into routine clinical use in 1952 following a report by Handley and Stewart (1952) (Eadie and Tyrer, 1989). It is an effective agent against generalised convulsive and partial seizures, though it is of less value in myoclonic seizures (Eadie and Tyrer, 1989; Engel, 1989) . Absence seizures do not respond to treatment with primidone. Due to adverse side effects including vertigo, dizziness, nausea, vomiting, ataxia and diplopia it is less well tolerated than other first line AEDs. It is, however, a useful adjunctive therapy particularly in patients who have shown a limited response to phenytoin or carbamazepine.

2.5.b.v Ethosuximide

Ethosuximide is one of the succinimide group of drugs, which were introduced specifically for the treatment of absence seizures (Engel, 1989). Ethosuximide was introduced in 1958 and is a highly effective agent against typical absence seizures (Shorvon, 1987). It may provide some protection against myoclonic seizures, but does not seem to be useful in other seizure types (Eadie and Tyrer, 1989) . It is noted for its low toxicity. Dose related side effects include tiredness, headache and gastrointestinal disturbances (Browne, 1983; Eadie and Tyrer, 1989).

2.5.b.vi Carbamazepine

Carbamazepine is chemically related to the tricyclic antidepressants. It was first synthesised by Schinder in 1953 (Eadie and Tyrer, 1989), coming into clinical use as an anticonvulsant in 1962 (Shorvon, 1987) . It is one of the most important antiepileptic agents and is the drug of first choice for tonic-clonic, clonic and partial (both simple and complex partial) seizures (Engel, 1989). It is reported to have fewer sedative effects than the other main-line antiepileptic drugs (PHT, PHB, PRM) and has been related to improvements in cognitive function when substituted for other AEDs (Trimble and Thompson, 1983) . There is also a suggestion that this compound may have a psychotropic effect, though this topic remains controversial (Rodin, 1983) .

2.5.b.vii Sodium Valproate

The valproate molecule was synthesised in 1881 (Eadie and Tyrer, 1989) , but it was not until 1961 that its potential as an anticonvulsant agent was accidentally discovered (Eadie and Tyrer, 1989). It entered the armamentarium of anticonvulsant agents in the early 1970's. It is a simple branched-chain carboxylic acid with a broad spectrum of anticonvulsant action, being particularly indicated for the treatment of typical absence, myoclonic and generalised tonic-clonic seizures (Shorvon, 1987). Due to its broad range of action, it is a drug of choice for mixed seizure types (Engel, 1989). It is most effective against generalised convulsive and non- convulsive seizures, but it is may also be of some value in the treatment of partial seizures (Eadie and Tyrer, 1989). Sodium valproate has the reputation of being one of the least sedative of the antiepileptic drugs. This drug has a low side effect profile. Dose related gastrointestinal effects (anorexia, nausea, vomiting) occur in approximately 16% of patients (Engel, 1989); CNS side effects (sedation, ataxia, tremor) occur infrequently, in contrast to many of the other AEDs. Alopecia and appetite stimulation/weight gain may be problematic in some patients (Shorvon, 1987). Fatal hepatoxicity has been reported in a number of cases and is a risk which limits the use of this drug, particularly in children (Engel, 1989).

2.5.b.viii Benzodiazepines

The benzodiazepines were first synthesised by Dziewonski and Sternbach in 1933 (Dreifuss and Sato, 1982) . In addition to their sedative-hypnotic and anxiolytic properties, a number of the benzodiazepines have anticonvulsant properties. Diazepam, nitrazepam and clonazepam are the main benzodiazepines used as primary therapy for epilepsy, although others may be useful as adjunctive therapy (eg. clobazam, midazolam) (Eadie and Tyrer, 1989). Sedation and the development of tolerance to the antiepileptic effect are the main restrictions on the use of these drugs.

Clonazepam (Rivotril/Clonopin): this 1,4-benzodiazepine was first evaluated in 1966 by Swinyard and Castellion, its use in routine clinical practice starting in the early 1970's. It is indicated for myoclonic seizures and non-epileptic myoclonic phenomena (Engel, 1989). Clonazepam is also highly effective against absence seizures, although ethosuximide remains the drug of choice for this seizure type due to the higher incidence of side effects and tolerance with clonazepam. Partial seizures, particularly those originating in the temporal lobes, may also respond to treatment with clonazepam (Eadie and Tyrer, 1989) . Due to its broad spectrum of action, it may be useful in patients with mixed seizure types (Engel, 1989) . This drug is also used parenterally in status epilepticus. Side effects from oral administration are common with patients often experiencing ataxia, drowsiness and mood changes. Severe toxicity, however, is rare (Dreifuss and Sato, 1982) . Hyperactivity in children has also been noted. Tolerance is a major problem, developing in 1/3 of patients within 3 month of starting therapy (Engel, 1989).

Nitrazepam (Moqodon) : this drug is reasonably effective for myoclonic seizures, infantile spasms and the Lennox-Gastaut syndrome (Baruzzi et al;, 1982). The reflex epilepsies respond well to nitrazepam. Side effects are common, but mild and tolerance may be a problem.

Diazepam (Valium) : while this drug is not an effective oral agent for the treatment of chronic epilepsy it has a major role to play in the treatment of status epilepticus. It is the drug of first choice for status epilepticus due to its rapid

penetration into the brain, its prompt therapeutic action and its rare toxicity (Schmidt, 1982). Oral use of diazepam as an anticonvulsant agent is rare due to the development of tolerance: it is useful, however, in treating accompanying psychiatric problems, for example, anxiety in the patient with epilepsy.

Clobazam (Frisium): this 1,5 benzodiazepine has a broad spectrum of antiepileptic properties, with a reduced incidence of sedative and motor side-effects (Engel, 1989) .

M i d a zolam: this benzodiazepine may be useful as an intravenous