Phenobarbitone

Phenobarbitone50-52 is a drug of choice for the treatment of established status epilepticus. It is highly effective, has a rapid onset of action, and prolonged anticonvulsant effects. It has stable and non-reactive physical properties, and convenient pharmacokinetics. Wide experience has been gained of its use in adults and in children, and few drugs are as well tried in the newborn. It has stronger anticonvulsant properties than most other barbiturates, and may be preferentially concentrated in metabolically active epileptic foci. As well as excellent anticonvulsant properties, it may also have cerebral-protective action. Acute tolerance to the antiepileptic effect is unusual, in contrast to the benzodiazepines and, once controlled, seizures do not tend to recur. Indeed, there is evidence to suggest that given with barbiturate anaesthesia, it can reduce the relapse rate with anaesthetic withdrawal. The main disadvantages of phenobarbitone are its potential to cause sedation, respiratory depression, and hypotension, although in practice these effects seem slight except at high levels or with rapidly rising levels. Its safety at even high doses is well established. The well known chronic side effects of phenobarbitone in long term therapy are of little relevance in the emergency situation of status epilepticus. The drug is eliminated slowly and, although this is of no importance on initial phenobarbitone loading, on prolonged therapy there is a danger of accumulation and blood level monitoring is essential. In the newborn period dosing is more difficult than in adults, as the pharmacokinetics change rapidly during the first weeks and months of life. The drug has a strong tendency to autoinduction. Phenobarbitone is a stable preparation, which does not easily decompose, and the drug is not absorbed by plastic. It should not be used in a solution containing other drugs (for example, phenytoin), as this may result in precipitation.

The usual recommended adult intravenous loading dose is 10 mg/kg (doses of up to 20 mg/kg have been used and recommended), given at a rate of 100 mg/min (that is, a total of about 700 mg in seven minutes). This should be followed by daily maintenance doses of 1-4 mg/kg. In neonates, initial phenobarbitone loading doses of between 12 and 20 mg/kg have been recommended to produce therapeutic levels, with subsequent supplementation of 3-4 mg/kg per day, to a maximum dose of 40 mg/kg. In older children, loading doses of between 5 and 20 mg/kg are recommended and maintenance doses of 1-4 mg/kg, although much higher doses have been safely given. After loading, maintenance doses can be given by the oral, intravenous, or intramuscular route. Phenobarbitone is usually presented in 1 ml ampoules containing 200 mg of phenobarbitone sodium.

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