Lorazepam

Lorazepam34,35,40-49 has a lesser volume of distribution and is less lipid soluble than diazepam. It enters the brain more slowly, taking up to 30 minutes to reach peak levels. Its distribution half-life is much longer, two to three hours, and its elimination half-life is shorter, approximately 10-12 hours. These characteristics result in a slower onset of action, but a longer duration of action. Lorazepam is indicated in the early stage of status epilepticus only, where its lack of accumulation in lipid stores, its strong cerebral binding, and long duration of action due to its distribution half-life are very significant advantages over diazepam. The pharmacology and clinical effects of lorazepam have been well characterised in adults, in children, and in the newborn, and the drug has been the subject of large scale clinical trials. Lorazepam is remarkably effective in controlling seizures in the early stage of status epilepticus. Its main disadvantage is the rapid development of tolerance. Initial injections of lorazepam are effective for about 12 hours (longer than with diazepam), but repeated doses are much less effective, and the drug has no place as long term therapy. Lorazepam has sedative effects shared by all the benzodiazepine drugs used in status epilepticus, but sudden hypotension or respiratory collapse is less likely because of its relative lipid insolubility and the lack of accumulation after single bolus injections. Lorazepam is administered by intravenous bolus injection. As distribution is slow, the rate of injection is not critical. In adults, a bolus dose of 0 07 mg/kg (to a maximum of 4 mg) is given, and this can be repeated once after 20 minutes if no effect has been observed. In children under 10 years, bolus doses of 01 mg/kg are recommended. Long term infusion of lorazepam should not be used. It is usually available as a 1 ml ampoule containing 4 mg of lorazepam.

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