Lorazepam chemical structure
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Lorazepam

Lorazepam (marketed under the brand names Ativan®, Temesta®, Tavor®) is a drug which is a benzodiazepine derivative. Pharmacologically, it is classified as a sedative-hypnotic, anxiolytic and anticonvulsant. more...

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Pharmacology and pharmacokinetics

Lorazepam is rapidly and nearly completely absorbed after any mode of application (oral, sublingual, i.m., i.v.). The onset of action is several minutes after i.v. injections, 30 to 45 minutes after oral/sublingual administration, and up to 1 hour after i.m. injections.

The duration of action depends on the dose, and is normally 6 to 12 hours. The half-life of lorazepam in patients with normal liver function is 11 to 18 hours. Therefore, 2 to 4 daily doses are often needed.

0.5mg (500µg) of lorazepam is equivalent to 5mg of diazepam . Other experts estimate a proportion of 1mg lorazepam to 5mg diazepam.

Indications

Lorazepam is indicated for:

  • Treatment of anxiety disorders
  • Short-term treatment of insomnia, particularly if associated with severe anxiety
  • Treatment of symptoms associated with alcohol withdrawal
  • As a premedication,
    • To facilitate unpleasant procedures, such as endoscopies and dental surgery.
    • To augment the action of the primary anaesthetic drug.
    • To produce varying degrees of anterograde amnesia for the duration of the procedure.
  • Long-term treatment of otherwise resistant forms of petit mal epilepsy
  • Acute therapy of status epilepticus
  • Acute therapy of catatonic states alone/or with haloperidol
  • As an initial adjunctive treatment for depressions, mania and psychosis
  • Treatment of acute delirium, preferrably together with haloperidol
  • Supportive therapy of nausea/emesis frequently associated with cancer chemotherapy, usually together with firstline antiemetics like 5-HT3-antagonists

Lorazepam is available in tablets and as a solution for intramuscular and intravenous injections. It is also available as a parenteral patch.

Dosage

Daily doses vary greatly from 0.5 mg bedtime for insomnia and 2.5 mg every 6 hours and more in the acute treatment of mania, before the firstline drugs (lithium, valproic acid) control the situation.

Catatonia with inability to speak is very responsive and sometimes controlled with a single dose of 2 mg oral or slow i.v. injection. Catatonia may reoccur and treatment for some days may be necessary. Sometimes haloperidol is given concomitantly.

The control of status epilepticus requires slow i.v. injections of 2 to 4 (or even 8) mg. Patients should be closely monitored for respiratory depression and hypotensive effects.

In any case, dose requirements have to be individualized especially in the elderly and debilitated patients in whom the risk of oversedation is greater. Safety and effectiveness of lorazepam is not well determined in children under 18 years of age, but it is used to treat serial seizures. With higher doses (preferably i.v.-doses) the patient is frequently not able to recall unpleasant events (anterograde amnesia) such as therapeutic interventions (endoscopies etc.), which is a desirable effect. But in these cases the risk is given that a patient later makes unjustified allegations of sexual abuse during treatment due to poor recall.

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Continuous Enteral Lorazepam In The Trauma Patient - Abstract
From CHEST, 10/1/99 by Jose E Perez

Purpose: To determine if continuous enteral lorazepam (CEL) was efficacious and cost effective in the mechanically ventilated trauma patient.

Methods: A retrospective chart review of 10 eases was performed. Patients were treated with CEL if they were requiring continuous intravenous (IV) sedation and tolerating tube feeds at their goal rate for at least 48 hours. Materials used were a Medifusion 2001 Syringe Pump, a Baxter Anti-siphon PCA extension set and an Add to catheter adapter. Blue dye was added to the solution and it was labeled for enteral use only. The IV sedation was weaned over a period of 6 hours after initiation of CEL.

Results: All patients needed intermittent IV sedation for breakthrough agitation. Of the 10 patients 6 had been on IV midazolam and 4 on IV lorazepam prior to CEL. The mean duration of CEL was 18 days with a range of 5 to 30 days. The mean age was 55 years with a range of 18 to 81 years. Of the 10 patients CEL was discontinued in 2 patients. One patient developed an ileus and another diarrhea. The CEL was titrated to the desired level of sedation with a range of 2-26 mg/hour, and a mean of 10 mg/hour. The acquisition cost based on the mean dosage and duration of CEL versus pre-CEL IV infusion was $583/day for midazolam, $143/day for IV lorazepam, and $122/day for CEL. This amounts to a cost savings with CEL of $24,680 versus midazolam, and $3,600 versus IV lorazepam.

Conclusion: CEL is effective in the mechanically ventilated trauma patient with adequate bowel function. CEL can also free up an IV site for other medications.

Clinical Implications: A definite cost saving can be seen with this effective mode of sedation.

Jose E Perez, MD(*) and J E Nash, RPh. Pulmonary and Pharmacy, St. Joseph's Hospital, Tampa, FL.

COPYRIGHT 1999 American College of Chest Physicians
COPYRIGHT 2000 Gale Group

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