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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Low-dose lorazepam can reverse morphine-induced hypothermia - Post Cesarean Section
From OB/GYN News, 7/15/02 by Kathryn DeMott

HILTON HEAD ISLAND, S.C. -- Among patients who received morphine after cesarean section, 7% developed hypothermia, and lorazepam normalized temperatures in 80% of these women, according to the findings of an early report presented at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

Although larger studies are needed to confirm the effectiveness of lorazepam, low doses of the antianxiety medication are safe and not associated with any side effects. Physicians may want to consider using it if active warming is not effective, said Dr. Jason Wang, an obstetric anesthesia fellow at Beth Israel Deaconess Medical Center, Boston.

Morphine-induced hypothermia is a well-described phenomenon in animals.

"For some reason, morphine decreases the central thermal temperature setting in the brain," he said. The body then perceives the normal temperature of 37[degrees]C to be a fever, spurring peripheral vasodilatation, heat loss, and sweating. Yet this cause of hypothermia is not a commonly recognized phenomenon. Obstetricians and anesthesiologists miss it, because they assume that the patient's temperature has dropped as a result of simply having undergone surgery.

Although active warming measures usually resolve hypothermia caused by surgery patients who have morphine-induced hypothermia tend to remain cold for several hours regardless of heating efforts.

During that time, they're losing water from sweating and increasing their risk of developing cardiac arrhythmias, he said during an interview with this newspaper.

In a study involving 208 women undergoing C-sections, 193 received spinal morphine, and 15 received epidural morphine. A total of 14 patients (7%) became hypothermic, with temperatures dropping below 95.5[degrees]F.

Patients with hypothermia tended to feel hot and sweaty, despite the fact that their temperatures were well below normal.

"One patient's temperature was down to 93[degrees]F, and she still complained of feeling hot," Dr. Wang observed.

Among the 10 patients who received lorazepam, a bolus dose of up to 1 mg by intravenous push, symptoms resolved and temperatures normalized in 8 of the women within 90 minutes.

By comparison, patients who received active warming with commercial warming blankets, hot air pumps, and heated saline intravenously tended to take much longer for their symptoms and temperatures to normalize, he commented.

These findings shouldn't discourage physicians from using intrathecal morphine, Dr. Wang emphasized in an interview. Morphine's benefits in terms of providing powerful and prolonged anesthesia are unrivaled, and the side effect of hypothermia is manageable.

Animal studies have shown that other drugs, such as diazepam, are also effective in at least partially resolving morphine-induced hypothermia, but lorazepam appears to be ideal because it's fast acting and lasts 6-8 hours, which is long enough to prevent a relapse, he said.

COPYRIGHT 2002 International Medical News Group
COPYRIGHT 2002 Gale Group

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