Lorazepam
Lorazepam
Ativan®
Classification:
Anesthetics
» Benzodiazepines
Neurological Agents
» Anticonvulsants
» Benzodiazepines
Psychotropic Agents
» Anxiolytics, Sedatives, and Hypnotics
» Benzodiazepines
Toxicology Agents
» Substance Abuse Agents
» Withdrawal agents
NOTE: Lorazepam is a schedule C-IV controlled substance.
Description: Lorazepam is an oral and parenteral benzodiazepine used in the treatment of anxiety and status epilepticus. Other uses include perioperative sedation induction and anterograde amnesia. Intravenous lorazepam has replaced intravenous diazepam as the drug of choice for the treatment of status epilepticus because lorazepam persists in the CSF longer than diazepam. Some clinicians also prefer lorazepam over chlordiazepoxide or diazepam for controlling anxiety and agitation during ethanol withdrawal because lorazepam is not metabolized to active metabolites. Lorazepam was approved by the FDA in September 1977. It is a DEA schedule IV controlled substance. An orally-disintegrating formulation is currently under development by Biovail Pharmaceuticals.
Mechanism of Action: Benzodiazepines act at the level of the limbic, thalamic, and hypothalamic regions of the CNS, and can produce any level of CNS depression required including sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and coma. The action of these drugs is mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Central benzodiazepine receptors interact allosterically with GABA receptors, potentiating the effects of GABA and thereby increasing the inhibition of the ascending reticular activating system. Benzodiazepines block the cortical and limbic arousal that occurs following stimulation of the reticular pathways.
As an anticonvulsant, lorazepam has become the preferred parenteral benzodiazepine. Although lorazepam has a shorter elimination half-life than diazepam, lorazepam persists in the CNS longer than diazepam.
Pharmacokinetics: Lorazepam is administered orally and parenterally. The drug has also been given sublingually; although, specific sublingual dosage forms are not available in the United States. Lorazepam is absorbed rapidly following an oral dose, with wide distribution throughout the body tissues. Approximately 91% of lorazepam present in the blood is protein-bound. Lorazepam has been reported to cross the placental barrier and has been detected in human breast milk.
 Ativan Tablet (Tablet 1 mg)
Lorazepam is glucuronidated by the liver to lorazepam glucuronide, an inactive metabolite. The half-life of lorazepam is approximately 42, 10.5, and 12 hours in neonates, older children, and adults, respectively. The plasma half-life is much longer in neonates because their glucuronidation pathways are not mature. The metabolites of lorazepam are excreted in the urine.
- Special Populations: A comparison of elderly adults aged > 65 years to younger adults revealed that lorazapam pharmacokinetics remain unaltered with age. Because lorazepam undergoes conjugative metabolism as opposed to oxidative metabolism, the pharmacokinetics of the drug are less likely to be altered in the presence of hepatic dysfunction versus many other benzodiazepines.
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[ Revised 2/27/2007 6:04:00 PM ]
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