indication
For the management of anxiety disorders, and for treatment of status epilepticus.
pharmacology
Lorazepam, a benzodiazepine not transformed to active metabolites, is used to treat anxiety, status epilepticus, and for sedation induction and anterograde amnesia.
mechanism of action
Lorazepam binds to an allosteric site on GABA-A receptors, which are pentameric ionotropic receptors in the CNS. Binding potentiates the effects of the inhibitory neurotransmitter GABA, which upon binding opens the chloride channel in the receptor, allowing chloride influx and causing hyperpolerization of the neuron.
toxicity
Somnolence, confusion, and coma, LD
50=3178mg/kg (orally in mice).
biotransformation
Hepatic
absorption
Readily absorbed with an absolute bioavailability of 90%.
half life
12 hours
route of elimination
Lorazepam is rapidly conjugated at its 3-hydroxy group into lorazepam glucuronide which is then excreted in the urine.
drug interactions
Clozapine: Increased risk of toxicity
Kava: Kava may increase the effect of the benzodiazepine, lorazepam.
Triprolidine: The CNS depressants, Triprolidine and Lorazepam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Valproic Acid: Valproic acid may increase the serum concentration of Lorazepam by reducing Lorazepam metabolism. The Lorazepam dose should be reduced by 50% during concomitant therapy. Monitor for increased Lorazepam effects and toxicity.
