Drug information of Lorazepam
Mechanism of effect
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.
Lorazepam, a benzodiazepine not transformed to active metabolites, is used to treat anxiety, status epilepticus, and for sedation induction and anterograde amnesia.
Readily absorbed with an absolute bioavailability of 90% when given orally. When intramuscularly administered, lorazepam is completely and rapidly absorbed. It achieves max serum concentration in 3 hours. 91±2% bound to plasma proteins when given parenterally. When given orally, it is 85% bound to plasma proteins. Lorazepam is hepatically metabolized and is extensively conjugated to the 3-0-phenolic glucuronide. This is an inactive metabolite and is eliminated mainly by the kidneys.
Usual Adult Dose for Anxiety Oral: Initial dose: 1 mg orally 2 to 3 times a day. Maintenance dose: 1 to 2 mg orally 2 to 3 times a day. The daily dosage may vary from 1 to 10 mg/day orally. IV: Alternatively, an initial intravenous dose of 2 mg or 0.044 mg/kg, whichever is smaller, may be given. Usual Adult Dose for Insomnia 2 to 4 mg orally at bedtime
Side effectsnausea , Headache , constipation , dizziness , fatigue , Seizures , Increased risk of suicidal thinking , Depression , asthenia , impotence , confusion , Hypersensitivity , ataxia , Anaphylactic reaction , jaundice , coma , memory loss
InteractionsEthosuximide , Buspirone , Pregabalin , Dactinomycin , Deferasirox , Risperidone , Zolpidem , Cyclopentolate , Fluticasone propinate , Lactulose , Aminophiline , Clozapine , Methimazole , Nervoxin , Neurogol , Sedamin , Chlorpheniramine , Clonidine , Yohimbine , Tranquival , valirest , Valerian , probenecid , Vancomycin , Quetiapine , Sodium Oxybate , Tapentadol , codeine , Procaine , Pindolol , Zaleplon , Triazolam , Acetaminophen and benzhydrocodone , Oxymorphone , Ethchlorvynol , Aminophenazone , Cannabidiol
1-The use of benzodiazepines, including Lorazepam, may lead to physical and psychological dependence. 2-In patients with depression, a possibility for suicide should be borne in mind; benzodiazepines should not be used in such patients without adequate antidepressant therapy. 3-Lorazepam should be used with caution in patients with compromised respiratory function (e.g. COPD, sleep apnea syndrome). 4-Elderly or debilitated patients may be more susceptible to the sedative effects of Lorazepam. Therefore, these patients should be monitored frequently and have their dosage adjusted carefully according to patient response; the initial dosage should not exceed 2 mg. 5-The usual precautions for treating patients with impaired renal and hepatic function should be observed.
Points of recommendation
1-Abrupt termination of treatment may be accompanied by withdrawal symptoms. To assure the safe and effective use of Lorazepam, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing this drug. 2-Some patients on Lorazepam have developed leukopenia, and some have had elevations of LDH. As with other benzodiazepines, periodic blood counts and liver-function tests are recommended for patients on long-term therapy.