BRAND NAMES
 MECHANISM OF ACTION
Lorazepam, like other Benzodiazepines bind to specific sites on the gamma-aminobutyric acid-A (GABAA) receptors. This enhances the effects of GABA by increasing its affinity for the GABAA receptor.
Activation of the GABAA receptor, which is linked to a chloride channel (Cl-), results in an influx of Cl- into the neurone causing hyperpolarisation, which results in inhibitory effects on the central nervous system.
Benzodiazepines action on GABAA receptors appears to produce their anxiolytic, sedative, muscle relaxant, hypnotic and anticonvulsant actions.
Lorazepam is rapidly absorbed after oral administration, with mean peak plasma concentrations at 2 hours (range between 1-6 hours). Following intravenous administration, peak plasma levels are reached within minutes, whereas following administration by the intramuscular route, peak plasma levels occur between 60 to 90 minutes. After sublingual administration, peak plasma levels occur at 60 minutes. Bioavailability was shown to be identical by all routes of administration.
Lorazepam is rapidly conjugated to a glucuronide which has no demonstrable pharmacological activity and is excreted mainly in the urine. Its half-life ranges between 12 to 15 hours.
- Short-term relief of manifestations of excessive anxiety in patients with anxiety and prior to surgical interventions. Anxiety and tension associated with the stresses of everyday life usually do not require treatment with anxiolytic drugs.
Generalized Anxiety Disorder: The recommended initial adult daily oral dosage is 2 mg in divided doses. The daily dosage should be carefully increased or decreased by 0.5 mg depending upon tolerance and response.
The usual daily dosage is 2 to 3 mg. However, the optimal dosage may range from 1 to 4 mg daily in individual patients. Usually, a daily dosage of 6 mg should not be exceeded.
In elderly and debilitated patients, the initial daily dose should not exceed 0.5 mg and should be very carefully and gradually adjusted, depending upon tolerance and response.
Excessive Anxiety Prior to Surgical Procedures: Adults: Usually 0.05 mg/kg to a maximum of 4 mg total, given by the sublingual route 1 to 2 hours before surgery. As with all premedicant drugs, the dose should be individualized. Doses of other central nervous system depressant drugs should be ordinarily reduced.
Lorazepam is contraindicated in patients with myasthenia gravis or acute narrow angle glaucoma, and in those with known hypersensitivity to benzodiazepines
 WARNINGS AND PRECAUTIONS
- Benzodiazepines, including Lorazepam, produce additive CNS depressant effects when co-administered with other medications which themselves produce CNS depression (e.g. barbiturates, alcohol, sedatives, tricyclic antidepressants, antipsychotics, skeletal muscle relaxants, antihistamines or narcotic analgesics and anaesthetics).
- Haloperidol: There have been reports of apnea, coma, bradycardia, heart arrest, and death with the concomitant use of lorazepam injection
- Clozapine: Concomitant use of clozapine and lorazepam may produce marked sedation, excessive salivation, and ataxia.
- Valproate: Concurrent administration of lorazepam with valproate may result in increased plasma concentrations and reduced clearance of lorazepam. Lorazepam dosage should be reduced to approximately 50% when co-administered with valproate.
- Probenecid: Concurrent administration of lorazepam with probenecid may result in a more rapid onset or prolonged effect of lorazepam due to increased half-life and decreased total clearance. Lorazepam dosage needs to be reduced by approximately 50% when co-administered with probenecid.
- Scopolamine: When scopolamine is used concomitantly with injectable lorazepam, an increased incidence of sedation, hallucinations and irrational behaviour has been observed.
- Theophylline or Aminophylline: Administration of theophylline or aminophylline may reduce the sedative effects of benzodiazepines, including lorazepam
 PREGNANCY AND LACTATION
 SIDE EFFECTS
Most adverse reactions to benzodiazepines, including CNS effects and respiratory depression, are dose dependent, with more severe effects occurring with high doses.
In a sample of about 3500 patients treated for anxiety, the most frequent adverse reaction to lorazepam was sedation (15.9%), followed by dizziness (6.9%), weakness (4.2%), and unsteadiness (3.4%). The incidence of sedation and unsteadiness increased with age.
Other adverse reactions to benzodiazepines, including lorazepam are fatigue, drowsiness, amnesia, memory impairment, confusion, disorientation, depression, unmasking of depression, disinhibition, euphoria, suicidal ideation/attempt, ataxia, asthenia, extrapyramidal symptoms, convulsions/seizures tremor, vertigo, eye-function/visual disturbance (including diplopia and blurred vision), dysarthria/slurred speech, change in libido, impotence, decreased orgasm; headache, coma; respiratory depression, apnea, worsening of sleep apnea, worsening of obstructive pulmonary disease; gastrointestinal symptoms including nausea, change in appetite, constipation, jaundice, increase in bilirubin, increase in liver transaminases, increase in alkaline phosphatase; hypersensitivity reactions, anaphylactic/oid reactions; dermatological symptoms, allergic skin reactions, alopecia; SIADH, hyponatremia; thrombocytopenia, agranulocytosis, pancytopenia; hypothermia; and autonomic manifestations.
Paradoxical reactions, including anxiety, excitation, agitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, and hallucinations may occur. Small decreases in blood pressure and hypotension may occur but are usually not clinically significant, probably being related to the relief of anxiety produced by lorazepam.
 RELATED LINKS
|Sedatives / Hypnotics / Anxiolytics|
|Benzodiazepines||Benzodiazepines (Anxiolytics)||Alprazolam (Xanax) • Bromazepam (Lexotan, Lexotanil) • Chlordiazepoxide (Librium) • Clobazam (Frisium) • Clorazepate (Tranxene) • Clotiazepam (Rizen, Tienor) • Delorazepam (EN) • Diazepam (Valium) • Etizolam (Depas) • Ketazolam • Lorazepam (Ativan, Control, Lorans, Tavor, Temesta) • Lormetazepam (Noctamid) • Nordazepam (Nordaz) • Oxazepam (Serepax) • Prazepam (Demetrin, Lysanxia)|
|Benzodiazepines (Hypnotics)||Brotizolam (Lendormin, Bondormin, Dormex, Sintonal, Noctilan) • Clobazam (Frisium) • Estazolam (Esilgan, ProSom) • Etizolam (Depas, Pasaden, Etilaam, Etizest) • Flunitrazepam (Rohypnol) • Flurazepam (Dalmadorm, Dalmane, Felison, Flunox, Valdorm) • Ketazolam (Anseren, Anxon) • Lorazepam (Ativan, Control, Lorans, Tavor, Temesta) • Lormetazepam (Loramet, Minias, Noctamid, Pronoctan, Evamyl) • Midazolam (Dormicum, Hypnovel) • Nitrazepam (Mogadon, Nitrados, Numbon, Radedorm, Alodorm) • Nordazepam (Madar, Nordaz, Stilny, Tranxilium N) • Temazepam (Normison, Restoril, Tenox, Temaze) • Triazolam (Halcion, Hypam, Rilamir)|
|Non-Benzodiazepine Hypnotics||Eszopiclone (Lunesta) • Zolpidem (Ambien, Stilnox, Hypnogen, Sanval, Stilnoct, Zoldem, Zolsana) • Zopiclone (Imovane, Zimovane)|
|Melatonin agonists||Melatonin (Circadin) • Ramelteon (Rozerem)|
|Orexin agonists||Suvorexant (Belsomra)|