Lorazepam

Indications

Lorazepam is used for: Anxiety, Status epilepticus, Sedation, psychosomatic, organic or psychotic illness, insomnia associated with anxiety, nervousness, restlessness, nausea and vomiting, related to chemotherapy and anticonvulsants, and as a premedicant before dental or general surgery or prior to investigative procedures where there may be discomfort.

Adult Dose

Oral Anxiety Disorders Adult: 1-6 mg/day in 2 or 3 divided doses, up to 10 mg/day. Insomnia associated w/ anxiety 1-4 mg/day at bedtime. Premed in surgery 2-3 mg the night before operation, then a smaller dose in the morning if needed. Parenteral Preoperative Sedation, Anxiety Relief, & Anterograde Amnesia 0.05 mg/kg IM for 1 dose; 2 hours before surgery; not to exceed 4 mg (2 mg/dose in elderly), OR 0.044 mg/kg IV for 1 dose; 15-20 minutes before surgery; not to exceed 4 mg (2 mg/dose in elderly) Status Epilepticus Usual 4 mg/dose slow IV at 2 mg/min If seizure persists after 5-10 min, administer 4 mg IV again Anxiolytic/Sedation in ICU Intubated and mechanically ventilated patients 0.02-0.04 mg/kg loading dose IV 0.02-0.06 mg/kg intermittent IV q2-6hr PRN, OR 0.01-0.1 mg/kg/hr continuous IV; not to exceed 10 mg/hr Elderly: Half the usual adult dose or less. Hepatic impairment: Mild to moderate: May require reduced doses. Severe: Contraindicated.

Child Dose

Status Epilepticus Infants and children: 0.05-0.1 mg/kg IV over 2-5 minutes; not to exceed 4 mg/dose; may repeat q10-15min PRN Alternatively, 0.1 mg/kg at slow IV rate not to exceed rate of 2 mg/min; not to exceed dose of 4 mg Adolescents: 4 mg slow IV; if seizure persists after 10-15 minutes, administer 4 mg IV again

Renal Dose

Renal impairment PO: Dose adjustment not necessary IV/IM: Use with caution in mild-to-moderate impairment; not recommended in severe impairment or renal failure

Administration

May be taken with or without food. Reconstitution: Dilute w/ an equal volume of compatible diluent (e.g. sterile water for inj, NaCl 0.9% inj, dextrose 5% inj). Oral concentrate soln: Dose should be added to 30 mL or more of diluent (e.g. water, juice, carbonated or soda-like beverage) or to semi-solid food (e.g. applesauce, pudding).

Contra Indications

Severe hepatic impairment; respiratory depression; acute narrow-angle glaucoma; pregnancy and lactation.

Precautions

Patient w/ compromised pulmonary function (decreased reserve), myasthenia gravis, CV or cerebrovascular disease, impaired gag reflex; at risk of falls. Patient w/ history of alcohol or drug abuse and those w/ personality disorders. Not intended for treatment of primary depressive or psychotic disorders. It should not be administered by intra-arterial inj. Avoid abrupt withdrawal. Renal and mild to moderate hepatic impairment. Elderly or debilitated patients, childn. Pregnancy and lactation. Patient Counselling May impair ability to perform activities requiring mental alertness or physical coordination (e.g. driving, operating machinery) for 24-48 hr following admin of the drug. Monitoring Parameters Monitor resp and CV status, BP, heart rate, symptoms of anxiety, CBC and LFTs. Lactation: Excreted in human breast milk; not recommended

Pregnancy-Lactation

Pregnancy category: D Lactation: Excreted in human breast milk; not recommended Risk of serious adverse effects, including CNS and respiratory depression, exist Minor tranquilizers should be avoided in first trimester of pregnancy, due to increased risk of congenital malformations Maternal use shortly before delivery is associated with floppy infant syndrome (good and consistent evidence) Prenatal benzodiazepine exposure slightly increased oral cleft risk (limited or inconsistent evidence)

Interactions

Drugs that affect the CNS (e.g. barbiturates, phenothiazines, antidepressants, MAOIs) may have additive CNS effects. Scopolamine may increase sedation, hallucinations and irrational behaviour. May reduce sedative and anxiolytic effect w/ caffeine, theophylline or aminophylline. May increase plasma level w/ Na valproate or probenecid.

Adverse Effects

Side effects of Lorazepam : Sedation, drowsiness, ataxia, dizziness, confusion, depression, unmasking of depression, hypotension, fatigue, muscle weakness, asthenia, transient anterograde amnesia or memory impairment, changes in vital signs (e.g. resp rate, BP). Thrombocytopenia, agranulocytosis, pancytopenia, hyponatraemia, disinhibition, euphoria, suicidal ideation, nausea, constipation, change in libido, impotence, decreased orgasm. Increase in bilirubin, liver transaminases or alkaline phosphatase. Potentially Fatal: Resp depression.

Mechanism of Action

Lorazepam is a short acting benzodiazepine. It increases neuronal membrane permeability to Cl ions by binding to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron w/in the CNS (including the limbic system, reticular formation) and enhancing the GABA inhibitory effects resulting in hyperpolarisation and stabilisation.