Lorazepam is a potent, intermediate-acting benzodiazepine derivative used primarily for its anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant properties. It acts as a positive allosteric modulator of the GABA-A receptor, enhancing the inhibitory effects of GABA in the central nervous system. In the Indian context, it is a widely prescribed Schedule H1 drug for anxiety disorders, insomnia, and as a premedication.
Adult: Anxiety: 1-2 mg orally, 2-3 times daily. Usual range: 2-6 mg/day in divided doses. Insomnia: 2-4 mg orally at bedtime. Premedication: 2-4 mg orally the night before surgery and/or 2-4 mg 1-2 hours pre-op.
Note: Take orally with or without food. Tablet can be swallowed whole. For insomnia, take immediately before bedtime. Do not crush or chew sublingual tablets. Avoid abrupt discontinuation after prolonged use (>2-4 weeks). Taper dose gradually to prevent withdrawal syndrome.
Lorazepam binds to a specific, high-affinity site (distinct from the GABA binding site) on the GABA-A receptor complex, which is a ligand-gated chloride channel. This binding potentiates the inhibitory effect of the neurotransmitter gamma-aminobutyric acid (GABA), leading to increased frequency of chloride channel opening. The influx of chloride ions hyperpolarizes the neuronal membrane, making it more resistant to depolarization and reducing neuronal excitability.
Pregnancy: Category D (US FDA). Should be avoided, especially in first trimester due to risk of congenital malformations (cleft lip/palate). Use in late pregnancy can cause neonatal flaccidity, respiratory depression, and withdrawal syndrome ('floppy infant syndrome'). Use only if benefit outweighs risk.
Driving: STRONGLY DISCOURAGED. Lorazepam impairs alertness, reaction time, motor coordination, and vision. Effects may persist into the next day ('hangover effect').
| Alcohol, Opioids (Morphine, Tramadol) | Profound additive CNS and respiratory depression, sedation, risk of death. | Major |
| Other CNS Depressants (Antipsychotics, Antihistamines, Barbiturates) | Increased sedation and psychomotor impairment. | Major |
| Sodium Valproate/Valproic Acid | May increase lorazepam plasma concentrations and potentiate CNS effects. | Moderate |
| Probenecid | Inhibits glucuronidation, increasing lorazepam levels and prolonging half-life. | Moderate |
| Theophylline | May antagonize the sedative effects of lorazepam. | Moderate |
| Oral Contraceptives | May slightly increase clearance of lorazepam, potentially reducing effect. | Minor |
| Clozapine | Increased risk of marked sedation, delirium, and respiratory depression. | Major |