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# Lorazepam
## Overview
Lorazepam is a high-potency, intermediate-acting benzodiazepine that acts as a positive allosteric modulator of the $\text{GABA}_A$ receptor, enhancing the inhibitory effects of GABA in the central nervous system.
## Primary Indications
* Anxiety disorders
* Status epilepticus (first-line)
* Preoperative sedation/anxiolysis
* Insomnia
* Alcohol withdrawal syndrome
## Adult Dosing
* **Anxiety:** 2–6 mg daily in divided doses (titrate to response; max 10 mg/day).
* **Status Epilepticus:** 4 mg IV push; may repeat once after 10–15 minutes if seizures continue (max 8 mg).
* **Insomnia:** 2–4 mg PO at bedtime.
* **Procedural Sedation:** 0.044 mg/kg IV (up to 2 mg total dose).
## Pediatric Dosing
* **Status Epilepticus:** 0.05–0.1 mg/kg IV/IO (max 4 mg per dose). May repeat once in 10–15 minutes if necessary.
* **Sedation/Anxiolysis:** 0.05 mg/kg IV/IM (max 2 mg).
## Dose Adjustments
* **Hepatic Impairment:** Reduce dose; metabolism is via glucuronidation (not CYP450 dependent), making it preferred in patients with liver disease.
* **Renal Impairment:** Generally well-tolerated, but use caution; accumulation of inactive glucuronide metabolites may occur.
* **Geriatric Patients:** Start at lowest effective dose (e.g., 0.5 mg) due to increased sensitivity and risk of falls/delirium.
## Contraindications
* Hypersensitivity to benzodiazepines
* Acute narrow-angle glaucoma
* Severe respiratory insufficiency
* Severe sleep apnea
* Myasthenia gravis
## Adverse Effects
* **Common:** Sedation, dizziness, ataxia, weakness, fatigue.
* **Serious:** Paradoxical CNS excitation (especially in children/elderly), respiratory depression (synergistic with opioids), anterograde amnesia, dependence, and withdrawal syndrome upon abrupt cessation.
## Key Drug Interactions
* **CNS Depressants:** Avoid concomitant use with opioids, alcohol, or other sedative-hypnotics due to the high risk of fatal respiratory depression.
* **Valproic Acid:** May inhibit lorazepam glucuronidation, increasing serum concentrations.
* **Probenecid:** May prolong the effect of lorazepam.
## Monitoring
* **Assess:** Respiratory rate, oxygen saturation, sedation level (RASS score), and seizure control.
* **Chronic Use:** Monitor for misuse, dependence, and potential for metabolic/psychiatric adverse events.
## Clinical Pearls
* **Status Epilepticus:** IV lorazepam is preferred over diazepam for its longer duration of action in the CNS (reduced seizure recurrence).
* **Storage:** IV/IM formulations should be refrigerated; however, they are stable at room temperature for up to 30 days.
* **IV Administration:** Ensure IV line patency to prevent phlebitis. Dilute injectable forms 1:1 with sterile water, NS, or D5W before administration.
* **Withdrawal:** Taper slowly after prolonged use to prevent withdrawal seizures.
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**Educational Disclaimer:** This summary is for educational purposes and does not substitute clinical judgment. Dosing may vary based on local institutional protocols and patient-specific factors. Always verify prescribing information through official software (e.g., Lexicomp, UpToDate) or the manufacturer's package insert before administration.
