Lorazepam
Ativan
Intermediate-acting benzodiazepine
Allosteric positive modulator at GABA-A receptors → ↑frequency of Cl⁻ channel opening → membrane hyperpolarization. Hypnotic, anxiolytic, anticonvulsant, anterograde amnesia. Glucuronidated only — no CYP metabolism — useful in liver disease.
Indications
- •Status epilepticus (first-line per AAN/NCS — 4 mg IV; equivalent to 10 mg IM midazolam in RAMPART)
- •Anxiolysis preop / procedural
- •Alcohol withdrawal (CIWA-driven)
- •Severe agitation in PACU
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| Status epilepticus | 4 mg IV slow push; repeat × 1 in 5 min if seizure persists; max 8 mg | 0.1 mg/kg IV (max 4 mg/dose) |
| Anxiolysis / preop | 0.5–2 mg PO/IV q4–6 h prn | — |
| Alcohol withdrawal | 1–4 mg IV/PO q15–60 min based on CIWA score | — |
Pharmacokinetics
IV onset 5 min. Peak 30–60 min. Half-life 12–18 h. Hepatic glucuronidation only — no CYP.
Hemodynamic effects
Mild hypotension on rapid IV push; minimal at usual doses.
Respiratory effects
Dose-dependent respiratory depression — especially with opioids (synergistic).
Side effects
- !Sedation (often desired)
- !Respiratory depression with rapid push or opioid combination
- !Paradoxical agitation (elderly, peds)
- !Anterograde amnesia
- !Withdrawal in chronic use
- !Propylene glycol toxicity with prolonged high-dose IV (anion-gap acidosis, AKI)
Contraindications
- ×Acute narrow-angle glaucoma
- ×Severe respiratory depression without monitoring
- ×Pregnancy (Category D)
- ×Concurrent strong CNS depressants without titration
Clinical pearls
- ★FIRST-LINE STATUS EPILEPTICUS: AAN 2016 + NCS guidelines — 4 mg IV lorazepam (NOT diazepam, which redistributes too fast). RAMPART (NEJM 2012) showed 10 mg IM midazolam equivalent when no IV access.
- ★GLUCURONIDATION ONLY: no CYP metabolism makes lorazepam the safest benzo in liver disease and in patients on multiple CYP-interacting drugs. Same for oxazepam and temazepam ('LOT' rule).
- ★PROPYLENE GLYCOL: high-dose continuous infusions (>10 mg/h × days) can cause AG metabolic acidosis and AKI from the IV vehicle. Switch to midazolam or propofol after 24–48 h.
- ★REVERSAL: flumazenil reverses, but precipitates seizure in chronic users — avoid in alcohol/benzo dependence.
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Other drugs in Benzodiazepines & Reversal
- Midazolam
GABA-A potentiation at benzodiazepine receptor.
- Flumazenil
Competitively binds benzodiazepine site on GABA-A receptor → displaces benzo agonists → reverses sedation, respiratory depression, amnesia.
- Diazepam
Allosteric positive modulator at GABA-A. Hypnotic, anxiolytic, anticonvulsant, skeletal-muscle relaxant. Produces highly lipid-soluble + active metabolites (desmethyldiazepam, oxazepam, temazepam) → very long total duration in elderly + chronic dosing.
Browse all classes: /reference/drugs