Ativan
Lorazepam
Generic Name
Lorazepam
Mechanism
Lorazepam acts as a positive allosteric modulator of the GABA‑A receptor complex.
• Enhances chloride ion influx → neuronal hyperpolarization.
• Produces fast onset of central nervous system depression.
• Lacks intrinsic agonist activity; requires GABA binding to exert pharmacologic effects.
Pharmacokinetics
- Route of administration: Oral, IV, rectal, IM, SC.
- Absorption: Oral bioavailability ~93 %; peak plasma concentration in 1–3 h; IV onset 65 yr and renal impairment → dosing adjustment; no hepatic contraindication.
Indications
- Acute anxiety and panic attacks (short‑term).
- Pre‑operative sedation and anxiolysis for minor procedures.
- Seizure control: status epilepticus, breakthrough seizures, adjunct to antiepileptics.
- Alcohol withdrawal – reduces delirium tremens risk.
- Episodic insomnia with associated anxiety (short‑term use).
- Acute agitation or delirium in the emergency setting.
Contraindications
- Contraindicated in: severe respiratory insufficiency, acute narrow‑angle glaucoma, myasthenia gravis (possible worsening).
- Warnings: Dependence, tolerance, and withdrawal syndrome; respiratory depression (especially with opioids or CNS depressants); hepatotoxicity unlikely.
- Cautions: Use minimal effective dose in pregnancy (category C); avoid in nursing‑age patients; co‑administration with opioids increases fall risk.
- Special: Use with caution in patients with a history of abuse or psychiatric instability.
Dosing
| Patient | Route | Initial Dose | Maintenance | Notes |
| Adults | Oral | 0.5–2 mg QID | 1–10 mg/day in divided doses | Titrate slowly; avoid >5 mg/day unless controlled alternatives fail |
| IV | 0.5–1 mg q15‑30 min | 1–2 mg/h (max 4 mg/h) | Use in status epilepticus, sedative intubation | |
| IM/SC | 1–2 mg | As above | Can be used for procedural sedation | |
| Pediatric | Oral | 0.02–0.05 mg/kg QID | 0.04–0.1 mg/kg/day | Neonates/infants: 0.01–0.02 mg/kg IV |
| Renal impairment | Oral | 0.5–1 mg QID (if CrCl >30 mL/min) | Reduce by 50 % if CrCl 15–30 mL/min; discontinue if <15 | Monitor for accumulation |
| Elderly | Oral | 0.25–0.5 mg QID | 0.5–2 mg/day | Start low, go slow |
Adverse Effects
- Common: Sedation, somnolence, dizziness, ataxia, mild muscle weakness, fatigue, dry mouth.
- Serious: Respiratory depression, paradoxical agitation or aggression in <10 % of patients, anterograde amnesia, seizures (rare with correct dosing), impaired coordination leading to falls.
Monitoring
- Vitals: Respiratory rate, blood pressure, pulse.
- Level of consciousness (Glasgow Coma Scale).
- Respiratory pattern in high‑dose or co‑administration with opioids.
- Renal function (CrCl) when dosing >2 weeks or in patients >65 yr.
- Seizure activity for patients with epilepsy or withdrawal.
- Pregnancy status if prescribing to women of childbearing age.
Clinical Pearls
- Renal‑safe: Lorazepam is ideal for patients with chronic kidney disease because it is primarily glucuronidated and not dependent on hepatic CYP metabolism.
- IV sedation for rapid‑sequence intubation: 0.15–0.2 mg/kg IV provides timely and predictable sedative effect without lingering peri‑operative side‑effects.
- Bridge therapy: Use lorazepam as a short‑term bridge to long‑acting benzodiazepines (e.g., diazepam) when withdrawal or acute agitation is present; avoid prolonged monotherapy to reduce tolerance.
- Alcohol withdrawal: Start with 2–3 mg PO per 4 h; titrate to effect; monitor for delirium tremens, especially in the first 48 h.
- Dosing in pregnancy: Category C; consider lorazepam only with clear benefit, as alternatives (e.g., haloperidol) may carry lower teratogenic risk.
--
• Key Takeaway
Lorazepam (Ativan) is a fast‑acting, metabolically reliable benzodiazepine suitable for a variety of anxiolytic, sedative, anticonvulsant, and procedural uses, especially in patients with renal impairment or requiring short‑term control. Use the lowest effective dose, titrate slowly, and monitor for respiratory suppression and withdrawal phenomena.