Lorazepam
Lorazepam
Generic Name
Lorazepam
Mechanism
- Lorazepam is a *benzodiazepine* that binds to the benzodiazepine site on the GABA‑A receptor complex, acting as a positive allosteric modulator.
- This binding increases the frequency of chloride channel opening, hyperpolarizing neuronal membranes and reducing excitatory neurotransmission.
- The result is rapid anxiolytic, sedative‑hypnotic, anticonvulsant, and muscle‑relaxant activity.
Pharmacokinetics
- Absorption: Oral bioavailability ~ 85 %; IV bioavailability 100 %.
- Distribution: Highly lipophilic; CNS penetration is efficient. Plasma protein binding ≈ 20 – 30 %.
- Metabolism: Primarily glucuronidation in the liver; negligible CYP450 involvement.
- Excretion: Renally excreted unchanged or as glucuronide conjugates.
- Half‑life: 12 – 18 h (shorter in elderly, renal impairment).
- Peak plasma concentration: 1–2 h after oral dose; 10 min after IV.
Indications
- Acute anxiety (including panic attacks).
- Panic disorder short‑term control.
- Seizure emergencies (status epilepticus, non‑convulsive status).
- Premedication before anesthesia.
- Short‑term insomnia in medically ill patients.
- Management of alcohol withdrawal seizures.
Contraindications
- Contraindications:
- *Pregnancy * (category D) – avoid unless essential.
- Known hypersensitivity to benzodiazepines.
- Severe respiratory insufficiency or COPD exacerbation.
- Warnings:
- Use cautiously in elderly or with hepatic/renal impairment.
- Potential for dependence, tolerance, and withdrawal syndrome; taper slowly.
- CNS depression risk when combined with alcohol, opioids, or other CNS depressants.
- Hypotension and respiratory depression in overdose.
Dosing
| Indication | Adult Dose | Route | Notes |
| Acute anxiety | 2 mg PO q6‑8h PRN | PO | Max 10 mg/day. |
| Seizures (status) | 0.1 mg/kg IV (max 4 mg) | IV | Repeat 2 mg after 5‑10 min if needed. |
| Premedication | 1–2 mg PO/IV | PO/IV | Start 30 min before anesthesia. |
| Insomnia | 1 mg PO at bedtime | PO | Limited to <2 weeks. |
| Alcohol withdrawal seizures | 1–2 mg PO PO | PO | Titrate to effect. |
*Pediatric dosing (4–17 y)*: 0.05–0.1 mg/kg PO (max 1–2 mg) or 0.05 mg/kg IV; adjust for weight.
Adverse Effects
- Common:
- Somnolence, dizziness, fatigue, blurred vision.
- Ataxia, loss of coordination.
- Dry mouth, blurred vision, constipation.
- Serious (rare):
- Respiratory depression, especially in overdose or combined with opioids.
- Severe hypotension and cardiac arrhythmias.
- Hallucinations, delirium (particularly in elderly).
- Severe rash/angioedema indicating hypersensitivity.
Monitoring
- Neurologic: Level of consciousness, respiratory rate, muscle tone.
- Cardiovascular: Blood pressure, heart rate, oxygen saturation.
- Renal function: Serum creatinine and eGFR (especially if dose >10 mg/day or chronic use).
- If used >4 weeks: Screen for dependence signs, conduct drug level/withdrawal assessment.
Clinical Pearls
- Short‑acting profile: Lorazepam’s shorter half‑life relative to midazolam or diazepam makes it ideal for seizure rescue and *pre‑operative sedation* where a rapid offset is desired.
- Avoid first‑line therapy for chronic insomnia: Due to accumulation and tolerance, limiting use to <2 weeks prevents long‑term dependence.
- Renal dosing: Since clearance is renal, reduce the dose or extend dosing interval in patients with eGFR 1 week), start a taper of 10–20 % per week to avoid rebound anxiety or seizures.
- Drug interactions: Avoid concurrent use with opioids, ethanol, or other CNS depressants—risk of profound sedation and respiratory depression is synergistic.
- Elderly guidance: Begin at the lowest dose (0.5–1 mg PO) and titrate slowly; monitor for delayed sedation.
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• *This drug card compiles the most essential pharmacological information for Lorazepam to support rapid clinical decision‑making and education.*