Onset of Action of Lorazepam (Ativan)
Lorazepam has an onset of action of 1-5 minutes when administered intravenously, 15-30 minutes when administered intramuscularly, and approximately 20-30 minutes when taken orally.
Route-Specific Onset Times
The onset of action for lorazepam varies significantly based on the route of administration:
Intravenous (IV) Administration
Intramuscular (IM) Administration
- Onset: 15-30 minutes 1
- Peak effect: 60 minutes after administration
- Duration: Approximately 6-8 hours 1
Oral Administration
- Onset: 20-30 minutes 1
- Peak plasma concentration: Approximately 2 hours after administration 3
- Duration: 6-8 hours 1
Pharmacokinetic Considerations
Several factors affect lorazepam's onset of action and overall pharmacokinetics:
- Bioavailability: Lorazepam has an absolute bioavailability of 90% when taken orally 3
- Half-life: The mean half-life of unconjugated lorazepam in human plasma is about 12 hours 3, 4
- Metabolism: Lorazepam is conjugated with glucuronic acid to form inactive lorazepam glucuronide, which is then excreted in the urine 4
- Protein binding: At clinically relevant concentrations, lorazepam is approximately 85% bound to plasma proteins 3
Clinical Applications and Considerations
Factors Affecting Onset and Response
- Age: Elderly patients may experience enhanced sensitivity to lorazepam's effects and may require dose reduction 2
- Hepatic/renal function: Unlike some other benzodiazepines, lorazepam does not produce active metabolites, making it potentially safer in patients with hepatic or renal impairment 5
- Drug interactions: Concurrent use with other CNS depressants, particularly opioids, can potentiate sedative effects and respiratory depression 2
Special Populations
- Elderly patients: Require dose reduction (typically 50% or more) due to increased sensitivity to benzodiazepines 1
- Patients with respiratory compromise: Use with caution due to risk of respiratory depression 1
Common Pitfalls and Caveats
Delayed respiratory depression: Respiratory depression may occur up to 30 minutes after administration, requiring extended monitoring 2
Paradoxical reactions: Some patients, particularly children and those with developmental disabilities, may experience paradoxical behavioral disinhibition 1
Amnesia effects: Lorazepam produces significant amnesia that may persist longer than its sedative effects 6
Withdrawal phenomena: Abrupt discontinuation after regular use can lead to rebound insomnia and increased anxiety 7
Contraindications: Lorazepam is contraindicated in patients with acute alcohol intoxication 1
By understanding lorazepam's onset of action across different administration routes, clinicians can better plan for appropriate monitoring and anticipate when the medication will take effect in various clinical scenarios.