Key Differences Between Naltrexone and Naloxone
Naltrexone and naloxone are both opioid antagonists that block opioid receptors, but they differ significantly in their duration of action, routes of administration, and clinical applications, with naltrexone having a much longer half-life (4 hours vs. 45 minutes) and primarily used for maintenance treatment of addiction, while naloxone is used primarily for acute opioid overdose reversal. 1
Pharmacological Properties
Naltrexone
- Semisynthetic competitive opioid receptor antagonist derived from oxymorphine with substitution of the N-methyl group with a methylcyclopropyl group 1
- Antagonizes mu (highest affinity), kappa, and delta opioid receptors 1
- Plasma half-life of 4 hours; active metabolite (6-β-naltrexol) has half-life of 13 hours 1
- Effects may persist for 2-3 days after stopping due to metabolite accumulation during long-term therapy 1
- Oral bioavailability ranges from 5-40% due to significant first-pass metabolism 2
Naloxone
- Competitive antagonist that displaces narcotics at the opioid receptor 1
- Antagonizes mu (highest affinity), kappa, and delta opioid receptors 1
- Short duration of action: 45 minutes to 3-4 hours depending on dose and route 1
- Rapidly metabolized by the liver into inactive metabolites and renally excreted 1
- Poor oral bioavailability; primarily used via parenteral routes (IV, IM, SC) or nasal spray 1, 3
Clinical Applications
Naltrexone
- Used for long-term management of opioid and alcohol dependence 1, 2
- Prevents patients from experiencing euphoric effects of narcotics and alcohol 1
- May reset reward pathway through opponent process mechanism 1
- Available as:
- Low-dose naltrexone (1-5 mg) has emerging applications for chronic pain conditions, fibromyalgia, and inflammatory conditions 4, 5
Naloxone
- Primarily used for emergency reversal of opioid overdose 1
- Reverses respiratory depression, sedation, and hypotension caused by opioids 1
- Can precipitate acute withdrawal in opioid-dependent patients 1
- Available in injectable and nasal spray formulations 1
- When given orally, is inactivated and has no systemic effect 1
Perioperative Management Considerations
Naltrexone
- Oral naltrexone should be held for 2-3 days prior to elective surgical procedures if opioids are expected to be used perioperatively 1
- Extended-release naltrexone should be held for 24-30 days after the last injection before elective surgical procedures 1
- Patients on naltrexone may have up-regulated opiate receptors, potentially leading to increased sensitivity to respiratory effects of opioids 1
Naloxone
- If given within 4 hours preoperatively, the anesthesiologist should be informed of the reason, timing, route, and dose 1
- No need to hold oral naloxone preoperatively as it has no systemic effect 1
- When not given orally, naloxone is typically administered for respiratory depression in unstable patients, and this information should be communicated to the perioperative team 1
Clinical Pitfalls and Considerations
- Patients on naltrexone who require opioid analgesia may need alternative pain management strategies, as naltrexone blocks opioid analgesic effects 1, 2
- Patients discontinuing naltrexone are at increased risk of opioid overdose due to decreased tolerance 1
- Both medications can precipitate withdrawal in opioid-dependent patients, but naloxone's effect is more immediate and shorter-acting 1
- Liver function tests are recommended at baseline and every 3-6 months for patients on naltrexone due to potential hepatic injury at supratherapeutic doses 1
- When combined with other opioid antagonists, both drugs require monitoring for symptoms of opioid withdrawal 1