Naloxone (Narcan®)
| Naloxone |  |
|---|---|
| Brand Names | Narcan®, Kloxxado® |
| Drug Class | Opioid Antagonist |
| Primary Indication | Opioid Overdose |
| Mechanism | Competitive μ receptor antagonist |
| Onset | 1–2 minutes (IV) |
| Duration | 30–90 minutes |
| Controlled Substance | No |
| FDA Approval | 1971 |
Overview
Naloxone is a competitive opioid receptor antagonist used for the reversal of opioid-induced respiratory depression.
It has highest affinity for the μ-opioid receptor and rapidly displaces opioid agonists such as morphine, oxycodone, fentanyl, and heroin.
Naloxone reverses respiratory depression but may precipitate acute withdrawal in opioid-dependent patients.
Mechanism of Action
Receptor Activity
- Competitive antagonist at μ-opioid receptors
- Also antagonizes κ and δ receptors
Pharmacologic Effect
- Displaces opioid agonists from receptors
- Reverses respiratory depression
- Reverses CNS depression
No intrinsic agonist activity.
Indications
- Suspected opioid overdose
- Respiratory depression from opioid use
- Iatrogenic opioid-induced respiratory depression
Used in:
- Emergency departments
- Prehospital settings
- Community overdose response
Dosing
IV (hospital setting):
- 0.04–0.4 mg initially
- Titrate to adequate respiratory effort
Intranasal (community use):
- 4 mg per spray
- Repeat every 2–3 minutes if needed
Goal:
- Restore spontaneous breathing
- NOT full arousal
May require repeat dosing due to short half-life.
Pharmacokinetics
Onset:
- IV: 1–2 minutes
- Intranasal: 2–3 minutes
Half-life:
- ~30–90 minutes
Duration:
- Often shorter than long-acting opioids
Metabolism:
- Hepatic
Elimination:
- Renal
Re-sedation can occur after naloxone wears off.
Adverse Effects
- Acute opioid withdrawal
- Agitation
- Tachycardia
- Hypertension
- Nausea / vomiting
- Pulmonary edema (rare)
In opioid-dependent patients, rapid reversal may cause severe withdrawal symptoms.
Clinical Pearls
- Naloxone reverses respiratory depression, not necessarily pain.
- Duration is shorter than many opioids → monitor for re-sedation.
- May require repeated dosing for long-acting opioids (e.g., methadone).
- Use lowest effective dose to restore respirations.
- Widely available over-the-counter in many states.
Toxicology Considerations
Classic opioid toxidrome:
- CNS depression
- Respiratory depression
- Miosis
Naloxone confirms diagnosis if rapid improvement occurs.
Comparison Within Class
Compared to Naltrexone:
- Short-acting
- Used for acute reversal
Compared to Methylnaltrexone:
- Crosses blood-brain barrier
- Reverses central effects