Naloxone
Naloxone
Generic Name
Naloxone
Mechanism
- Naloxone is a non‑selective, high‑affinity opioid receptor antagonist.
- It competitively binds to μ, κ, and δ opioid receptors, displacing opioid agonists and reversing their pharmacologic effects.
- Rapid onset (≤1 min IV) and short duration (~30–90 min) are due to its high affinity but relatively low intrinsic activity.
- The blockade is reversible; if the opioid plasma concentration remains high, re‑dosing or continuous infusion may be required.
Pharmacokinetics
- Absorption:
- *IV*: 100 % bioavailability, immediate onset.
- *IM/SC*: peak plasma concentration in 20–45 min; bioavailability ~70 %.
- *Nasal*: ~40–60 % bioavailability, onset 5–10 min.
- *Inhalational*: minimal systemic exposure.
- Distribution: Volume of distribution ~3.9 L/kg; crosses the blood‑brain barrier readily.
- Protein Binding: ~20 % bound to plasma proteins, primarily albumin.
- Half‑life: 30–90 min (IV/IM/SC); ~120 min after intranasal.
- Elimination: Hepatic metabolism (CYP3A4, CYP2D6) and renal excretion of metabolites; unchanged drug excreted minimally.
Indications
- Emergency opioid overdose reversal (IV, IM, SC, or intranasal).
- Prevention of morphine‑induced respiratory depression during anesthesia.
- Reversal of opioid‑induced sedation or sedation in post‑operative settings.
- Short‑term reversal of opioid analgesia for diagnostic procedures.
- Not indicated for chronic addiction treatment; used only acutely.
Contraindications
- Contraindications:
- No absolute contraindication; cautious use in patients with seizure disorders or uncontrolled cardiovascular disease, as abrupt withdrawal may precipitate seizures or hemodynamic instability.
- Warnings:
- May precipitate acute opioid withdrawal in dependent patients—anticipate withdrawal symptoms and monitor.
- Use with caution in patients with hypovolemia or hypoxia; rapid reversal can unmask underlying issues.
- May cause transient hypertension, tachycardia, or agitation.
- Precautions:
- Verify opioid presence before administration (clinical assessment, urine tox screen).
- Ensure follow‑up care for patient’s underlying opioid use disorder.
Dosing
| Route | Typical Dose | Notes |
| IV | 0.4 mg → 2 mg, repeat every 2–3 min | Use until fully reversed; total cumulative dose may exceed 10–20 mg for long‑acting opioids. |
| IM/SC | 0.4 mg → 2 mg | Peak effect 15–30 min; may need additional dose. |
| Nasal | 4 mg (one spray) | Delayed onset (5–10 min); appropriate for field settings. |
| Intravenous infusion | 0.01–0.1 mg/min | For severe overdose or long‑acting opioids; monitor for sustained reversal. |
• Re‑dosing: Every 2–3 min until patient is fully reversed; no single “maximum dose.”
• Pregnancy: Category C; risk–benefit analysis warranted.
• Pediatrics: Weight‑based dosing (0.01–0.1 mg/kg IV, 0.03–0.13 mg/kg IM/SC).
• Elderly: Consider reduced dose and extended monitoring; higher sensitivity to withdrawal.
Adverse Effects
- Common
- Acute withdrawal (nausea, vomiting, diaphoresis, agitation).
- Hypertension, tachycardia, anxiety.
- Headache, dizziness.
- Serious
- Severe opioid withdrawal in dependent patients leading to seizures or arrhythmias.
- Hypoxemia if airway not secured.
- Rare anaphylactoid reactions.
- Mitigation: Provide supportive care, airway management, and antihypertensives as needed.
Monitoring
- Vital signs: Respiratory rate, SpO₂, blood pressure, heart rate every 5 min during first 30 min.
- Neurologic: Level of consciousness, signs of withdrawal.
- Cardiac: EKG in patients with cardiovascular disease or overdose of mixed agents.
- Laboratory: If severe overdose, obtain blood alcohol, serum electrolytes, lactate (especially for high‑dose opioid use).
- Disposition: Admit for observation when >4 h drug half‑life or risk of delayed respiratory depression (e.g., long‑acting opioids, methadone).
Clinical Pearls
- “One‑in‑Five” rule: If a patient has received ≥5 mg of IV morphine or methadone, start naloxone at 10 mg IV and titrate, because half‑life of those opioids exceeds naloxone.
- Intranasal dosing is convenient but requires a rapid–acting setting; 2 mg can be split into two 1 mg sprays if needed.
- Continuous infusion should be kept running for ≥1 hr after reversal to prevent “re‑observation” of respiratory depression.
- In patients with chronic opioid use, a higher cumulative dose (10–30 mg IV) may be necessary; avoid abrupt cessation as it may precipitate seizures.
- Store naloxone on an “always‑ready” basis at ED, pre‑hospital sites, and in any setting where opioid analgesia is used; keep expiry dates visible.
- Naloxone does not interfere with acetaminophen or other analgesics—use as adjunct, not replacement.
For detailed guidelines, see the 2024 American College of Emergency Physicians (ACEP) and the International Narcotics Control Board (INCB) protocols.