Narcan | Pharmacology Mentor

Generic Name

Naloxone

Mechanism

Naloxone is a *high‑affinity, non‑selective opioid antagonist* that competitively displaces opioid ligands (e.g., morphine, fentanyl, oxycodone) from μ‑, κ‑, and δ‑opioid receptors.
• Rapidly reverses opioid‑induced respiratory depression and sedation by restoring normal neurotransmission.
• Fewer downstream effects on noradrenergic and dopaminergic pathways compared to pure morphine withdrawal.
• No intrinsic agonist activity; ineffective in the absence of an opioid; thus, no "ceiling" effect on sedation.

Pharmacokinetics

Parameter	Intravenous (IV)	Intramuscular (IM)	Intranasal (IN)
Onset	< 5 min	5–10 min	5–15 min
Peak	5–15 min	10–20 min	10–20 min
Duration	20–90 min	60–90 min	30–60 min
Absorption	Immediate	55–70 %	70–90 % (nasal mucosa)
Metabolism	Phase‑II glucuronidation (UGT2B7)	Same as IV	Same as IV
Elimination	Renal (low‑mw metabolites)	Same	Same
Half‑life	2.5–3 h	2–3 h	2–3 h
Food Interaction	None	Minor	Minor

*Pharmacodynamic window*: Naloxone’s fast onset ensures reversals can be achieved before airway compromise.

Indications

Immediate reversal of opioid overdose (respiratory, cardiovascular, or CNS depression).
Diagnostic test for opioid intoxication.
Pre‑hospital or emergency department management of suspected fentanyl or heroin overdose.
Adjunct in treating opioid‑induced hypotension (rare).

Contraindications

Contraindications: None formally listed.
Warnings:
May precipitate acute withdrawal in chronic opioid users → risk of agitation, nausea, tachycardia.
Use caution in patients on monoamine oxidase inhibitors (MAOIs) or serotonergic drugs – risk of serotonin syndrome.
Limited data on use in severe hepatic disease; monitor for hypotension.
Not a substitute for comprehensive airway support, especially with long‑acting opioids.

Dosing

Intravenous (IV) / Intramuscular (IM): 0.4 mg initial push; repeat every 2–3 min if needed; total cumulative dose 2–4 mg.
Intranasal (IN) Spray: 4 mg per spray (0.1 mg/mL).
*Adult:* 4 mg (two sprays);
*Pediatric (≥12 yrs):* same dosing;
*Pediatric (<12 yrs):* weight‑based (0.1 mg/kg).
Subcutaneous: Not routinely recommended; used off‑label in some settings.

*Administration guidelines:*
• IM/IV: Administer in thigh, gluteal, or upper arm.
• IN: Apply one spray to each nostril; patient should be awake to sniff.
• Auto‑injector (Narcan® Biphasic): For out‑of‑hospital use; delivers 0.4 mg IM automatically.

Adverse Effects

Adverse Effect	Frequency	Notes
Withdrawal (crampy abdominal pain, tachycardia, hypertension)	Common (30–70 %) in opioid‑dependent patients	Manage with benzodiazepines or clonidine if severe
Nausea/Vomiting	Common	Provide antiemetics if needed
Hypertension / Tachycardia	Rare	Monitor pulse & BP
Seizures	Very rare	Ensure proper dosing, avoid repeated high doses
Allergic Reactions (rash, pruritus)	Rare	Treat with antihistamines; no anaphylaxis reported
Hypotension	Very rare	Re‑evaluation of airway and ventilation required

Monitoring

Airway & Breathing: Monitor oxygen saturation, capnography if available.
Cardiovascular: Pulse, blood pressure, ECG for bradycardia or arrhythmia.
Neurologic: Glasgow Coma Scale (GCS) or equivalent.
Repeat naloxone dose if respiratory depression recurs >5 min after initial effect.
After Reversal: Observe patient until sustained recovery; consider post‑treatment observation for 4–6 h for long‑acting opioids (e.g., methadone).

Clinical Pearls

“High‑dose” overlay: In fentanyl or synthetic opioid overdose, titrate beyond standard 2–4 mg IV; up to 10–20 mg total may be needed due to receptor affinity.
Intranasal first‑line: When IV access is delayed, the 4 mg IN dose provides >90 % bioavailability, and the patient can self‑administer.
Store‑away strategy: Narcan auto‑injectors are ideal for patients on long‑acting opioids (maintenance buprenorphine, methadone) to counter accidental overdose.
Plasma half‑life vs. effect: Naloxone’s half‑life (~2–3 h) exceeds the duration of most opioid LOS; monitor for re‑intoxication if the causative opioid has a longer half‑life.
Combination use: Pair with benzodiazepines (for anxiety, agitation) and opioids (for analgesia) only after complete reversal; otherwise, increases risk of inadequate ventilation.
Age & weight adjustment: Children 5 mg IM) may precipitate dizziness or headaches; use a calm titration approach.

Key Takeaway: Naloxone (Narcan) is the life‑saving antidote for opioid poisoning. Its *rapid onset* and *short duration* require vigilant monitoring and readiness to repeat dosing, especially with high‑potency opioids.