Naloxone Blocks All Opioid Medications
Naloxone is a pure opioid antagonist that blocks all opioid medications by competitively antagonizing mu (μ), kappa (κ), and delta (δ) opioid receptors, with highest affinity for the mu receptor. 1
Mechanism of Action
Naloxone prevents or reverses all central nervous system effects of opioids including respiratory depression, sedation, hypotension, and analgesia by competing for opioid receptor sites in the CNS. 2, 1 It exhibits essentially no pharmacologic activity in the absence of opioids and possesses no intrinsic agonist properties. 1
Specific Opioids Blocked by Naloxone
Natural and Semi-Synthetic Opioids
- Morphine - fully reversed by naloxone 2
- Codeine - fully reversed by naloxone 2
- Hydromorphone - fully reversed by naloxone 2
- Oxycodone - fully reversed by naloxone 2
- Hydrocodone - fully reversed by naloxone 2
- Heroin - effectively reversed by naloxone 3
Synthetic Opioids
- Fentanyl - effectively reversed by naloxone 2, 3
- Carfentanil (ultrapotent fentanyl analog) - reversed by naloxone, though may require higher or repeated doses 3
- 3-Methylfentanyl (ultrapotent fentanyl analog) - reversed by naloxone, though may require higher or repeated doses 3
- Methadone - reversed by naloxone 2
- Tramadol - reversed by naloxone 2
- Tapentadol - reversed by naloxone 2
- Meperidine - reversed by naloxone 2
Mixed Agonist-Antagonists
- Nalbuphine - effects reversed by naloxone 2
- Butorphanol - effects reversed by naloxone 2
- Pentazocine - psychotomimetic and dysphoric effects reversed by naloxone 1
Important Clinical Caveat: Buprenorphine
Buprenorphine requires significantly larger doses of naloxone for reversal due to its high affinity for the mu-opioid receptor and slow dissociation kinetics. 1, 4 The antagonism is characterized by gradual onset of reversal effects and decreased duration of action. 1
What Naloxone Does NOT Block
Naloxone is ineffective for reversing effects of non-opioid drugs including:
Duration and Dosing Considerations
The onset of action after intravenous naloxone is 1-2 minutes, with a half-life of 30-45 minutes. 2 Since the duration of action of naloxone may be shorter than many opioids, the effects of the opioid may return as naloxone dissipates, requiring repeat doses. 1 This is particularly important with:
- Long-acting opioids (methadone, extended-release formulations) 1
- High-affinity opioids (buprenorphine, carfentanil) 1, 3
- Ultrapotent fentanyl analogs 3, 4
Initial dosing is typically 0.2-0.4 mg (0.5-1.0 μg/kg) intravenously every 2-3 minutes until desired response, with monitoring for up to 2 hours. 2 For opioid overdose reversal, intranasal and intramuscular formulations are both effective. 2, 5
Critical Safety Warning
Naloxone precipitates acute opioid withdrawal in physically dependent patients, which can manifest as agitation, nausea, vomiting, tremor, tachycardia, hypertension, seizures, and potentially life-threatening complications including pulmonary edema and cardiac arrhythmias. 2, 1, 6 Caution is particularly warranted in patients with pre-existing cardiovascular disease or those receiving chronic opioid therapy. 1