How potent is fentanyl compared to morphine?

Fentanyl Potency Compared to Morphine

Fentanyl is approximately 80 times more potent than morphine when administered parenterally, making option (b) incorrect as it understates fentanyl's potency. 1

Pharmacological Properties of Fentanyl

Fentanyl is a semi-synthetic opioid with several distinctive properties:

• Potency: Fentanyl is approximately 80 times more potent than parenteral morphine according to the European Association for Palliative Care (EAPC) guidelines 1
• Origin: Fentanyl is not naturally found in the body (making option (a) incorrect) but is synthetically manufactured 1
• Duration of action: Fentanyl does not have twice the duration of action compared to morphine (making option (c) incorrect); in fact, when used in single doses, fentanyl often has a shorter duration of action due to redistribution 2
• Hemodynamic effects: Fentanyl does not cause hypotension through histamine release (making option (d) incorrect); unlike morphine, fentanyl has minimal effects on histamine release 1, 3

Clinical Pharmacology of Fentanyl

Pharmacokinetics

• Fentanyl is highly lipophilic with an octanol:water partition coefficient >700 4
• It crosses the blood-brain barrier rapidly with a transfer half-life of 4.7-6.6 minutes 4
• Undergoes first-pass metabolism via cytochrome P450 3A, resulting in low oral bioavailability (~30%) 4
• Alternative routes of administration (transmucosal, intranasal, transdermal) bypass first-pass metabolism, increasing bioavailability to 50-90% 4

Route-Specific Considerations

• Transdermal: Provides constant zero-order release for 2-3 days, suitable for chronic pain management 1
• Oral transmucosal: Reaches maximum plasma concentration in approximately 20 minutes 4
• Intranasal: Reaches maximum plasma concentration in approximately 12 minutes, with partial direct delivery to brain target sites 4

Clinical Applications and Safety

Indications

• Moderate to severe cancer pain, particularly in patients with stable opioid requirements 1
• Particularly valuable for patients unable to take oral morphine 1
• Safe option for patients with chronic kidney disease (stages 4 or 5) 1

Safety Considerations

• Fentanyl's high potency requires careful dosing and monitoring 3
• Naloxone (opioid antagonist) is less effective in reversing fentanyl-induced respiratory depression compared to morphine, which may contribute to its potential lethality 3
• More lipophilic antagonists like diprenorphine may be more effective for fentanyl overdose 3

Important Cautions

• Fentanyl's rapid onset of action can lead to faster respiratory depression compared to equipotent doses of morphine or heroin 3
• Cross-tolerance from other opioids like morphine may be incomplete, increasing overdose risk 3
• The illicit production and distribution of fentanyl has led to significant increases in overdose deaths 5

In summary, fentanyl is a highly potent synthetic opioid that is approximately 80 times more potent than morphine, not naturally found in the body, does not have twice the duration of action of morphine, and does not cause hypotension through histamine release.