Pharmacology · Opioids and antagonists
Fentanyl !
A very potent, fast synthetic opioid, key in anesthesia and cancer pain. Illegally made fentanyl drives a severe overdose crisis.
Updated 2026-11-01
The figure shows fentanyl in the μ receptor bound to its Gi protein; the viewer crops the image to the receptor.
Mechanism of action
Fentanyl, a synthetic phenylpiperidine, is a full μ-receptor agonist 50 to 100 times more potent than morphine. It is highly lipid soluble and acts almost at once intravenously. After a single dose it redistributes to muscle and fat, so its effect is short; with continued use it accumulates in those tissues.
- Highly lipid soluble: acts almost at once intravenously
- Potently activates the μ receptor and its Gi protein
- Blocks pain transmission: strong, fast analgesia
- In excess it shuts down the breathing center; naloxone reverses it
Pharmacokinetics
- Absorption
- Used intravenously, transdermally (patch), transmucosally and intranasally.
- Distribution
- Highly lipid soluble; redistributes to and accumulates in fat and muscle.
- Metabolism
- Liver, mainly by CYP3A4, to norfentanyl and other inactive metabolites.
- Elimination
- Kidney, as metabolites.
- Half-life
- About 3 to 7 hours after an intravenous dose; after patch removal, levels fall more slowly.
- Onset and duration
- Almost immediate intravenously; with the patch, levels rise over 12 to 24 hours.
Indications
- Analgesia during general anesthesia and surgery
- Analgesia and sedation in intensive care
- Chronic cancer pain in patients already opioid tolerant (patch)
Adverse effects
Common
- Nausea and vomiting
- Drowsiness
- Constipation
- Bradycardia
- Miosis
Contraindications
- Patch in opioid-naive patients or for acute pain
- Significant respiratory depression without monitoring or support
- Paralytic ileus
Key interactions
- CYP3A4 inhibitors (ritonavir, erythromycin, ketoconazole, grapefruit juice)
- Raise levels and the risk of respiratory depression.
- Benzodiazepines, alcohol and other CNS depressants
- Add sedation and respiratory depression.
- SSRIs, monoamine oxidase inhibitors and other serotonergic drugs
- Risk of serotonin syndrome.
- Heat on the patch (fever, electric blankets)
- Increases drug release and can cause overdose.
What is monitored
- Respiratory rate, oxygen saturation and sedation
- Blood pressure and heart rate in the operating room
Test yourself
Think of the answer, then tap the question to see it.
Why does a single intravenous dose of fentanyl wear off quickly even though its half-life is hours?
It redistributes rapidly from the brain to fat and muscle. With continued use those stores fill up and release the drug slowly.
Which muscular adverse effect of fentanyl can make ventilation hard during anesthesia?
Muscle rigidity, especially of the respiratory muscles.
Why are CYP3A4 inhibitors dangerous in a patient with a fentanyl patch?
Fentanyl is cleared mainly by CYP3A4; inhibiting it raises fentanyl levels and the risk of respiratory depression.
Which antidote reverses a fentanyl overdose, and what may it require?
Naloxone. Because fentanyl is so potent, repeated doses may be needed, and the patient must be watched in case respiratory depression returns.
Related drugs
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Fentanyl | Overdose Prevention | CDC (Centers for Disease Control and Prevention, 2025); FENTANYL CITRATE injection, solution (DailyMed (U.S. National Library of Medicine), 2026); FENTANYL TRANSDERMAL patch, extended release (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.