fentanyl
Summary
Fentanyl is a synthetic opioid agonist, roughly 50-100 times more potent than morphine, used for anesthesia and severe pain management. It acts primarily on mu-opioid receptors, providing rapid onset and short duration of action. It carries high abuse potential and is a major contributor to opioid overdose deaths.
Detail
Fentanyl is a synthetic phenylpiperidine opioid that acts as a full agonist at mu-opioid receptors in the CNS, causing analgesia, sedation, euphoria, and respiratory depression. Its high lipophilicity allows rapid CNS penetration, giving it a fast onset (1-2 min IV) and short duration of action (30-60 min after single dose), making it useful for procedural sedation, anesthesia induction/maintenance, and management of breakthrough cancer pain (transdermal patches, lozenges). Mechanism: Gi-protein coupled receptor activation → decreased cAMP, opening of K+ channels (hyperpolarization), and closing of voltage-gated Ca2+ channels → decreased neurotransmitter release (e.g., substance P) and decreased neuronal excitability, blunting pain transmission. Clinical uses: general anesthesia adjunct, epidural/spinal analgesia, ICU sedation, chronic pain (transdermal patch), and palliative care. Adverse effects: respiratory depression (dose-limiting toxicity), sedation, miosis, constipation, nausea/vomiting, bradycardia, chest wall rigidity (with rapid high-dose IV administration - 'wooden chest syndrome'), and physical dependence/tolerance. Overdose triad: pinpoint pupils, respiratory depression, and CNS depression (coma) - reversed with naloxone (mu-receptor antagonist), though multiple doses may be needed due to fentanyl's high potency and lipophilicity. Fentanyl is a major driver of the opioid epidemic due to illicit synthesis and mixing with heroin/other drugs, often leading to unintentional fatal overdoses because of its potency (small quantities can be lethal). Fentanyl analogs (e.g., carfentanil) are even more potent and dangerous. Pharmacokinetics: metabolized hepatically via CYP3A4 to inactive metabolites; caution with CYP3A4 inhibitors (risk of toxicity) and inducers. Context for boards: differentiate from morphine (fentanyl more lipophilic, faster onset, shorter duration, doesn't cause histamine release/hypotension like morphine), understand opioid receptor pharmacology, and recognize toxidrome features and naloxone reversal mechanism.
Sources
- Katzung's Basic and Clinical Pharmacology
- First Aid for the USMLE Step 1
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- UpToDate: Fentanyl drug information
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