Fentanyl
Fentanyl is a highly potent synthetic opioid of the piperidine family, used primarily as pain medication. It is 50 to 100 times more potent than morphine. Its primary clinical use is in pain management for cancer patients and those recovering from surgery. Fentanyl is also used as a sedative for intubated patients. Fentanyl has a short duration of action. Fentanyl works by activating μ-opioid receptors. Brand names include Actiq, Duragesic, and Sublimaze, among others.
Fentanyl was first synthesized by Paul Janssen in 1960 and was approved for medical use in the United States in 1968. In 2015, 1,600 kilograms (3,500 pounds) were used in healthcare globally. As of 2017, fentanyl was the most widely used synthetic opioid in medicine; in 2019, it was the 278th most commonly prescribed medication in the United States, with more than a million prescriptions. It is on the World Health Organization's List of Essential Medicines.
The effects of fentanyl are similar to those of other opioids, causing sedation and analgesia at clinical doses. The most common adverse effects are respiratory depression, emesis, and asthenia. Bradycardia and apnea are uncommon side effects but are serious and can lead to death outside of clinical settings. Fentanyl exerts its actions as an agonist of the μ-opioid receptor and κ-opioid receptor. The μ-receptor agonism is responsible for the respiratory depression and generalized analgesia whilst the κ-receptor agonism is responsible for sedation and spinal analgesia. Fentanyl is a potent μ-receptor agonist but has less affinity for the κ-receptor.
Fentanyl is contributing to an epidemic of synthetic opioid drug overdose deaths in the United States. From 2011 to 2021, overdose deaths involving prescription opioid (natural and semi-synthetic opioids and methadone) per year remained stable, while synthetic opioid (primarily fentanyl) associated overdose deaths per year increased from 2,600 overdoses to 70,601. Fentanyl was involved in the most drug overdose deaths in the United States in 2018. The United States National Forensic Laboratory estimates fentanyl reports by federal, state, and local forensic laboratories increased from 4,697 reports in 2014 to 117,045 reports in 2020. Fentanyl is often mixed, cut, or ingested alongside other drugs, including cocaine and heroin. Fentanyl has been reported in pill form, including pills mimicking pharmaceutical drugs such as oxycodone. Mixing with other drugs or disguising as a pharmaceutical makes it difficult to determine the correct treatment in the case of an overdose, resulting in more deaths. Emerging adulterants have further complicated the evolving fentanyl supply. In recent years, community drug checking programs have identified medetomidine — a potent veterinary α₂-adrenergic agonist — as a new adulterant in the fentanyl supply.
In an attempt to reduce the number of overdoses from taking other drugs mixed with fentanyl, drug testing kits, strips, and labs are available.
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