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Fentanyl, also spelled fentanil, is an opioid used as a pain medication and together with other medications for anesthesia.^[3] It is also used as a recreational drug, sometimes mixed with heroin, methamphetamine, or cocaine.^[5] It has a rapid onset and its effects generally last under two hours.^[3] Medically, it is used by injection, nasal spray, skin patch, or absorbed through the cheek (transmucosal) as a lozenge or tablet.

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Common side effects include nausea or vomiting, constipation, sedation, confusion, and injuries related to poor coordination.^[3][7] Serious side effects may include decreased respiratory rate (respiratory depression), serotonin syndrome, low blood pressure, or development of an opioid use disorder.^[3][7] Fentanyl works primarily by activating μ-opioid receptors.^[3] It is around 100 times stronger than morphine, about 50 times stronger than heroin. Some fentanyl analogues such as carfentanil are up to ~10,000 times stronger than morphine.^[8]

Fentanyl was first made by Paul Janssen in 1960 and approved for medical use in the United States in 1968.^[3][9] In 2015, 1,600 kilograms (3,500 lb) were used in healthcare globally.^[10] As of 2017, fentanyl was the most widely used synthetic opioid in medicine.^[11] Fentanyl patches for cancer pain are on the World Health Organization’s List of Essential Medicines.^[12] In 2016, fentanyl and fentanyl analogues were the most common cause of overdose deaths in the United States at more than 20,000, about half of all opioid-related deaths.^[13][14][15] Most of these overdose deaths were due to illegally made fentanyl.^[16]

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In recent years, fentanyl has disrupted the North American drug market, capitalizing on pre-existing demand for opiates such as heroin and prescription pharmaceuticals. In 2017, it was the 250th most commonly prescribed medication in the United States, with more than 1.7 million prescriptions.^[17][18] At the same time, there is concern that the growing demand may prove highly attractive to organized crime and aspiring criminals, especially those operating in areas around the Golden Triangle in Southeast Asia and Shan State in Myanmar where production of synthetic drugs has expanded dramatically over the last decade. Compared to heroin, it is more potent, has higher profit margins and, because it is compact, has simpler logistics. It can be cut into, or even replace entirely, the supply of heroin and other opiates

Medical uses

Anesthesia

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Intravenous fentanyl is often used for anesthesia and to treat pain.^[20] To induce anesthesia, it is given with a sedative-hypnotic, like propofol or thiopental, and a muscle relaxant.^[21] To maintain anesthesia, inhaled anesthetics and additional fentanyl may be used.^[21] These are often given in 15–30 minute intervals throughout procedures such as endoscopy, surgeries, and in emergency rooms.^[22][23]

For pain relief after surgery, use can decrease the amount of inhalational anesthetic needed for emergence from anesthesia.^[21] Balancing this medication and titrating the drug based on expected stimuli and the person’s responses can result in a stable blood pressure and heart rate throughout a procedure and a faster emergence from anesthesia with minimal pain.^[21]

Obstetrics

Fentanyl is sometimes given intrathecally as part of spinal anesthesia or epidurally for epidural anaesthesia and analgesia. Because of fentanyl’s high lipid solubility, its effects are more localized than morphine, and some clinicians prefer to use morphine to get a wider spread of analgesia.^[24] However, it is widely used in obstetrical anesthesia because of its short time to action peak (about 5 min), the rapid termination of its effect after a single dose, and the occurrence of relative cardiovascular stability.^[25] In obstetrics, the dose must be closely regulated in order to prevent large amounts of transfer from mother to fetus. At high doses, the drug may act on the fetus to cause postnatal respiratory distress.^[25] For this reason, shorter acting agents such as alfentanyl or remifentanil may be more suitable in the context of inducing general anaesthesia