Fentanyl

Fentanyl is a synthetic opioid from the piperidine class, roughly 50 to 100 times stronger than morphine. It is mainly prescribed for pain in cancer patients and after surgery, and it can also sedate people on breathing machines. The drug works by activating μ-opioid receptors and has a short duration of action. It is sold under brand names like Actiq, Duragesic, and Sublimaze. Paul Janssen first made fentanyl in 1960, and the U.S. approved it for medical use in 1968. By 2015, about 1,600 kilograms were used in healthcare worldwide. As of 2017, it was the most common synthetic opioid in medicine; in 2019, it ranked 278th among U.S. prescriptions, with over a million written. The World Health Organization lists it as an essential medicine.

Fentanyl’s effects resemble other opioids: it causes sedation and pain relief at clinical doses. Common side effects include slowed breathing, vomiting, and weakness. Less common but serious issues are a slow heart rate and stopped breathing, which can be fatal outside a hospital. The drug acts as an agonist at both μ-opioid and κ-opioid receptors. The μ-receptor drives respiratory depression and general pain relief, while the κ-receptor produces sedation and spinal pain relief. Fentanyl strongly binds to the μ-receptor but less so to the κ-receptor.

Fentanyl is fueling a U.S. epidemic of synthetic opioid overdose deaths. Between 2011 and 2021, yearly deaths from prescription opioids stayed steady, but deaths from synthetic opioids—mostly fentanyl—jumped from 2,600 to 70,601. In 2018, fentanyl was involved in more overdose deaths than any other drug. The National Forensic Laboratory reports that fentanyl identifications by labs rose from 4,697 in 2014 to 117,045 in 2020. The drug is often mixed with cocaine or heroin, or pressed into pills that look like oxycodone. This mixing makes overdoses harder to treat, raising the death toll. New adulterants are further complicating the supply. To reduce risks, drug testing kits, strips, and labs are available.

**Medical uses**

**Anesthesia** Intravenous fentanyl is used for anesthesia and pain relief. It is given with a sedative like propofol or thiopental to start anesthesia, and inhaled anesthetics plus more fentanyl keep it going. Doses are repeated every 15 to 30 minutes during procedures like endoscopy, surgery, or in emergency rooms. After surgery, fentanyl reduces the amount of inhaled anesthetic needed for a person to wake up. Carefully adjusting the dose based on the patient’s response can keep blood pressure and heart rate stable and allow a quicker, less painful emergence from anesthesia.

**Regional anesthesia** Fentanyl is the most common opioid given into the spinal fluid because it is lipophilic, so it acts fast (5–10 minutes) and lasts a moderate time (60–120 minutes). A mix of hyperbaric bupivacaine with fentanyl is often the best choice for spinal injection. The quick onset reduces belly discomfort and nausea during the procedure.

**Obstetrics** Fentanyl is given into the spinal fluid or epidural space for labor pain. Because it is highly fat-soluble, its effects stay more localized than morphine’s; some doctors prefer morphine for wider pain coverage. It is widely used in obstetrics because it peaks in about 5 minutes, wears off quickly after a single dose, and keeps the heart and blood vessels stable. The dose must be tightly controlled to prevent too much from reaching the fetus. High doses can cause withdrawal in the newborn. For this reason, shorter-acting drugs like alfentanil or remifentanil may be better for general anesthesia in pregnant women.

**Pain management** Nasal fentanyl has about 70–90% bioavailability, though accuracy can suffer from clogged nostrils, swallowing, or poor technique. For emergency and palliative care, it comes in 50, 100, 200, or 400 microgram doses (PecFent). A study of about 900 out-of-hospital patients found it safe, with few side effects and good pain relief. In children, nasal fentanyl works well for moderate to severe pain and is well tolerated. A 2017 study also showed that fentanyl lozenges are effective in children as young as five and as light as 13 kilograms. Lozenges let the child control the dose, which is an advantage over buccal tablets.

**Chronic pain** Fentanyl is also used for long-term pain, often through transdermal patches. These patches release the drug slowly through the skin over 48 to 72 hours, providing steady pain relief. The patch size determines the dose.