Fentanyl

Abstract Fentanyl is a potent synthetic opioid that was engineered to have good lipid solubility to aid its use in medicinal settings. Fentanyl is relatively easy to synthesize and for this and other reasons it has infiltrated the illicit heroin supply throughout North America. Fentanyl is unique relative to other opioids; it has a different pharmacodynamic and pharmacokinetic profile of effects. These characteristics contribute to its heightened side effect profile, which includes opioid-related respiratory depression, as well as additional medical comorbidities. This chapter reviews a brief history of fentanyl in the United States and its pharmacokinetic and pharmacodynamic profiles with particular emphasis on its unique biphasic excretion pattern and risk for delayed onset of respiratory depression. The chapter also reviews the fentanyl-related withdrawal syndrome; its overdose profile, which includes components consistent with other opioid agonists (e.g., respiratory depression) and components unique to fentanyl (e.g., muscle rigidity/wooden chest syndrome, hypoxia, laryngospasm/vocal cord closure); the complexities of using naloxone in the context of fentanyl; and how fentanyl may be contributing to otherwise rare medical comorbidities, like an amnestic syndrome and bacterial infections. Finally, the chapter reviews fentanyl-related complexities in treatment, spanning harm reduction efforts to interactions with medications for opioid use disorder (most notably buprenorphine).