Current Concepts of Phenylpiperidine Derivatives Use in the Treatment of Acute and Chronic Pain

Phenylpiperidines are a chemical class of drugs with a phenyl moiety directly attached to piperidine. These agents have an important role in many aspects of medicine including anesthesia and pain medicine. After the development of meperidine, fentanyl, which is a second generation synthetic phenylpiperidine series opioid, was synthesized and introduced into clinical anesthesia practice as fentanyl citrate in 1968. Fentanyl-mediated or modulated responses involve action at the muopioid receptor as an agonist at the dorsal horn inhibiting ascending pain pathways in the rostral ventral medulla, increasing pain threshold, and producing both analgesic and sedative effects. Since fentanyl is metabolized mainly via CYP3A4, potential adverse effects can occur with concomitant use of any drug which affects CYP3A4 activity. Discontinuation of CYP3A4 inducers can also result in an increase in fentanyl plasma concentration. Fentanyl-based formulations can be administered via intravenous, intramuscular, transdermal, transmucosal, and neuraxial routes. We describe the clinical utility of remifentanil, an ultra short-acting analgesic and newer formulations of sufentanil currently being evaluated for acute pain management. We examine the routes of administration and clinical considerations, including the role of opioids such as fentanyl as a natural killer cell suppressive agent. Fentanyl and other opioids have been shown to potentiate propagation of infection and cancer. In recent years, fentanyl and other phenylpiperidine formulations have been developed and successfully marketed for chronic pain management. Because all opioids have complex physiological responses and potential drug-drug interactions, the clinician should appreciate all aspects of this drug class and consider all available options in appropriate clinical settings. Key words: Fentanyl, remifentanil, sufentanil, opioids, analgesics, pain, perioperative formulations, management