Fentanyl was developed in 1960 by Paul Janssen and was the first anilinopiperidine at that time. Some modifications to the molecular formula have since allowed some derivatives to be developed from fentanyl that are more controllable.
What is fentanyl?
Fentanyl is used in anesthesia as an analgesic and in the treatment of chronic pain. Fentanyl is a synthetic opiod that is used in anesthesia as a potent analgesic and in the therapy of chronic pain as a transdermal therapeutic system. It acts as a so-called agonist. In Germany as well as in Switzerland, fentanyl falls under the Narcotics Act; in Austria, it falls under the Narcotic Substances Act.
Pharmacological effect
Fentanyl has primarily analgesic (strongly analgesic) and sedative (calming) effects. In this regard, it is 120 times more potent than morphine, resulting in greater efficacy and a shorter duration of action. For example, fentanyl takes effect after only two to five minutes when administered intravenously, and the so-called half-life is around three to twelve hours. The dose for effective treatment is 0.01 mg per kilogram of body weight, the dose that leads to death is 3.1 mg per kilogram of body weight, the last figure referring to rats. Even lower doses can therefore lead to death in humans due to respiratory depression. However, the side effects can generally be compared to those of morphine. Fentanyl dissolves well in fat and can therefore be distributed well in fatty tissue. It is mainly metabolized in the liver, with less than ten percent excreted unchanged by the kidneys. Depending on the patient’s condition and the dose administered, fentanyl can impair the ability to perceive, have a sedative effect, cause clouding of consciousness or induce a sleep-like state. The latter point is reason for its use in anesthesia. Mainly used as an analgesic during surgery in conjunction with a sleeping pill, fentanyl can optionally be used as a muscle relaxant. Since fentanyl is difficult to store and release in fatty tissue in a controlled manner due to its lipophilic nature, the substances remifentanil, alfentanil or sufentanil are often used as alternatives. Fentanyl has a sedative effect; this effect can be increased by other sedatives as well as alcohol or decreased by taking other opiods. Severe circulatory and respiratory disorders may occur in conjunction with the use of so-called monoamiooxidase inhibitors, which is why there should be a period of at least 14 days between each use. When pain patches are used, they may also interact with preparations such as omeprazole, furosemide or glibenclamide. Interactions may also occur with preparations containing St. John’s wort. For smokers, it may be necessary to adjust the dose of fentanyl. If a fentanyl-containing drug is taken together with a serotonergic drug, dangerous serotonin syndrome may occur, the symptoms of which may include blood pressure crises, hallucinations, or even coma.
Medical use and application
Fentanyl is used as fentanyl dihydrogen citrate in three forms: as a transdermal therapeutic system, as intravenous administration in anesthesia and emergency medicine, and as an oral transmucosal therapeutic system (as a lozenge for breakthrough pain). For breakthrough pain, Nycomed’s Instanyl, the first approved fentanyl nasal spray EU-wide, has been approved since September 1, 2009. This drug is suitable for treatment of breakthrough pain in adult patients who are already receiving basic opioid therapy for chronic tumor pain. Fentanyl has a strong analgesic effect and is therefore mostly used perioperatively (before surgery) or even after surgery. For severe, chronic pain in cancer patients, it is used in the form of a skin patch as an analgesic; it can also be used in analgesia for chronic pain that is not related to a tumor. Emergency physicians are allowed to use fentanyl for acute pain in the ambulance service.
Risks and side effects
A side effect of fentanyl may include respiratory impairment and even respiratory depression.Furthermore, side effects such as cramped or stiffened muscles, slowed heart activity, euphoria or anxiety, constricted pupils, vomiting, nausea and constipation are possible. If a rapid injection is given, it may also cause a brief coughing spell in rare cases.