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fentanyl
Fentanyl is an opioid analgesic, first synthesized by Janssen Pharmaceutica ( Belgium) in the late 1950s, with an analgesic potency of about 80 times that of morphine. Fentanyl was introduced into medical practice in the 1960s as an intravenous anesthetic under the trade name of Sublimaze. Fentanyl has an LD50 of 3.1 milligrams per kilogram in rats, and, 0.03 milligrams per kilogram in monkeys. The LD50 in humans is not known. In the United States, fentanyl is a Schedule II drug. ChemistrySynthesisThe synthesis of fentanyl (N-phenyl-N-(1-phenethyl-4-piperidinyl)propanamide) by Janssen Pharmaceutica was achieved in four steps, starting from 4-piperidinone hydrochloride. The 4-piperidinone hydrochloride was first reacted with phenethyl bromide to give N-phenethyl-4-piperidinone (NPP). Treatment of the NPP intermediate with aniline followed by reduction with sodium borohydride afforded 4-anilino-N-phenethyl-piperidine (ANPP). finally ANPP and propionic anhydride are reacted to form the amide product. AnaloguesThe pharmaceutical industry has developed several analogues of fentanyl:
Therapeutic useFentanyls are extensively used for anesthesia and analgesia, most often in the operating room and intensive care unit. Duragesic, by Janssen Pharmaceutica, is a fentanyl transdermal patch used in chronic pain management. Duragesic patches work by releasing fentanyl into body fats, which then slowly release the drug into the blood stream over 72 hours, allowing for long lasting relief from pain. In the past few years, the patches have gone generic and are available for lower costs. Duragesic is manufactured in five patch sizes: 12.5 micrograms/h, 25 µg/h, 50 µg/h, 75 µg/h, and 100 µg/h. Dosage is based on the size of the patch, since the transdermal absorption rate is generally constant at a constant skin temperature. Rate of absorption is dependent on a number of factors. Body temperature, skin type and placement of the patch can have major effects. The different delivery systems used by different makers will also affect individual rates of absorption. 
Actiq, by
Cephalon, is a recently-developed solid formulation of fentanyl citrate on a
stick in the form of a lollipop that dissolves slowly in the mouth for transmucosal absorption. Actiq is intended for opioid-tolerant individuals and is effective in treating
breakthrough cancer pain. It is also useful for breakthrough pain for those suffering bone injuries, severe back pain, neuropathy, arthritis, and some other examples of chronic nonmalignant pain. The unit is a berry-flavored lozenge on a stick which is swabbed on the mucosal surfaces inside the mouth—inside of the cheeks, under and on the tongue and gums—to release the fentanyl quickly into the system. It is most effective when the lozenge is consumed in 15 minutes. The drug is less effective if swallowed, absorption from the alimentary tract being poor. Actiq is available in six dosages, from 200 to 1600 µg in 200 µg increments (excluding 1000 µg and 1400 µg). Actiq is now available in the United states in generic form,
[1] through an
FTC consent agreement.
[2] Fentora™ is a new delivery method of fentanyl; it is an effervescent tablet placed in the cheek and is absorbed through the buccal mucosa. It was introduced on 2006-09-25. [3] One advantage of Fentora, according to the prescribing information, [4] is quicker absorption into the bloodstream at lower dosage levels. Fentanyl is frequently given intrathecally as part of spinal anesthesia or epidurally for epidural anesthesia and analgesia. It is also used as a sedative. Adverse effectsLike other lipid soluble drugs, the pharmacokinetics of fentanyl are poorly understood. The manufacturers acknowledge there is no data on the pharmacokinetics of fentanyl in elderly, cachectic or debilitated patients, frequently the type of patient for which transdermal fentanyl is being used. This may explain the increasing number of reports of respiratory depression events since the late 1970s. [5], [6], [7], [8], [9], [10], [11] In 2006 the U.S. Food and Drug Administration started investigating several respiratory deaths. The precise reason for sudden respiratory depression is unclear, but there are several hypotheses:
In palliative care fentanyl has a definite, but limited, role for:
Fentanyl is not considered a first line opioid in palliative care— morphine remains the first line choice, and safer opiate derivatives such as oxycodone and hydromorphone are usually tried before resorting to fentanyl. Illicit use
Illicit use of pharmaceutical fentanyls first appeared in the mid- 1970s in the medical community and continues in the present. United States authorities classify fentanyl as a narcotic. To date, over 12 different analogues of fentanyl have been produced clandestinely and identified in the U.S. drug traffic. The biological effects of the fentanyls are similar to those of heroin, with the exception that there is less of a euphoric 'high' associated with the drug and a stronger analgesic effect. Additionally, fentanyl may be hundreds of times more potent — though in some places, it is sold as heroin, often leading to overdoses. Fentanyl also has a shorter half-life than that of heroin, and is most commonly used orally, but like heroin, can also be smoked, snorted or injected. Many fentanyl overdoses were initially classified as heroin overdoses. [12]
Some heroin dealers mix fentanyl powder with larger amounts of heroin in order to increase potency or compensate for low-quality heroin, and to increase the volume of their product. As of December 2006, a mix of fentanyl and either cocaine or heroin has caused an outbreak in overdose deaths in the United States, heavily concentrated in the cities of Detroit, Philadelphia, Pittsburgh, Milwaukee, Camden, Chicago, [13] Little Rock, and Dallas. [14] The mixture of fentanyl and heroin is known as "magic", among other names, on the street. [15] Several large quantities of illicitly-produced fentanyl have been seized by U.S. law enforcement agencies. In June 2006, 945 grams of 83% pure fentanyl powder were seized by Border Patrol agents in California from a vehicle which had entered from Mexico. [16] Mexico is the source of much of the illicit fentanyl for sale in the U.S. However, there has been one domestic fentanyl lab discovered by law enforcement, in April 2006 in Azusa, California. The lab was a source of counterfeit 80 mg OxyContin tablets containing fentanyl instead of oxycodone, as well as bulk fentanyl and other drugs. [17] [18] The "china white" form of fentanyl refers to the clandestinely produced analogue α-methylfentanyl (AMF). [19] This has been reported in the literature to be twice the strength of regular fentanyl. [citation needed] The main bonus of the alpha-methyl is it provides a site of resistance to metabolic degradation resulting in a drug with an increased duration. [20] References
See alsoExternal links
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