Fentanyl,
a fast-acting opioid analgesic, was developed by a Belgian pharmaceutical
company called Janssen Pharmaceutica in 1960. Fentanyl is
extremely strong in small quantities, being about 80 times more potent
than morphine. Shortly after fentanyl was invented, fentanyl citrate was
first made, the active ingredient in the prescription lollipop, Actiq,
which is used for breakthrough pain. During the 1960s, doctors began using
fentanyl quite frequently as an anesthetic.
Opioid analgesics have assumed a huge role in the practice of general anesthesia during the past thirty years. Problems with morphine-oxygen anesthesia include "incomplete amnesia, occasional histamine-related reaction, and marked increases in intra- and postoperative respiratory depression." The invention of fentanyl was a huge breakthrough in the world of general anesthesia. Since then, two potent fentanyl analogues have been introduced into clinical practice — sufentanil and alfentanil.[1]
Some batchs of heroin in the United States have been, reportedly, mixed with fentanyl, and because of the inconsistencies in purity and potency, there have been many deaths and overdoses. Be cautious.
Chemical Name.N-(1-phenethyl-4-piperidyl)-N-phenyl-propanamide.
Classification. Opioid.
Primary Uses. Analgesic, anesthetic.
Brand Names. Actiq (oral transmucosal),
Duragesic (transdermal patch), Fentora (buccal), Sublimaze (liquid).
Slang. China White.
Pharmacology and Pharmacokinetics
Fentanyl acts mostly on the mu-opioid receptors, and exerts its primary pharmacologic effects on the central nervous system. The mu-opioid receptors are scattered in the brain, spinal cord, and other bodily tissues. The actions of therapeutic value include sedation, and analgesia. Other effects include respiratory depression, cough suppression, and pupil constriction. In addition, some common reactions include euphoria, dysphoria, drowsiness, and mood changes.[2]
The half-life of fentanyl is seven hours, but may range from 3-12 hours. Oral transmucosal fentanyl citrate (Oralet by Abbott Laboratories) resulted in a bioavailability ranging from 34% to 59%.[3] Transdermal fentanyl has a bioavailability of at least 90%. The use of fentanyl along with strong and moderate cytochrome P450 3A4 inhibitors can cause an increase in plasma concentrations of the opioid, and may result in death caused by respiratory depression.
Chemistry
Synthesis.
The following was the original procedure used by Janssen Pharmaceutica to produce fentanyl:[4]
- 4-piperidinone hydrochloride was first reacted with phenethyl bromide to give N-phenethyl-4-piperidinone (NPP).
- Treatment of the NPP intermediate with aniline.
- Reduction with sodium borohydride afforded 4-anilino-N-phenethyl-piperidine (ANPP).
- A final acylation reaction between ANPP and propionic anhydride led to the fentanyl.
Analogues.
- Alfentanil - Opioid analgesic with rapid onset of action. Used for surgery. Injectable alfentanil marketed under the brand name, Alfenta. Lasts about 30 minutes.
- Carfentanil - Marketed under the name Wildnil as a tranquilizer for large animals. 10,000 times stronger than morphine, and 100 times stronger than fentanyl. Also discovered by Janssen Pharmaceutica.
- Remifentanil - Opioid analgesic marketed under the name Ultiva. Extremely rapid onset and offset. Blood concentration decreases by 50% in 3-6 minutes, after a one-minute infusion of remifentanil.
- Sufentanil - 5-10 times more potent than fentanyl. Marketed as Sufenta and Sufentil. Like the a lot of the other analogues, it is used during anesthesia. A transdermal patch for chronic pain sufferers is currently in the development stages.
In
the United States, fentanyl is a Schedule II substance, making it illegal
to use/possess without a prescription. Schedule II substances, such as
dextroamphetamine, morphine,
and cocaine, meet the following criteria according to the Controlled
Substances Act:
- The drug or other substance has a high potential for abuse.
- The drug or other substance has a currently accepted medical use in treatment in the United States (or) a currently accepted medical use with severe restrictions.
- Abuse of the drug may lead to severe psychological or physical dependence.
Pain relief
Euphoria/dysphoria
Mood changes
Reduced anxiety
Sedation
Itching
Nausea/vomiting
Decreased libido (sex drive)
Constipation
Facial flushing
Vertigo
Fentanyl, in any form, is highly addictive, and many users eventually become mentally and physically dependent. Withdrawal typically begins within 24-36 hours after the last dose, though it can start sooner for chronic users, and peaks in intensity around 72-96 hours. Withdrawal symptoms can include gooseflesh, restless legs/arms, anxiety, nausea, vomiting, depression, muscle aches, insomnia, diarrhea, headache, and dilated pupils.
Additional Information
[1] Stanley TH, The history and development of the
fentanyl series. Entrez PubMed [1517629]. J Pain Symptom Manage.
1992 Apr;7(3 Suppl):S3-7. [Abstract]
Accessed: May 8, 2007.
[2] DrugBank: Fentanyl. DrugBank [APRD00347]. Feb. 2007. [link]
Accessed: May 8, 2007.
[3] Melissa Wheeler, M.D., Patrick K. Birmingham, M.D., Ralph A. Lugo,
Pharm.D.,
Corri L. Heffner, R.N., and Charles J. Coté, M.D. The Pharmacokinetics
of the Intravenous Formulation of Fentanyl Citrate Administered Orally in
Children Undergoing General Anesthesia. International Anesthesia Research
Society. Anesth Analg 2004;99:1347-1351. [Abstract] Accessed: May 8, 2007.
[4] Fentanyl. Wikipedia, the free encyclopedia. May 3, 2007. [link]
Accessed: May 8, 2007.