Molecule

Drug Groups

illicit; approved; investigational

Description

A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)

Indication

For the treatment of cancer patients with severe pain that breaks through their regular narcotic therapy.

Pharmacology

Fentanyl is an opioid analgesic. Fentanyl interacts predominately with the opioid mu-receptor but also binds to kappa and delta-type opioid receptors. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, Fentanyl exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Fentanyl may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Fentanyl depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.

Toxicity

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.

Affected Organisms

Biotransformation

Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system.

Absorption

Bioavailability is 92% following transdermal administration and 50% following buccal administration.

Half Life

7 (range 3-12) hours

Protein Binding

80-85%

Elimination

Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system and mostly eliminated in urine. Within 72 hours of IV fentanyl administration, approximately 75% of the dose is excreted in urine, mostly as metabolites with less than 10% representing unchanged drug.

Distribution

* 3 to 8 L/kg [Surgical Patients]
* 0.8 to 8 [Hepatically Impaired Patients]

Clearance

* 27 – 75 L/h [Surgical Patients receving IV administration]
* 3 – 80 L/h [Hepatically Impaired Patients receving IV administration]
* 30 – 78 L/h [Renally Impaired Patients receving IV administration]

References

External Links