Pharmaniaga Fentanyl Mechanism of Action

Pharmacology: Pharmacodynamics: Fentanyl is a potent opioid analgesic which may be used as an analgesic supplement with general anaesthesia or as an anaesthetic agent alone. Fentanyl possesses μ-agonistic properties.
The agonistic behaviour to δ- and κ-receptors is comparable to morphine. A dose of 100 microgram (2 ml) has an analgesic action which is comparable with 10 mg morphine.
Fentanyl has a rapid onset of action. The maximum analgesic effect and the depressant action on the respiration take place within a few minutes. The average duration of action of the analgesic effect is about 30 minutes after a single bolus injection of 100 microgram.
The level of analgesia is dose related and may be adjusted to the pain level of the surgical procedure.
Fentanyl exhibits relatively small cardio-circulatory effects but has a strong depressive effect on respiration. Stress induced hormonal changes are not reliably suppressed by fentanyl. An increase in blood pressure due to intraoperative pain stimuli may occur in spite of high dose fentanyl treatment.
Depending on dosage and rate of injection, fentanyl may cause muscle rigidity, euphoria, miosis and bradycardia. Intradermal tests and serum determinations of histamine in humans, as well as in-vivo tests in dogs, showed that clinically significant histamine release after fentanyl application is rarely observed.
All effects of fentanyl can be antagonised by specific opioid-antagonists like naloxone.
Pharmacokinetics: After intravenous injection, the fentanyl plasma concentrations decrease rapidly. The disposition of fentanyl is triphasic with half-lifes of about 1 minute, 15 minutes and 6 hours. Fentanyl has a volume of distribution of the central compartment of about 15 litres and a total volume of distribution of about 400 litres.
Especially in elderly patients or after repeated administration, half-lifes may be prolonged. Secondary peak plasma levels may occur.
Fentanyl is bound to plasma proteins for 80-85%.
Fentanyl is metabolised rapidly, mainly in the liver and mainly by oxidative N-desalkylation. The clearance is about 0.5 l/hour/kg. About 75% of the administered dose is eliminated within 24 hours. Only 10% of the dose is excreted as intact substance.