Fentanyl-Piramal Mechanism of Action



Piramal Critical Care


Evercare Pharma
Full Prescribing Info
Pharmacotherapeutic group: anesthetics general, opioid anesthetics. ATC Code: N01AH01.
Pharmacology: Pharmacodynamics: Mechanism of action: Fentanyl is a potent, opioid analgesic.
Pharmacodynamic effects: Fentanyl is an opioid analgesic interacting predominantly with the μ-opioid receptor. Fentanyl can be used as an analgesic supplement to general anesthesia or as the sole anesthetic. Fentanyl preserves cardiac stability and obtunds stress-related hormonal changes at higher doses. A dose of 100 mcg (2.0 mL) is approximately equivalent in analgesic activity to 10 mg of morphine. The onset of action is rapid. However, the maximum analgesic and respiratory depressant effect may not be noted for several minutes. The usual duration of action of the analgesic effect is approximately 30 minutes after a single IV dose of up to 100 mcg. Depth of analgesia is dose-related and can be adjusted to the pain level of the surgical procedure.
Like other opioid analgesics, FENTANYL, depending upon the dose and speed of administration, can cause muscle rigidity, as well as euphoria, miosis and bradycardia.
Histamine assays and skin-wheal testing have indicated that clinically significant histamine release is rare with FENTANYL.
All actions of FENTANYL are reversed by a specific opioid antagonist.
Pharmacokinetics: Distribution: After intravenous injection, fentanyl plasma concentrations fall rapidly, with sequential distribution half-lives of about 1 minute and 18 minutes and a terminal elimination half-life of 475 minutes. Fentanyl has a Vc (volume of distribution of the central compartment) of 13 L, and a total Vdss (distribution volume at steady-state) of 339 L. The plasma protein binding of Fentanyl is about 84%.
Metabolism: Fentanyl is rapidly metabolized, mainly in the liver by CYP3A4. The major metabolite is norfentanyl. Fentanyl clearance is 574 mL/min.
Excretion: Approximately 75% of the administered dose is excreted in the urine within 24 hours and only 10% of the dose eliminated in urine is present as unchanged drug.
Special Populations: Pediatrics: The plasma protein binding of fentanyl in newborns is approximately 62% which is lower than in adults. The clearance and the volume of distribution are higher in infants and children. This may result in an increased dose requirement for FENTANYL.
Renal impairment: Data obtained from a study administering IV fentanyl in patients undergoing renal transplantation suggest that the clearance of fentanyl may be reduced in this patient population. If patients with renal impairment receive FENTANYL, they should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary (see Dosage & Administration).
Adult patients with burns: An increase in clearance up to 44% together with a larger volume of distribution results in lower fentanyl plasma concentrations. This may require an increased dose of FENTANYL.
Obese patients: An increase in clearance of fentanyl is observed with increased body weight. In patients with a BMI>30, clearance of fentanyl increases by approximately 10% per 10 kg increase of the fat free mass (lean body mass).
Toxicology: Non-Clinical Information: Fentanyl has a broad safety-margin. In rats the ratio LD50/ED50 for the lowest level of analgesia is 281.8, as compared with 69.5 and 4.8 for morphine and pethidine respectively.
Carcinogenicity and Mutagenicity: In vitro fentanyl showed, like other opioid analgesics, mutagenic effects in a mammalian cell culture assay, only at cytotoxic concentrations and along with metabolic activation. Fentanyl showed no evidence of mutagenicity when tested in in vivo rodent studies and bacterial assays. In a two-year carcinogenicity study conducted in rats, fentanyl was not associated with an increased incidence of tumors at subcutaneous doses up to 33 mcg/kg/day in males or 100 mcg/kg/day in females, which were the maximum tolerated doses for males and females.
Reproductive Toxicology: Fertility: Some tests on female rats showed reduced fertility as well as embryo mortality. These findings were related to maternal toxicity and not a direct effect of the drug on the developing embryo.
There was no evidence of teratogenic effects.
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