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alfentanil

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alfentanil Basic information

Product Name:
alfentanil
Synonyms:
  • alfentanil
  • Alfentanyl
  • N-[1-[2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)-ethyl]-4-(methoxymethyl)-4-piperidyl]propionanilide
  • N-[1-[2-(4-Ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-piperidinyl]-N-phenyl-propanamide
  • Rapifen
  • 70879-28-6 (Hydrochloride)
  • Alfentanilum
  • Alfentanilum [inn-latin]
CAS:
71195-58-9
MF:
C21H32N6O3
MW:
416.52
Mol File:
71195-58-9.mol
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alfentanil Chemical Properties

Melting point:
140.8 °C
Boiling point:
511.8±60.0 °C(Predicted)
Density 
1.22±0.1 g/cm3(Predicted)
pka
pKa 6.5 (Uncertain)
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Safety Information

Hazardous Substances Data
71195-58-9(Hazardous Substances Data)
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alfentanil Usage And Synthesis

Uses

Analgesic (narcotic).

Uses

The low pKa of alfentanil (6.9) results in it being largely unionised at plasma pH, allowing rapid diffusion to the effect site (t1.2keo ~1min) and rapid onset of action despite it being less lipid soluble than other opioids. It does not bind strongly to opioid receptors, and the effect-site concentration also decreases rapidly as plasma concentrations decrease. Alfentanil is metabolised by the hepatic cytochrome P450 isoform CYP3A4. Genetic variability in the activity of this enzyme may result in two- to threefold variations in pharmacokinetic values when given by infusion. Low, medium or high metabolisers have been identified; this has implications for duration of action when prolonged use is contemplated.

Definition

ChEBI: A member of the class of piperidines that is piperidine having a 2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl group at the 1-position as well as N-phenylpropanamido- and methoxymethyl groups at the 4-position.

brand name

Alfenta (Akorn).

General Description

The addition of a methoxy methyl on the 4-piperidine and thesubstitution of the phenethyl ring for an ethyl-substitutedtetrazole-one yielded a compound with about one fourth toone third the potency of fentanyl. Although lesspotent, it has a quicker onset of action, a shorter duration ofaction, and thus a better, safety profile for use as an anestheticadjunct. The piperidine amine has a pKa of 6.5 compared withfentanyl’s pKa of 8.4. This results in a higher proportion ofunionized drug for alfentanil leading to quicker penetrationthrough the blood-brain barrier and thus onset of action.Alfentanil (Alfenta) is available as an IV injection for use asan analgesic adjunct for induction of general anesthesia and tomaintain analgesia during general surgical procedures.

Clinical Use

Opioid analgesic:
Short surgical procedures
Intensive care sedation

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: concentration increased by erythromycin; metabolism accelerated by rifampicin.
Antidepressants: possible CNS excitation or depression (hypertension or hypotension) in patients also receiving MAOIs (including moclobemide) - avoid; possibly increased sedative effects with tricyclics.
Antifungals: metabolism inhibited by fluconazole and ketoconazole (risk of prolonged or delayed respiratory depression); metabolism possibly inhibited by itraconazole; concentration increased by voriconazole, consider reducing alfentanil dose.
Antihistamines: increased sedative effects with sedating antihistamines.
Antipsychotics: enhanced hypotensive and sedative effects.
Antivirals: concentration possibly increased by ritonavir; increased risk of ventricular arrhythmias with saquinavir - avoid.
Cytotoxics: use crizotinib with caution.
Dopaminergics: avoid with selegiline.
Sodium oxybate: enhanced effect of sodium oxybate - avoid.

Metabolism

Alfentanil is metabolised in the liver; oxidative N- and O-dealkylation by the cytochrome P450 isoenzyme CYP3A4 leads to inactive metabolites, which are excreted in the urine.

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