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.
