alfentanil

Absorption

For intravenous injection or infusion only.

Toxicity

Symptoms of overexposure include characteristic rigidity of the skeletal muscles, cardiac and respiratory depression, and narrowing of the pupils.

The Uses of alfentanil

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.

The Uses of alfentanil

Analgesic (narcotic).

Indications

For the management of postoperative pain and the maintenance of general anesthesia.

Background

A short-acting opioid anesthetic and analgesic derivative of fentanyl. It produces an early peak analgesic effect and fast recovery of consciousness. Alfentanil is effective as an anesthetic during surgery, for supplementation of analgesia during surgical procedures, and as an analgesic for critically ill patients.

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.

Pharmacokinetics

Alfentanil is a synthetic opioid analgesic. Alfentanil interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, alfentanil exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Alfentanil 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. Alfentanil depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.

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

The liver is the major site of biotransformation.

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.