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Alfentanil: Biological mechanisms, surgical application and side effects

Alfentanil is a short-acting opioid drug that can be used as an analgesic or sedative in adults and children at least 12 years of age.1 Alfentanil was developed in the 1970s by Janssen Pharmaceutica as a less potent derivative of fentanyl, which is a widely used synthetic opioid agonist.2-4 Alfentanil is sold under the names Alfenta, Rapifen, Limifen and Fanaxal, depending on region and language.5 Alfentanil has a variety of biological mechanisms, surgical applications and side effects.

Alfentanil’s full name is alfentanil hydrochloride,6 and its molecular formula is C21H32N6O3.5 Alfentanil influences neural function by altering the activities of neurotransmitters and opioid receptors in the brain.6 Specifically, alfentanil binds to the m-opioid receptor, a G-protein-coupled receptor, mimicking the action of other opioids.1 This causes sedative responses due to inhibition of release of various neurotransmitters, including substance P, GABA, dopamine, acetylcholine and noradrenaline.6 Alfentanil’s actions also block the release of hormones such as vasopressin, somatostatin, insulin and glucagon.6 Alfentanil is a tetrazole derivative of fentanyl, and it is about one-eighth as potent as fentanyl and has an onset about three times faster than fentanyl.1 Alfentanil exhibits different pharmacokinetics depending on method of administration, but it is primarily metabolized in the liver.7 In comparison to fentanyl and sufentanil, hepatic metabolism of alfentanil is less predictable because of the variability between individual CYP3A4 enzymes, the primary enzymes involved in alfentanil biotransformation.

The use of alfentanil is limited to certain settings and situations due to its short half-life.1 It is often used during rapid sequence intubation,8 as it can prevent the hypertensive response or increased intracranial pressure associated with intubation.9 Alfentanil can also be used for analgesia during a surgical procedure.1 When administered intravenously, alfentanil induction can be controlled by the patient for optimal pain management.10 Because alfentanil has minimal recovery time, it may be preferred over fentanyl for analgesia during brief procedures.3,11 However, its short duration of analgesic effect makes it less than ideal for intravenous, patient-controlled analgesia.10 Alternatively, alfentanil can also be used for epidural analgesia.10 Alfentanil can be used in place of fentanyl for its quicker onset of action, shorter duration of effect, lower potency and shorter recovery time.

Like other opioids, alfentanil should be used cautiously.1 Alfentanil is associated with several side effects, including hypertension, tachycardia (fast heart rate), nausea and vomiting.1,4 While alfentanil increases the patient’s tolerance for pain and decreases awareness of suffering, it can also cause alterations in mood and drowsiness.12 Alfentanil depresses respiration and the cough reflex, which contributes to risk of respiratory depression.12 Other serious adverse effects include a slow or uneven heart rate, hypotension, chest wall rigidity and apnea.1 Chest wall rigidity is more likely when alfentanil is given in high doses during anesthesia induction.4 For patients with a history of seizures, alfentanil administration can cause seizure-like activity.1 Given the addictive properties of alfentanil and other opioids, clinicians should carefully consider its risks and benefits, and perhaps opt for alternatives such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), topical medications, ketamine or intravenous lidocaine.1 Alfentanil is a short-acting, relatively low-potency opioid drug that is primarily used for rapid sequence intubation, sedation and analgesia. Like other opiate drugs, alfentanil binds to the brain’s m-opioid receptors to inhibit release of various neurotransmitters and hormones. Alfentanil is associated with hypertension, tachycardia, nausea and vomiting, and can cause fatal issues such as respiratory depression. Alfentanil has addiction potential and should be used minimally if alternatives are available.

1.         Moman RN, Ahmed AA, Kelley B. Alfentanil. StatPearls. Web: StatPearls Publishing LLC; October 24, 2019.

2.         Stanley TH. The history and development of the fentanyl series. Journal of Pain and Symptom Management. 1992;7(3 Suppl):S3–7.

3.         Edgin WA, Ford ML, Mansfield MJ. Alfentanil for general anesthesia in oral and maxillofacial surgery. Journal of Oral and Maxillofacial Surgery. 1989;47(10):1039–1042.

4.         Larijani GE, Goldberg ME. Alfentanil hydrochloride: A new short-acting narcotic analgesic for surgical procedures. Clinical Pharmacology. 1987;6(4):275–282.

5.         Alfentanil. PubChem Database. Web: National Center for Biotechnology Information; 2020.

6.         National Cancer Institute. Alfentanil hydrochloride. In: National Institutes of Health, ed. NCI Drug Dictionary 2020.

7.         Ogura T, Egan TD. 17—Intravenous Opioid Agonists and Antagonists. In: Hemmings HC, Egan TD, eds. Pharmacology and Physiology for Anesthesia (Second Edition). Philadelphia: Elsevier; 2019:332–353.

8.         Pouraghaei M, Moharamzadeh P, Soleimanpour H, et al. Comparison Between the Effects of Alfentanil, Fentanyl and Sufentanil on Hemodynamic Indices During Rapid Sequence Intubation in the Emergency Department. Anesthesiology and Pain Medicine. 2014;4(1):e14618.

9.         Heard CMB, Fletcher JE. Chapter 123—Sedation and Analgesia. In: Fuhrman BP, Zimmerman JJ, eds. Pediatric Critical Care (Fourth Edition). Saint Louis: Mosby; 2011:1654–1681.

10.       Koyyalagunta D. Chapter 113—Opioid Analgesics. In: Waldman SD, Bloch JI, eds. Pain Management. Philadelphia: W.B. Saunders; 2007:939–964.

11.       Meyer WJ, Jeevendra Martyn JA, Wiechman S, Thomas CR, Woodson L. 64—Management of Pain and Other Discomforts in Burned Patients. In: Herndon DN, ed. Total Burn Care (Fifth Edition): Elsevier; 2018:679–699.e676.

12.       Alfentanil. DrugBank February 9, 2020; https://www.drugbank.ca/drugs/DB00802.