fentanyl

 

  • [45] Other[edit] Some routes of administration such as nasal sprays and inhalers generally result in a faster onset of high blood levels, which can provide more immediate
    analgesia but also more severe side effects, especially in overdose.

  • Under normal circumstances, the patch will reach its full effect within 12 to 24 hours; thus, fentanyl patches are often prescribed with a fast-acting opioid (such as morphine
    or oxycodone) to handle breakthrough pain.

  • [22] Balancing this medication and titrating the drug based on expected stimuli and the person’s responses can result in stable blood pressure and heart rate throughout a
    procedure and a faster emergence from anesthesia with minimal pain.

  • [57] Other factors that increase the risk of respiratory depression are:[57] • High fentanyl doses • Sleep • Older age • Simultaneous use of CNS depressants like benzodiazepines,
    barbiturates, alcohol, and inhaled anesthetics • Hyperventilation • Decreased CO2 levels in the serum • Respiratory acidosis • Decreased fentanyl clearance from the body • Decreased blood flow to the liver • Renal insufficiency Sustained release
    fentanyl preparations, such as patches, may also produce unexpected delayed respiratory depression.

  • [122] In 2009, the US Food and Drug Administration (FDA) approved Onsolis (fentanyl buccal soluble film), a fentanyl drug in a new dosage form for cancer pain management in
    opioid-tolerant subjects.

  • Naloxone (also known as Narcan) can reverse the effects of an opioid overdose; however, because fentanyl is so potent, multiple doses might be necessary.

  • [87][88] Topical (or transdermal; via the skin) and inhalative exposure to fentanyl is extremely unlikely to cause intoxication or overdose (except in cases of prolonged exposure
    with very large quantities of fentanyl), and first responders such as paramedics and police officers are at minimal risk of fentanyl poisoning through accidental contact with intact skin.

  • In emergency medicine, safe administration of intranasal fentanyl with a low rate of side effects and a promising pain-reducing effect was demonstrated in a prospective observational
    study in about 900 out-of-hospital patients.

  • The CDC recommended the following four actions to counter this rise:[96] 1. local need to expand the distribution and use of naloxone and overdose prevention education, 2.
    expand awareness, access, and availability of treatment for substance use disorders, 3. intervene early with individuals at highest risk for overdose, and 4. improve detection of overdose outbreaks to facilitate more effective response.

  • When enough fentanyl has been absorbed, the (sedated) person generally lets the lollipop fall from the mouth, indicating sufficient analgesia and somewhat reducing the likelihood
    of overdose and associated risks.

  • [19] Mixing with other drugs or disguising as a pharmaceutical makes it difficult to determine the correct treatment in the case of an overdose, resulting in more deaths.

  • [27] It is widely used in obstetrical anesthesia because of its short time to action peak (about 5 minutes), the rapid termination of its effect after a single dose, and the
    occurrence of relative cardiovascular stability.

  • [39] Palliative care[edit] A fentanyl transdermal patch with a release rate of 12 micrograms per hour, on a person’s arm In palliative care, transdermal fentanyl patches have
    a definitive, but limited role for: • people already stabilized on other opioids who have persistent swallowing problems and cannot tolerate other parenteral routes such as subcutaneous administration.

  • [120] In the mid-1990s, Janssen Pharmaceutica developed and introduced into clinical trials the Duragesic patch, which is a formulation of an inert alcohol gel infused with
    select fentanyl doses, which are worn to provide constant administration of the opioid over a period of 48 to 72 hours.

  • • Reduced sedation, losing a useful early warning sign of opioid toxicity and resulting in levels closer to respiratory-depressant levels.

  • [92] A 2021 paper expressed concern that these physical fears over fentanyl may inhibit effective emergency response to overdoses by causing responding officers to spend additional
    time on unnecessary precautions, and that the media coverage could also perpetuate a wider social stigma that people who use drugs are dangerous to be around.

  • [100][49] It attenuates “second pain” with primary effects on slow-conducting, unmyelintated C-fibers and is less effective on neuropathic pain and “first pain” signals through
    small, myelinated A-fibers.

  • However, the PCTS method proved superior to the placebo, showing lower mean VAS pain scores and having no significant respiratory depression effects.

  • [7] Fentanyl’s ease of manufacture and high potency makes it easier to produce and smuggle, resulting in fentanyl replacing other abused narcotics and becoming more widely
    used.

  • [30] In children, intranasal fentanyl is useful for the treatment of moderate and severe pain and is well tolerated.

  • [7] Depending on the method of delivery, fentanyl can be very fast acting and ingesting a relatively small quantity can cause overdose.

  • [66] Over 85% of overdoses involved at least one other drug, and there was no clear correlation showing at which level the mixtures were fatal.

  • [20] • Pronunciation: /ˈfɛntənɪl/ or /ˈfɛntənəl/; Trade names: Actiq, Duragesic, Sublimaze, others, AHFS/Drugs.com; Monograph: MedlinePlus, a605043; License data: EU EMA:
    by INN, US DailyMed: Fentanyl; Pregnancy category: AU: C; Dependence liability: High[1]; Routes of administration; Buccal, epidural, intramuscular, intrathecal, intravenous, sublingual, transdermal; Drug class: Opioid; ATC code: N01AH01 (WHO)
    N02AB03 (WHO); Legal status: AU: S8 (Controlled drug), BR: Class A1 (Narcotic drugs), CA: Schedule I, DE: Anlage III (Special prescription form required), UK: Class A, US: Schedule II, UN: Narcotic Schedule I, EU: Rx-only; Pharmacokinetic
    data: Bioavailability: 92% (transdermal), 65% (intranasal), 50% (buccal), 33% (ingestion), 100% (intramuscular), 80% (inhaled)100% (intravenous); Protein binding: 80–85%[2]; Metabolism: Liver, primarily by CYP3A4; Onset of action: 5 minutes[3];
    Elimination half-life: IV: 6 mins (T1/2 α), 1 hours (T1/2 β), 16 hours (T1/2 ɣ), Intranasal: 15-25 hours[4], Transdermal: 20–27 hours[4], Sublingual (single dose): 5–13.5 hours[4], Buccal: 3.2-6.4 hours[4]; Duration of action: IV: 30–60 minutes[3][5];
    Excretion: Mostly urinary (metabolites,
    < 10% unchanged drug)[4]; Identifiers: CAS Number: 437-38-7 ; PubChem CID: 3345; IUPHAR/BPS: 1626; DrugBank: DB00813 ; ChemSpider: 3228 ; UNII: UF599785JZ; KEGG: D00320 ; ChEBI: CHEBI:119915 ; ChEMBL: ChEMBL596 ; PDB ligand: 7V7 (PDBe, RCSB PDB); CompTox
    Dashboard (EPA): DTXSID9023049 ; ECHA InfoCard: 100.006.468 Medical uses Anesthesia[edit] Intravenous fentanyl is often used for anesthesia and as an analgesic.

  • [63] Wooden chest syndrome is unique to the most powerful opioids—which today comprise fentanyl and its analogs—while other less-powerful opioids like heroin produce mild
    rigidity of the respiratory muscles to a much lesser degree.

  • Because fentanyl is 50 to 100 times more potent than morphine, its primary clinical utility is in pain management for cancer patients and those recovering from painful surgical
    operations.

  • [58][59][60] The precise reason for sudden respiratory depression is unclear, but there are several hypotheses: • Saturation of the body fat compartment in people with rapid
    and profound body fat loss (people with cancer, cardiac or infection-induced cachexia can lose 80% of their body fat).

  • ), which can trigger the release and absorption of too much medication and cause potentially deadly complications.

  • [31] A fentanyl patient-controlled transdermal system (PCTS) is under development, which aims to allow patients to control administration of fentanyl through the skin to treat
    postoperative pain.

  • [37] Such forms are particularly useful for breakthrough cancer pain episodes, which are often rapid in onset, short in duration, and severe in intensity.

  • [49] The duration of action of fentanyl has sometimes been underestimated, leading to harm in a medical context.

  • [46] The technology consists of a “preprogrammed, self-contained drug-delivery system” that uses electrotransport technology to administer on-demand does of 40 µg of fentanyl
    hydrochloride over ten minutes.

  • [11] As of 2017, fentanyl was the most widely used synthetic opioid in medicine;[12] in 2019, it was the 278th most commonly prescribed medication in the United States, with
    more than a million prescriptions.

  • [57] After receiving a bolus dose of fentanyl, people can also experience paradoxical coughing, which is a phenomenon that is not well understood.

  • [83] The LD50 in humans is unknown,[84][85] but it is estimated that the lethal dose may be as low as 2 mg in some people depending on body size, tolerance, and past usage.

  • [123] It uses a medication delivery technology called BEMA (BioErodible MucoAdhesive), a small dissolvable polymer film containing various fentanyl doses applied to the inner
    lining of the cheek.

  • [57] This is much more profound in patients who have an already increased sympathetic drive, like patients who have high blood pressure or congestive heart failure.

  • “[91] The effects being reported in these cases, including rapid heartbeat, hyperventilation and chills, were not symptoms of a fentanyl overdose, and were more commonly associated
    with a panic attack.

  • [68] In July 2014, the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK issued a warning about the potential for life-threatening harm from accidental
    exposure to transdermal fentanyl patches, particularly in children,[69] and advised that they should be folded, with the adhesive side in, before being discarded.

  • [19] The patches work by slowly releasing fentanyl through the skin into the bloodstream over 48 to 72 hours, allowing for long-lasting pain management.

  • [121] Following the patch, a flavored lollipop of fentanyl citrate mixed with inert fillers was introduced in 1998 under the brand name of Actiq, becoming the first quick-acting
    formation of fentanyl for use with chronic breakthrough pain.

  • At high doses, the drug may act on the fetus to cause postnatal respiratory distress.

  • Because of fentanyl’s high lipid solubility, its effects are more localized than morphine, and some clinicians prefer to use morphine to get a wider spread of analgesia.

  • [89][90] A 2020 article from the Journal of Medical Toxicology stated that “the consensus of the scientific community remains that illness from unintentional exposures is
    extremely unlikely, because opioids are not efficiently absorbed through the skin and are unlikely to be carried in the air.

  • [95] A December 2020 HAN Advisory warned of: substantial increases in drug overdose deaths across the United States, primarily driven by rapid increases in overdose deaths
    involving… illicitly manufactured fentanyl; a concerning acceleration of the increase in drug overdose deaths, with the largest increase recorded from March 2020 to May 2020, coinciding with the implementation of widespread mitigation measures
    for the COVID-19 pandemic; significant increases in overdose deaths involving methamphetamine.

  • The Marquis Color test may also be used to detect the presence of fentanyl.

  • Another related complication of fentanyl overdoses includes the so-called wooden chest syndrome, which quickly induces complete respiratory failure by paralyzing the thoracic
    muscles, explained in more detail in the Muscle rigidity section below.

  • The different delivery systems used by different makers will also affect individual rates of absorption, and route of administration.

  • [32] Chronic pain[edit] It is also used in the management of chronic pain including cancer pain.

  • [55] Respiratory depression[edit] The most dangerous adverse effect of fentanyl is respiratory depression,[56] that is, decreased sensitivity to carbon dioxide leading to
    reduced rate of breathing, which can cause anoxic brain injury or death.

  • [22] Regional anesthesia[edit] Fentanyl is the most commonly used intrathecal opioid because its lipophilic profile allows a quick onset of action (5–10 min.)

  • [57] Wooden chest syndrome[edit] A prominent idiosyncratic adverse effect of fentanyl also includes a sudden onset of rigidity of the abdominal muscles and the diaphragm,
    which induces respiratory failure; this is seen with high doses and is known as wooden chest syndrome.

  • [65] In contexts of poly-substance use, blood fentanyl concentrations of approximately 7 ng/ml or greater have been associated with fatalities.

  • [106] Therapeutic effects[edit] • Pain relief: Primarily, fentanyl provides the relief of pain by acting on the brain and spinal μ-receptors.

  • Lozenges are more inclined to be used as the child is in control of sufficient dosage, in contrast to buccal tablets.

  • [111] A portion of the Janssen Method is shown below, in this instance, to synthesize a related opioid.

  • [70] In the US, fentanyl and fentanyl analogs caused over 29,000 deaths in 2017, a large increase over the previous four years.

  • Fentanyl is especially useful for concomitant treatment in palliative care settings where pain and shortness of breath are severe and need to be treated with high strength
    opioids.

  • [57] The chemical structure of fentanyl has been used as a basis in modern chemistry for the discovery and nomenclature of many new fentanyl analogues, sometimes called fentalogs.

  • [15] Fentanyl continues to fuel an epidemic of synthetic opioid drug overdose deaths in the United States.

  • [126] In the U.S., fentanyl is a Schedule II controlled substance per the Controlled Substance Act.

  • While Mexico and China are the primary source countries for fentanyl and fentanyl-related substances trafficked directly into the United States, India is emerging as a source
    for finished fentanyl powder and fentanyl precursor chemicals..[79][80] The United Kingdom illicit drug market is no longer reliant on China, as domestic fentanyl production is replacing imports.

  • Body temperature, skin type, amount of body fat, and placement of the patch can have major effects.

  • [57] • Sedation: Fentanyl produces sleep and drowsiness, as the dosage is increased, and can produce the δ-waves often seen in natural sleep on electroencephalogram.

  • [57] All of these factors allow it to rapidly cross cellular membranes, contributing to its quick effect in the body and the central nervous system.

 

Works Cited

[‘Bonewit-West K, Hunt SA, Applegate E (2012). Today’s Medical Assistant: Clinical and administrative procedures. Elsevier Health Sciences. p. 571. ISBN 978-1-4557-0150-6. Archived from the original on 10 January 2023. Retrieved 20 August 2019.
2. ^
Bista SR, Haywood A, Hardy J, Lobb M, Tapuni A, Norris R (March 2015). “Protein binding of fentanyl and its metabolite nor-fentanyl in human plasma, albumin and α-1 acid glycoprotein”. Xenobiotica; the Fate of Foreign Compounds in Biological Systems.
45 (3): 207–212. doi:10.3109/00498254.2014.971093. PMID 25314012. S2CID 21109003.
3. ^ Jump up to:a b Clinically Oriented Pharmacology (2nd ed.). Quick Review of Pharmacology. 2010. p. 172.
4. ^ Jump up to:a b c d e f g “Fentanyl, Fentanyl Citrate,
Fentanyl Hydrochloride”. The American Society of Health-System Pharmacists. Archived from the original on 14 December 2017. Retrieved 8 December 2017.
5. ^ “Guideline for administration of fentanyl for pain relief in labour” (PDF). RCP. Archived
(PDF) from the original on 4 March 2016. Retrieved 7 October 2015. Onset of action after I.V. administration of Fentanyl is 3–5 minutes; duration of action is 30–60 minutes.
6. ^ “Fentanyl”. Centers for Disease Control and Prevention. 7 October
2022. Retrieved 20 February 2023.
7. ^ Jump up to:a b c d Ramos-Matos CF, Bistas KG, Lopez-Ojeda W (2022). “Fentanyl”. StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 29083586. Retrieved 20 February 2023.
8. ^ “Fentanyl”. National
Institute on Drug Abuse. 21 December 2021. Retrieved 20 February 2023.
9. ^ Jump up to:a b “Fentanyl DrugFacts”. National Institute on Drug Abuse. 1 June 2021. Retrieved 20 February 2023.
10. ^ Stanley TH (April 1992). “The history and development
of the fentanyl series”. Journal of Pain and Symptom Management. 7 (3 Suppl): S3–S7. doi:10.1016/0885-3924(92)90047-L. PMID 1517629.
11. ^ Narcotic Drugs Estimated World Requirements for 2017 / Statistics for 2015 (PDF) (Report). New York: United
Nations. 2016. p. 40. ISBN 978-92-1-048163-2. Archived (PDF) from the original on 22 October 2017. Retrieved 14 December 2017.
12. ^ “Fentanyl and analogues”. LverTox. 16 October 2017. Archived from the original on 7 January 2017. Retrieved 14 December
2017.
13. ^ “The Top 300 of 2019”. ClinCalc. Archived from the original on 12 February 2021. Retrieved 7 October 2022.
14. ^ “Fentanyl Drug Usage Statistics”. ClinCalc. Archived from the original on 11 April 2020. Retrieved 7 October 2022.
15. ^
World Health Organization model list of essential medicines (22nd list (2021) ed.). Geneva, CH: World Health Organization. 2021. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
16. ^ Jump up to:a b c “Drug Overdose Death Rates”. National Institute on
Drug Abuse. 9 February 2023. Retrieved 20 February 2023.
17. ^ Jump up to:a b “Fentanyl overtakes heroin as the No. 1 opioid overdose killer”. www.cbsnews.com. 12 December 2018. Retrieved 20 February 2023.
18. ^ “U.S. Overdose Deaths In 2021 Increased
Half as Much as in 2020 – But Are Still Up 15%”. www.cdc.gov. 11 May 2022. Retrieved 5 May 2023.
19. ^ Jump up to:a b c d “Fentanyl”. www.dea.gov (factsheet). Drug Enforcement Agency. Archived from the original on 4 December 2018. Retrieved 4 December
2018.
20. ^ Falco G (8 January 2023). “China’s Role in Illicit Fentanyl Running Rampant on US Streets”. Congressman David Trone. Retrieved 20 February 2023.
21. ^ Brunton LL, Hilal-Dandan R, Knollmann BC (5 December 2017). Goodman & Gilman’s:
The pharmacological basis of therapeutics (13th ed.). New York, NY. ISBN 978-1-259-58473-2. OCLC 993810322.
22. ^ Jump up to:a b c d Gropper MA, Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Cohen LH, Leslie K (7 October 2019). Miller’s
Anesthesia (9th ed.). Philadelphia, PA. ISBN 978-0-323-61264-7. OCLC 1124935549.
23. ^ Godwin SA, Burton JH, Gerardo CJ, Hatten BW, Mace SE, Silvers SM, Fesmire FM (February 2014). “Clinical policy: procedural sedation and analgesia in the emergency
department”. Annals of Emergency Medicine. 63 (2): 247–58.e18. doi:10.1016/j.annemergmed.2013.10.015. PMID 24438649.
24. ^ Smith HS, Colson J, Sehgal N (April 2013). “An update of evaluation of intravenous sedation on diagnostic spinal injection
procedures”. Pain Physician. 16 (2 Suppl): SE217–SE228. doi:10.36076/ppj.2013/16/SE217. PMID 23615892. Archived from the original on 19 October 2015. Retrieved 1 May 2017.
25. ^ Gudin MA, López R, Estrada J, Ortigosa E (28 November 2011). “Neuraxial
blockade: Subarachnoid anesthesia”. Essentials of Regional Anesthesia. New York, NY: Springer New York. pp. 261–291. doi:10.1007/978-1-4614-1013-3_11. ISBN 978-1-4614-1012-6. Archived from the original on 8 February 2023. Retrieved 4 July 2021.
26. ^
Buggy D (1 July 2008). “Anesthesiology: Longnecker DE, Brown DL, Newman MF, Zapol WM, Editors, McGraw Hill, New York (2007) ISBN: 978-0-07-145984-6, 2278 pp, hardcover, $249 …” Regional Anesthesia and Pain Medicine (book review). BMJ Journals. 33
(4): 380. doi:10.1016/j.rapm.2008.03.003. ISSN 1098-7339. Archived from the original on 18 July 2021. Retrieved 18 July 2021.
27. ^ Bujedo BM (July 2014). “Current evidence for spinal opioid selection in postoperative pain”. The Korean Journal of
Pain. 27 (3): 200–209. doi:10.3344/kjp.2014.27.3.200. PMC 4099232. PMID 25031805.
28. ^ Jump up to:a b Moisés EC, de Barros Duarte L, de Carvalho Cavalli R, Lanchote VL, Duarte G, da Cunha SP (August 2005). “Pharmacokinetics and transplacental distribution
of fentanyl in epidural anesthesia for normal pregnant women”. European Journal of Clinical Pharmacology. 61 (7): 517–522. doi:10.1007/s00228-005-0967-9. PMID 16021436. S2CID 26065578.
29. ^ White LD, Hodsdon A, An GH, Thang C, Melhuish TM, Vlok
R (November 2019). “Induction opioids for caesarean section under general anaesthesia: a systematic review and meta-analysis of randomised controlled trials”. International Journal of Obstetric Anesthesia. 40: 4–13. doi:10.1016/j.ijoa.2019.04.007.
hdl:10072/416502. PMID 31230994. S2CID 181816438. Archived from the original on 22 May 2022. Retrieved 23 May 2022.
30. ^ Karlsen AP, Pedersen DM, Trautner S, Dahl JB, Hansen MS (June 2014). “Safety of intranasal fentanyl in the out-of-hospital
setting: a prospective observational study”. Annals of Emergency Medicine. 63 (6): 699–703. doi:10.1016/j.annemergmed.2013.10.025. PMID 24268523.
31. ^ Jump up to:a b Murphy A, O’Sullivan R, Wakai A, Grant TS, Barrett MJ, Cronin J, et al. (October
2014). “Intranasal fentanyl for the management of acute pain in children”. The Cochrane Database of Systematic Reviews. 10 (10): CD009942. doi:10.1002/14651858.CD009942.pub2. PMC 6544782. PMID 25300594.
32. ^ Coombes L, Burke K, Anderson AK (October
2017). “The use of rapid onset fentanyl in children and young people for breakthrough cancer pain”. Scandinavian Journal of Pain. 17 (1): 256–259. doi:10.1016/j.sjpain.2017.07.010. PMID 29229211. S2CID 8577873.
33. ^ Plante GE, VanItallie TB (October
2010). “Opioids for cancer pain: the challenge of optimizing treatment”. Metabolism. 59 (Suppl 1): S47–S52. doi:10.1016/j.metabol.2010.07.010. PMID 20837194.
34. ^ Jump up to:a b c Jasek W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna,
AU: Österreichischer Apothekerverlag. pp. 2621 ff. ISBN 978-3-85200-181-4.
35. ^ “Fentanyl patches (Durogesic) for chronic pain”. NPS Medicinewise. August 2006. Archived from the original on 7 December 2021. Retrieved 7 December 2021.
36. ^ Derry
S, Stannard C, Cole P, Wiffen PJ, Knaggs R, Aldington D, Moore RA (October 2016). “Fentanyl for neuropathic pain in adults”. The Cochrane Database of Systematic Reviews. 10 (5): CD011605. doi:10.1002/14651858.CD011605.pub2. PMC 6457928. PMID 27727431.
37. ^
Jump up to:a b c “Abstral sublingual tablets”. Summary of product characteristics. UK Electronic Medicines Compendium. May 2016. Archived from the original on 23 March 2017. Retrieved 1 May 2017.
38. ^ “Abstral (Fentanyl Sublingual Tablets for Breakthrough
Cancer Pain)”. P & T. 36 (2): 2–28. February 2011. PMC 3086091. PMID 21560267.
39. ^ Ward J, Laird B, Fallon M (2011). “The UK breakthrough cancer pain registry: Origin, methods and preliminary data”. BMJ Supportive & Palliative Care. 1: A24. doi:10.1136/bmjspcare-2011-000020.71.
S2CID 73185220.
40. ^ Roy PJ, Weltman M, Dember LM, Liebschutz J, Jhamb M (November 2020). “Pain management in patients with chronic kidney disease and end-stage kidney disease”. Current Opinion in Nephrology and Hypertension. 29 (6): 671–680. doi:10.1097/MNH.0000000000000646.
PMC 7753951. PMID 32941189.
41. ^ Aurilio C, Pace MC, Pota V, Sansone P, Barbarisi M, Grella E, Passavanti MB (May 2009). “Opioids switching with transdermal systems in chronic cancer pain”. Journal of Experimental & Clinical Cancer Research. 28
(1): 61. doi:10.1186/1756-9966-28-61. PMC 2684533. PMID 19422676.
42. ^ Minami S, Kijima T, Nakatani T, Yamamoto S, Ogata Y, Hirata H, et al. (8 October 2014). “Opioid switch from low dose of oral oxycodone to transdermal fentanyl matrix patch for
patients with stable thoracic malignancy-related pain”. BMC Palliative Care. 13 (1): 46. doi:10.1186/1472-684X-13-46. PMC 4195703. PMID 25313295.
43. ^ “Fentanyl (Transdermal Route) Precautions – Mayo Clinic”. www.mayoclinic.org. IBM Watson Health.
Archived from the original on 19 January 2023. Retrieved 19 January 2023.
44. ^ Jump up to:a b Shachtman N (10 September 2009). “Airborne EMTs Shave Seconds to Save Lives in Afghanistan”. Danger Room. Wired. Archived from the original on 6 July
2010. Retrieved 1 July 2010.
45. ^ van Dijk M, Mooren KJ, van den Berg JK, van Beurden-Moeskops WJ, Heller-Baan R, de Hosson SM, et al. (September 2021). “Opioids in patients with COPD and refractory dyspnea: literature review and design of a multicenter
double blind study of low dosed morphine and fentanyl (MoreFoRCOPD)”. BMC Pulmonary Medicine. 21 (1): 289. doi:10.1186/s12890-021-01647-8. PMC 8431258. PMID 34507574.
46. ^ Koo PJ (June 2005). “Postoperative pain management with a patient-controlled
transdermal delivery system for fentanyl”. American Journal of Health-System Pharmacy. 62 (11): 1171–1176. doi:10.1093/ajhp/62.11.1171. PMID 15914877. Archived from the original on 6 August 2018. Retrieved 28 March 2016.
47. ^ Chelly JE, Grass J,
Houseman TW, Minkowitz H, Pue A (February 2004). “The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial”. Anesthesia and Analgesia. 98 (2): 427–433. doi:10.1213/01.ANE.0000093314.13848.7E.
PMID 14742382. S2CID 24551941.
48. ^ Jump up to:a b “Fentanyl”. Drugs@FDA. FDA approved drug products. U.S. Food and Drug Administration (FDA). Archived from the original on 13 March 2013. Retrieved 4 September 2013.
49. ^ Jump up to:a b c Mayes
S, Ferrone M (December 2006). “Fentanyl HCl patient-controlled iontophoretic transdermal system for the management of acute postoperative pain”. The Annals of Pharmacotherapy. 40 (12): 2178–2186. doi:10.1345/aph.1H135. PMID 17164395. S2CID 24454875.
Archived from the original on 1 October 2012. Retrieved 17 December 2010.
50. ^ Smydo J (1979). “Delayed respiratory depression with fentanyl”. Anesthesia Progress. 26 (2): 47–48. PMC 2515983. PMID 295585.
51. ^ van Leeuwen L, Deen L, Helmers
JH (August 1981). “A comparison of alfentanil and fentanyl in short operations with special reference to their duration of action and postoperative respiratory depression”. Der Anaesthesist. 30 (8): 397–399. PMID 6116461.
52. ^ Brown DL (November
1985). “Postoperative analgesia following thoracotomy. Danger of delayed respiratory depression”. Chest. 88 (5): 779–780. doi:10.1378/chest.88.5.779. PMID 4053723. S2CID 1836168.
53. ^ Nilsson C, Rosberg B (June 1982). “Recurrence of respiratory
depression following neurolept analgesia”. Acta Anaesthesiologica Scandinavica. 26 (3): 240–241. doi:10.1111/j.1399-6576.1982.tb01762.x. PMID 7113633. S2CID 9232457.
54. ^ “Fentanyl patches: serious and fatal overdose from dosing errors, accidental
exposure, and inappropriate use”. Drug Safety Update. 2 (2): 2. September 2008. Archived from the original on 1 January 2015.
55. ^ “Fentanyl patch can be deadly to children”. U.S. Food and Drug Administration (FDA). 19 April 2012. Archived from
the original on 25 July 2013. Retrieved 30 July 2013.
56. ^ Topacoglu H, Karcioglu O, Cimrin AH, Arnold J (November 2005). “Respiratory arrest after low-dose fentanyl”. Annals of Saudi Medicine. 25 (6): 508–510. doi:10.5144/0256-4947.2005.508. PMC
6089740. PMID 16438465.
57. ^ Jump up to:a b c d e f g h i j k l m n o p q r s t Hemmings HC, Egan TD (19 October 2018). Pharmacology and Physiology for Anesthesia: Foundations and clinical application (2nd ed.). Philadelphia, PA. ISBN 978-0-323-56886-9.
OCLC 1063667873.
58. ^ McLoughlin R, McQuillan R (September 1997). “Transdermal fentanyl and respiratory depression”. Palliative Medicine. 11 (5): 419. doi:10.1177/026921639701100515. PMID 9472602.
59. ^ Bülow HH, Linnemann M, Berg H, Lang-Jensen
T, LaCour S, Jonsson T (August 1995). “Respiratory changes during treatment of postoperative pain with high dose transdermal fentanyl”. Acta Anaesthesiologica Scandinavica. 39 (6): 835–839. doi:10.1111/j.1399-6576.1995.tb04180.x. PMID 7484044. S2CID
22781991.
60. ^ Regnard C, Pelham A (December 2003). “Severe respiratory depression and sedation with transdermal fentanyl: four case studies”. Palliative Medicine. 17 (8): 714–716. doi:10.1191/0269216303pm838cr. PMID 14694924. S2CID 32985050.
61. ^
Chambers D, Huang CL, Matthews G (1 September 2019) [2015]. “Section 2 – Respiratory physiology: Chapter 25: Anaesthesia and the lung”. Basic Physiology for Anaesthetists. Cambridge medicine (2nd ed.). Cambridge, UK: Cambridge University Press. pp.
107–110. doi:10.1017/CBO9781139226394.027. ISBN 978-1-108-46399-7. OCLC 1088737571. Archived from the original on 8 February 2023. Retrieved 9 August 2021 – via Google Books.
62. ^ Burns G, DeRienz RT, Baker DD, Casavant M, Spiller HA (June 2016).
Seifert SA, Buckley N, Seger D, Thomas S, Caravati EM (eds.). “Could chest wall rigidity be a factor in rapid death from illicit fentanyl abuse?”. Clinical Toxicology. McLean, VA: American Academy of Clinical Toxicology (AACT) / European Association
of Poisons Centres and Clinical Toxicologist / Taylor & Francis. 54 (5): 420–423. doi:10.3109/15563650.2016.1157722. OCLC 8175535. PMID 26999038. S2CID 23149685.
63. ^ Jump up to:a b Torralva R, Janowsky A (November 2019). Trew KD, Dodenhoff R,
Vore M, Siuciak JA, Perry J, Wood C, Blumer J (eds.). “Noradrenergic Mechanisms in Fentanyl-Mediated Rapid Death Explain Failure of Naloxone in the Opioid Crisis” (PDF). The Journal of Pharmacology and Experimental Therapeutics. Rockville, Maryland,
United States of America: American Society for Pharmacology and Experimental Therapeutics. 371 (2): 453–475. doi:10.1124/jpet.119.258566. LCCN sf80000806. OCLC 1606914. PMC 6863461. PMID 31492824. Archived from the original (PDF) on 9 March 2020.
Retrieved 9 August 2021.
64. ^ Petrou I (1 September 2016). Levine L, Tan TQ, Shippoli J (eds.). “Chest wall rigidity in fentanyl abuse: illicit fentanyl could be a major factor in sudden onset of this potentially lethal adverse event”. Contemporary
Pedriatics. Cranbury, New Jersey, United States of America: Intellisphere, LLC./ MJH Life Sciences (Multimedia Medical LLC). 33 (9). ISSN 8750-0507. OCLC 10956598. Retrieved 9 August 2021 – via Gale Academic OneFile.[permanent dead link]
65. ^ Cheema
E, McGuinness K, Hadi MA, Paudyal V, Elnaem MH, Alhifany AA, et al. (7 December 2020). “Causes, Nature and Toxicology of Fentanyl-Associated Deaths: A Systematic Review of Deaths Reported in Peer-Reviewed Literature”. Journal of Pain Research. 13:
3281–3294. doi:10.2147/JPR.S280462. PMC 7732170. PMID 33324089.
66. ^ “Fentanyl drug profile”. European Monitoring Centre for Drugs and Drug Addiction. Archived from the original on 10 September 2022. Retrieved 10 September 2022.
67. ^ “Fatalities
caused by novel opioids: a review” Olaf H. Drummer 2018.
68. ^ “Narcan (Naloxone hydrochloride injection)”. RxList. Side effects, warnings, uses. Archived from the original on 24 October 2019. Retrieved 3 March 2020.
69. ^ “Fentanyl patches warning”.
Pharmaceutical Journal. Archived from the original on 8 April 2016. Retrieved 28 March 2016.
70. ^ “MHRA warns about fentanyl patches after children exposed”. Pharmaceutical Journal. Archived from the original on 9 April 2016. Retrieved 28 March
2016.
71. ^ Katz J (2 September 2017). “The first count of Fentanyl deaths in 2016 – up 540% in three years”. The New York Times. Archived from the original on 4 September 2017. Retrieved 4 September 2017.
72. ^ Overdose Death Rates (Report).
National Institute on Drug Abuse (NIDA). 29 January 2021. Archived from the original on 28 November 2015. Retrieved 22 November 2017.
73. ^ “Reported law enforcement encounters testing positive for Fentanyl increase across U.S.” (Press release).
U.S. Centers for Disease Control and Prevention (CDC). 9 August 2021. Archived from the original on 2 March 2022. Retrieved 3 March 2022.
74. ^ “Fentanyl Overdose”. Huffington Post. 20 May 2016. Archived from the original on 5 June 2016. Retrieved
4 June 2016.
75. ^ Fentanyl-detected in illicit drug overdose deaths, January 1, 2012 to April 30, 2016 (PDF) (Report). British Columbia Coroners Service. Archived from the original (PDF) on 25 June 2016. Retrieved 9 June 2016.
76. ^ “Fentanyl
contributed to hundreds of deaths in Canada so far this year”. globalnews.ca. 31 July 2017. Archived from the original on 14 September 2017. Retrieved 14 September 2017.
77. ^ Scaccia A (9 October 2018). “How Fentanyl is contaminating America’s
cocaine supply”. Rolling Stone. Archived from the original on 6 November 2018. Retrieved 5 November 2018.
78. ^ Daly M (30 July 2019). “Exclusive data reveals just how often Fentanyl is in cocaine”. Vice. Archived from the original on 24 January
2020. Retrieved 9 January 2020.
79. ^ Chang A (3 December 2018). “What it means for the U.S. that China will label Fentanyl as ‘a controlled substance'”. All Things Considered. NPR. Archived from the original on 6 December 2018. Retrieved 6 December
2018.
80. ^ “Fentanyl Flow to the United States” (PDF). www.dea.gov. Government Intelligence Report. January 2020. Retrieved 24 July 2019.
81. ^ “Coronavirus triggers UK shortage of illicit drugs”. Society. The Guardian. 12 April 2020. Archived
from the original on 9 May 2020. Retrieved 23 April 2020.
82. ^ “Fentanyl citrate injection, USP” (PDF). U.S. Food and Drug Administration (FDA). Archived (PDF) from the original on 31 October 2020. Retrieved 3 March 2019.
83. ^ Yadav SK, Maurya
CK, Gupta PK, Jain AK, Ganesan K, Bhattacharya R (June 2014). “Synthesis and biological evaluation of some novel 1-substituted fentanyl analogs in Swiss albino mice”. Interdisciplinary Toxicology. 7 (2): 93–102. doi:10.2478/intox-2014-0013. PMC 4427721.
PMID 26109885.
84. ^ “Fentanyl”. Drugbank. Archived from the original on 11 July 2017. Retrieved 18 January 2019.
85. ^ Vardanyan RS, Hruby VJ (March 2014). “Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical
applications”. Future Medicinal Chemistry. 6 (4): 385–412. doi:10.4155/fmc.13.215. PMC 4137794. PMID 24635521.
86. ^ “Facts about Fentanyl”. Drug Enforcement Administration. Archived from the original on 29 June 2022. Retrieved 29 June 2022.
87. ^
Ross C (9 August 2017). “Are people really falling ill from touching fentanyl? In most cases, scientists say no”. Stat News. Archived from the original on 7 August 2021. Retrieved 7 August 2021.
88. ^ Bump P (15 July 2022). “Analysis | Why you’re
hearing so much about fentanyl these days”. The Washington Post. Archived from the original on 15 July 2022. Retrieved 16 September 2022.
89. ^ “Position Statement on Fentanyl Exposure”. American College of Medical Toxicology (Press release). 18
July 2017. Archived from the original on 31 August 2018.
90. ^ Thors L, Öberg L, Forsberg E, Wigenstam E, Larsson A, Bucht A (September 2020). “Skin penetration and decontamination efficacy following human skin exposure to fentanyl”. Toxicology
in Vitro. 67: 104914. doi:10.1016/j.tiv.2020.104914. PMID 32540164. S2CID 219704174.
91. ^ Herman PA, Brenner DS, Dandorf S, Kemp S, Kroll B, Trebach J, et al. (April 2020). “Media Reports of Unintentional Opioid Exposure of Public Safety First
Responders in North America”. Journal of Medical Toxicology. 16 (2): 112–115. doi:10.1007/s13181-020-00762-y. PMC 7099103. PMID 32096007.
92. ^ “State Departments Issue Guidance Around Fentanyl Exposure”. www.tn.gov. Archived from the original on
13 September 2022. Retrieved 16 September 2022.
93. ^ Del Pozo B, Sightes E, Kang S, Goulka J, Ray B, Beletsky LA (November 2021). “Can touch this: training to correct police officer beliefs about overdose from incidental contact with fentanyl”.
Health & Justice. 9 (1): 34. doi:10.1186/s40352-021-00163-5. PMC 8612110. PMID 34817717.Accessed 5 April 2023.
94. ^ “Increases in Fentanyl Drug Confiscations and Fentanyl-related Overdose Fatalities HAN 00384”. Health Alert Network. U.S. Centers
for Disease Control and Preventation. 15 October 2015. Archived from the original on 21 December 2022. Retrieved 21 December 2022.
95. ^ “Rising Numbers of Deaths Involving Fentanyl and Fentanyl Analogs, Including Carfentanil, and Increased Usage
and Mixing with Non-opioids – 00413”. Health Alert Network (HAN). U.S. Centers for Disease Control and Preventation. 11 July 2018. Archived from the original on 21 December 2022. Retrieved 21 December 2022.
96. ^ Jump up to:a b c “Increase in Fatal
Drug Overdoses Across the United States Driven by Synthetic Opioids Before and During the COVID-19 Pandemic – HAN 00438 – Health Alert Network Advisory”. emergency.cdc.gov. U.S. Centers for Disease Control and Prevention. 17 December 2020. Archived
from the original on 20 December 2022. Retrieved 21 December 2022.
97. ^ “Fentanyl | CDC’s Response to the Opioid Overdose Epidemic | CDC”. U.S. Centers for Disease Control and Prevention (CDC). 2 October 2021. Archived from the original on 28
April 2022. Retrieved 27 April 2022.
98. ^ “One Pill Can Kill”. www.dea.gov. Archived from the original on 26 April 2022. Retrieved 27 April 2022.
99. ^ “Drug Free NJ – Home”. drugfreenj.org. Archived from the original on 6 May 2022. Retrieved
27 April 2022.
100. ^ Jump up to:a b c Yaksh T, Wallace M (2011). Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. New York, NY: McGraw-Hill. ISBN 978-0-07-162442-8.
101. ^ Katzung BG (2017). Basic & Clinical Pharmacology (14th
ed.). New York, NY. ISBN 978-1-259-64115-2. OCLC 1015240036.
102. ^ “Commission on Narcotic Drugs takes decisive step to help prevent deadly fentanyl overdoses” (Press release). Commission on Narcotic Drugs, United Nations Office on Drugs and Crime.
16 March 2017. Archived from the original on 20 March 2017. Retrieved 19 March 2017.
103. ^ Raynor K, Kong H, Chen Y, Yasuda K, Yu L, Bell GI, Reisine T (February 1994). “Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid
receptors”. Molecular Pharmacology. 45 (2): 330–334. PMID 8114680.
104. ^ Jump up to:a b Suzuki J, El-Haddad S (February 2017). “A review: Fentanyl and non-pharmaceutical fentanyls”. Drug and Alcohol Dependence. 171: 107–116. doi:10.1016/j.drugalcdep.2016.11.033.
PMID 28068563.
105. ^ “Fentanyl”. www.drugbank.ca. Archived from the original on 11 July 2017. Retrieved 18 January 2019.
106. ^ Jump up to:a b Butterworth IV JV, Wasnick JD, MacKey DC (21 August 2018). Morgan & Mikhail’s Clinical Anesthesiology
(6th ed.). New York, NY. ISBN 978-1-259-83442-4. OCLC 1039081701.
107. ^ Baselt, R. (2017) Disposition of Toxic Drugs and Chemicals in Man, 11th edition, Biomedical Publications, Foster City, CA, pp. 883–886.
108. ^ Vandergrift GW, Hessels AJ,
Palaty J, Krogh ET, Gill CG (April 2018). “Paper spray mass spectrometry for the direct, semi-quantitative measurement of fentanyl and norfentanyl in complex matrices”. Clinical Biochemistry. 54: 106–111. doi:10.1016/j.clinbiochem.2018.02.005. PMID
29432758.
109. ^ Vandergrift GW, Hessels AJ, Palaty J, Krogh ET, Gill CG (April 2018). “Paper spray mass spectrometry for the direct, semi-quantitative measurement of fentanyl and norfentanyl in complex matrices”. Clinical Biochemistry. 54: 106–111.
doi:10.1016/j.clinbiochem.2018.02.005. PMID 29432758. 10.25316/IR-4343.
110. ^ Vardanyan RS, Hruby VJ (March 2014). “Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications”. Future Medicinal
Chemistry. 6 (4): 385–412. doi:10.4155/fmc.13.215. PMC 4137794. PMID 24635521.
111. ^ “Fentanyl Synthesis”. GPTA India. 18 June 2020. Archived from the original on 28 December 2022.
112. ^ “Synthesis of Fentanyl”. Rhodium. Seigfried. Archived
from the original on 5 August 2022. Retrieved 24 January 2023.
113. ^ “Designation of Benzylfentanyl and 4-Anilinopiperidine, Precursor Chemicals Used in the Illicit Manufacture of Fentanyl, as List I Chemicals”. federalregister.gov. DEA. 15 April
2020. Archived from the original on 5 November 2021. Retrieved 28 January 2023.
114. ^ Gupta P (9 November 2005). “A Convenient One-Pot Synthesis of Fenta4nyl”. ChemInform. 36 (49). doi:10.1002/chin.200549130. Archived from the original on 24 January
2023. Retrieved 24 January 2023.
115. ^ “Fentanyl Profiling Program Report” (PDF). Special Testing and Research Laboratory. Drug Enforcement Administration. p. 1-2. Archived (PDF) from the original on 25 January 2023. Retrieved 25 January 2023.
116. ^
Suh YG, Cho KH, Shin DY (February 1998). “Total synthesis of fentanyl”. Archives of Pharmacal Research. 21 (1): 70–2. doi:10.1007/BF03216756. PMID 9875518. S2CID 31408546.
117. ^ López-Muñoz F, Alamo C (April 2009). “The consolidation of neuroleptic
therapy: Janssen, the discovery of haloperidol and its introduction into clinical practice”. Brain Research Bulletin. 79 (2): 130–141. doi:10.1016/j.brainresbull.2009.01.005. PMID 19186209. S2CID 7720401.
118. ^ Black J (March 2005). “A personal
perspective on Dr. Paul Janssen” (PDF). Journal of Medicinal Chemistry. 48 (6): 1687–1688. doi:10.1021/jm040195b. PMID 15771410. Archived from the original (PDF) on 10 October 2007.
119. ^ “Fentanyl citrate injection, solution [Hospira, Inc.]”.
Daily Med (Dailymed.nlm.nih.gov). U.S. National Institutes of Health. Archived from the original on 21 March 2010. Retrieved 31 March 2022.
120. ^ “Fentanyl (sublimaze)”. Clinical Pharmacology and Therapeutics. 9 (5): 704–706. September 1968. doi:10.1002/cpt196895704.
PMID 5676808. S2CID 9743189.
121. ^ Mandal A (11 April 2010). SRobertson S (ed.). “Fentanyl History”. News-Medical.net. AZoNetwork. Archived from the original on 27 January 2023. Retrieved 27 January 2023.
122. ^ “ACTIQ® (fentanyl citrate) oral
transmucosal lozenge (1968 version revised in 2011)” (PDF). U.S. Food and Drug Administration (FDA). December 2011. Archived (PDF) from the original on 10 February 2017. Retrieved 26 December 2017.
123. ^ Jump up to:a b “Questions and Answers about
Onsolis (fentanyl buccal soluble film)”. U.S. Food and Drug Administration (FDA). 16 July 2009. Archived from the original on 22 July 2017. Retrieved 26 December 2017.
124. ^ “2022 Aggregate Production Quota History for Selected Substances” (PDF).
Archived (PDF) from the original on 19 January 2023.
125. ^ “Misuse of Drugs Act 1971”. Archived from the original on 14 November 2012. Retrieved 22 March 2017.
126. ^ “Opiumwet” [Opium Act]. Ministerie van Binnenlandse Zaken en Koninkrijksrelaties
[Ministry of the Interior and Kingdom Relations] (in Dutch). Archived from the original on 19 January 2023. Retrieved 19 January 2023.
127. ^ “RelayHealth’s pharmacy connectivity network and reach, aligned with McKesson Specialty Care Solutions’
REMS expertise, expands cancer patients’ access to pain therapy”. Atlanta. 20 January 2011. Archived from the original on 29 January 2016. Retrieved 5 November 2015.
128. ^ Shelley S (22 April 2011). “With a few stumbles, REMS begins to hit its
atride”. Pharmaceutical Commerce. Archived from the original on 29 January 2016. Retrieved 5 November 2015.
129. ^ “Procedures, programs and drugs that require precertification: Participating provider precertification list” (PDF). Aetna Inc. Archived
from the original (PDF) on 9 July 2021. Retrieved 4 July 2021.
130. ^ “Notice regarding precertification requirement” (PDF). BlueCross BlueShield of Arizona. 5 November 2007. Archived from the original (PDF) on 28 August 2008.
131. ^ “Medications
requiring precertification”. Oxford Health Plans. Archived from the original on 15 October 2006.
132. ^ “Canada’s Controlled Drugs and Substances Act”. laws.justice.gc.ca. Archived from the original on 28 September 2018. Retrieved 8 September 2018.
133. ^
Naylor A (6 January 2020). “What we can learn from a tiny Baltic country’s two-decade Fentanyl crisis”. Vice. Archived from the original on 8 March 2021. Retrieved 31 January 2021.
134. ^ Townsend M (1 December 2018). “Dark web dealers voluntarily
ban deadly fentanyl”. The Guardian. Archived from the original on 2 December 2018. Retrieved 3 December 2018.
135. ^ “As fentanyl crisis grows, U.S.-Mexico divide deepens”. www.washingtonpost.com. Retrieved 1 May 2023.
136. ^ Ducharme J (3 December
2018). “China has promised to crack down on Fentanyl. Here’s what that could mean for overdose deaths in the U.S.” Time. Archived from the original on 6 December 2018. Retrieved 6 December 2018.
137. ^ Boddiger D (August 2006). “Fentanyl-laced
street drugs “kill hundreds””. Lancet. 368 (9535): 569–570. doi:10.1016/S0140-6736(06)69181-2. PMID 16909503. S2CID 39788629.
138. ^ “Synthetic drug fentanyl causes overdose boom in Estonia”. BBC News. 30 March 2012. Archived from the original on
28 July 2018. Retrieved 21 June 2018.
139. ^ Jump up to:a b “Fentanyl” (PDF). U.S. Drug Enforcement Administration. March 2015. Archived (PDF) from the original on 11 June 2016. Retrieved 2 June 2016.
140. ^ Jump up to:a b “Mims B (11 November
2004). “Painkiller is topic of inquiry”. The Salt Lake Tribune. Archived from the original on 24 December 2007.
141. ^ Mars SG, Rosenblum D, Ciccarone D (May 2019). “Illicit fentanyls in the opioid street market: desired or imposed?”. Addiction.
114 (5): 774–780. doi:10.1111/add.14474. PMC 6548693. PMID 30512204.
142. ^ Centers for Disease Control Prevention (CDC) (July 2008). “Nonpharmaceutical fentanyl-related deaths–multiple states, April 2005-March 2007” (PDF). MMWR Morb Mortal Wkly
Rep. 57 (29): 793–6. PMID 18650786. Archived (PDF) from the original on 2 December 2022. Retrieved 2 December 2022.
143. ^ “DEA Microgram Bulletin”. Office of Forensic Sciences. Washington, DC: U.S. Drug Enforcement Administration. June 2006. Archived
from the original on 21 July 2009. Retrieved 22 June 2009.
144. ^ Tanner C (2016). “Thousands of fentanyl pills confiscated in Utah drug raid”. The Salt Lake Tribune. Archived from the original on 24 November 2016. Retrieved 23 November 2016.
145. ^
“Cottonwood Heights drug bust one of the largest in Utah history”. fox13now.com. 22 November 2016. Archived from the original on 23 November 2016. Retrieved 23 November 2016.
146. ^ “U.S. border officers make largest-ever fentanyl bust: 254 pounds
hidden under cucumbers”. The Washington Post. 31 January 2019. Archived from the original on 8 June 2020. Retrieved 8 June 2020.
147. ^ Jump up to:a b “List of Schedule I Drugs”. U.S. Department of Justice. Archived from the original on 9 January
2010.
148. ^ Kram TC, Cooper DA, Allen AC (October 1981). “Behind the identification of China White”. Analytical Chemistry. 53 (12): 1379A–1386A. doi:10.1021/ac00235a003. PMID 7294353.
149. ^ Van Bever WF, Niemegeers CJ, Janssen PA (October 1974).
“Synthetic analgesics. Synthesis and pharmacology of the diastereoisomers of N-(3-methyl-1-(2-phenylethyl)-4-piperidyl)-N-phenylpropanamide and N-(3-methyl-1-(1-methyl-2-phenylethyl)-4-piperidyl)-N-phenylpropanamide”. Journal of Medicinal Chemistry.
17 (10): 1047–1051. doi:10.1021/jm00256a003. PMID 4420811.
150. ^ CDC Health Alert Network (20 June 2013). “Recommendations for Laboratory Testing for Acetyl Fentanyl and Patient Evaluation and Treatment for Overdose with Synthetic Opioids”. U.S.
Centers for Disease Control and Prevention (CDC). Archived from the original on 24 June 2013. Retrieved 20 June 2013.
151. ^ Characteristics of Fentanyl overdose — Massachusetts, 2014–2016 (Report). U.S. Centers for Disease Control and Prevention
(CDC). 14 April 2017.
152. ^ Burgmann T (6 August 2015). “Lethal fentanyl profiting gangs in Western Canada while deaths climb”. CTV Photo credit: https://www.flickr.com/photos/nahidv/14116780333/’]