China
Africa
Explore chapters and articles related to this topic
Toxicology
Published in John M. Wayne, Cynthia A. Schandl, S. Erin Presnell, Forensic Pathology Review, 2017
John M. Wayne, Cynthia A. Schandl, S. Erin Presnell
Answer A is incorrect. Acetyl fentanyl is not a metabolite of fentanyl, but another synthetic opioid that is an analog of fentanyl. Norfentanyl is a major metabolite of fentanyl created by piperidine N-dealkylation by the liver.
Development of palliative medicine in the United Kingdom and Ireland
Published in Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita, Textbook of Palliative Medicine and Supportive Care, 2015
Fentanyl is predominantly metabolized in the liver and produces phenylacetic acid, norfentanyl, and small amounts of the active metabolite, p-hydroxy (phenethyl)fentanyl 103 (see Table 43.1). It is highly lipid soluble, which facilitates rapid transfer across the blood-brain barrier and into the central nervous system (CNS). This is reflected in the half-life for equilibration between the plasma and the CSF of approximately 5 min. 104
Pharmacology of opioids
Published in Pamela E. Macintyre, Stephan A. Schug, Acute Pain Management, 2014
Pamela E. Macintyre, Stephan A. Schug
It is primarily metabolized in the liver by CYP3A4 to inactive norfentanyl and it is therefore a good choice of opioid in patients with renal impairment (Grape et al., 2010). It may be that genetic variability in the activity of CYP3A4 can alter the amount of fentanyl required for acute pain management (Smith and Muralidharan, 2012), but any differences will be difficult to detect in general populations given the already large inter-patient variation in the dose of opioids required for pain relief.
A potential paradigm shift in opioid crisis management: The role of pharmacogenomics
Published in The World Journal of Biological Psychiatry, 2022
David Eapen-John, Ayeshah G. Mohiuddin, James L. Kennedy
Fentanyl is most extensively metabolised into the inactive metabolite norfentanyl via an N-dealkylation process, performed by CYP3A4 and CYP3A5 (Zhang et al. 2011; Barratt et al. 2014; Kuip et al. 2017; Saiz-Rodríguez et al. 2019; Gerhard et al. 2020). The most studied polymorphism in CYP-mediated fentanyl metabolism is the CYP3A5*3 allele. This produces an inactive copy of the CYP3A5 enzyme which has been shown to reduce fentanyl clearance when compared to the wild-type allele (CYP3A5*1) by 30–50% (Zhang et al. 2011; Takashina et al. 2012; Tanaka et al. 2014). Many researchers have observed an increased incidence of central adverse effects and up to a 2-fold higher normalised plasma concentration of fentanyl in individuals with the *3/*3 genotype when compared to other genotypes (Zhang et al. 2011; Takashina et al. 2012; Tanaka et al. 2014). Interestingly, CYP3A5*3 represents population diversity where allele frequencies range from 0.14 in sub-Saharan Africans to >0.95 in European populations (Ncbi 2021). Furthermore, the occurrence of CYP3A5*3/*3 homozygous genotype, varies in African populations, from as low as 0 to as high as 53% (Bains et al. 2013). Overall, there is significant evidence that the 3A5*3 polymorphism increases exposure to fentanyl.
Wastewater analysis for psychoactive substances at music festivals across New South Wales, Australia in 2019–2020
Published in Clinical Toxicology, 2022
Jonathan Brett, Krista J. Siefried, Amy Healey, Mary Ellen Harrod, Erica Franklin, Monica J. Barratt, Jem Masters, Lynn Nguyen, Santosh Adiraju, Cobus Gerber
Of the approximately 74 non-benzodiazepine compounds that were screened for, 31 were detected in the samples collected. Some compounds were detected at all festivals and found in more than 80% of samples at each festival including: amphetamine; cocaine; ketamine; MDMA and MDA (Table 2). Other compounds were detected at all festivals but had substantial variability in the proportion of samples testing positive at each festival including: codeine (40–100%); methamphetamine (18–100%); and methylone (53–100%). Finally, there were some compounds that were not detected at all festivals; ethylone, methadone, methcathinone were detected at 4/6 (67%) festivals sampled and buprenorphine, mephedrone, morphine, n-ethylpentylone, and noroxycodone, an oxycodone metabolite at less than half of festivals. For festivals where mephedrone was detected (3/6), it was detected in between 68% and 100% of samples from those festivals. Norfentanyl, a fentanyl metabolite, was detected in one sample from each of two festivals. There were no significant differences in detection frequencies between male and female toilets and so stratified results were not reported here.
Sentanyl: a comparison of blood fentanyl concentrations and naloxone dosing after non-fatal overdose
Published in Clinical Toxicology, 2022
Alex J. Krotulski, Brittany P. Chapman, Sarah J. Marks, Sam T. Ontiveros, Katharine Devin-Holcombe, Melissa F. Fogarty, Hai Trieu, Barry K. Logan, Roland C. Merchant, Kavita M. Babu
Of the 20 blood specimens, fentanyl was present in 19 (95.0%). The mean (±SD) and median concentrations (excluding two cases in which fentanyl ≤0.1 ng/mL) were 6.2 (±5.4) and 3.6 ng/mL, respectively [range: 0.32–19 ng/mL]. Norfentanyl, the major inactive metabolite of fentanyl, was detected in 15 of the 19 blood specimens in which fentanyl was detected. 4-ANPP (despropionylfentanyl), a contaminant of fentanyl synthesis and minor inactive metabolite of fentanyl, was found in 4 of 19 blood specimens. In 11 participants, fentanyl and its metabolites were the only opioids identified. Only 6 (37.5%) of the 16 participants who reported “heroin” use had heroin metabolites including 6-MAM, morphine, and/or codeine detected. In the single participant for whom fentanyl was not detected, 6-MAM and morphine were identified.