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Pharmacology of Opioids
Published in Pamela E. Macintyre, Stephan A. Schug, Acute Pain Management, 2021
Pamela E. Macintyre, Stephan A. Schug
As the main effects of most opioids are mediated via their activity at the μ-opioid receptor, both their analgesic effect and the spectrum of possible adverse effects are very similar. The adverse effects reviewed in the next section relate to the use of opioids in the acute pain setting in the short-term as well as in the longer-term.
Pharmacogenetics of opioid addiction: Are they relevant to young people?
Published in Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros, Substance Misuse and Young People, 2019
Fleur Davey, Alexander Baldacchino
Genetic testing already has important clinical applications in preventing chronic relapsing diseases. Screening for deleterious variants in BRCA1/2 associated with increased risk of hereditary breast and ovarian cancer is already being offered to young women. However, implementation of genetic testing in prevention programmes for opiate addiction can be an attractive but also challenging prospect. Recipients of a SNP that corresponds to an amino acid change of Asn40Asp in the N-terminus of the µ-opioid receptor have a threefold greater binding of beta-endorphin. This makes morphine, methadone and a synthetic opioid peptide DAMGO less potent at inhibiting adenyl cyclase activity for receptors with the Asp-40 variant. The presence of this variant influences the diverse physiological functions under modulation by the μ-opioid receptor, such as stress responsivity and pain perception (Bond et al., 1998). Although we are still far from having sufficiently powerful genetic predictors for addiction, the example cited above could be useful to illustrate how clinicians could inform young people carrying the loss-of-function variant that they are at elevated risk of opioid dependence.
Basic psychopharmacology
Published in Jonathan P Rogers, Cheryl CY Leung, Timothy RJ Nicholson, Pocket Prescriber Psychiatry, 2019
Jonathan P Rogers, Cheryl CY Leung, Timothy RJ Nicholson
Classic opioids (such as morphine, diamorphine and methadone) are agonists at the μ-opioid receptor. Naloxone and naltrexone are antagonists at all three opioid receptors, with highest affinity for the μ-receptor. Buprenorphine is a μ partial agonist and a δ/κ antagonist. Nalmefene is a μ/δ antagonist and a κ partial agonist.
Appropriate use of tapentadol: focus on the optimal tapering strategy
Published in Current Medical Research and Opinion, 2023
Renato Vellucci, Diego Fornasari
The therapeutic pain-relieving effects of classical opioids are primarily mediated via activation of mu-opioid receptors, a component of a major afferent nociceptive pathway3,12,24,25. Unfortunately, mu-opioid receptor agonism is also the mechanism which produces the major adverse effects of classical opioids (e.g. constipation and respiratory depression)3,12,24,25. Atypical opioids, such as tapentadol, combine multiple mechanisms of analgesic action, including mu-opioid receptor agonism along with other mechanisms targeting alternative pain (patho) physiologies3,24. The pharmacologic effect is only partially due to conventional opioid mechanisms, and sparing mu receptors may limit the appearance of certain adverse effects such as gastrointestinal toxicities. Clinicians should be aware of the specific advantages and disadvantages of different opioids when selecting between them based on the patient’s profile. For example, tapentadol could be selected over other opioids because of its fewer gastrointestinal adverse effects and lower risk of drug–drug interactions6.
Sucrose drinking mimics effects of nucleus accumbens µ-opioid receptor stimulation on fat intake and brain c-Fos-expression
Published in Nutritional Neuroscience, 2022
L.L. Koekkoek, A. Masís-Vargas, T. Kool, L. Eggels, L.L. van der Gun, K. Lamuadni, M. Slomp, C. Diepenbroek, A. Kalsbeek, S.E. la Fleur
While the effects of intra-NAC infusion of DAMGO on fat intake have been well described [9–13], we now show for the first time that a prior bolus of sucrose drinking diminishes this DAMGO-induced increase in fat intake. Sucrose has known analgesic effects [21], which are thought to be due to the release of endogenous opioids [22]. Indeed, sucrose drinking has been found to trigger endogenous opioid release in multiple brain areas, including the dorsal striatum [23] and the NAC [15]. Remarkably, the binding of the endogenous opioids β-endorphin and met-enkephalin can cause the internalization of the μ-opioid receptor [24]. We, therefore, hypothesize that due to the release of endogenous opioids in the NAC upon sucrose drinking and subsequent internalization of the μ-opioid receptor, fewer μ-opioid receptors are available once DAMGO is infused. This reduced availability prevents the increased fat intake that is typically observed upon intra-NAC DAMGO infusion.
Opioid epidemic: lessons learned and updated recommendations for misuse involving prescription versus non-prescription opioids
Published in Expert Review of Clinical Pharmacology, 2022
Ajda Bedene, Albert Dahan, Frits R. Rosendaal, Eveline L.A. van Dorp
Cellular changes in response to opioid use begin immediately after the initial exposure. Opioids bind to opioid receptors, which are G-protein-coupled receptors, that upon activation regulate many downstream biochemical pathways [71]. Both cytoplasmic G-protein subunits of the receptor interact with several cellular-effector mechanisms, inhibiting adenylyl cyclase and voltage-gated calcium channels, and stimulating inwardly rectifying potassium channels (GIRKs) and phospholipase C beta (PLCB) [72,73]. Ultimately, these biochemical changes are inhibitory on a cellular level, but can produce diverse effects based on receptor location (i.e. at pre- or post-synaptic neurons) [72,74]. Although four different opioid receptor subtypes have been identified, the analgesic and adverse actions of morphine (and morphine-like agonists) require predominantly activation of the mu-opioid receptor (MOR) subtype, as demonstrated in knockout mice models [75].