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Acta Obstetricia Et Gynecologica... Aug 2023Opioids are used for pain relief during the first stage of labor. Oxycodone can cause maternal hypotension that may modify utero- and fetoplacental circulatory... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Opioids are used for pain relief during the first stage of labor. Oxycodone can cause maternal hypotension that may modify utero- and fetoplacental circulatory physiology. We hypothesized that maternal intravenous (i.v.) oxycodone has no detrimental effect on utero- and fetoplacental hemodynamics during the early first stage of labor.
MATERIAL AND METHODS
Twenty-two parturients requiring pain relief during the first stage of labor were randomized in a double-blinded and placebo-controlled study. By Doppler ultrasonography, both uterine artery (Ut) and umbilical vein (UV) volume blood flows (Q), Ut pulsatility index (PI), and Ut vascular resistance (RUt) were calculated. Blood flow velocity waveforms were obtained between uterine contractions. After baseline measurements, women received oxycodone 0.05 mg/kg or a placebo intravenous. Doppler ultrasonography was repeated up to 120 min after the first drug administration. The second dose of oxycodone 0.05 mg/kg was allowed at 60 min to all parturients with contraction pain ≥5/10. Maternal plasma samples were collected at each study phase and after delivery with umbilical cord plasma samples, to measure oxycodone concentrations.
CLINICALTRIALS
gov identifier (NCT no. NCT02573831).
RESULTS
At baseline, mean QUt and QUV did not differ significantly between the placebo-first (478 mL/min and 57 mL/min/kg) and the oxycodone-first (561 mL/min and 71 mL/min/kg) groups. In addition, RUt and Ut PI were comparable between the groups. Following oxycodone at 60 min, mean QUt and QUV (714 mL/min and 52 mL/min/kg) were similar to the placebo-first (520 mL/min and 55 mL/min/kg) group. Furthermore, all the measured parameters were comparable to the baseline values. At 60 min after the first study drug administration, all the parturients in the placebo-first group needed intravenous oxycodone 0.05 mg/kg. At 120 min, we found no statistically significant change in any of the measured parameters. No significant correlation was found between maternal oxycodone concentration and QUt or QUV. Furthermore, newborn oxycodone concentration did not correlate with QUV.
CONCLUSIONS
Oxycodone did not have any detrimental effect on either utero- or fetoplacental circulatory physiology during the early first stage of labor. Maternal plasma oxycodone did not correlate with utero- and fetoplacental hemodynamics. No correlation was found between newborn oxycodone concentration and fetoplacental hemodynamics.
Topics: Humans; Female; Adult; Oxycodone; Placenta; Labor Stage, First; Injections, Intravenous; Pregnancy
PubMed: 37344997
DOI: 10.1111/aogs.14603 -
Foot & Ankle Orthopaedics Jul 2023The misuse and abuse of opioid pain medications have become a public health crisis. Because orthopedic surgeons are the third highest prescribers of opioids,...
BACKGROUND
The misuse and abuse of opioid pain medications have become a public health crisis. Because orthopedic surgeons are the third highest prescribers of opioids, understanding their postoperative pain medication prescribing practices is key to solving the opioid crisis. To this end, we conducted a study of the variability in orthopedic foot and ankle surgery postoperative opioid prescribing practice patterns.
METHODS
Three hundred fifty orthopedic foot and ankle surgeons were contacted; respondents completed a survey with 4 common patient scenarios and surgical procedures followed by questions regarding typical postoperative pain medication prescriptions. The scenarios ranged from minimally painful procedures to those that would be expected to be significantly more painful. Summaries were calculated as percentages and chi-square or Fisher exact tests were used to compare survey responses between groups stratified by years in practice and type of practice.
RESULTS
Sixty-four surgeons responded to the survey (92.8% male), 31% were in practice less than 5 years, 34% 6 to 15 years and 34% more than 15 years. For each scenario, there was variation in the type of pain medication prescribed (: 17% 5 mg hydrocodone, 22% 10 mg hydrocodone, 52% oxycodone, and 3% oxycodone sustained release [SR]; : 15% 5 mg hydrocodone, 13% 10 mg hydrocodone, 58% oxycodone, and 9% oxycodone SR; : 11% 5 mg hydrocodone, 13% 10 mg hydrocodone, 56% oxycodone, and 14.1% oxycodone SR; : 3% 5 mg hydrocodone, 5% 10 mg hydrocodone, 44% oxycodone, and 45% oxycodone SR) and the number of pills dispensed. Use of multimodal pain management was variable but most physicians use regional nerve blocks for each scenario (76%, 87%, 69%, 94%). Less experienced surgeons (less than 5 years in practice) supplement with tramadol more for scenario 1 ( = .034) as well as use regional nerve blocks for scenario 2 ( = .039) more than experienced surgeons (more than 15 years in practice).
CONCLUSION
It is evident that variation exists in narcotic prescription practices for postoperative pain management by orthopedic foot and ankle surgeons. With new AAOS guidelines, it is important to try to create some standardization in opioid prescription protocols.
PubMed: 37732950
DOI: 10.1177/24730114231195057 -
Cureus Sep 2023Patients with diminished renal function necessitate special care. In patients with chronic kidney disease (CKD), opioid analgesics should be prescribed based on the... (Review)
Review
Patients with diminished renal function necessitate special care. In patients with chronic kidney disease (CKD), opioid analgesics should be prescribed based on the severity of renal insufficiency; this will determine treatment options at the beginning and throughout the management of pain in CKD patients. The dosage of hydrophilic drugs and drugs with active metabolites should be adjusted according to the severity of CKD, and the process of treatment should be monitored by modifying drug dosages as necessary for background and breakthrough pain. Patients with CKD may benefit from opioid analgesics that are lipophilic, such as methadone, fentanyl, and buprenorphine, as the first line; however, fentanyl is inappropriate for patients undergoing hemodialysis. Opioid prescription in CKD patients is the subject of this systematic review, which aims to compare their safety and efficacy. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Using three databases (PubMed, ScienceDirect, and Google Scholar), we collected and reviewed articles, including literature reviews, randomized control trials (RCTs), and systematic reviews published between 1980 and 2022, to enable us to gather enough valuable data on this rare topic. After applying appropriate filters, a total of 109 results were obtained. They were further screened and subjected to quality assessment tools, which finally yielded 11 studies included in this systematic review. This consisted of two RCTs, two systematic reviews, and seven narrative reviews. This review focused on the safety and appropriate use of opioids in patients with CKD. The accumulation of morphine and codeine metabolites may result in neurotoxic side effects. Hydromorphone and oxycodone are considered safe to administer but require careful adjustments in dosage. Common comorbidities among patients with CKD may amplify opioid-related adverse effects.
PubMed: 37727840
DOI: 10.7759/cureus.45485 -
PeerJ 2023This study aimed to investigate the interactions between icotinib/apatinib and oxycodone in rats and to unveil the underlying mechanism. An ultra-performance liquid...
This study aimed to investigate the interactions between icotinib/apatinib and oxycodone in rats and to unveil the underlying mechanism. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine oxycodone and its demethylated metabolite simultaneously. , Sprague-Dawley (SD) male rats were administered oxycodone with or without icotinib or apatinib. Blood samples were collected and subjected to UPLC-MS/MS analysis. An enzyme incubation assay was performed to investigate the mechanism of drug-drug interaction using both rat and human liver microsomes (RLM and HLM). The results showed that icotinib markedly increased the AUC and AUC of oxycodone but decreased the CL. The C of oxycodone increased significantly upon co-administration of apatinib. , the K value of oxycodone metabolism was 101.7 ± 5.40 μM and 529.6 ± 19.60 μM in RLMs and HLMs, respectively. Icotinib and apatinib inhibited the disposition of oxycodone, with a mixed mechanism in RLM (IC = 3.29 ± 0.090 μM and 0.95 ± 0.88 μM, respectively) and a competitive and mixed mechanism in HLM (IC = 22.34 ± 0.81 μM and 0.48 ± 0.05 μM, respectively). In conclusion, both icotinib and apatinib inhibit the metabolism of oxycodone and . Therefore, the dose of oxycodone should be reconsidered when co-administered with icotinib or apatinib.
Topics: Rats; Male; Humans; Animals; Rats, Sprague-Dawley; Chromatography, Liquid; Oxycodone; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry
PubMed: 38089912
DOI: 10.7717/peerj.16601 -
Drug and Alcohol Dependence Aug 2023Fentanyl- and methamphetamine-based counterfeit prescription drugs have driven escalating overdose death rates in the US, however their presence in Mexico has not been...
BACKGROUND
Fentanyl- and methamphetamine-based counterfeit prescription drugs have driven escalating overdose death rates in the US, however their presence in Mexico has not been assessed. Our ethnographic team has conducted longitudinal research focused on illicit drug markets in Northern Mexico since 2018. In 2021-2022, study participants described the arrival of new, unusually potent tablets sold as ostensibly controlled substances, without a prescription, directly from pharmacies that cater to US tourists.
AIMS
To characterize the availability of counterfeit and authentic controlled substances at pharmacies in Northern Mexico available to English-speaking tourists without a prescription.
METHODS
We employed an iterative, exploratory, mixed methods design. Longitudinal ethnographic data was used to characterize tourist-oriented micro-neighborhoods and guide the selection of n=40 pharmacies in n=4 cities in Northern Mexico. In each pharmacy, samples of "oxycodone", "Xanax", and "Adderall" were sought as single pills, during English-language encounters, after which detailed ethnographic accounts were recorded. We employed immunoassay-based testing strips to check each pill for the presence of fentanyls, benzodiazepines, amphetamines, and methamphetamines. We used Fourier-Transform Infrared Spectroscopy to further characterize drug contents.
RESULTS
Of n=40 pharmacies, one or more of the requested controlled substances could be obtained with no prescription (as single pills or in bottles) at 28 (70.0%) and as single pills at 19 (47.5%). Counterfeit pills were obtained at 11 pharmacies (27.5%). Of n=45 samples sold as one-off controlled substances, 18 were counterfeit. 7 of 11 (63.6%) samples sold as "Adderall" contained methamphetamine, 8 of 27 (29.6%) samples sold as "Oxycodone" contained fentanyl, and 3 "Oxycodone" samples contained heroin. Pharmacies providing counterfeit drugs were uniformly located in tourist-serving micro-neighborhoods, and generally featured English-language advertisements for erectile dysfunction medications and "painkillers". Pharmacy employees occasionally expressed concern about overdose risk and provided harm reduction guidance.
DISCUSSION
The availability of fentanyl-, heroin-, and methamphetamine-based counterfeit medications in tourist-oriented independent pharmacies in Northern Mexico represents a public health risk, and occurs in the context of 1) the normalization of medical tourism as a response to rising unaffordability of healthcare in the US, 2) plummeting rates of opioid prescription in the US, affecting both chronic pain patients and the availability of legitimate pharmaceuticals on the unregulated market, 3) the rise of fentanyl-based counterfeit opioids as a key driver of the fourth, and deadliest-to-date, wave of the opioid crisis. It was not possible to distinguish counterfeit medications based on appearance of pills or geography of pharmacies, because identically-appearing authentic and counterfeit versions were often sold in close geographic proximity. Nevertheless, people who consume drugs may be more trusting of controlled substances purchased directly from pharmacies. Due to Mexico's limited opioid overdose surveillance infrastructure, the current death rate from these substances remains unknown.
Topics: Male; Humans; Heroin; Fentanyl; Controlled Substances; Pharmacies; Mexico; Analgesics, Opioid; Drug Overdose; Methamphetamine; Oxycodone
PubMed: 37348270
DOI: 10.1016/j.drugalcdep.2023.110819 -
Genes, Brain, and Behavior Apr 2024Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD....
Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide insight into the early stages of OUD development. Here, we present findings from a behavioral phenotyping protocol using several inbred strains from the Hybrid Rat Diversity Panel. Our behavioral protocol included a modified "up-down" von Frey procedure to measure inherent strain differences in the sensitivity to a mechanical stimulus on the hindpaw. We also performed the tail immersion assay, which measures the latency to display tail withdrawal in response to a hot water bath. Initial withdrawal thresholds were taken in drug-naïve animals to record baseline thermal sensitivity across the strains. Oxycodone-induced analgesia was measured after administration of oxycodone over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and display moderate heritability (h = 0.23-0.40). All strains displayed oxycodone-induced analgesia that peaked at 15-30 min and returned to baseline by 2 h. There were significant differences between the strains in the magnitude and duration of their analgesic response to oxycodone, although the heritability estimates were quite modest (h = 0.10-0.15). These data demonstrate that genetic background confers differences in mechanical sensitivity, thermal sensitivity, and oxycodone-induced analgesia.
Topics: Rats; Animals; Oxycodone; Analgesics, Opioid; Analgesia; Opioid-Related Disorders
PubMed: 38597363
DOI: 10.1111/gbb.12894 -
Scandinavian Journal of Pain Jan 2024Multimodal pain management is one component in enhanced recovery after surgery protocol. Here we evaluate the efficacy of tramadol-paracetamol in acute postoperative... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Multimodal pain management is one component in enhanced recovery after surgery protocol. Here we evaluate the efficacy of tramadol-paracetamol in acute postoperative pain and pain outcome at 12 months after spine surgery in randomized, double-blind, placebo-controlled trial.
METHODS
We randomized 120 patients undergoing spine surgery to receive, for add-on pain management, two tramadol-paracetamol 37.5 mg/325 mg ( = 61) or placebo tablets ( = 59) twice a day for 5 postoperative days. In the hospital, multimodal pain management consisted of dexketoprofen and oxycodone. After discharge, patients were prescribed ibuprofen 200 mg, maximum 1,200 mg/day. Pain, analgesic use, and satisfaction with pain medication were followed up with the Brief Pain Inventory questionnaire before surgery and at 1 and 52 weeks after surgery. The primary outcome was patients' satisfaction with pain medication 1 week after surgery.
RESULTS
At 1 week after surgery, patients' satisfaction with pain medication was similarly high in the two groups, 75% [interquartile range, 30%] in the placebo group and 70% [40%] in the tramadol-paracetamol group ( = 0.949) on a scale: 0% = not satisfied, 100% = totally satisfied. At 1 week, ibuprofen dose was lower in the placebo group 200 mg [1,000] compared to the tramadol-paracetamol group, 800 mg [1,600] ( = 0.016). There was no difference in the need for rescue oxycodone. Patients in the tramadol-paracetamol group had more adverse events associated with analgesics during the first postoperative week (relative risk = 1.8, 95% confidence interval, 1.2-2.6).
CONCLUSION
Add-on pain treatment with tramadol-paracetamol did not enhance patients' satisfaction with early pain management after back surgery.
Topics: Humans; Pain, Postoperative; Tramadol; Double-Blind Method; Acetaminophen; Male; Female; Middle Aged; Analgesics, Opioid; Patient Satisfaction; Oxycodone; Analgesics, Non-Narcotic; Adult; Spine; Treatment Outcome; Ibuprofen; Pain Measurement; Aged
PubMed: 38708610
DOI: 10.1515/sjpain-2023-0105 -
Pharmaceutical Research Nov 2023Oxycodone active uptake across the blood-brain barrier (BBB) is associated with the putative proton-coupled organic cation (H/OC) antiporter system. Yet, the activity of...
BACKGROUND
Oxycodone active uptake across the blood-brain barrier (BBB) is associated with the putative proton-coupled organic cation (H/OC) antiporter system. Yet, the activity of this system at the blood-cerebrospinal fluid barrier (BCSFB) is not fully understood. Additionally, sex differences in systemic pharmacokinetics and pharmacodynamics of oxycodone has been reported, but whether the previous observations involve sex differences in the function of the H/OC antiporter system remain unknown. The objective of this study was, therefore, to investigate the extent of oxycodone transport across the BBB and the BCSFB in female and male Sprague-Dawley rats using microdialysis.
METHODS
Microdialysis probes were implanted in the blood and two of the following brain locations: striatum and lateral ventricle or cisterna magna. Oxycodone was administered as an intravenous infusion, and dialysate, blood and brain were collected. Unbound partition coefficients (K) were calculated to understand the extent of oxycodone transport across the blood-brain barriers. Non-compartmental analysis was conducted using Phoenix 64 WinNonlin. GraphPad Prism version 9.0.0 was used to perform t-tests, one-way and two-way analysis of variance followed by Tukey's or Šídák's multiple comparison tests. Differences were considered significant at p < 0.05.
RESULTS
The extent of transport at the BBB measured in striatum was 4.44 ± 1.02 (K), in the lateral ventricle 3.41 ± 0.74 (K) and in cisterna magna 2.68 ± 1.01 (K). These K values indicate that the extent of oxycodone transport is significantly lower at the BCSFB compared with that at the BBB, but still confirm the presence of active uptake at both blood-brain interfaces. No significant sex differences were observed in neither the extent of oxycodone delivery to the brain, nor in the systemic pharmacokinetics of oxycodone.
CONCLUSIONS
The findings clearly show that active uptake is present at both the BCSFB and the BBB. Despite some underestimation of the extent of oxycodone delivery to the brain, CSF may be an acceptable surrogate of brain ISF for oxycodone, and potentially also other drugs actively transported into the brain via the H/OC antiporter system.
Topics: Rats; Female; Male; Animals; Blood-Brain Barrier; Oxycodone; Microdialysis; Sex Characteristics; Rats, Sprague-Dawley; Brain; Antiporters
PubMed: 37610619
DOI: 10.1007/s11095-023-03583-0 -
Sleep Medicine Sep 2023Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been...
OBJECTIVE
Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been suggested to increase the number of hypocretin-producing neurons. We aimed to assess opioid use and its self-reported effect on narcolepsy type 1 symptom severity through a literature review and questionnaire study.
METHODS
We systematically reviewed literature on opioid use in narcolepsy. We also recruited 100 people with narcolepsy type 1 who completed an online questionnaire on opioid use in the previous three years. The main questionnaire topics were the indication for use, and the possible effects on narcolepsy symptom severity. Structured follow-up interviews were conducted when opioid use was reported.
RESULTS
The systematic literature review mainly showed improvements in narcolepsy symptom severity. Recent opioid use was reported by 16/100 questionnaire respondents, who had used 20 opioids (codeine: 7/20, tramadol: 6/20, oxycodone: 6/20, fentanyl: 1/20). Narcolepsy symptom changes were reported in 11/20. Positive effects on disturbed nocturnal sleep (9/20), excessive daytime sleepiness (4/20), hypnagogic hallucinations (3/17), cataplexy (2/18), and sleep paralysis (1/13) were most pronounced for oxycodone (4/6) and codeine (4/7).
CONCLUSIONS
Opioids were relatively frequently used compared to a similarly young general Dutch sample. Oxycodone and, to a lesser extent, codeine were associated with self-reported narcolepsy symptom severity improvements. Positive changes in disturbed nocturnal sleep and daytime sleepiness were most frequently reported, while cataplexy effects were less pronounced. Randomised controlled trials are now needed to verify the potential of opioids as therapeutic agents for narcolepsy.
Topics: Humans; Cataplexy; Analgesics, Opioid; Orexins; Oxycodone; Narcolepsy; Disorders of Excessive Somnolence; Surveys and Questionnaires
PubMed: 37437491
DOI: 10.1016/j.sleep.2023.06.008 -
Pharmacology Research & Perspectives Aug 2023Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of the spinal 5-HT release induced by morphine are not well understood. The...
Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of the spinal 5-HT release induced by morphine are not well understood. The purpose of this study was to define the role and mechanism of spinal 5-HT release induced by oral morphine. We also examined whether persistent pain affected the spinal 5-HT release induced by oral morphine. Spinal 5-HT release was measured using microdialysis of lumbar cerebrospinal fluid (CSF). Two opioids, morphine and oxycodone, were orally administered and 5-HT release was measured in awake rats. Naloxone and β-funaltrexamine (β-FNA) were used to determine whether the effect of morphine on 5-HT release was mediated by opioid receptor activation. To study persistent pain, a formalin test was used. At 45 min after oral morphine administration, the formalin test was started and spinal 5-HT release was measured. Oral morphine, but not oral oxycodone, increased 5-HT release at the spinal cord to approximately 4000% of the baseline value. This effect of morphine was not antagonized by either naloxone or β-FNA at a dose that antagonized the antinociceptive effect of morphine. Formalin-induced persistent pain itself had no effect on spinal 5-HT release but enhanced the oral morphine-induced spinal 5-HT release. Oral morphine-induced spinal 5-HT release was not mediated by opioid receptor activation. Spinal 5-HT induced by oral morphine did not play a major role in the antinociceptive effect of morphine in the hot plate test. Persistent pain increased oral morphine-induced spinal 5-HT release.
Topics: Animals; Rats; Receptors, Opioid; Serotonin; Oxycodone; Morphine; Analgesics, Opioid; Naloxone; Pain
PubMed: 37488088
DOI: 10.1002/prp2.1119