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Psychopharmacology May 2020Over the last decade, oxycodone has become one of the most widely abused drugs in the USA. Oxycodone use disorder (OUD) is a serious health problem that has prompted a...
RATIONALE
Over the last decade, oxycodone has become one of the most widely abused drugs in the USA. Oxycodone use disorder (OUD) is a serious health problem that has prompted a need to develop animal models of OUD that have both face and predictive validity. Oxycodone use in humans is more prevalent in women and leads to pronounced hyperalgesia and irritability during withdrawal. However, unclear is whether current animal models of oxycodone self-administration recapitulate these characteristics in humans.
OBJECTIVES
We assessed the face validity of a model of extended-access oxycodone self-administration in rats by examining the escalation of oxycodone intake and behavioral symptoms of withdrawal, including irritability-like behavior and mechanical nociception, in male and female Wistar rats.
RESULTS
Both male and female rats escalated their oxycodone intake over fourteen 12-h self-administration sessions. After escalation, female rats administered more drug than male rats. No differences in plasma oxycodone levels were identified, but males had a significantly higher level of oxycodone in the brain at 30 min. Extended access to oxycodone significantly decreased aggressive-like behavior and increased defensive-like behaviors when tested immediately after a 12-h self-administration session, followed by a rebound increase in aggressive-like behavior 12 h into withdrawal. Tests of mechanical nociception thresholds during withdrawal indicated pronounced hyperalgesia. No sex differences in irritability-like behavior or pain sensitivity were observed.
CONCLUSIONS
The present study demonstrated the face validity of the extended access model of oxycodone self-administration by identifying sex differences in the escalation of oxycodone intake and pronounced changes in pain and affective states.
Topics: Analgesics, Opioid; Animals; Brain; Emotions; Female; Male; Oxycodone; Pain Threshold; Rats; Rats, Wistar; Self Administration; Sex Characteristics; Substance Withdrawal Syndrome
PubMed: 32114633
DOI: 10.1007/s00213-020-05479-y -
Oxycodone-Related Deaths: The Significance of Pharmacokinetic and Pharmacodynamic Drug Interactions.European Journal of Drug Metabolism and... Mar 2022Oxycodone is frequently prescribed as well as detected in postmortem cases. Concurrent use of pharmacodynamically or pharmacokinetically interacting drugs can cause...
BACKGROUND AND OBJECTIVES
Oxycodone is frequently prescribed as well as detected in postmortem cases. Concurrent use of pharmacodynamically or pharmacokinetically interacting drugs can cause adverse effects or even fatal intoxication. The aims of this study were to investigate differences in prescriptions for and toxicological findings of pharmacodynamically and pharmacokinetically interacting drugs in fatal oxycodone-related intoxications and other causes of death. We also aimed to investigate the differences in prevalence of oxycodone prescriptions, and the detected postmortem oxycodone concentrations between fatal oxycodone-related intoxications and other causes of death.
METHODS
Forensic autopsy cases (2012-2018) where oxycodone was identified in femoral blood (n = 1236) were included. Medical history and prescription data were retrieved from national databases and linked to the forensic toxicology findings.
RESULTS
Oxycodone-related deaths were found to have higher blood concentrations of oxycodone (median 0.30 µg/g vs. 0.05 µg/g) and were less likely to have a prescription for oxycodone (OR 0.62) compared to nonintoxication deaths. Pharmacodynamically interacting drugs were prescribed in 79% and found in blood in 81% of the cases. Pharmacokinetically interacting drugs were rarely prescribed (1%). Oxycodone-related deaths were more likely to have prescriptions for a pharmacodynamically interacting drug (OR 1.7) and more often have co-findings of one or multiple pharmacodynamically interacting drugs (OR 5.6).
CONCLUSION
The results suggest that combined use of oxycodone and pharmacodynamically interacting drugs is associated with oxycodone-related death and that non-medical use of oxycodone is a potential risk factor for oxycodone-related intoxication.
Topics: Analgesics, Opioid; Databases, Factual; Drug Interactions; Forensic Toxicology; Oxycodone; Risk Factors
PubMed: 35025054
DOI: 10.1007/s13318-021-00750-9 -
Scientific Reports Aug 2023Anesthesia for laparoscopic sleeve gastrectomy and perioperative management remains a challenge. Several clinical studies indicate that opioid-free anesthesia (OFA) may... (Randomized Controlled Trial)
Randomized Controlled Trial
Anesthesia for laparoscopic sleeve gastrectomy and perioperative management remains a challenge. Several clinical studies indicate that opioid-free anesthesia (OFA) may be beneficial, but there is no consensus on the most optimal anesthesia technique in clinical practice. The aim of our study was to assess the potential benefits and risks of intraoperative OFA compared to multimodal analgesia (MMA) with remifentanil infusion. In a prospective, randomized study, we analyzed 59 patients' data. Primary outcome measures were oxycodone consumption and reported pain scores (numerical rating scale, NRS) at 1, 6, 12, and 24th hours after surgery. Postoperative sedation on the Ramsay scale, nausea and vomiting on the PONV impact scale, desaturation episodes, pruritus, hemodynamic parameters, and hospital stay duration were also documented and compared. There were no significant differences in NRS scores or total 24-h oxycodone requirements. In the first postoperative hour, OFA group patients needed an average of 4.6 mg of oxycodone while the MMA group 7.72 mg (p = 0.008, p < 0.05 statistically significant). The PONV impact scale was significantly lower in the OFA group only in the first hour after the operation (p = 0.006). Patients in the OFA group required higher doses of ephedrine 23.67 versus 15.69 mg (p = 0.039) and more intravenous fluids 1160 versus 925.86 ml (p = 0.007). The mode of anesthesia did not affect the pain scores or the total dose of oxycodone in the first 24 postoperative hours. Only in the first postoperative hour were an opioid-sparing effect and reduction of PONV incidence seen in the OFA group when compared with remifentanil-based anesthesia. However, patients in the OFA group showed significantly greater hemodynamic lability necessitating higher vasopressor doses and more fluid volume.
Topics: Humans; Analgesics, Opioid; Remifentanil; Oxycodone; Prospective Studies; Postoperative Nausea and Vomiting; Pain, Postoperative; Anesthesia; Laparoscopy; Gastrectomy
PubMed: 37542100
DOI: 10.1038/s41598-023-39856-2 -
British Journal of Clinical Pharmacology Mar 2022Tapentadol and oxycodone are commonly used analgesics. Preclinical studies have shown that oxycodone modulates brain metabolites related to opioid pathways, whereas... (Randomized Controlled Trial)
Randomized Controlled Trial
Tapentadol and oxycodone are commonly used analgesics. Preclinical studies have shown that oxycodone modulates brain metabolites related to opioid pathways, whereas tapentadol also affects noradrenergic activity. However, knowledge about the function of the medications in the human brain is limited. The aim was to investigate effects of tapentadol and oxycodone on brain glutamate, the most important neurotransmitter in pain processing. Magnetic resonance spectroscopy was obtained in 21 healthy subjects from the anterior cingulate cortex, prefrontal cortex, and insula at baseline and after 14 days of treatment with either 50 mg tapentadol, 10 mg oxycodone (equipotent dose, both extended release) or placebo twice daily in a randomized double-blind cross-over study. Compared to baseline, decreased glutamate/creatine levels were identified in anterior cingulate cortex after tapentadol (1.26 ± 0.14 vs. 1.35 ± 0.18, P = .04) and oxycodone (1.26 ± 0.10 vs. 1.35 ± 0.12, P = .05) treatments, both with 7% reduction. This indicates that both analgesics modulate the glutamatergic system at the supraspinal level in humans.
Topics: Analgesics; Analgesics, Opioid; Cross-Over Studies; Double-Blind Method; Glutamic Acid; Healthy Volunteers; Humans; Oxycodone; Phenols; Tapentadol
PubMed: 34427941
DOI: 10.1111/bcp.15050 -
ENeuro 2021The rat oxycodone and cocaine biobanks contain samples that vary by genotypes (by using genetically diverse genotyped HS rats), phenotypes (by measuring addiction-like... (Review)
Review
The rat oxycodone and cocaine biobanks contain samples that vary by genotypes (by using genetically diverse genotyped HS rats), phenotypes (by measuring addiction-like behaviors in an advanced SA model), timepoints (samples are collected longitudinally before, during, and after SA, and terminally at three different timepoints in the addiction cycle: intoxication, withdrawal, and abstinence or without exposure to drugs through age-matched naive rats), samples collected (organs, cells, biofluids, feces), preservation (paraformaldehyde-fixed, snap-frozen, or cryopreserved) and application (proteomics, transcriptomics, microbiomics, metabolomics, epigenetics, anatomy, circuitry analysis, biomarker discovery, etc.Substance use disorders (SUDs) are pervasive in our society and have substantial personal and socioeconomical costs. A critical hurdle in identifying biomarkers and novel targets for medication development is the lack of resources for obtaining biological samples with a detailed behavioral characterization of SUD. Moreover, it is nearly impossible to find longitudinal samples. As part of two ongoing large-scale behavioral genetic studies in heterogeneous stock (HS) rats, we have created two preclinical biobanks using well-validated long access (LgA) models of intravenous cocaine and oxycodone self-administration (SA) and comprehensive characterization of addiction-related behaviors. The genetic diversity in HS rats mimics diversity in the human population and includes individuals that are vulnerable or resilient to compulsive-like responding for cocaine or oxycodone. Longitudinal samples are collected throughout the experiment, before exposure to the drug, during intoxication, acute withdrawal, and protracted abstinence, and include naive, age-matched controls. Samples include, but are not limited to, blood plasma, feces and urine, whole brains, brain slices and punches, kidney, liver, spleen, ovary, testis, and adrenal glands. Three preservation methods (fixed in formaldehyde, snap-frozen, or cryopreserved) are used to facilitate diverse downstream applications such as proteomics, metabolomics, transcriptomics, epigenomics, microbiomics, neuroanatomy, biomarker discovery, and other cellular and molecular approaches. To date, >20,000 samples have been collected from over 1000 unique animals and made available free of charge to non-profit institutions through https://www.cocainebiobank.org/ and https://www.oxycodonebiobank.org/.
Topics: Animals; Behavior, Addictive; Biological Specimen Banks; Cocaine; Cocaine-Related Disorders; Oxycodone; Rats; Rats, Sprague-Dawley; Self Administration
PubMed: 33875455
DOI: 10.1523/ENEURO.0033-21.2021 -
Forensic Science International. Genetics Jul 2021Genetic disposition can cause variation in oxycodone pharmacokinetic characteristics and decrease or increase the expected clinical response. In forensic medicine,...
Genetic disposition can cause variation in oxycodone pharmacokinetic characteristics and decrease or increase the expected clinical response. In forensic medicine, determination of cause of death or assessing time between drug intake and death can be facilitated by knowledge of parent and metabolite concentrations. In this study, the aim was to investigate if CYP2D6 genotyping can facilitate interpretation by investigating the frequency of the four CYP2D6 phenotypes, poor metabolizer, intermediate metabolizer, extensive metabolizer, and ultra-rapid metabolizer in postmortem cases, and to study if the CYP2D6 activity was associated with a certain cause of death, concentration, or metabolic ratio. Cases positive for oxycodone in femoral blood (n = 174) were genotyped by pyrosequencing for CYP2D6*3, *4, and *6 and concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone were determined by LC-MS/MS (LLOQ 0.005 µg/g). Digital droplet PCR was used to determine the copy number variation for CYP2D6*5. Cases were categorized by cause of death. It was found that poor and intermediate CYP2D6 metabolizers had significantly higher oxycodone and noroxycodone concentrations compared to extensive and ultra-rapid metabolizers. CYP2D6 phenotype were equally distributed between cause of death groups, showing that no phenotype was overrepresented in any of the cause of death groups. We also found that the concentration ratio between oxymorphone and oxycodone depended on the CYP2D6 activity when death was unrelated to intoxication. In general, a low metabolite to parent ratio indicate an acute intake. By using receiver operating characteristic (ROC) analysis, we conclude that an oxymorphone/oxycodone ratio lower than 0.075 has a high sensitivity for separating intoxications with oxycodone from other intoxications and non-intoxications. However, the phenotype needs to be known to reach a high specificity. Therefore, the ratio should not be used as a biomarker on its own to distinguish between different causes of death but needs to be complemented by genotyping.
Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Cytochrome P-450 CYP2D6; DNA Copy Number Variations; Female; Forensic Genetics; Genotype; High-Throughput Nucleotide Sequencing; Humans; Male; Middle Aged; Morphinans; Oxycodone; Pharmacogenomic Testing; Phenotype; Polymorphism, Single Nucleotide; Young Adult
PubMed: 33799050
DOI: 10.1016/j.fsigen.2021.102510 -
British Journal of Clinical Pharmacology Dec 2022The aim of this study was to investigate the effects of tapentadol and oxycodone using the nociceptive withdrawal reflex and sensory evoked potentials. (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
The aim of this study was to investigate the effects of tapentadol and oxycodone using the nociceptive withdrawal reflex and sensory evoked potentials.
METHODS
Twenty-one healthy volunteers completed a cross-over trial with oxycodone (10 mg), tapentadol (50 mg) extended-release tablets, or placebo treatment administered orally BID for 14 days. Electrical stimulations were delivered on the plantar side of the foot to evoke a nociceptive withdrawal reflex at baseline and post-interventions. Electromyography, recorded at tibialis anterior, and electroencephalography were recorded for analysis of: number of reflexes, latencies, and area under the curve of the nociceptive withdrawal reflex as well as latencies, amplitudes and dipole sources of the sensory-evoked potential.
RESULTS
Tapentadol decreased the odds ratio of eliciting nociceptive withdrawal reflex by -0.89 (P = .001, 95% confidence interval [CI] -1.46, -0.32), whereas oxycodone increased the latency of the N1 component of the sensory-evoked potential at the vertex by 12.5 ms (P = .003, 95% CI 3.35, 21.69). Dipole sources revealed that the anterior cingulate component moved caudally for all three interventions (all P < .02), and the insula components moved caudally in both the oxycodone and tapentadol arms (all P < .03).
CONCLUSION
A decrease in the number of nociceptive withdrawal reflex was observed during tapentadol treatment, possibly relating to the noradrenaline reuptake inhibition effects on the spinal cord. Both oxycodone and tapentadol affected cortical measures possible due to μ-opioid receptor agonistic effects evident in the dipole sources, with the strongest effect being mediated by oxycodone. These findings could support the dual effect analgesic mechanisms of tapentadol in humans as previously shown in preclinical studies.
Topics: Humans; Tapentadol; Oxycodone; Phenols; Analgesics, Opioid; Spinal Cord; Brain; Electrophysiology; Double-Blind Method
PubMed: 35776835
DOI: 10.1111/bcp.15453 -
The American Journal of Nursing Mar 2021This series on palliative care is developed in collaboration with the Hospice and Palliative Nurses Association (HPNA; https://advancingexpertcare.org). The HPNA aims to...
This series on palliative care is developed in collaboration with the Hospice and Palliative Nurses Association (HPNA; https://advancingexpertcare.org). The HPNA aims to guide nurses in preventing and relieving suffering and in giving the best possible care to patients and families, regardless of the stage of disease or the need for other therapies. The HPNA offers education, certification, advocacy, leadership, and research.
Topics: Administration, Oral; Analgesics, Opioid; Dose-Response Relationship, Drug; Hospice and Palliative Care Nursing; Humans; Infusions, Parenteral; Morphine; Nurse's Role; Oxycodone; Pain Measurement; Palliative Care
PubMed: 33625014
DOI: 10.1097/01.NAJ.0000737312.95932.4d -
Pharmacology, Biochemistry, and Behavior Dec 2021Regular alcohol consumption is on the rise among older adults and has the potential of altering the subjective experience of pain and response to pain medications. This...
BACKGROUND
Regular alcohol consumption is on the rise among older adults and has the potential of altering the subjective experience of pain and response to pain medications. This study examined the cognitive, analgesic and side effect response to oxycodone in middle age and older adults with elevated levels of customary alcohol consumption in a human laboratory setting.
METHODS
After refraining from alcohol for one day, eligible participants underwent baseline assessment cognition and side effects by means of questionnaires that were repeated at three time points (90 min, 5 and 8 h) following administration of a 10 mg oral dose of oxycodone. Response to pain stimulus (Cold Pressor Test (CPT)), pupil size, and plasma oxycodone were also measured.
RESULTS
One hundred twenty-eight adults (age 35-85) completed the study day. Compared to those with lower customary alcohol consumption, participants with elevated alcohol consumption showed attenuated opioid-induced pupil constriction and cognitive decline on objective measures of working memory, sustained attention, inhibitory control, coordination on a simulated driving task, and subjective dysphoric effects with enhanced subjective euphoric effects. Oxycodone pharmacokinetics, pain tolerance to CPT, and Berg balance were impacted comparably between alcohol consumption groups. Women endorsed greater negative drug effects, whereas men endorsed positive drug effects.
CONCLUSION
Independent of subject's age, elevated customary alcohol consumption attenuates opioid central effects (i.e., pupil miosis, impaired cognition) and gender influences subjective drug effects. Clinicians should consider alcohol consumption and gender when prescribing opioid medications.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Alcohol Drinking; Analgesics, Opioid; Attention; Automobile Driving; Cognition; Ethanol; Female; Humans; Male; Memory, Short-Term; Middle Aged; Miosis; Oxycodone; Pain; Sex Factors; Surveys and Questionnaires
PubMed: 34742948
DOI: 10.1016/j.pbb.2021.173295 -
Annals of Surgery Dec 2022This study was designed to test the hypothesis that patients prescribed hydrocodone consume a similar number of tablets as those prescribed oxycodone after surgery.
OBJECTIVE
This study was designed to test the hypothesis that patients prescribed hydrocodone consume a similar number of tablets as those prescribed oxycodone after surgery.
SUMMARY OF BACKGROUND DATA
In October 2017, the Michigan Opioid Prescribing Engagement Network released opioid prescribing guidelines for surgeries. For each procedure, these guidelines recommended prescribing 50% more tablets of hydrocodone than tablets of oxycodone to adjust for potency differences. These guidelines were simplified in January 2019 to recommend the same number of 5 mg hydrocodone tablets as 5 mg oxycodone tablets for each procedure.
METHODS
Retrospective, observational analysis of opioid-naïve adults who underwent surgical procedures across 64 hospitals in Michigan and were prescribed 5 mg tablets of hydrocodone or oxycodone between January 1, 2018 and May 31, 2019. The primary outcome was number of tablets consumed. We defined a meaningful difference in consumption as 5 pills a priori. Secondary outcomes included self-reported pain, satisfaction, and opioid refills.
RESULTS
A total of 6842 patients were included. Adjusting for covariates, patients prescribed hydrocodone consumed 7 tablets (95% confidence interval 6.79-7.18) while patients prescribed oxycodone consumed 6 tablets (95% confidence interval 5.58-6.40.) Comparing patients prescribed oxycodone with those prescribed hydrocodone, there were no differences in satisfaction, pain, or refills.
CONCLUSIONS
Although patients prescribed hydrocodone consumed more tablets than patients prescribed oxycodone, this difference was not clinically significant and did not result in differences in satisfaction, pain, or refills. Perioperative opioid prescribing guidelines may recommend the same number of 5 mg oxycodone and hydrocodone tablets without sacrificing patient-reported outcomes.
Topics: Adult; Humans; Analgesics, Opioid; Oxycodone; Hydrocodone; Retrospective Studies; Pain, Postoperative; Practice Patterns, Physicians'
PubMed: 33605582
DOI: 10.1097/SLA.0000000000004793