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Journal of Pain and Symptom Management May 2005Oxycodone has been in clinical use since 1917. Parenteral oxycodone was used mainly for the treatment of acute postoperative pain whereas combinations, for example,... (Review)
Review
Oxycodone has been in clinical use since 1917. Parenteral oxycodone was used mainly for the treatment of acute postoperative pain whereas combinations, for example, oxycodone and acetaminophen, were used for moderate pain. Since the introduction of controlled-release oxycodone, it has been used to manage cancer-related pain and chronic non-cancer-related pain problems. Controlled studies have been performed in postoperative pain, cancer pain, osteoarthritis-related pain, and neuropathic pain due to postherpetic neuralgia and diabetic neuropathy. The pharmacodynamic effects of oxycodone are typical of a mu-opioid agonist. Oxycodone closely resembles morphine but it has some distinct differences, particularly in its pharmacokinetic profile. Being an old drug, the basic pharmacology of oxycodone has been a neglected field of research.
Topics: Analgesics, Opioid; Animals; Biological Availability; Drug Interactions; History, 20th Century; Humans; Liver Failure; Neoplasms; Oxycodone; Pain; Pain, Postoperative; Renal Insufficiency
PubMed: 15907646
DOI: 10.1016/j.jpainsymman.2005.01.010 -
Pharmacogenomics Apr 2021Oxycodone is a semisynthetic μ- and κ-opioid receptor with agonist with a broad scope of use including postoperative analgesia as well as control of neuropathic and... (Review)
Review
Oxycodone is a semisynthetic μ- and κ-opioid receptor with agonist with a broad scope of use including postoperative analgesia as well as control of neuropathic and cancer pain. Advantages over other opioids include prolonged duration of action, greater potency than morphine and lack of histamine release or ceiling effect. Individual responses to oxycodone can vary due to genetic differences. This review article aims to summarize the oxycodone literature and provide context on its pharmacogenomics and pharmacokinetics. The evidence for clinical effect of genetic polymorphisms on oxycodone is conflicting. There is stronger evidence linking polymorphic genetic enzymes CYP2D6 and CYP3A with therapeutic outcomes. Further, research is needed to discern all of oxycodone's metabolites and their contribution to the overall analgesic effect.
Topics: Analgesics, Opioid; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Humans; Morphine; Oxycodone; Pharmacogenetics; Polymorphism, Genetic
PubMed: 33728947
DOI: 10.2217/pgs-2020-0143 -
Neuropharmacology Jun 2019Opioid drugs are important tools to alleviate pain of different origins, but they have strong addictive potential and their abuse at higher doses often results in... (Review)
Review
Opioid drugs are important tools to alleviate pain of different origins, but they have strong addictive potential and their abuse at higher doses often results in serious health complications. Respiratory depression that leads to brain hypoxia is perhaps the most dangerous symptom of acute intoxication with opioids, and it could result in lethality. The development of substrate-specific sensors coupled with amperometry made it possible to directly evaluate physiological and drug-induced fluctuations in brain oxygen levels in awake, freely-moving rats. The goal of this review paper is to consider changes in brain oxygen levels induced by several opioid drugs (heroin, fentanyl, oxycodone, morphine). While some of these drugs are widely used in clinical practice, they all are abused, often at doses exceeding the clinical range and often resulting in serious health complications. First, we consider some basic knowledge regarding brain oxygen, its physiological fluctuations, and mechanisms involved in regulating its entry into brain tissue. Then, we present and discuss data on brain oxygen changes induced by each opioid drug within a wide range of doses, from low, behaviorally relevant, to high, likely to be self-administered by drug users. These data allowed us to compare the effects of these drugs on brain oxygen in terms of their potency, time-course, and their potential danger when used at high doses via rapid-onset administration routes. While most data discussed in this work were obtained in rats, we believe that these data have clear human relevance in addressing the alarming rise in lethality associated with the opioid abuse.
Topics: Analgesics, Opioid; Animals; Brain; Fentanyl; Heroin; Humans; Hypoxia, Brain; Morphine; Oxycodone; Rats; Respiratory Insufficiency
PubMed: 30735692
DOI: 10.1016/j.neuropharm.2019.02.008 -
Cellular and Molecular Neurobiology Jul 2021It is estimated that nearly a third of people who abuse drugs started with prescription opioid medicines. Approximately, 11.5 million Americans used prescription drugs... (Review)
Review
It is estimated that nearly a third of people who abuse drugs started with prescription opioid medicines. Approximately, 11.5 million Americans used prescription drugs recreationally in 2016, and in 2018, 46,802 Americans died as the result of an opioid overdose, including prescription opioids, heroin, and illicitly manufactured fentanyl (National Institutes on Drug Abuse (2020) Opioid Overdose Crisis. https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis . Accessed 06 June 2020). Yet physicians will continue to prescribe oral opioids for moderate-to-severe pain in the absence of alternative therapeutics, underscoring the importance in understanding how drug choice can influence detrimental outcomes. One of the opioid prescription medications that led to this crisis is oxycodone, where misuse of this drug has been rampant. Being one of the most highly prescribed opioid medications for treating moderate-to-severe pain as reflected in the skyrocketed increase in retail sales of 866% between 1997 and 2007, oxycodone was initially suggested to be less addictive than morphine. The false-claimed non-addictive formulation of oxycodone, OxyContin, further contributed to the opioid crisis. Abuse was often carried out by crushing the pills for immediate burst release, typically by nasal insufflation, or by liquefying the pills for intravenous injection. Here, we review oxycodone pharmacology and abuse liability as well as present the hypothesis that oxycodone may exhibit a unique pharmacology that contributes to its high likability and abuse susceptibility. We will discuss various mechanisms that likely contribute to the high abuse rate of oxycodone including clinical drug likability, pharmacokinetics, pharmacodynamics, differences in its actions within mesolimbic reward circuity compared to other opioids, and the possibility of differential molecular and cellular receptor interactions that contribute to its selective effects. We will also discuss marketing strategies and drug difference that likely contributes to the oxycodone opioid use disorders and addiction.
Topics: Analgesics, Opioid; Animals; Behavior, Addictive; Humans; Opioid Epidemic; Opioid-Related Disorders; Oxycodone; Pain; Reward
PubMed: 33245509
DOI: 10.1007/s10571-020-01013-y -
Tidsskrift For Den Norske Laegeforening... May 2020Inadequate pain relief after caesarean section is a topic of international concern. At Oslo University Hospital, Ullevål, patients receive bupivacaine infiltration...
BACKGROUND
Inadequate pain relief after caesarean section is a topic of international concern. At Oslo University Hospital, Ullevål, patients receive bupivacaine infiltration local anaesthesia as well as oral paracetamol, ibuprofen and oxycodone for pain management during the first 24 hours post-surgery. The aim of this study was to survey pain after acute and elective caesarean sections in our department.
MATERIAL AND METHOD
The study included 50 patients who had undergone acute or elective caesarean section. Pain intensity on an 11-point numerical scale, pain duration, degree of mobilisation, and use of analgesia on postoperative day one were obtained from patient interviews and medical records.
RESULTS
Inadequate pain relief was defined as an average pain intensity of ≥ 4 and was reported by 34 patients (68 %). Total opioid consumption on postoperative day one exceeded 40 mg oral oxycodone equivalents in 28 patients. Of these, seven patients received more than 60 mg oral oxycodone equivalents.
INTERPRETATION
A large proportion of patients had high pain intensity and opioid requirement in the first 24 hours after caesarean section.
Topics: Analgesics, Opioid; Cesarean Section; Female; Humans; Oxycodone; Pain Management; Pain, Postoperative; Pregnancy
PubMed: 32378860
DOI: 10.4045/tidsskr.19.0506 -
CMAJ : Canadian Medical Association... Nov 2021
Topics: Accidents, Traffic; Acetaminophen; Analgesics, Opioid; Anxiety; Drug Combinations; Family Relations; Female; Humans; Musculoskeletal Pain; Opioid-Related Disorders; Oxycodone; Professional-Patient Relations; Self Concept
PubMed: 34782383
DOI: 10.1503/cmaj.211817 -
Missouri Medicine 2019
Topics: Drug Industry; Drug Overdose; Humans; Ownership; Oxycodone
PubMed: 31040484
DOI: No ID Found -
Drug and Alcohol Dependence May 2022To identify and characterize oxycodone related deaths in Sweden from 2006 to 2018 and to compare them to other opioid-related deaths.
AIM
To identify and characterize oxycodone related deaths in Sweden from 2006 to 2018 and to compare them to other opioid-related deaths.
METHODS
To assess the factors contributing to the deaths, we used multinomial logistic regression to compare oxycodone-related deaths extracted from all forensic autopsy examinations and toxicology cases in the age groups 15-34 (reference group), 35-54 and 55-74 with regard to sex, presence of benzodiazepines and alcohol at the time of death, prescription of oxycodone, benzodiazepines and antidepressants, previous substance use-related (SUD) treatment, and manner of death. The oxycodone related deaths were compared with deaths with presence of other opioids.
RESULT
We identified 575 oxycodone-related deaths, and the rate increased during the study period from 0.10 to 1.12 per 100,000 in parallel with an increase of oxycodone prescriptions from 3.17 to 30.33 per 1000. Oxycodone-related deaths amounted to 10.0% of all opioid-related deaths. The deaths occurred mainly in older patients previously being prescribed oxycodone. Benzodiazepines were present at the time of death in 403 (70%) and alcohol in 259 (45%). Prescriptions of any opioid for pain (61%), oxycodone (50%), benzodiazepines (67%) and antidepressants (55%) were common. Only 15% had received treatment for SUD during the last year.
CONCLUSION
Oxycodone-related deaths increased in Sweden between 2006 and 2018 in parallel to an increase in oxycodone prescriptions. The increase occurred mainly in older patients being prescribed oxycodone for pain. There might be specific interventions needed to avoid oxycodone-related deaths compared to other opioid-related deaths associated with illicit opioid use.
Topics: Aged; Analgesics, Opioid; Benzodiazepines; Humans; Opioid-Related Disorders; Oxycodone; Pain; Sweden
PubMed: 35306392
DOI: 10.1016/j.drugalcdep.2022.109402 -
Journal of Analytical Toxicology Feb 2022The purpose of this research was to develop and validate an analytical method for the detection and quantification of noroxymorphone-3β-D-glucuronide (NOMG),...
The purpose of this research was to develop and validate an analytical method for the detection and quantification of noroxymorphone-3β-D-glucuronide (NOMG), oxymorphone-3β-D-glucuronide (NOMG), noroxymorphone (NOM), oxymorphone (OM), 6α-oxycodol (αOCL), 6β-oxycodol (βOCL), noroxycodone (NOC) and oxycodone (OC) in urine by liquid chromatography tandem mass spectrometry to be used in a human study. The method was validated according to the Academy Standards Board Standard Practices for Method Development in Forensic Toxicology. The method was then applied to a single-dose pilot study of a subject. Urine samples were collected from the subject after ingesting 10-mg OC as an immediate-release tablet. Additionally, urine specimens (n = 15) that had previously been confirmed positive for OC were analyzed using the validated method. The calibration range for NOMG and OMG was 0.05-10 μg/mL; for all other analytes, it was 0.015-10 μg/mL. Validation parameters such as bias, precision, carryover and dilution integrity, all met the validation criteria. After the method was validated, urine samples from the first subject in the controlled dose study were analyzed. It was observed that OC, NOC and OMG contained the highest concentrations and were present in either the 0.5 or 1 h void. NOC and OMG were detected until the 48 h collection, while OC was detectable till the 24 h collection. Time to reach maximum concentration (Tmax) in the urine was achieved within 1.5 h for OC and within 3 h for NOC and OMG. Maximum concentration (Cmax) in the urine for OC, NOC and OMG was 3.15, 2.0 and 1.56 μg/mg, respectively. OC concentrations in authentic urines ranged from 0.015 to 12 μg/mL. Ranges for NOMG and OMG were 0.054-9.7 μg/mL and 0.14-67 μg/mL, respectively. A comprehensive method for the quantification of NOMG, OMG, NOM, OM, αOCL, βOCL, NOC and OC in urine was optimized and met the validation criteria. The concentrations of NOMG and OMG presented in this study provide the details needed in the forensic community to better comprehend OC pharmacokinetics.
Topics: Chromatography, Liquid; Humans; Oxycodone; Oxymorphone; Pilot Projects; Tandem Mass Spectrometry
PubMed: 33270113
DOI: 10.1093/jat/bkaa186 -
Molecular Neurobiology Dec 2021Sex differences in opioid analgesia occur in rodents and humans, and could be due to differences in drug and metabolite levels. Thus, we investigated the sex and cycle...
Sex differences in opioid analgesia occur in rodents and humans, and could be due to differences in drug and metabolite levels. Thus, we investigated the sex and cycle differences in analgesia (nociception) from oxycodone in rats and related these to sex and cycle differences in brain and plasma oxycodone and metabolite levels. Since numerous opioids are CYP2D enzyme substrates and variation in CYP2D alters opioid drug levels and response, we also initiated studies to see if the sex and cycle differences observed might be due to differences in brain CYP2D activity. Across oxycodone doses, females in diestrus had higher analgesia (using tail flick latency) compared to males and females in estrus; we also demonstrated a direct effect of estrous cycle on analgesia within females. Consistent with the analgesia, females in diestrus had highest brain oxycodone levels (assessed using microdialysis) compared to males and females in estrus. Analgesia correlated with brain oxycodone, but not brain oxymorphone or noroxycodone levels, or plasma drug or metabolite levels. Propranolol (a CYP2D mechanism-based inhibitor), versus vehicle pre-treatments, increased brain oxycodone, and decreased brain oxymorphone/oxycodone drug level ratios (an in vivo CYP2D activity phenotype in the brain) in males and females in estrus, but not in females in diestrus. Brain oxymorphone/oxycodone inversely correlated with analgesia. Together, both sex and estrous cycle impact oxycodone analgesia and brain oxycodone levels, likely through regulation of brain CYP2D oxycodone metabolism. As CYP2D6 is expressed in human brain, perhaps similar sex and cycle influences also occur in humans.
Topics: Analgesia; Analgesics, Opioid; Animals; Brain; Estrous Cycle; Female; Male; Oxycodone; Pain Measurement; Rats; Rats, Wistar; Sex Characteristics
PubMed: 34581987
DOI: 10.1007/s12035-021-02560-1