Oxycodone Explained

Verifiedrevid:464196835
Width:183
Width2:225
Tradename:OxyContin, Endone, others
Dailymedid:Oxycodone
Pregnancy Au:C
Pregnancy Au Comment:[1]
Dependency Liability:High[2]
Addiction Liability:High[3]
Routes Of Administration:By mouth, sublingual, intramuscular, intravenous, intranasal, subcutaneous, transdermal, rectal, epidural
Class:Opioid
Atc Prefix:N02
Atc Suffix:AA05
Atc Supplemental:
Legal Au:Schedule 8
Legal Br:A1
Legal Ca:Schedule I
Legal De:Anlage III
Legal Uk:Class A
Legal Us:Schedule II
Legal Un:N I
Bioavailability:By mouth: 60–87%[4]
Protein Bound:45%
Metabolism:Liver

mainly CYP3A, and, to a much lesser extent, CYP2D6 (~5%); 95% metabolized (i.e., 5% excreted unchanged)

Metabolites:• Noroxycodone (25%)[5]
• Noroxymorphone (15%, free and conjugated)
• Oxymorphone (11%, conjugated)
• Others (e.g., minor metabolites)
Onset:

10–30 minutes
: 1 hour[6]

Elimination Half-Life:By mouth (IR): 2–3 hrs (same for all)
By mouth (CR): 4.5 hrs
Duration Of Action:By mouth (IR): 3–6 hrs
By mouth (CR): 10–12 hrs
Excretion:Urine (83%)
Index2 Label:as HCl
Cas Number:76-42-6
Pubchem:5284603
Iuphar Ligand:7093
Drugbank:DB00497
Chemspiderid:4447649
Unii:CD35PMG570
Kegg:D05312
Kegg2:D00847
Chebi:7852
Chembl:656
Synonyms:Eukodal, eucodal; dihydrohydroxycodeinone, 7,8-dihydro-14-hydroxycodeinone, 6-deoxy-7,8-dihydro-14-hydroxy-3-O-methyl-6-oxomorphine
Iupac Name:(5R,9R,13S,14S)-4,5α-Epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one
C:18
H:21
N:1
O:4
Smiles:O=C4[C@@H]5Oc1c2c(ccc1OC)C[C@H]3N(CC[C@]25[C@@]3(O)CC4)C
Stdinchi:1S/C18H21NO4/c1-19-8-7-17-14-10-3-4-12(22-2)15(14)23-16(17)11(20)5-6-18(17,21)13(19)9-10/h3-4,13,16,21H,5-9H2,1-2H3/t13-,16+,17+,18-/m1/s1
Stdinchikey:BRUQQQPBMZOVGD-XFKAJCMBSA-N
Melting Point:219
Solubility:166
Sol Units: (HCl)

Oxycodone, sold under various brand names such as Roxicodone, Endone, and OxyContin (which is the extended-release form), is a semi-synthetic opioid used medically for treatment of moderate to severe pain. It is highly addictive[7] and is a commonly abused drug.[8] It is usually taken by mouth, and is available in immediate-release and controlled-release formulations. Onset of pain relief typically begins within fifteen minutes and lasts for up to six hours with the immediate-release formulation. In the United Kingdom, it is available by injection.[9] Combination products are also available with paracetamol (acetaminophen), ibuprofen, naloxone, naltrexone, and aspirin.

Common side effects include euphoria, constipation, nausea, vomiting, loss of appetite, drowsiness, dizziness, itching, dry mouth, and sweating.[8] Side effects may also include addiction and dependence, substance abuse, irritability, depression or mania, delirium, hallucinations, hypoventilation, gastroparesis, bradycardia, and hypotension.[8] Those allergic to codeine may also be allergic to oxycodone.[8] Use of oxycodone in early pregnancy appears relatively safe.[8] Opioid withdrawal may occur if rapidly stopped.[8] Oxycodone acts by activating the μ-opioid receptor.[10] When taken by mouth, it has roughly 1.5 times the effect of the equivalent amount of morphine.[11]

Oxycodone was originally produced from the opium poppy opiate alkaloid thebaine in 1916. It was first used medically in Germany in 1917.[12] It is on the World Health Organization's List of Essential Medicines.[13] It is available as a generic medication.[8] In 2021, it was the 59th most commonly prescribed medication in the United States, with more than 11million prescriptions.[14] [15] A number of abuse-deterrent formulations are available, such as in combination with naloxone or naltrexone.[16] [17]

Medical uses

Oxycodone is used for managing moderate to severe acute or chronic pain when other treatments are not sufficient.[8] It may improve quality of life in certain types of pain.[18] Numerous studies have been completed, and the appropriate use of this compound does improve the quality of life of patients with long term chronic pain syndromes.[19] [20] [21]

Oxycodone is available as a controlled-release tablet, intended to be taken every 12 hours.[22] A 2006 review found that controlled-release oxycodone is comparable to immediate-release oxycodone, morphine, and hydromorphone in management of moderate to severe cancer pain, with fewer side effects than morphine. The author concluded that the controlled-release form is a valid alternative to morphine and a first-line treatment for cancer pain. In 2014, the European Association for Palliative Care recommended oxycodone by mouth as a second-line alternative to morphine by mouth for cancer pain.[23]

In children between 11 and 16, the extended-release formulation is FDA-approved for the relief of cancer pain, trauma pain, or pain due to major surgery (for those already treated with opioids, who can tolerate at least 20 mg per day of oxycodone) - this provides an alternative to Duragesic (fentanyl), the only other extended-release opioid analgesic approved for children.[24]

Oxycodone, in its extended-release form and/or in combination with naloxone, is sometimes used off-label in the treatment of severe and refractory restless legs syndrome.[25]

Available forms

See also: Oxycodone/paracetamol, Oxycodone/aspirin, Oxycodone/ibuprofen and Oxycodone/naloxone.

Oxycodone is available in a variety of formulations for by mouth or under the tongue:[26] [27] [28] [29]

In the US, oxycodone is only approved for use by mouth, available as tablets and oral solutions. Parenteral formulations of oxycodone (brand name OxyNorm) are also available in other parts of the world, however, and are widely used in the European Union.[35] [36] [37] In Spain, the Netherlands and the United Kingdom, oxycodone is approved for intravenous (IV) and intramuscular (IM) use. When first introduced in Germany during World War I, both IV and IM administrations of oxycodone were commonly used for postoperative pain management of Central Powers soldiers.[38]

Side effects

Most common side effects of oxycodone include reduced sensitivity to pain, delayed gastric emptying, euphoria, anxiolysis (a reduction in anxiety), feelings of relaxation, and respiratory depression. Common side effects of oxycodone include constipation (23%), nausea (23%), vomiting (12%), somnolence (23%), dizziness (13%), itching (13%), dry mouth (6%), and sweating (5%).[39] Less common side effects (experienced by less than 5% of patients) include loss of appetite, nervousness, abdominal pain, diarrhea, urinary retention, dyspnea, and hiccups.

Most side effects generally become less intense over time, although issues related to constipation are likely to continue for the duration of use.[40] Chronic use of this compound and associated constipation issues can become very serious, and have been implicated in life-threatening bowel perforations,[41] a number of specific medications including naloxegol[42] have been developed to address opioid induced constipation.

Oxycodone in combination with naloxone in managed-release tablets has been formulated to both deter abuse and reduce opioid-induced constipation.[43]

Dependence and withdrawal

See also: Opioid dependence.

The risk of experiencing severe withdrawal symptoms is high if a patient has become physically dependent and discontinues oxycodone abruptly. Medically, when the drug has been taken regularly over an extended period, it is withdrawn gradually rather than abruptly. People who regularly use oxycodone recreationally or at higher than prescribed doses are at even higher risk of severe withdrawal symptoms. The symptoms of oxycodone withdrawal, as with other opioids, may include "anxiety, panic attack, nausea, insomnia, muscle pain, muscle weakness, fevers, and other flu-like symptoms".[44] [45]

Withdrawal symptoms have also been reported in newborns whose mothers had been either injecting or orally taking oxycodone during pregnancy.[46]

Hormone levels

As with other opioids, chronic use of oxycodone (particularly with higher doses) can often cause concurrent hypogonadism (low sex hormone levels).[47] [48]

Overdose

In high doses, overdoses, or in some persons not tolerant to opioids, oxycodone can cause shallow breathing, slowed heart rate, cold/clammy skin, pauses in breathing, low blood pressure, constricted pupils, circulatory collapse, respiratory arrest, and death.

In 2011, it was the leading cause of drug-related deaths in the U.S.[49] However, from 2012 onwards, heroin and fentanyl have become more common causes of drug-related deaths.[49]

Oxycodone overdose has also been described to cause spinal cord infarction in high doses and ischemic damage to the brain, due to prolonged hypoxia from suppressed breathing.[50]

Interactions

Oxycodone is metabolized by the enzymes CYP3A4 and CYP2D6. Therefore, its clearance can be altered by inhibitors and inducers of these enzymes, increasing and decreasing half-life, respectively. (For lists of CYP3A4 and CYP2D6 inhibitors and inducers, see here and here, respectively.) Natural genetic variation in these enzymes can also influence the clearance of oxycodone, which may be related to the wide inter-individual variability in its half-life and potency.

Ritonavir or lopinavir/ritonavir greatly increase plasma concentrations of oxycodone in healthy human volunteers due to inhibition of CYP3A4 and CYP2D6.[51] Rifampicin greatly reduces plasma concentrations of oxycodone due to strong induction of CYP3A4.[52] There is also a case report of fosphenytoin, a CYP3A4 inducer, dramatically reducing the analgesic effects of oxycodone in a chronic pain patient.[53] Dosage or medication adjustments may be necessary in each case.

Pharmacology

Pharmacodynamics

Oxycodone (and metabolite) at opioid receptors
Compound Affinities Ratio
MOR:DOR:KOR
Oxycodone 18 nM 958 nM 677 nM 1:53:38
Oxymorphone 0.78 nM 50 nM 137 nM 1:64:176 [54]

Equianalgesic doses[55] [56] [57]
Compound Dose
200 mg
20–30 mg
7.5 mg
1.5 mg
30 mg
10 mg
Oxycodone 20 mg
Oxycodone 10 mg
10 mg
1 mg

Oxycodone, a semi-synthetic opioid, is a highly selective full agonist of the μ-opioid receptor (MOR). This is the main biological target of the endogenous opioid neuropeptide β-endorphin. Oxycodone has low affinity for the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR), where it is an agonist similarly. After oxycodone binds to the MOR, a G protein-complex is released, which inhibits the release of neurotransmitters by the cell by decreasing the amount of cAMP produced, closing calcium channels, and opening potassium channels.[58] Opioids like oxycodone are thought to produce their analgesic effects via activation of the MOR in the midbrain periaqueductal gray (PAG) and rostral ventromedial medulla (RVM).[59] Conversely, they are thought to produce reward and addiction via activation of the MOR in the mesolimbic reward pathway, including in the ventral tegmental area, nucleus accumbens, and ventral pallidum.[60] [61] Tolerance to the analgesic and rewarding effects of opioids is complex and occurs due to receptor-level tolerance (e.g., MOR downregulation), cellular-level tolerance (e.g., cAMP upregulation), and system-level tolerance (e.g., neural adaptation due to induction of ΔFosB expression).[62]

Taken orally, 20 mg of immediate-release oxycodone is considered to be equivalent in analgesic effect to 30 mg of morphine,[63] [64] while extended release oxycodone is considered to be twice as potent as oral morphine.[65]

Similarly to most other opioids, oxycodone increases prolactin secretion, but its influence on testosterone levels is unknown. Unlike morphine, oxycodone lacks immunosuppressive activity (measured by natural killer cell activity and interleukin 2 production in vitro); the clinical relevance of this has not been clarified.

Active metabolites

A few of the metabolites of oxycodone have also been found to be active as MOR agonists, some of which notably have much higher affinity for (as well as higher efficacy at) the MOR in comparison.[66] [67] [68] Oxymorphone possesses 3- to 5-fold higher affinity for the MOR than does oxycodone,[69] while noroxycodone and noroxymorphone possess one-third of and 3-fold higher affinity for the MOR, respectively,[69] and MOR activation is 5- to 10-fold less with noroxycodone but 2-fold higher with noroxymorphone relative to oxycodone. Noroxycodone, noroxymorphone, and oxymorphone also have longer biological half-lives than oxycodone.[70]

Pharmacology of oxycodone and metabolites
Compound
Oxycodone 16.0 nM 343 nM 23.2 ± 8.6 ng/mL 236 ± 102 ng/h/mL
0.36 nM 42.8 nM 0.82 ± 0.85 ng/mL 12.3 ± 12 ng/h/mL
57.1 nM 1930 nM 15.2 ± 4.5 ng/mL 233 ± 102 ng/h/mL
5.69 nM 167 nM

However, despite the greater in vitro activity of some of its metabolites, it has been determined that oxycodone itself is responsible for 83.0% and 94.8% of its analgesic effect following oral and intravenous administration, respectively. Oxymorphone plays only a minor role, being responsible for 15.8% and 4.5% of the analgesic effect of oxycodone after oral and intravenous administration, respectively. Although the CYP2D6 genotype and the route of administration result in differential rates of oxymorphone formation, the unchanged parent compound remains the major contributor to the overall analgesic effect of oxycodone. In contrast to oxycodone and oxymorphone, noroxycodone and noroxymorphone, while also potent MOR agonists, poorly cross the blood–brain barrier into the central nervous system, and for this reason are only minimally analgesic in comparison.

κ-opioid receptor

In 1997, a group of Australian researchers proposed (based on a study in rats) that oxycodone acts on KORs, unlike morphine, which acts upon MORs.[71] Further research by this group indicated the drug appears to be a high-affinity κ2b-opioid receptor agonist.[72] However, this conclusion has been disputed, primarily on the basis that oxycodone produces effects that are typical of MOR agonists.[73] In 2006, research by a Japanese group suggested the effect of oxycodone is mediated by different receptors in different situations.[74] Specifically in diabetic mice, the KOR appears to be involved in the antinociceptive effects of oxycodone, while in nondiabetic mice, the μ1-opioid receptor seems to be primarily responsible for these effects.[75]

Pharmacokinetics

Instant-release absorption profiles and Tmax

Oxycodone can be administered orally, intravenously, via intravenous, intramuscular, or subcutaneous injection. Along with rectal, sublingual, buccal or intranasal drug delivery. The bioavailability of oral administration of oxycodone averages within a range of 60 to 87%, with rectal administration yielding the same results; Intranasal administration of oxycodone has a bioavailability of ~77%, the same half life as oral oxycodone, along with faster Tmax[76] previously reported as 47% for nasal spray administration due to the solution in the study exceeding the 0.3- to 0.4-mL nasal mucosa limit.[77] Buccal bioavailability ~55%, Tmax ~60 min.[78] Sublingual bioavailability 20% (non alkalized) ~55% (alkalized) Tmax ~60 minutes.[79] [80]

After a dose of conventional (immediate-release) oral oxycodone, the onset of action is 10 to 30 minutes,[69] [26] and peak plasma levels of the drug are attained within roughly 30 to 60 minutes;[69] [26] in contrast, after a dose of OxyContin (an oral controlled-release formulation), peak plasma levels of oxycodone occur in about three hours.[81] The duration of instant-release oxycodone is 3 to 6 hours, although this can be variable depending on the individual.[69]

Distribution

Oxycodone has a volume of distribution of 2.6L/kg,[82] in the blood it is distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain. At equilibrium the unbound concentration in the brain is threefold higher than the unbound concentration in blood.[83] Conventional oral preparations start to reduce pain within 10 to 15 minutes on an empty stomach; in contrast, OxyContin starts to reduce pain within one hour.[8]

Metabolism

The metabolism of oxycodone in humans occurs in the liver mainly via the cytochrome P450 system and is extensive (about 95%) and complex, with many minor pathways and resulting metabolites.[84] Around 10% (range 8–14%) of a dose of oxycodone is excreted essentially unchanged (unconjugated or conjugated) in the urine.[69] The major metabolites of oxycodone are noroxycodone (70%), noroxymorphone ("relatively high concentrations"),[85] and oxymorphone (5%).[86] The immediate metabolism of oxycodone in humans is as follows:[69] [87] [88]

In humans, N-demethylation of oxycodone to noroxycodone by CYP3A4 is the major metabolic pathway, accounting for 45% ± 21% of a dose of oxycodone, while O-demethylation of oxycodone into oxymorphone by CYP2D6 and 6-ketoreduction of oxycodone into 6-oxycodols represent relatively minor metabolic pathways, accounting for 11% ± 6% and 8% ± 6% of a dose of oxycodone, respectively.[69]

Several of the immediate metabolites of oxycodone are subsequently conjugated with glucuronic acid and excreted in the urine.[69] 6α-Oxycodol and 6β-oxycodol are further metabolized by N-demethylation to nor-6α-oxycodol and nor-6β-oxycodol, respectively, and by N-oxidation to 6α-oxycodol-N-oxide and 6β-oxycodol-N-oxide (which can subsequently be glucuronidated as well).[69] [87] Oxymorphone is also further metabolized, as follows:[69] [87]

The first pathway of the above three accounts for 40% of the metabolism of oxymorphone, making oxymorphone-3-glucuronide the main metabolite of oxymorphone, while the latter two pathways account for less than 10% of the metabolism of oxymorphone. After N-demethylation of oxymorphone, noroxymorphone is further glucuronidated to noroxymorphone-3-glucuronide.

Because oxycodone is metabolized by the cytochrome P450 system in the liver, its pharmacokinetics can be influenced by genetic polymorphisms and drug interactions concerning this system, as well as by liver function. Some people are fast metabolizers of oxycodone, while others are slow metabolizers, resulting in polymorphism-dependent alterations in relative analgesia and toxicity.[89] [90] While higher CYP2D6 activity increases the effects of oxycodone (owing to increased conversion into oxymorphone), higher CYP3A4 activity has the opposite effect and decreases the effects of oxycodone (owing to increased metabolism into noroxycodone and noroxymorphone).[91] The dose of oxycodone must be reduced in patients with reduced liver function.[92]

Elimination

The clearance of oxycodone is 0.8 L/min.[82] Oxycodone and its metabolites are mainly excreted in urine.[93] Therefore, oxycodone accumulates in patients with kidney impairment. Oxycodone is eliminated in the urine 10% as unchanged oxycodone, 45% ± 21% as N-demethylated metabolites (noroxycodone, noroxymorphone, noroxycodols), 11 ± 6% as O-demethylated metabolites (oxymorphone, oxymorphols), and 8% ± 6% as 6-keto-reduced metabolites (oxycodols).[66]

Duration of action

Oral oxycodone has a half-life of 4.5 hours.[82] It is available as a generic medication. The manufacturer of OxyContin, a controlled-release preparation of oxycodone, Purdue Pharma, claimed in their 1992 patent application that the duration of action of OxyContin is 12 hours in "90% of patients". It has never performed any clinical studies in which OxyContin was given at more frequent intervals. In a separate filing, Purdue claims that controlled-release oxycodone "provides pain relief in said patient for at least 12 hours after administration".[94] However, in 2016 an investigation by the Los Angeles Times found that "the drug wears off hours early in many people", inducing symptoms of opiate withdrawal and intense cravings for OxyContin. One doctor, Lawrence Robbins, told journalists that over 70% of his patients would report that OxyContin would only provide 4–7 hours of relief. Doctors in the 1990s often would switch their patients to a dosing schedule of once every eight hours when they complained that the duration of action for OxyContin was too short to be taken only twice a day.[94] [95]

Purdue strongly discouraged the practice: Purdue's medical director Robert Reder wrote to one doctor in 1995 that "OxyContin has been developed for [12-hour] dosing...I request that you not use a [8-hourly] dosing regimen." Purdue repeatedly released memos to its sales representatives ordering them to remind doctors not to deviate from a 12-hour dosing schedule. One such memo read, "There is no Q8 dosing with OxyContin... [8-hour dosing] needs to be nipped in the bud. NOW!!"[94] The journalists who covered the investigation argued that Purdue Pharma has insisted on a 12-hour duration of action for nearly all patients, despite evidence to the contrary, to protect the reputation of OxyContin as a 12-hour drug and the willingness of health insurance and managed care companies to cover OxyContin despite its high cost relative to generic opiates such as morphine.[94]

Purdue sales representatives were instructed to encourage doctors to write prescriptions for larger 12-hour doses instead of more frequent dosing. An August 1996 memo to Purdue sales representatives in Tennessee entitled "$$$$$$$$$$$$$ It's Bonus Time in the Neighborhood!" reminded the representatives that their commissions would dramatically increase if they were successful in convincing doctors to prescribe larger doses. Los Angeles Times journalists argue using interviews from opioid addiction experts that such high doses of OxyContin spaced 12 hours apart create a combination of agony during opiate withdrawal (lower lows) and a schedule of reinforcement that relieves this agony fostering addiction.[94]

Chemistry

See also: List of opioids.

Oxycodone's chemical name is derived from codeine. The chemical structures are very similar, differing only in that

It is also similar to hydrocodone, differing only in that it has a hydroxyl group at carbon-14.[92]

Biosynthesis

In terms of biosynthesis, oxycodone has been found naturally in nectar extracts from the orchid family Epipactis helleborine; together along with another opioid: 3-

Notes and References

  1. Web site: Oxycodone Use During Pregnancy . Drugs.com . 14 October 2019 . 12 April 2020 . 19 June 2020 . https://web.archive.org/web/20200619114900/https://www.drugs.com/pregnancy/oxycodone.html . live .
  2. Book: Bonewit-West K, Hunt SA, Applegate E . Today's Medical Assistant: Clinical and Administrative Procedures . 2012 . 571 . Elsevier Health Sciences . 978-1-4557-0150-6 . en . 20 August 2019 . 6 October 2022 . https://web.archive.org/web/20221006090150/https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 . live .
  3. Book: Bonewit-West K, Hunt SA, Applegate E . Today's Medical Assistant: Clinical and Administrative Procedures . 2012 . 571 . Elsevier Health Sciences . 9781455701506 . 20 August 2019 . 10 January 2023 . https://web.archive.org/web/20230110030031/https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 . live .
  4. Web site: Roxicodone, OxyContin (oxycodone) dosing, indications, interactions, adverse effects, and more . Medscape Reference . WebMD . 8 April 2014 . 13 April 2014 . https://web.archive.org/web/20140413145108/http://reference.medscape.com/drug/roxicodone-oxycontin-oxycodone-343321#showall . live .
  5. Web site: Roxicodone, OxyContin (oxycodone) dosing, indications, interactions, adverse effects, and more . Medscape Reference . WebMD . 4 January 2019 . 13 April 2014 . https://web.archive.org/web/20140413145108/http://reference.medscape.com/drug/roxicodone-oxycontin-oxycodone-343321#showall . live .
  6. Book: Yarbro CH, Wujcik D, Gobel BH . Cancer Nursing: Principles and Practice . 15 November 2010 . Jones & Bartlett Publishers . 978-1-4496-1829-2 . 695–.
  7. Remillard D, Kaye AD, McAnally H . Oxycodone's Unparalleled Addictive Potential: Is it Time for a Moratorium? . Current Pain and Headache Reports . 23 . 2 . 15 . February 2019 . 30820686 . 10.1007/s11916-019-0751-7 . 73488265 .
  8. Web site: Oxycodone Monograph for Professionals . Drugs.com . AHFS . 28 December 2018 . 28 December 2018 . https://web.archive.org/web/20181228174726/https://www.drugs.com/monograph/oxycodone.html . live .
  9. Book: British national formulary : BNF 74. 2017. British Medical Association. 978-0-85711-298-9. 442. 74.
  10. Book: Talley NJ, Frankum B, Currow D . Essentials of Internal Medicine 3e. 10 February 2015. Elsevier Health Sciences. 978-0-7295-8081-6. 491–.
  11. Web site: Stanford School of Medicine, Palliative Care. Opioid Conversion / Equivalency Table. 20 April 2013. 27 October 2017. 9 September 2020. https://web.archive.org/web/20200909012800/https://palliative.stanford.edu/opioid-conversion/equivalency-table/. dead.
  12. Kalso E . Oxycodone . Journal of Pain and Symptom Management . 29 . 5 Suppl . S47–S56 . May 2005 . 15907646 . 10.1016/j.jpainsymman.2005.01.010 . free .
  13. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 22nd list (2021) . 2021 . 10665/345533 . World Health Organization . World Health Organization . Geneva . WHO/MHP/HPS/EML/2021.02 . free .
  14. Web site: The Top 300 of 2021 . ClinCalc . 14 January 2024 . 15 January 2024 . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . live .
  15. Web site: Oxycodone – Drug Usage Statistics . ClinCalc . 14 January 2024 .
  16. Pergolizzi JV, Taylor R, LeQuang JA, Raffa RB . Managing severe pain and abuse potential: the potential impact of a new abuse-deterrent formulation oxycodone/naltrexone extended-release product . Journal of Pain Research . 11 . 301–311 . 2018 . 29445297 . 5810535 . 10.2147/JPR.S127602 . free .
  17. Dart RC, Iwanicki JL, Dasgupta N, Cicero TJ, Schnoll SH . Do abuse deterrent opioid formulations work? . Journal of Opioid Management . 13 . 6 . 365–378 . 2017 . 29308584 . 10.5055/jom.2017.0415 .
  18. Riley J, Eisenberg E, Müller-Schwefe G, Drewes AM, Arendt-Nielsen L . Oxycodone: a review of its use in the management of pain . Current Medical Research and Opinion . 24 . 1 . 175–192 . January 2008 . 18039433 . 10.1185/030079908X253708 . 9099037 .
  19. Ueberall MA, Eberhardt A, Mueller-Schwefe GH . Quality of life under oxycodone/naloxone, oxycodone, or morphine treatment for chronic low back pain in routine clinical practice . International Journal of General Medicine . 9 . 39–51 . 24 February 2016 . 26966387 . 4771398 . 10.2147/IJGM.S94685 . free .
  20. Dowell D, Haegerich TM, Chou R . CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016 . en-us . MMWR. Recommendations and Reports . 65 . 1 . 1–49 . March 2016 . 26987082 . 10.15585/mmwr.rr6501e1er . free . 6390846 .
  21. Roth AR, Lazris A, Haskell H, James J . Appropriate Use of Opioids for Chronic Pain . en-US . American Family Physician . 102 . 6 . 335–337 . September 2020 . 32931211 .
  22. Biancofiore G . Oxycodone controlled release in cancer pain management . Therapeutics and Clinical Risk Management . 2 . 3 . 229–234 . September 2006 . 18360598 . 1936259 . 10.2147/tcrm.2006.2.3.229 . free .
  23. Hanks GW, Conno F, Cherny N, Hanna M, Kalso E, McQuay HJ, Mercadante S, Meynadier J, Poulain P, Ripamonti C, Radbruch L, Casas JR, Sawe J, Twycross RG, Ventafridda V . Morphine and alternative opioids in cancer pain: the EAPC recommendations . British Journal of Cancer . 84 . 5 . 587–593 . March 2001 . 11237376 . 2363790 . 10.1054/bjoc.2001.1680 .
  24. Web site: FDA approves OxyContin for kids 11 to 16. www.msn.com. 11 February 2018. https://web.archive.org/web/20170630065901/http://www.msn.com/en-us/news/us/fda-approves-oxycontin-for-kids-11-to-16/ar-BBlK3zS?ocid=spartandhp. 30 June 2017. dead.
  25. Web site: Restless Legs Syndrome Baylor Medicine . 6 November 2023 . www.bcm.edu . en.
  26. Book: Elliott JA, Smith HS . Handbook of Acute Pain Management . 19 April 2016 . CRC Press . 978-1-4665-9635-1 . 82–.
  27. Book: Gould III HJ . Understanding Pain: What It Is, Why It Happens, and How It's Managed . 11 December 2006. Demos Medical Publishing. 978-1-934559-82-6. 71–.
  28. Book: Graves K . Drug I.D. & Symptom Guide . 6th . QWIK-CODE . 29 September 2015. LawTech Publishing Group. 978-1-56325-225-9 . 99–.
  29. Book: Skidmore-Roth L . Mosby's Drug Guide for Nursing Students, with 2016 Update . 16 July 2015 . Elsevier Health Sciences . 978-0-323-17297-4 . 789– . 5 October 2016 . 7 October 2022 . https://web.archive.org/web/20221007000409/https://books.google.com/books?id=g_BwCgAAQBAJ&pg=PA789 . live.
  30. Sunshine A, Olson NZ, Colon A, Rivera J, Kaiko RF, Fitzmartin RD, Reder RF, Goldenheim PD . July 1996 . Analgesic efficacy of controlled-release oxycodone in postoperative pain . Journal of Clinical Pharmacology . 36 . 7 . 595–603 . 10.1002/j.1552-4604.1996.tb04223.x . 8844441 . 35076787 . Treatment with CR oxycodone was safe and effective in this study, and its characteristics will be beneficial in the treatment of pain..
  31. Web site: accessdata.fda.gov. 11 February 2018. 12 February 2017. https://web.archive.org/web/20170212033248/http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022272Orig1s014ClinPharmR.pdf. live.
  32. Book: Sinatra RS, de Leon-Cassasola OA. Acute Pain Management. 27 April 2009. Cambridge University Press. 978-0-521-87491-5. 198–. 5 October 2016. 7 October 2022. https://web.archive.org/web/20221007000410/https://books.google.com/books?id=ORpBaZnBSaQC&pg=PA198. live.
  33. Book: Staats PS, Silverman SM. Controlled Substance Management in Chronic Pain: A Balanced Approach. 28 May 2016. Springer. 978-3-319-30964-4. 172–. 5 October 2016. 7 October 2022. https://web.archive.org/web/20221007000410/https://books.google.com/books?id=-WxBDAAAQBAJ&pg=PA172. live.
  34. Web site: FDA Approves Troxyca® ER (Oxycodone Hydrochloride and Naltrexone Hydrochloride) Extended-release Capsules CII with Abuse-deterrent Properties for the Management of Pain . 19 August 2016 . 21 June 2018 . 25 September 2020 . https://web.archive.org/web/20200925173435/https://www.pfizer.com/news/press-release/press-release-detail/fda_approves_troxyca_er_oxycodone_hydrochloride_and_naltrexone_hydrochloride_extended_release_capsules_cii_with_abuse_deterrent_properties_for_the_management_of_pain . live.
  35. Book: Davis MP . Opioids in Cancer Pain . 28 May 2009 . OUP Oxford . 978-0-19-923664-0 . 155–158 . 5 October 2016 . 7 October 2022 . https://web.archive.org/web/20221007000410/https://books.google.com/books?id=aEzg6i2nPMQC&pg=PA158 . live.
  36. Book: Forbes K . Opioids in Cancer Pain . 29 November 2007 . OUP Oxford . 978-0-19-921880-6 . 64–65.
  37. Book: Bradbury H, Hodge BS . Practical Prescribing for Medical Students . 8 November 2013 . SAGE Publications . 978-1-4462-9753-7 . 93– . 5 October 2016 . 7 October 2022 . https://web.archive.org/web/20221007000411/https://books.google.com/books?id=U5L3AgAAQBAJ&pg=PT93 . live.
  38. Kalso E . Oxycodone . Journal of Pain and Symptom Management . 29 . 5 Suppl . S47–S56 . May 2005 . 15907646 . 10.1016/j.jpainsymman.2005.01.010 . free.
  39. Web site: Oxycodone Side Effects . Drugs.com . 22 May 2013 . 21 June 2013 . https://web.archive.org/web/20130621052514/http://www.drugs.com/sfx/oxycodone-side-effects.html . live .
  40. Ordóñez Gallego A, González Barón M, Espinosa Arranz E . Oxycodone: a pharmacological and clinical review . Clinical & Translational Oncology . 9 . 5 . 298–307 . May 2007 . 17525040 . 10.1007/s12094-007-0057-9 . 44986791 .
  41. Poitras R, Warren D, Oyogoa S . Opioid drugs and stercoral perforation of the colon: Case report and review of literature . International Journal of Surgery Case Reports . 42 . 94–97 . 7 December 2017 . 29232630 . 5730425 . 10.1016/j.ijscr.2017.11.060 .
  42. Web site: Movantik for the Treatment of Opioid-Induced Constipation . 11 November 2023 . Clinical Trials Arena . en-US.
  43. Simpson K, Leyendecker P, Hopp M, Müller-Lissner S, Löwenstein O, De Andrés J, Troy Ferrarons J, Bosse B, Krain B, Nichols T, Kremers W, Reimer K . Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain . Current Medical Research and Opinion . 24 . 12 . 3503–3512 . December 2008 . 19032132 . 10.1185/03007990802584454 . 73061000 .
  44. Web site: Oxycodone . 25 March 2009 . 2 May 2005 . Center for Substance Abuse Research . 6 April 2009 . https://web.archive.org/web/20090406010900/http://www.cesar.umd.edu/cesar/drugs/oxycodone.asp . dead .
  45. Web site: Tapering off opioids: When and how. Mayo Clinic. 10 October 2020.
  46. Rao R, Desai NS . OxyContin and neonatal abstinence syndrome . Journal of Perinatology . 22 . 4 . 324–325 . June 2002 . 12032797 . 10.1038/sj.jp.7210744 . 22539877 .
  47. Coluzzi F, Billeci D, Maggi M, Corona G . Testosterone deficiency in non-cancer opioid-treated patients . . 41 . 12 . 1377–1388 . December 2018 . 30343356 . 6244554 . 10.1007/s40618-018-0964-3.
  48. Brennan MJ . The effect of opioid therapy on endocrine function . The American Journal of Medicine . 126 . 3 Suppl 1 . S12–S18 . March 2013 . 23414717 . 10.1016/j.amjmed.2012.12.001 .
  49. Web site: Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 2011–2016 . CDC . 21 December 2018 . 12 December 2018 . 13 December 2018 . https://web.archive.org/web/20181213221854/https://www.cdc.gov/nchs/data/nvsr/nvsr67/nvsr67_09-508.pdf . live .
  50. Ntranos A, Shoirah H, Dhamoon MS, Hahn D, Naidich TP, Shin S . Clinical Reasoning: A young woman with respiratory failure, hearing loss, and paraplegia . Neurology . 88 . 10 . e78–e84 . March 2017 . 28265044 . 10.1212/WNL.0000000000003684 . free .
  51. Nieminen TH, Hagelberg NM, Saari TI, Neuvonen M, Neuvonen PJ, Laine K, Olkkola KT . Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir . European Journal of Clinical Pharmacology . 66 . 10 . 977–985 . October 2010 . 20697700 . 10.1007/s00228-010-0879-1 . 25770818 .
  52. Nieminen TH, Hagelberg NM, Saari TI, Pertovaara A, Neuvonen M, Laine K, Neuvonen PJ, Olkkola KT . Rifampin greatly reduces the plasma concentrations of intravenous and oral oxycodone . Anesthesiology . 110 . 6 . 1371–1378 . June 2009 . 19417618 . 10.1097/ALN.0b013e31819faa54 . free .
  53. Pon D, Hwang J, Lo T, Zyl CV . Decreased responsiveness to oxycodone: A case of a pharmacokinetic drug interaction? . Journal of Opioid Management . 11 . 4 . 357–361 . 2015 . 26312962 . 10.5055/jom.2015.0284 .
  54. Book: Corbett AD, Paterson SJ, Kosterlitz HW . Selectivity of Ligands for Opioid Receptors . Opioids . 104 . 1 . 1993 . 645–679 . 0171-2004 . 10.1007/978-3-642-77460-7_26 . Handbook of Experimental Pharmacology . 978-3-642-77462-1.
  55. Book: King TL, Brucker MC . Pharmacology for Women's Health. 25 October 2010. Jones & Bartlett Publishers. 978-1-4496-1073-9. 332–.
  56. Book: Chestnut DH, Wong CA, Tsen LC, Ngan Kee WD, Beilin YM, Mhyre J. Chestnut's Obstetric Anesthesia: Principles and Practice E-Book. 28 February 2014. Elsevier Health Sciences. 978-0-323-11374-8. 611–. 22 June 2018. 6 October 2022. https://web.archive.org/web/20221006145548/https://books.google.com/books?id=FMU0AwAAQBAJ&pg=PA611. live.
  57. Book: Tiziani AP. Havard's Nursing Guide to Drugs. 1 June 2013. Elsevier Health Sciences. 978-0-7295-8162-2. 933–. 22 June 2018. 6 October 2022. https://web.archive.org/web/20221006145548/https://books.google.com/books?id=XpzQAgAAQBAJ&pg=PA933. live.
  58. Chahl L . 1996 . Opioids- mechanism of action . Aust Prescr . 19 . 3. 63–65 . 10.18773/austprescr.1996.063. free .
  59. Book: Stein C. Opioids in Pain Control: Basic and Clinical Aspects. 1999. Cambridge University Press. 978-0-521-62269-1. 46–. 21 June 2018. 7 October 2022. https://web.archive.org/web/20221007000411/https://books.google.com/books?id=4Rfr8cQayvgC&pg=PA46. live.
  60. Book: Squire L, Berg D, Bloom FE, du Lac S, Ghosh A, Spitzer NC . Fundamental Neuroscience . 17 December 2012 . Academic Press . 978-0-12-385871-9 . 884– . 21 June 2018 . 7 October 2022 . https://web.archive.org/web/20221007000411/https://books.google.com/books?id=QGzJFu_NyzcC&pg=PA884 . live .
  61. Book: Kringelbach ML, Berridge KC . Pleasures of the Brain . 2010. Oxford University Press . 978-0-19-533102-8. 33–.
  62. Book: Sinatra RS, Jahr JS, Watkins-Pitchford JM . The Essence of Analgesia and Analgesics . 14 October 2010. Cambridge University Press. 978-1-139-49198-3. 167–.
  63. Web site: Treatment of Pain. Merck Manuals Professional Edition. 24 April 2016. 3 May 2016. https://web.archive.org/web/20160503150513/http://www.merckmanuals.com/professional/neurologic-disorders/pain/treatment-of-pain. live.
  64. Book: https://books.google.com/books?id=Q5iNSuBma0AC . Pain Assessment and Pharmacologic Management . Ferrell BR, Pasero C, McCaffery M . 2010 . Elsevier Health Sciences . 978-0-323-08263-1 . en . Table 16-1 Equianalgesic Dose Chart . 24 April 2016 . 7 October 2022 . https://web.archive.org/web/20221007000412/https://books.google.com/books?id=Q5iNSuBma0AC . live .
  65. Book: Levy EF, Victor J. Opioids in medicine a comprehensive review on the mode of action and the use of analgesics in different clinical pain states. 2007. Springer Science+Business Media B.V.. New York. 978-1-4020-5947-6. 371. 1 February 2016. 7 October 2022. https://web.archive.org/web/20221007000913/https://books.google.com/books?id=ybtX0GZGhk8C&pg=PA371. live.
  66. Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen LY, Shen DD . Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites . Clinical Pharmacology and Therapeutics . 79 . 5 . 461–479 . May 2006 . 16678548 . 10.1016/j.clpt.2006.01.009 . 21372271 .
  67. Klimas R, Witticke D, El Fallah S, Mikus G . Contribution of oxycodone and its metabolites to the overall analgesic effect after oxycodone administration . Expert Opinion on Drug Metabolism & Toxicology . 9 . 5 . 517–528 . May 2013 . 23488585 . 10.1517/17425255.2013.779669 . 22857902 .
  68. Lemberg KK, Siiskonen AO, Kontinen VK, Yli-Kauhaluoma JT, Kalso EA . Pharmacological characterization of noroxymorphone as a new opioid for spinal analgesia . Anesthesia and Analgesia . 106 . 2 . 463–70, table of contents . February 2008 . 18227301 . 10.1213/ane.0b013e3181605a15 . 16524280 . free .
  69. Book: Smith H, Passik S . Pain and Chemical Dependency . 25 April 2008 . Oxford University Press USA . 978-0-19-530055-0 . 195– . 5 October 2016 . 7 October 2022 . https://web.archive.org/web/20221007000913/https://books.google.com/books?id=T88C-9VTDXMC&pg=PA195 . live .
  70. Book: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR . Kelley and Firestein's Textbook of Rheumatology . 21 June 2016 . Elsevier Health Sciences . 978-0-323-31696-5 . 2016009254 . 1080– . 5 October 2016 . 7 October 2022 . https://web.archive.org/web/20221007000913/https://books.google.com/books?id=kBZ6DAAAQBAJ&pg=PA1080 . live .
  71. Ross FB, Smith MT . The intrinsic antinociceptive effects of oxycodone appear to be kappa-opioid receptor mediated . Pain . 73 . 2 . 151–157 . November 1997 . 9415500 . 10.1016/S0304-3959(97)00093-6 . 53165907 .
  72. Smith MT . Differences between and combinations of opioids re-visited . Current Opinion in Anesthesiology . 21 . 5 . 596–601 . October 2008 . 18784485 . 10.1097/ACO.0b013e32830a4c4a . 14293344 .
  73. Kalso E . How different is oxycodone from morphine? . Pain . 132 . 3 . 227–228 . December 2007 . 17961923 . 10.1016/j.pain.2007.09.027 . 45689872 .
  74. Nozaki C, Saitoh A, Kamei J . Characterization of the antinociceptive effects of oxycodone in diabetic mice . European Journal of Pharmacology . 535 . 1–3 . 145–151 . March 2006 . 16533506 . 10.1016/j.ejphar.2006.02.002 .
  75. Nozaki C, Kamei J . Involvement of mu1-opioid receptor on oxycodone-induced antinociception in diabetic mice . European Journal of Pharmacology . 560 . 2–3 . 160–162 . April 2007 . 17292346 . 10.1016/j.ejphar.2007.01.021 .
  76. Lofwall MR, Moody DE, Fang WB, Nuzzo PA, Walsh SL . Pharmacokinetics of intranasal crushed OxyContin and intravenous oxycodone in nondependent prescription opioid abusers . Journal of Clinical Pharmacology . 52 . 4 . 600–606 . April 2012 . 21610203 . 4006196 . 10.1177/0091270011401620 .
  77. Analgesic Expert Group. Therapeutic Guidelines: Analgesic. Version 4. Melbourne: Therapeutic Guidelines Ltd, 2007.
  78. Kinnunen M, Piirainen P, Kokki H, Lammi P, Kokki M . Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone . Clinical Pharmacokinetics . 58 . 6 . 705–725 . June 2019 . 30652261 . 10.1007/s40262-018-00731-3 . Data indicate that after buccal and sublingual administration of oxycodone 0.1 mg/kg, the rate and extent of absorption is appropriate for clinical use. After transmucosal administration, Cmax was between 16 and 22 ng/mL, Tmax was 60 min, and bioavailability was 55% . free .
  79. https://link.springer.com/article/10.1007/s40262-018-007313#:~:text=Data%20indicate%20that%20after%20buccal,%25%20%5B82%2C%2083%5D.
  80. Li Y, Sun D, Palmisano M, Zhou S . Slow drug delivery decreased total body clearance and altered bioavailability of immediate- and controlled-release oxycodone formulations . Pharmacology Research & Perspectives . 4 . 1 . e00210 . February 2016 . 26977300 . 10.1002/prp2.210 . 4777261 .
  81. Book: 1. Package insert Oxycontin. Purdue Pharma L.P. 5 November 2007. Stamfbord, CT. 23 March 2009. dead. https://web.archive.org/web/20090326125214/http://www.purduepharma.com/PI/Prescription/Oxycontin.pdf. 26 March 2009.
  82. Web site: Oxycodone . www.drugbank.ca . 24 January 2019 . 25 January 2019 . https://web.archive.org/web/20190125074846/https://www.drugbank.ca/drugs/DB00497 . live .
  83. Boström E, Simonsson US, Hammarlund-Udenaes M . In vivo blood-brain barrier transport of oxycodone in the rat: indications for active influx and implications for pharmacokinetics/pharmacodynamics . Drug Metabolism and Disposition . 34 . 9 . 1624–1631 . September 2006 . 16763013 . 10.1124/dmd.106.009746 . 772550 .
  84. Moore KA, Ramcharitar V, Levine B, Fowler D . Tentative identification of novel oxycodone metabolites in human urine . Journal of Analytical Toxicology . 27 . 6 . 346–352 . September 2003 . 14516487 . 10.1093/jat/27.6.346 . free .
  85. Book: Fitzgibbon DR, Loeser JD . Cancer Pain. 28 March 2012. Lippincott Williams & Wilkins. 978-1-4511-5279-1. 198–.
  86. Book: Preedy VR . Neuropathology of Drug Addictions and Substance Misuse Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. 25 April 2016. Elsevier Science. 978-0-12-800677-1. 462–464.
  87. Book: McPherson RA, Pincus MR . Henry's Clinical Diagnosis and Management by Laboratory Methods . 31 March 2016 . Elsevier Health Sciences . 978-0-323-41315-2 . 336–.
  88. Book: Anzenbacher P, Zanger UM. Metabolism of Drugs and Other Xenobiotics. 29 May 2012. John Wiley & Sons. 978-3-527-32903-8. 420–. 5 October 2016. 7 October 2022. https://web.archive.org/web/20221007000913/https://books.google.com/books?id=ulcB7zYIresC&pg=PA420. live.
  89. Gasche Y, Daali Y, Fathi M, Chiappe A, Cottini S, Dayer P, Desmeules J . Codeine intoxication associated with ultrarapid CYP2D6 metabolism . The New England Journal of Medicine . 351 . 27 . 2827–2831 . December 2004 . 15625333 . 10.1056/NEJMoa041888 . free .
  90. Otton SV, Wu D, Joffe RT, Cheung SW, Sellers EM . Inhibition by fluoxetine of cytochrome P450 2D6 activity . Clinical Pharmacology and Therapeutics . 53 . 4 . 401–409 . April 1993 . 8477556 . 10.1038/clpt.1993.43 . 39724277 .
  91. Samer CF, Daali Y, Wagner M, Hopfgartner G, Eap CB, Rebsamen MC, Rossier MF, Hochstrasser D, Dayer P, Desmeules JA . Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety . British Journal of Pharmacology . 160 . 4 . 919–930 . June 2010 . 20590588 . 2935998 . 10.1111/j.1476-5381.2010.00709.x .
  92. Web site: Oxycodone . The American Society of Health-System Pharmacists . 3 April 2011 . 28 December 2018 . https://web.archive.org/web/20181228174726/https://www.drugs.com/monograph/oxycodone.html . live .
  93. Book: Davis PJ, Cladis FP . Smith's Anesthesia for Infants and Children E-Book . 15 October 2016 . Elsevier Health Sciences . 978-0-323-38869-6 . 234–.
  94. News: Ryan H, Girion L, Glover S . You want a description of hell?' OxyContin's 12-hour problem . 8 July 2018 . Los Angeles Times . 7 July 2016 . 1 July 2018 . https://web.archive.org/web/20180701135355/http://www.latimes.com/projects/oxycontin-part1/ . live .
  95. News: 'Q12' Workshops, 2001 . Los Angeles Times . 8 July 2018 . 21 April 2018 . https://web.archive.org/web/20180421121121/http://documents.latimes.com/q12-workshops-2001/ . live .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Oxycodone".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.