Oxycodone

from Wikipedia, the free encyclopedia
Structural formula
Structure of oxycodone
General
Non-proprietary name Oxycodone
other names

(5 R , 9 R , 13 S , 14 S ) -14-Hydroxy-3-methoxy-17-methyl-4,5-epoxymorphinan-6-one

Molecular formula C 18 H 21 NO 4
External identifiers / databases
CAS number
EC number 200-960-2
ECHA InfoCard 100,000,874
PubChem 5284603
ChemSpider 4447649
DrugBank DB00497
Wikidata Q407535
Drug information
ATC code

N02 AA05 , N02 AA55

Drug class

Opioid analgesic

properties
Molar mass 315.36 g · mol -1
Physical state

firmly

Melting point

219 ° C

solubility

Practically not soluble in water, but soluble in ethanol and chloroform
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances

Hydrochloride

07 - Warning

Caution

H and P phrases H: 302
P: no P-phrases
Toxicological data

320 mg kg −1 ( LD 50 ,  mouse ,  ip )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Two 10 mg oxycodone hydrochloride tablets from two manufacturers and a safety blister

Oxycodone (also dihydroxycodeinone ) is a powerful semi - synthetic opioid of level III in the WHO level scheme (classification of pain therapy) with high addictive potential, which is used as a pain reliever for severe to very severe pain. The drug, formerly traded as Eukodal , was brought back onto the German market in 2003 by the manufacturer Mundipharma under the new brand name Oxygesic . It has been available as a generic since 2007 .

Development history

Oxycodone was developed in 1916 by Martin Freund (1863–1920) and Edmund Speyer (1878–1942) at the University of Frankfurt / Main and launched a year later by Merck in Darmstadt under the name Eukodal as an analgesic and cough suppressant. It has been used therapeutically as an analgesic since 1919 . Eukodal was on the market in Germany until 1990 and was withdrawn from the market because of its very high addiction and abuse potential.

In Germany and the United States , oxycodone is sold as a prescription drug under the brand names Oxygesic (and generic name forms) and Oxycontin . In addition, oxycodone is subject to the Narcotics Act in Germany . Oxycodone is available in various dosage forms . There are u. a. Tablets with rapid release, prolonged-release tablets (5-120 mg of active ingredient containing), suppositories , capsules (with 5-20 mg of active compound) and very fast-acting injection solutions (10 mg active ingredient per milliliter).

Oxycodone has been available as a combination product together with the opioid antagonist naloxone since autumn 2006 . These agonistic-antagonistic combination, under the trade name Targin (as sustained release tablet with 5 to 80 mg oxycodone and 2.5 to 40 mg naloxone) from Mundipharma sold to, mainly caused by opioids constipation counter (constipation). In addition, the naloxone component, as with the combination tilidine / naloxone, can prevent misuse, especially by drug addicts.

In connection with the dramatically increased abuse of oxycodone in the United States, a company developed a soft capsule called Remoxy . This protects the medicinal product contained therein against abuse. The opioid, oxycodone, is in a gel-like capsule, so swallowing it is not a problem. The oxycodone, which is in a sticky, viscous capsule, cannot be released either by soaking it in high-proof alcohol or by fundamentally crushing it after freezing (down to −80 ° C). However, the drug has not yet been released for the "free market" in the USA.

effect

Oxycodone acts as an agonist on various opioid receptors in the brain and has no antagonistic effects. The analgesic effect, i.e. the analgesic potency , is roughly twice that of morphine and lasts for 4 to 6 hours, or 8 to 12 hours for slow-release preparations. Due to its additional effect on the κ receptor , both better tolerability and a better effect on neuropathic pain were propagated, for which, however, there are no controlled, randomized studies.

Oxycodone also has a depressant effect on the cough center; The substance was therefore used in the past as a cough suppressant, like codeine .

Side effects

Oxycodone can be addictive. Like other opioids, it can cause psychological dependence and, with long-term use, physical dependence. There is also a potential for abuse similar to that of other strong opioids.

Oxycodone has a significant potential for euphoria . The stronger addictive effect compared to morphine is explained by the fact that (even with the delayed-release preparations) about a third of the active ingredient is released within the first 15 minutes, the effect then occurs after about 10-20 minutes. Controlled studies on this problem relevant to practice have not yet been published. It is warned that if the tablets are abusively ground or ground in a mortar, the retardation system will be destroyed and the entire contents will take effect immediately, so that an overdose can occur which leads to respiratory depression with a potentially fatal outcome.

Oxycodone also has the usual adverse effects of opioids, e.g. E.g .: spasms of the bronchial muscles, spasms of the smooth muscles of the bile ducts , miosis , changes in mood (including anxiety, depression , euphoria ), sleep disorders, nervousness, changes in performance (such as thought disorders, language disorders, confusion, memory gaps), perception disorders ( e.g. depersonalization , Hallucinations , taste disturbances, visual disturbances), sedation (tiredness to drowsiness), dizziness, headache, tremor , involuntary muscle contractions, coordination disorders, malaise, epileptic seizures (especially in the presence of epilepsy or a tendency to seizures), lower blood pressure, constipation, nausea, vomiting Gastrointestinal complaints, bladder emptying disorders ( urinary retention ), sweating.

Analytics

For reliable qualitative and quantitative determination in different test material, the coupling of gas chromatography or HPLC with mass spectrometry is used after appropriate sample preparation . As a test material are blood serum , blood plasma or urine is used. Also hair can be used as the test material. Semiquantitative immunoassays are also available for analysis.

Narcotics regulations

Oxycodone is a marketable and prescribable narcotic in Germany and may only be prescribed on a narcotic prescription. The unauthorized possession as well as the unauthorized trade and the passing on of narcotics are punished with imprisonment of up to five years or a fine ( Narcotics Act, Section 29).

Carrying an opioid ID (name of the drug, prescribed dose, name of the patient, date of birth, prescribing doctor) can be useful for drivers of motor vehicles or other insurance-relevant vehicles during traffic checks in order to prove that there is no drug abuse. When traveling abroad, the ID is not recognized as an official document.

Special regulations apply to travel with narcotics inside and outside Europe. Regulations and forms can be viewed on the website of the Federal Institute for Drugs and Medical Devices ( BfArM ).

Oxycodone as a social problem

The first cases of oxycodone abuse, called eucodalism by analogy with morphinism , were reported at the beginning of the 1920s. During the Second World War , the dictator Adolf Hitler was regularly given oxycodone injections by his personal physician Theo Morell .

The US pharmaceutical company Purdue Pharma LP was fined US $ 634.5 million in 2007 for failing to adequately state in the Oxycontin package insert that the oxycodone contained therein, like other opioids, has a high potential for dependence .

In 2010, Oxycontin , which had been aggressively promoted since the 1990s, was the fifth top-selling drug in the United States. Sales were over $ 3.5 billion. In recent years, however, sales have dropped significantly as stricter regulations have now been introduced. In 2013, Oxycontin was the 18th top-selling drug in the United States. Sales were just $ 2.5 billion.

In the United States, oxycodone is also used to treat moderate pain. So the active ingredient is there u. a. also prescribed for toothache. In Germany, however, the prescribing practice is much stricter and more restrictive. For example, for minor interventions, significantly weaker opioids / opiates, such as tilidine with added naloxone , are used (codeine, on the other hand, is more likely to be prescribed for bronchial diseases). In the USA, on the other hand, due to its rather easy availability, oxycodone became a widespread drug, especially among the white rural population - a circumstance that earned it the nickname Hillbilly Heroin . The US state of Florida has been fighting since 2010 against so-called pill mills , pain clinics in which opioids such as oxycontin are prescribed excessively. State regulation has since reduced availability. However, illegal trade in the substance has blossomed , and many Oxycontin addicts have also switched to heroin , as this is now cheaper and in some cases better available. This has contributed to the fact that the number of heroin addicts in the US has increased sharply in recent years, especially outside the metropolitan areas. One speaks of a real " epidemic ".

The documentary Oxyana (2013) by Sean Dunne uses the example of the small town of Oceana ( Wyoming County, West Virginia ) to show the dramatic consequences of the massive abuse of painkillers such as oxycodone for those affected, families and society. Musician Tom Petty died on October 2, 2017 after an overdose of fentanyl and oxycodone.

Trade names

literature

  • P. Rohr, R. Lang, RT Kiefer: Postoperative analgesia with retarded oxycodone (Oxygesic) compared to intravenous piritramide "on demand" after total hip replacement. A pilot study. In: The pain. 19 (Suppl 1), 2005, p. 101.
  • Eberhard Klaschik : Pain therapy and symptom control in palliative medicine. In: Stein Husebø , Eberhard Klaschik (ed.): Palliative medicine. Basics and practice. 5th edition, Springer, Heidelberg 2009, ISBN 3-642-01548-4 , pp. 207-313, here: pp. 233, 249 f., 461 and 464.

Web links

Commons : Oxycodone  - collection of images, videos and audio files

Individual evidence

  1. ↑ a b Entry on oxycodone in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  2. ↑ Entry on oxycodone. In: Römpp Online . Georg Thieme Verlag, accessed on May 30, 2014.
  3. ↑ a b Data sheet Oxycodone hydrochloride from Sigma-Aldrich , accessed on November 7, 2016 ( PDF ).
  4. ↑ M. Freund, E. Speyer: About the conversion of thebaine into oxycodeinone and its derivatives. In: Journal for Practical Chemistry. Vol. 94, number 1, 1917, pp. 135-178. doi: 10.1002 / prac.19160940112
  5. ^ VV Acharya, M. Richardson et al. a .: Guaranteed to Fail. Princeton University Press, 2011, ISBN 978-0-691-15078-9 , p. 165, limited preview in Google Book Search.
  6. ↑ W. Sneader: Drug discovery: a history. Wiley, 2005, ISBN 0-471-89980-1 , p. 119.
  7. ^ A b E. Menninger, C. Bachem: Eukodal poisoning, chronic. (Eucodalism.) . In: Collection of Poisoning Cases . tape 3 , 1932, p. 173-174 , doi : 10.1007 / BF02455131 .
  8. ↑ S. Bernschneider-Reif: Forced labor - processing - development work. Opportunities of a pharmaceutical company against oblivion and for the future. In: History of Pharmacy. 2002, pp. 33-37. (After a lecture at the Congressus Historiae Pharmaciae 2001 ).
  9. ↑ Drugs Commission of the German Medical Association: Oxycodon (Oxygesic®): Abuse, addiction and fatal consequences from the injection of crushed prolonged-release tablets , 2003, accessed on February 7, 2014.
  10. ↑ a b c Freye, E. (Enno): Opioids in medicine . 8th, updated edition. Springer Medizin Verlag, Heidelberg 2010, ISBN 978-3-540-88797-3 , p. 185 .
  11. ↑ Remoxy ER (oxycodone) FDA Approval Status. Retrieved April 8, 2020 .
  12. ↑ Postoperative pain therapy: better analgesia with oxycodone compared to demand-controlled medication. At: Journal Med. May 12, 2006.
  13. ↑ The state of emergency will not end analgesic addiction. on: zeit.de , August 11, 2017.
  14. ↑ TJ Cicero et al. a .: The Changing Face of Heroin Use in the United StatesA Retrospective Analysis of the Past 50 Years. 2014.
  15. ↑ a b Pain therapy with opioids. In: The medicament letter. No. 45, 2011, accessed February 7, 2014.
  16. ↑ Yellow List , website .
  17. ↑ Scheidel B, Maritz MA, Gschwind YJ, Steigerwald K, Guth V, Kovacs P, Rey H: Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet. , Int J Clin Pharmacol Ther. 2017 Nov; 55 (11): 881-890, PMID 28933336
  18. ↑ Goldberger BA, Chronister CW, Merves ML: Quantitation of oxycodone in blood and urine using gas chromatography-mass spectrometry (GC-MS). , Methods Mol Biol. 2010; 603: 453-60, PMID 20077097
  19. ↑ Jones J, Tomlinson K, Moore C: The simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, 6-acetylmorphine, and oxycodone in hair and oral fluid. , J Anal Toxicol. 2002 Apr; 26 (3): 171-5, PMID 11991534
  20. ↑ Kronstrand R, Forsman M, Roman M: Quantitative analysis of drugs in hair by UHPLC high resolution mass spectrometry. , Forensic Sci Int. 2018 Feb; 283: 9-15, PMID 29241093
  21. ^ Johnson-Davis KL, Sadler AJ, Genzen JR: A Retrospective Analysis of Urine Drugs of Abuse Immunoassay True Positive Rates at a National Reference Laboratory. , J Anal Toxicol. 2016 Mar; 40 (2): 97-107, PMID 26668238
  22. ↑ Dixon RB, Davis B, Dasgupta A: Comparison of Response of DRI Oxycodone Semiquantitative Immunoassay With True Oxycodone Values ​​Determined by Liquid Chromatography Combined With Tandem Mass Spectrometry: Sensitivity of the DRI Assay at 100 ng / ml Cut-Off and Validity of Semiquantitative Value . , J Clin Lab Anal. 2016 May; 30 (3): 190-5, PMID 25715994
  23. ↑ Annex III (to § 1 Paragraph 1) marketable and prescription narcotics to the Narcotics Act, gesetze-im-internet.de
  24. ^ BfArM: Traveling with narcotics
  25. ↑ L. Stern-Piper: The rate of sedimentation of the blood in chronic morphinism and eucodalism. In: Klin Wchnschr. Vol. 4, 1925, p. 548.
  26. ↑ Oliver Das Gupta: How Adolf Hitler became addicted to drugs , interview with Norman Ohler , Süddeutsche Zeitung , September 14, 2015.
  27. ^ E. Chasan: Purdue Frederick pleads guilty in OxyContin case. At: reuters.com on May 7, 2007.
  28. ^ Pharmaceutical Sales 2010. From : drugs.com , accessed August 10, 2012.
  29. ↑ Top 100 Drugs for 2013 by Sales. From: drugs.com , accessed July 31, 2014.
  30. ↑ K. Simpson, P. Leyendecker, M. Hopp, S. Müller-Lissner, O. Löwenstein, J. De Andrés, J. Troy Ferrarons, B. Bosse, B. Krain, T. Nichols, W. Kremers, K Reimer: Fixed-ratio combination oxycodone / naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain. In: Current medical research and opinion. Vol. 24, number 12, December 2008, pp. 3503-3512, doi: 10.1185 / 03007990802584454 . PMID 19032132 .
  31. ↑ Kathrin Werner: Everyday drug heroin: Hardly any other drug is addictive as quickly as heroin. In: Süddeutsche Zeitung. 4th February 2014.
  32. ↑ Chris McGreal: How cracking down on America's painkiller capital led to a heroin crisis. In: theguardian.com. May 25, 2016, accessed May 25, 2016 .
  33. ↑ Theodor Schaarschmidt: drug epidemic: 5 Facts about opioid crisis in the US , Spektrum.de , February 20, 2018
  34. ↑ imdb.com cf. imdb.com
  35. ↑ Marwa Eltagouri: Tom Petty died of an accidental drug overdose. His family shared the news to 'save lives.' In: Washington Post . 19th January 2018.