Oxymorphone

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Not to be confused with Oxymorphazone.
Oxymorphone
Oxymorphone2DCSD.svg
Oxymorphone3DanJ.gif
Systematic (IUPAC) name
4,5α-epoxy-3,14-dihydroxy-
17-methylmorphinan-6-one
Clinical data
Trade names Opana
AHFS/Drugs.com monograph
MedlinePlus a610022
Pregnancy
category
  • US: C (Risk not ruled out)
  • C
Legal status
Dependence
liability		 High
Routes of
administration		 intravenous, intramusucular, subcutaneous, oral, rectal, intranasal.
Pharmacokinetic data
Bioavailability 10% (oral), 90% (Intranasal), 100% (IV, IM)[1]
Protein binding 10%[1]
Metabolism Liver-mediated glucuronidation[1]
Biological half-life 7–9 hours[1]
Excretion Urine, faeces[1]
Identifiers
CAS Number 76-41-5 YesY
ATC code N02A (WHO)
PubChem CID: 5284604
IUPHAR/BPS 7094
DrugBank DB01192 YesY
ChemSpider 4447650 YesY
UNII 9VXA968E0C YesY
KEGG D08323 YesY
ChEMBL CHEMBL963 YesY
Synonyms 14-Hydroxydihydromorphinone
Chemical data
Formula C17H19NO4
Molecular mass 301.33706 g/mol
  • O=C1[C@@H]2OC3=C(O)C=CC4=C3[C@@]2([C@]5(CC1)O)CCN(C)[C@@H]5C4
  • InChI=1S/C17H19NO4/c1-18-7-6-16-13-9-2-3-10(19)14(13)22-15(16)11(20)4-5-17(16,21)12(18)8-9/h2-3,12,15,19,21H,4-8H2,1H3/t12-,15+,16+,17-/m1/s1 YesY
  • Key:UQCNKQCJZOAFTQ-ISWURRPUSA-N YesY
  (verify)

Oxymorphone (Opana, Numorphan, Numorphone) or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic (painkiller) first developed in Germany in 1914,[2] patented in the USA by Endo Pharmaceuticals in 1955[3] and introduced to the United States market in January 1959 and other countries around the same time.[1]

The brand name Numorphan is derived by analogy to the Nucodan name for an oxycodone product (or vice versa) as well as Paramorphan/Paramorfan for dihydromorphine and Paracodin (dihydrocodeine). The only commercially available salt of oxymorphone in most of the world at this time is the hydrochloride, which has a free base conversion ratio of 0.891, and oxymorphone hydrochloride monohydrate has a factor of 0.85.[4] It is a Schedule II controlled substance in the United States with an ACSCN of 9652. The 2013 DEA annual manufacturing quotas were 18 375 kilos for conversion (a number of drugs can be made from oxymorphone, both painkillers and opioid antagonists like naloxone) and 6875 kilos for direct manufacture of end-products.[5]

The onset of analgesia after parenteral administration is about 5–10 minutes and after rectal administration, 15–30 minutes.[1] The duration of analgesia is 3–4 hours for immediate-release tablets and 12 hours for extended-release tablets.[1] It is also a minor metabolite of oxycodone, which is formed by CYP2D6-mediated O-demethylation.[1]

Uses

Oxymorphone is indicated for the relief of moderate to severe pain and also as a preoperative medication to alleviate apprehension, maintain anaesthesia and as an obstetric analgesic. Additionally, it can be used for the alleviation of pain in patients with dyspnoea associated with acute left ventricular failure and pulmonary oedema.[4] It is practically devoid of antitussive activity.[4]

Opana extended-release tablets are indicated for the management of chronic pain and are indicated only for patients already on a regular schedule of strong opioids for a prolonged period. The immediate-release Opana tablets are recommended for management of breakthrough pain for patients on the extended-release version. Some protocols for chronic pain conditions characterised by severe breakthrough pain incidents add Numorphan ampoules as a third form of the drug for use when a breakthrough pain incident is in progress. An oxymorphone nasal spray is being developed for this purpose but the release date is unknown; some practitioners prefer fentanyl immediate-release formulations such as Actiq or Fentora for this purpose although some patients have severe side effects from fentanyl.[1]

Oxymorphone is mentioned, along with buprenorphine, oxycodone, dihydrocodeine, morphine and other opioids as a possible means of mitigating refractory depression.[6][7][8]

Adverse effects

The principal adverse effects of oxymorphone are similar to other opioids with constipation, nausea, vomiting, dizziness, dry mouth and drowsiness being the most common adverse effects. This drug is highly addictive as with other opioids and can lead to chemical dependence and withdrawal.[4]

Overdose

In common with other opioids, oxymorphone overdosage is characterized by respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In a severe case of overdose, apnoea, circulatory collapse, cardiac arrest and death may occur.[4]

Mechanism of action

It elicits its effects by binding to and activating the mu opioid receptor (MOR) and, to a lesser extent, the delta opioid receptor (DOR).[1] Its activity at the DOR likely augments its action at the MOR.[1] Oxymorphone is 10 times more potent than morphine.[9]

Physical and chemical properties

Oxymorphone is commercially produced from thebaine, which is a minor constituent of the opium poppy (Papaver somniferum) but thebaine is found in greater abundance (3%) in the roots of the oriental poppy (Papaver orientale).[1][10] German patents from the middle 1930s indicate that oxymorphone as well as hydromorphone, hydrocodone, oxycodone, and acetylmorphone can be prepared—without the need for hydrogen gas—from solutions of codeine, morphine, and dionine by refluxing an acidic aqueous solution, or the precursor drug dissolved in ethanol, in the presence of Column 7 metals, namely palladium and platinum in fine powder or colloidal form or platina black. It is unclear from information available if aluminium or nickel can be used as a catalyst in these reactions as well.[11]

Oxymorphone hydrochloride occurs as odourless white crystals or white to off-white powder. It darkens in colour with prolonged exposure to light. One gram of oxymorphone hydrochloride is soluble in 4 ml of water and it is sparingly soluble in alcohol and ether. It degrades upon contact with light.[4]

Society and culture

Brand names

  • Numorphan (suppository and injectable solution)
  • Opana ER (extended-release tablet)
  • Opana IR (immediate-release tablet)
  • O-Morphon (10mg tablet and 1mg/1ml injection) in Bangladesh by Ziska pharmaceutical ltd.

Other manufacturers and Endo themselves have also, according to reports in the mass media and professional journals[who?] over the last few years, considered and/or are currently developing a Duragesic-style oxymorphone skin plasters and oxymorphone and hydromorphone nasal sprays.

Generic pill markings:

ATV10/APO; HK10 (10 mgs) oblong white

ATV20/APO; HK20 (20mgs) oblong white

Abuse and overdose

In the United States, more than 12 million people abuse opioid drugs.[12] In 2010, 16,652 deaths were related to opioid overdose.[13] In September 2013, the FDA released new labeling guidelines for long-acting and extended-release opioids requiring manufacturers to remove moderate pain as indication for usage, instead stating the drug is for "pain severe enough to require daily, around-the-clock, long-term opioid treatment".[14] The updated labeling will not restrict physicians from prescribing opioids for moderate, as needed usage.[12]

In late March 2015, reports indicated Austin, Indiana, was the center of an outbreak of HIV caused by the use of Oxymorphone as an injectable recreational drug. The outbreak required emergency action by state officials.[15][16][17]

Oxymorphone is known as Opana with street names which include blues, moons, blue heaven, new blues, octagons, stop signs, pink, pink heaven, biscuits, pink lady, Mrs. O, Orgasna IR, OM, Pink-O, The O-Bomb, and others. The average street price for Opana [Oxymorphone hydrochloride] is $35–50 [US] per pill compared to $70–100 [US] per equal dose of Oxycontin. Oxycontin has been reformulated and further regulated to help prevent abuse and as a result Opana [Oxymorphone] has become a cheaper and more effective alternative for opiate addicts.

Synthesis

Oxymorphone synthesis:[18]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ US patent 2806033, Mozes Juda Leweustein, "Morphine derivative", published 1955-03-08, issued 1957-10-09 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ http://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0620.htm
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ 12.0 12.1 Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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