Oxymorphone
From Wikipedia, the free encyclopedia
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Oxymorphone
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| Systematic (IUPAC) name | |
| 4,5α-epoxy-3,14-dihydroxy- 17-methylmorphinan-6-one |
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| Identifiers | |
| CAS number | |
| ATC code | N02 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C17H19NO4 |
| Mol. mass | 301.337 g/mol |
| Pharmacokinetic data | |
| Bioavailability | 10% (oral) |
| Metabolism | hepatic |
| Half life | 1.3 +/- 0.7 hrs (with parenteral admin)[1]; 7.25-9.43 hr (with oral admin)[2] |
| Excretion | 35% urine, 65% feces |
| Therapeutic considerations | |
| Pregnancy cat. |
C(US) |
| Legal status | |
| Dependence Liability | High |
| Routes | intravenous, intramusucular, subcutaneous, oral, rectal |
Oxymorphone (Opana, Numorphan, Numorphone) or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic that is derived from thebaine, and is approximately 6–8 times more potent than morphine. Clinically, it is administered as its hydrochloride salt via injection, or suppository; typically in dosages of 1 mg (injected) to 5 mg (suppository). Endo Pharmaceuticals markets oxymorphone in the United States as Opana and Opana ER. Opana is available as 5 mg and 10 mg tablets; Opana ER, an extended-release form of oxymorphone, is available as tablets in strengths of 5 mg, 10 mg, 20 mg, and 40 mg. In some countries, hydromorphinol is distributed under the trade names Numorphan and Numorphan Oral. This is a relatively rare exception and the two drugs are, whilst both being strong opioid analgesics, notably different from one another.
As with other opioids, oxymorphone can cause physical dependency, and has the potential for abuse. Oxymorphone was patented for pharmaceutical use in the United States in 1955 after having been first synthesised in Germany c.a. 1914. Its 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 0.89.
Oxymorphone is also produced within the human body when the liver metabolises oxycodone by means of O demethylation; approximately 10 per cent of the dose is processed by the endocrine system in this respect. The codeine-hydrocodone group and morphinans exhibit the same characteristics.
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[edit] Uses
Oxymorphone is indicated for the relief of moderate to severe pain and also as a preoperative medication to alleviate apprehension, maintain anesthesia, and as an obstetric analgesic. Additionally, it can be used for the alleviation of pain in patients with dyspnea associated with acute left ventricular failure and pulmonary oedema.
Opana extended-release tablets are indicated for the management of chronic pain of all or most aetiologies 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.
Oxymorphone is used in veterinary medicine in many of the same uses as for humans, with induction and maintenance of anaesthetia and sometimes tranquillisation of small and medium-sized animals being the most common use. Morphine, hydromorphone, various fentanyls, levorphanol, and butorphanol are also common in veterinary settings and tramadol is reportedly being studied as a general analgesic for cats, dogs, ferrets, rats and other animals in that size range.
Oxymorphone is mentioned along with buprenorphine, oxycodone, dihydrocodeine, morphine and other opioids as a possible means of mitigating refractory depression (American Journal of Psychiatry,156:2017, December 1999... Pharmacopsychiatry 2005; 38 DOI: 10.1055/s-2005-918797...Pharmacol Biochem Behav 1995 Sep; 52(1):145-52) Opioids were commonly used for this indication up until the introduction of the tricyclic antidepressants in the 1950s, even though they appear to work in a smaller percentage of cases and are generally more toxic than most chemical classes of opioids. Conversely, tricyclic anti-depressants and chemcially-related drugs are the most commonly-used adjuvants and atypical analgesics used with opioids for pain, especially neuropathic pain.
[edit] Physical characteristics
Oxymorphone HCl occurs as odorless white crystals or white to off-white powder. It will darken in color with prolonged exposure to light although this does not have an effect on potency. One gram of oxymorphone is soluble in 4 ml of water and it is slightly soluble in alcohol and ether. The commercially available injection has a pH of 2.7–4.5.
[edit] Toxicity
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, apnea, circulatory collapse, cardiac arrest, and death may occur.
At equianalgesic doses oxymorphone is marginally more toxic than morphine but less so than fully synthetic opioids such as methadone and pethidine. At therapeutic doses, toxicity is primarily manifested as miosis, nausea, and possibly occasional mild involuntary muscle movements especially in the distal portions of the extremities and the shoulder area in some cases. This is most common in patients taking a number of other drugs for their condition, especially muscle relaxants and some adjuvant analgesics, and also appears to happen most often during and immediately after a significant upward titration in the single-dose and per 24 hour doses.
Instances of the body suddenly jerking bolt upright from a more relaxed sitting position is a sign of high and/or rapidly increasing serum levels of opioids and all of the above movements are likely due to the anticholinergic or anticholinergic-like effects of opioids and/or other medications prescribed at the same time, as they manifest in patients on atropine-like drugs as well. The primary risk here involves dropping objects, spilling liquids, striking body parts against walls, and potentially losing footing on flat ice surfaces.
While all this can be frightening at first, more than 85 percent of patients do not experience it at any time during treatment, and oxymorphone does not appear to induce seizures in neurologically healthy patients as does the pethidine series of opioids (pethidine, anileridine, alphaprodine, piminodine and others) nor does it have toxic metabolites which accumulate in the system as do the pethdine and methadone families of synthetic opioids. There is also no real evidence that oxymorphone significantly lowers the seizure threshold as do tramadol and some of the other synthetics mentioned above.
[edit] Brand Names
- Numorphan (suppository and injectable solution)
- Opana (tablet)
- Opana ER (extended-release tablet)
Other manufacturers and Endo themselves have also, according to reports in the mass media and professional journals over the last few years, considered and/or are currently developing a Duragesic-style oxymorphone skin plasters and oxymorphone and hydromorphone nasal sprays.
[edit] Illicit Use
Until its removal from the United States market in the early 1970s, oxymorphone in the form of Numorphan 10 mg instant-release tablets was one of the most sought-after and well-regarded opioids of the IV drug using community. Known popularly as "blues" for their light blue color, the tablets contained very few insoluble binders—making them easy to inject—and were extremely potent when used intravenously. "Blues" were also considered to be especially euphoric; comparable to or better than heroin. Numorphan tablets, and the oxymorphone they contained, are the "blues" referred to in the film Drugstore Cowboy.
Oxymorphone is not a component of "T's and blues", 1970s slang for a combination of pentazocine ("T's") and pyribenzamine ("blues").
The low bioavailability of oxymorphone after oral administration requires Opana extended-release to contain up to 40 mg of oxymorphone per tablet -- almost as much as an entire case of Numorphan ampoules; attempts to circumvent the extended-release mechanism by injecting or snorting the tablets are therefore particularly dangerous.
[edit] Chemistry
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). Oxymorphone can also be synthesized from morphine or oxycodone, and is an active metabolite of the latter drug. The structure-activity relationship of oxymorphone and its derivatives has been well-examined. Esterification of the hydroxyl groups yields stronger compounds. The acetyl ester is 2.5 times more potent and the propenyl ester six times more potent than the parent compound. If the 14-hydroxyl group is formed into the cinnamyl ester, the product is 114 times more potent. The most powerful oxymorphone derivative known is the 14-cinnamyl 3-acetyl ester, which is over 200 times more potent than morphine.[3] Another derivative of oxymorphone is the narcotic antagonist naloxone (Narcan).
[edit] See also
[edit] References
- ^ rxlist.com
- ^ Adams MP, Ahdieh H (2005). "Single- and multiple-dose pharmacokinetic and dose-proportionality study of oxymorphone immediate-release tablets". Drugs R D 6 (2): 91-9. doi:. PMID 15777102.
- ^ J Exp Ther. Pharm. (1964) 174–182.
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