Oxymorphone
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222351525
2008-06-28T21:55:35Z
SpellingBot
6773085
chemcially → chemically
{{drugbox
|| IUPAC_name = 4,5α-epoxy-3,14-dihydroxy-<br />17-methylmorphinan-6-one
| image = Oxymorphone.png
| CAS_number = 76-41-5
| ATC_prefix = N02
| ATC_suffix = A
| ATC_supplemental =
| PubChem = 5284604
| DrugBank = APRD00158
| C=17 | H=19 | N=1 | O=4
| molecular_weight = 301.337 g/mol
| bioavailability = 10% (oral)
| protein_bound =
| metabolism = hepatic
| elimination_half-life = 1.3 +/- 0.7 hrs (with parenteral admin)<ref>[http://www.rxlist.com/cgi/generic/oxymorphone_cp.htm rxlist.com]</ref>; 7.25-9.43 hr (with oral admin)<ref>{{cite journal | author=Adams MP, Ahdieh H| title=Single- and multiple-dose pharmacokinetic and dose-proportionality study of oxymorphone immediate-release tablets | journal=Drugs R D| year=2005 | pages=91–9 | volume=6 | issue=2 | pmid=15777102 | doi=10.2165/00126839-200506020-00004}}</ref>
| excretion = 35% urine, 65% feces
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = C
| pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_CA = Schedule I
| legal_UK = Class A
| legal_US = Schedule II
| legal_status =
| dependency_liability = High
| routes_of_administration = intravenous, intramusucular, subcutaneous, oral, rectal
}}
'''Oxymorphone''' ('''Opana''', '''Numorphan''', '''Numorphone''') or 14-Hydroxydihydro[[morphinone]] is a powerful semi-synthetic [[opioid]] [[analgesic]] first developed in Germany circa or about 1914, patented in the USA by [[Endo Pharmaceuticals]] in 1955 and introduced to the United States market in January 1959 and other countries around the same time. Related to [[morphine]] in the same fashion that [[oxycodone]] is to [[codeine]], is derived from [[thebaine]], and is approximately 6–8 times more potent than [[morphine]].
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 0.89.
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.
Oxymorphone is administered as its [[hydrochloride|hydrochloride salt]] via injection, or [[suppository]]; typically in dosages of 1 mg (injected) to 5 mg (suppository). Endo has been the major distributor of oxymorphone throughout the world and currently markets oxymorphone in the United States and elsewhere 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, 7½ mg, 10 mg, 15 mg, 20 mg, 30 mg, and 40 mg. Opana® Extended-Release tablets are based on the TIMERx® system developed by a consortium led by Endo and [[Penwest]]. In addition to the sustained-release version for Opana®, other versions of TIMERx® are available and being developed for other protocols such as decreasing dose delivery over time, single and multiple bursts of medication, and combinations of the above. The immediate-release tablets contain ingredients that turn the tablet into a blob so a marginal extended-release effect can be seen in some cases where they can provide analgesic effects for up to six hours and take up to an hour to reach full effect; patients may need Numorphan® ampoules or immediate-release formulations of [[hydromorphone]] or [[morphine]] for [[breakthrough pain]] incidents which are already in progress; an oxymorphone nasal spray is reportedly in development, along with a possible hydromorphone nasal spray and implantable osmotic pumps for both drugs.
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 [[morphinan]]s exhibit the same characteristics.
== 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 [[fentanyl]]s, [[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 chemically-related drugs are the most commonly-used adjuvants and atypical analgesics used with opioids for pain, especially neuropathic pain.
== 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.
== 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.
== 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.
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==Illicit Use==
Oxymorphone is like all other effective centrally-acting analgesics in that its positive side effects of joy from rapid pain relief, overall euphoria, anxiolysis, promotion of sociability, and the like can after a while impart a morbid seek orientation for the drug; it also produces physical dependence, and the combination of these two mean that oxymorphone is potentially habit-forming. However, the presence of real physical pain almost invariably prevents the development of true addiction to oxymorphone for a combination of psychological, neurological, and endocrinological reasons.
On the other hand oxymorphone can generate a serious narcotic habit rather quickly in those who take it for kicks in that it has powerful euphorigenic properties which some rank as the highest amongst narcotics, many placing it above heroin
Endo withdrew the original Numorphan® tablets from the market in 1972 as the result of regulatory and market pressures and other considerations as it was passionately sought, by any means necessary, by some narcotics addicts. Until its removal from the United States market at that point, oxymorphone in the form of Numorphan 10 mg instant-release tablets was one of the most sought-after and well-regarded opioids of the [[Intravenous therapy|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 "[[Pentazocine|T's and blues]]", 1970s slang for a combination of [[pentazocine]] ("''T's''") and [[pyribenzamine]] ("''blues''"). Nor are "blues" 10 mg Valium tablets, which are known as Blue Bombers and BBs.
Oxymorphone was available in the United States only as suppositories and ampoules for hospital use for 35 years until recently, making diversion of the ampoules and the time-consuming proceess of melting, mixing with water, then chilling the suppositories and drawing off the aqueous portion of the results and boiling down as the major means of use of oxymorphone pharmaceuticals in means inconsistent with their labelling in the USA. Rare cases of users baking their own at home by extracting oxycodone from pharmaceuticals and converting it to oxymorphone have been reported in the a number of countries. In some cases, [[codeine]] is the starting material with morphine, or more rarely thebaine, being the intermediate. In those cases, the more common end products sought are morphine salts, morphine base, [[heroin]], [[dihydromorphine]], [[desomorphine]], and hydromorphone.
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. However, chewing the tablets and/or taking with alcohol for the 70 per cent bioavailabilty boost from the latter appear to be the only means successful Opana® ER misuse aside from [[insufflation]] -- the TIMERx® system appears to be making the extended release tablets useless for preparing for injection. Indeed, it appears that the tablet was designed first and oxymorphone chosen as the active ingredient because all the others available in the USA for oral use (fentanils are rapidly destroyed almost completely in the digestive tract, leaving only injection, transdermal, transmucosal, sublingual, and buccal routes as options) with the possible exception of [[levorphanol]] or doses of [[hydromorphone]] in the 50 to 200 mg range as useful for making a TIMERx®-based analgesic preparation.

Drug Name
Opana/ Oxymorphone
Strength(s)
5 mg
10 mg
Imprint(s)
J 93/10 mg Beige/off-white, J 95/5mg Beige/off wihte Tablet Scored In Half on Back Side
Manufacturer / Distributor
JBL Laboratories LLC
==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 [[Quantitative structure-activity relationship|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.<ref>J Exp Ther. Pharm. (1964) 174–182.</ref> Another derivative of oxymorphone is the narcotic antagonist [[naloxone]] (Narcan).
==See also==
* [[Opioids]]
* [[Hydromorphone]]
* [[Oxycodone]]
* [[Drug addiction]]
== References ==
<references/>
{{Analgesics}}
{{Opioids}}
[[Category:Opioids]]
[[Category:Morphinans]]
[[Category:Semisynthetic opioids]]
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