Oxymorphone (oral)

Oxymorphone (oral)

File:Oxymorphone.png
Clinical data
Pregnancy category	US: C (Risk not ruled out)
Dependence liability	High
Routes of administration	intravenous, intramusucular, subcutaneous, oral, rectal
ATC code	N02A (WHO)
Legal status
Legal status	CA: Schedule I UK: Class A US: Schedule II
Pharmacokinetic data
Bioavailability	10% (oral)
Metabolism	hepatic
Elimination half-life	1.3 (+/-0.7) hours
Identifiers
IUPAC name 4,5α-epoxy-3,14-dihydroxy- 17-methylmorphinan-6-one
CAS Number	76-41-5
PubChem CID	5284604
DrugBank	APRD00158
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C17H19NO4
Molar mass	301.337 g/mol
Melting point	248–249 °C ( °F)

Oxymorphone (Opana, Numorphan) 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. As with other opioids, oxymorphone can cause physical dependency, and has the potential for abuse.

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 patients with dyspnea associated with acute left ventricular failure and pulmonary edema.

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.

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. 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 per cent 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, are considering and/or currently developing Duragesic®-style oxymorphone skin plasters and oxymorphone and hydromorphone nasal sprays.

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.

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.

See also

• Opioids
• Hydromorphone
• Oxycodone
• Drug addiction