Oxymorphone
Encyclopedia
Oxymorphone or 14-Hydroxydihydromorphinone
is a powerful semi-synthetic opioid
analgesic
first developed in Germany circa 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. It (along with hydromorphone) was designed to have less incidence of side effects than morphine and heroin. It was a success as it differs from morphine and heroin in its effects in that it generates less euphoria, sedation, itching and other histamine effects at equianalgesic doses. This also means a lower dependence liability.
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.
In some countries, hydromorphinol
is distributed under the trade names Numorphan and Numorphan Oral. This is a relatively rare exception and the two drugs, whilst both being strong opioid analgesics, are notably different from one another.
Oxymorphone is administered as its 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,10 mg, 20 mg, 30 mg, and 40 mg. As of July 21, 2011 generic strengths equivalent to Opana ER 7½ mg and 15 mg are available. Some resources assert that 2, 12 and/or 15 mg IR tablets and 25, 36 and 50 mg extended release tablets will be introduced although apparently the timeline on that is not known to the public at this time. Opana Extended-Release tablets are based on the TIMERx system developed by a consortium led by Endo and Penwest. Some of these strengths (notably not the 7.5 mg) are available in an Opana IR–immediate release–form for breakthrough pain to be used by patients already on 24/7 opioid care such as fentanyl patches and sustained-relief morphine drugs like Avinza.
In addition to the sustained-release version for Opana, other versions of TIMERx are available and being developed for other protocols such as increasing, decreasing, stepwise increasing, and stepwise decreasing dose delivery over time, single and multiple bursts of medication, and combinations of the above.
Specifically, the apparent extension of the duration of effect of the IR tablets (all other things being equal, oxymorphone has a duration of action of 5 to 8 hours in most patients) versus similar drugs in commonly used immediate-release forms—for example Dilaudid (hydromorphone
), morphine
, Vilan (nicomorphine
), Paramorfan (dihydromorphine
) as well as prodrugs for this group such as hydrocodone
, nicocodeine
, codeine
, dihydrocodeine
and others—is often attributed to a marginal extended-release effect from various excipients, particularly those that are hydrophilic and form a gel-like substance at the pH levels in the stomach and duodenum.
Both as the result of this and the pharmacokinetics of oxymorphone, the IR tablets have a de facto duration of action of 5 to 13 hours (the mean would seem to be around 7 hours with a moderately small standard deviation and a left-skewed and leptokurtic frequency distribution) in patients with normal kidney and liver function. As a result, patients rotated on to extended release oxymorphone preparations from other opioids may very well need the Opana IR tablets, Numorphan ampoules or phials with hypodermic needles and/or a PCA pump, or immediate-release formulations of hydromorphone
, dihydromorphine
, high dose oxycodone
, hydromorphinol
, nicomorphine
, diamorphine, or morphine
for breakthrough pain incidents 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.
The duration of action and metabolic half-life of oxymorphone mean that immediate-release tablets are more similar to analgesic preparations of methadone
, levorphanol
, piritramide
, and existing extended-release forms of morphine, oxycodone, ketobemidone
and so on. The extended-release Opana tablets can provide detectable analgesia for anywhere from 6 to 36+ hours (the mean appears to be very close to the lower end of the continuum), largely contingent on things that can alter the drug's liberation, absorption, distribution, metabolism, and elimination profile. One cause is unusual conditions in the upper and middle GI tract, such as created by misoprostol
and Arthrotec (misoprostol plus diclofenac
). Among other things, misoprostol is a smooth muscle agent with both a contact and systemic mucousagogue that coats the stomach and adjacent areas with increasing amounts of mucus. This can result in everything from even slower onset of action to intact tablets being passed with stool.
Oxymorphone is also produced within the human body when the liver metabolises oxycodone
by means of O demethylation catalysed by the CYP2D6
enzyme. Approximately 10% of the dose is processed by the endocrine system in this respect; this can vary widely from person to person. The codeine
-hydrocodone
group and morphinan
s exhibit the same characteristics.
Consuming alcohol with Opana extended-release tablets can be an extremely dangerous situation. The absorption of oxymorphone can vary wildly in the presence of alcohol. Plasma concentrations were found to be as low as -50% of expected to as much as 270% more than expected. Elevated plasma levels could result in overdose. Opana ER does not cause "dose dumping
," which creates a blast of drug release that plagues other long acting opioids.
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
, fentanyl and butorphanol
are also common in veterinary settings and tramadol
is now often used as an analgesic for cats, dogs, ferrets, rats and other small animals.
Oxymorphone is mentioned, along with buprenorphine, oxycodone, dihydrocodeine, morphine and other opioids as a possible means of mitigating refractory depression. Opioids were commonly used for this indication up until the introduction of the tricyclic antidepressants in the 1950s, even though the latter 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.
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 that accumulate in the system as do pethdine synthetic opioids. There is also no real evidence that oxymorphone significantly lowers the seizure threshold like tramadol and some of the other synthetics mentioned above.
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.
Opana does have euphoric effects, and they are short-lived. This is one of the crucial elements of a drug that can generate a serious narcotic habit rather quickly in those who take it for recreation and require more doses to maintain a stable level of euphoria. These effects however, barring enhancement with alcohol or other substances or means of administration other than oral, are less pronounced than that of morphine, fentanyl or dilaudid however, as mentioned previously, when taken intranasally the euphoric effects are far more pronounced.
The significant antidepressant
and empathogenic properties of oxymorphone and other dihydromorphinone class semi-synthetic opioids is currently of interest to both the underground and the medical establishment, the latter of whom are "re-discovering" the anti-depressant effect and its relatively low ratio of toxic effects and lack of association with patient suicide attempts (see the oxycodone discussion
for further information and footnotes) and Opana ER has been proposed as an alternative to methadone and other extended-release and/or long lasting drugs like Morphine
, extended-release dihydrocodeine, buprenorphine, and 24-hour hydromorphone tablets for opioid detoxification and maintenance.
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 IV
drug using community. Because of its low bioavailability, 10% when taken orally, a 10 mg tablet represents 10 times the average IV dose in a single tablet. Known popularly as "blues" or "Nu- 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
.
Slang terms for oxymorphone include: blues, biscuits, blue heaven, new blues (although the immediate-release tablets are pink and off-white), octagons (extended release), [strength] octagons, stop signs, pink, pink heaven, biscuits (could also be Dilaudid tablets, meprobamate
tablets, or formerly Quaaludes), pandas, pancakes, pink heaven, pink lady, Mrs O, Orgasna IR, OM, Pink O, The O Bomb (by analogy to the slang term for hydromorphone "H Bomb") and others.
Oxymorphone is not a component of "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.
Rare cases of users baking their own at home by extracting oxycodone from pharmaceuticals and converting it to oxymorphone have been reported in 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 bioavailability 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.
, 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. Another derivative of oxymorphone is the opioid antagonist naloxone
(Narcan).
As reported in the July 1993 issue of Applied Environmental Bacteriology (PDF available at http://aem.asm.org/cgi/reprint/61/10/3645.pdf), the bacterium Pseudomonas putida, serotype M10 turns oxymorphone into oxymorphol
by means of a one-step conversion involving morphine dehydrogenase and a naturally occurring NADH-dependent morphinone reductase that can work on unsaturated 7,8 bonds.
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.
However, the aforementioned patents deal specifically with hydrogenation reactions producing dihydrocodeinone (hydrocodone), dihydromorphinone (hydromorphone), and ethyldihydromorphinone as final products. Hence it is unclear at best and rather unlikely that these particular procedures can be applied for the synthesis of oxycodone or oxymorphone, as they are not typically synthesized in this manner.
The rare practise of making homebake oxymorphone generally uses oxycodone and pyridine
amongst others, and the production of homebake hydromorphone (Dilaudid) from hydrocodone does also exist but is extremely rare. This is similar to a method especially common in New Zealand to make morphine out of codeine
. The resultant morphine base is used as is, made into a salt (usually citrate, although ascorbate, acetate, hydrochloride, nitrate, phosphate, and sulphate are also possible) by dissolving the base in a solution containing the relevant acid, or treated with acetic anhydride
or rarely other chemicals capable of acetylating compounds to produce what is usually a mixture of heroin, morphine, 3-monoacetylmorphine and 6-monoacetylmorphine. Depending on the method, this can also contain acetylcodeine and leftover codeine.
Morphinone
Morphinone is itself not a very potent opioid but it is the intermediate when morphine is being converted to hydromorphone which is 4-6 times as potent as morphine.- Chemical structure :...
is a powerful semi-synthetic opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
first developed in Germany circa 1914, patented in the USA by Endo Pharmaceuticals
Endo Pharmaceuticals
Endo Pharmaceuticals Inc. is an American pharmaceutical company. It was created as a result of a management buyout from DuPont Merck in 1997. Three DuPont Merck executives Endo Pharmaceuticals Inc. is an American pharmaceutical company. It was created as a result of a management buyout from...
in 1955 and introduced to the United States market in January 1959 and other countries around the same time. It (along with hydromorphone) was designed to have less incidence of side effects than morphine and heroin. It was a success as it differs from morphine and heroin in its effects in that it generates less euphoria, sedation, itching and other histamine effects at equianalgesic doses. This also means a lower dependence liability.
The brand name Numorphan is derived by analogy to the Nucodan name for an oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
product (or vice versa) as well as Paramorphan/Paramorfan for dihydromorphine
Dihydromorphine
Dihydromorphine is a semi-synthetic opioid invented in Germany in 1900. In structure, it is very similar to morphine, the only difference being the reduction of the double bond between positions 7 and 8 in morphine to a single bond...
and Paracodin (dihydrocodeine
Dihydrocodeine
Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution-ACE, Huscode, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine,...
). 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.
In some countries, hydromorphinol
Hydromorphinol
Hydromorphinol is an opiate analogue that is a derivative of morphine, where the 14-position has been hydroxylated and the 7,8- double bond saturated. It has similar effects to morphine such as sedation, analgesia and respiratory depression, but is more potent and has a steeper dose-response curve...
is distributed under the trade names Numorphan and Numorphan Oral. This is a relatively rare exception and the two drugs, whilst both being strong opioid analgesics, are notably different from one another.
Oxymorphone is administered as its hydrochloride salt
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
via injection, or suppository
Suppository
A suppository is a drug delivery system that is inserted into the rectum , vagina or urethra , where it dissolves.They are used to deliver both systemically-acting and locally-acting medications....
; 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,10 mg, 20 mg, 30 mg, and 40 mg. As of July 21, 2011 generic strengths equivalent to Opana ER 7½ mg and 15 mg are available. Some resources assert that 2, 12 and/or 15 mg IR tablets and 25, 36 and 50 mg extended release tablets will be introduced although apparently the timeline on that is not known to the public at this time. Opana Extended-Release tablets are based on the TIMERx system developed by a consortium led by Endo and Penwest. Some of these strengths (notably not the 7.5 mg) are available in an Opana IR–immediate release–form for breakthrough pain to be used by patients already on 24/7 opioid care such as fentanyl patches and sustained-relief morphine drugs like Avinza.
In addition to the sustained-release version for Opana, other versions of TIMERx are available and being developed for other protocols such as increasing, decreasing, stepwise increasing, and stepwise decreasing dose delivery over time, single and multiple bursts of medication, and combinations of the above.
Specifically, the apparent extension of the duration of effect of the IR tablets (all other things being equal, oxymorphone has a duration of action of 5 to 8 hours in most patients) versus similar drugs in commonly used immediate-release forms—for example Dilaudid (hydromorphone
Hydromorphone
Hydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
), morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, Vilan (nicomorphine
Nicomorphine
Nicomorphine is the 3,6-dinicotinate ester of morphine. It is a strong opioid agonist analgesic two to three times as potent as morphine with a side effect profile similar to that of dihydromorphine, morphine, and diamorphine. Nicomorphine was patented as Vilan by Lannacher Heilmittel Ges. m.b.H...
), Paramorfan (dihydromorphine
Dihydromorphine
Dihydromorphine is a semi-synthetic opioid invented in Germany in 1900. In structure, it is very similar to morphine, the only difference being the reduction of the double bond between positions 7 and 8 in morphine to a single bond...
) as well as prodrugs for this group such as hydrocodone
Hydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
, nicocodeine
Nicocodeine
Nicocodeine is an opiate derivative, closely related to dihydrocodeine and the codeine analogue of nicomorphine developed as a cough suppressant and analgesic. It is not commonly used in most countries, but has activity similar to other opiates. Nicocodeine and nicomorphine were introduced in the...
, codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, dihydrocodeine
Dihydrocodeine
Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution-ACE, Huscode, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine,...
and others—is often attributed to a marginal extended-release effect from various excipients, particularly those that are hydrophilic and form a gel-like substance at the pH levels in the stomach and duodenum.
Both as the result of this and the pharmacokinetics of oxymorphone, the IR tablets have a de facto duration of action of 5 to 13 hours (the mean would seem to be around 7 hours with a moderately small standard deviation and a left-skewed and leptokurtic frequency distribution) in patients with normal kidney and liver function. As a result, patients rotated on to extended release oxymorphone preparations from other opioids may very well need the Opana IR tablets, Numorphan ampoules or phials with hypodermic needles and/or a PCA pump, or immediate-release formulations of hydromorphone
Hydromorphone
Hydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
, dihydromorphine
Dihydromorphine
Dihydromorphine is a semi-synthetic opioid invented in Germany in 1900. In structure, it is very similar to morphine, the only difference being the reduction of the double bond between positions 7 and 8 in morphine to a single bond...
, high dose oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
, hydromorphinol
Hydromorphinol
Hydromorphinol is an opiate analogue that is a derivative of morphine, where the 14-position has been hydroxylated and the 7,8- double bond saturated. It has similar effects to morphine such as sedation, analgesia and respiratory depression, but is more potent and has a steeper dose-response curve...
, nicomorphine
Nicomorphine
Nicomorphine is the 3,6-dinicotinate ester of morphine. It is a strong opioid agonist analgesic two to three times as potent as morphine with a side effect profile similar to that of dihydromorphine, morphine, and diamorphine. Nicomorphine was patented as Vilan by Lannacher Heilmittel Ges. m.b.H...
, diamorphine, or morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
for breakthrough pain incidents 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.
The duration of action and metabolic half-life of oxymorphone mean that immediate-release tablets are more similar to analgesic preparations of methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
, levorphanol
Levorphanol
Levorphanol is an opioid medication used to treat severe pain. It is the levorotatory stereoisomer of the synthetic morphinan and a pure opioid agonist, first described in Germany in 1948 as an orally active morphine-like analgesic...
, piritramide
Piritramide
Piritramide is a synthetic opioid analgesic with a potency 0.65 to 0.75 times that of morphine. A common starting dose is 15 mg IV, equivalent to 10 mg of morphine hydrochloride. Piritramide is commonly used for the treatment of postoperative pain...
, and existing extended-release forms of morphine, oxycodone, ketobemidone
Ketobemidone
Ketobemidone is a powerful opioid analgesic. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted by it's metabolite norketobemidone. This makes it useful for some types of pain that don't respond well to other opioids...
and so on. The extended-release Opana tablets can provide detectable analgesia for anywhere from 6 to 36+ hours (the mean appears to be very close to the lower end of the continuum), largely contingent on things that can alter the drug's liberation, absorption, distribution, metabolism, and elimination profile. One cause is unusual conditions in the upper and middle GI tract, such as created by misoprostol
Misoprostol
Misoprostol is a drug that is used for the prevention of non steroidal anti inflammatory drug induced gastric ulcers, for early abortion, to treat missed miscarriage, and to induce labor. The latter use is controversial in the United States. Misoprostol was invented and marketed by G.D...
and Arthrotec (misoprostol plus diclofenac
Diclofenac
Diclofenac is a non-steroidal anti-inflammatory drug taken to reduce inflammation and as an analgesic reducing pain in certain conditions....
). Among other things, misoprostol is a smooth muscle agent with both a contact and systemic mucousagogue that coats the stomach and adjacent areas with increasing amounts of mucus. This can result in everything from even slower onset of action to intact tablets being passed with stool.
Oxymorphone is also produced within the human body when the liver metabolises oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
by means of O demethylation catalysed by the CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...
enzyme. Approximately 10% of the dose is processed by the endocrine system in this respect; this can vary widely from person to person. The codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
-hydrocodone
Hydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
group and morphinan
Morphinan
Morphinan is the base chemical structure of a large chemical class of psychoactive drugs, consisting of opioid analgesics, cough suppressants, and dissociative hallucinogens, among others.- Chemical Derivatives :Immediate derivatives of morphinan include:...
s exhibit the same characteristics.
Consuming alcohol with Opana extended-release tablets can be an extremely dangerous situation. The absorption of oxymorphone can vary wildly in the presence of alcohol. Plasma concentrations were found to be as low as -50% of expected to as much as 270% more than expected. Elevated plasma levels could result in overdose. Opana ER does not cause "dose dumping
Dose dumping
Dose dumping is a phenomenon of drug metabolism in which environmental factors can cause the premature and exaggerated release of a drug. This can greatly increase the concentration of a drug in the body and thereby produce adverse effects or even drug-induced toxicity.Dose dumping is most commonly...
," which creates a blast of drug release that plagues other long acting opioids.
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
Actiq
Actiq by Cephalon, is a solid formulation of fentanyl citrate on a plastic stick that dissolves slowly in the mouth for absorption across the buccal mucosa. Generically Actiq is a form of oral transmucosal fentanyl citrate . In the UK, Fentanyl is a Class A drug under the Misuse of Drugs Act 1971....
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
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, hydromorphone
Hydromorphone
Hydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
, fentanyl and butorphanol
Butorphanol
Butorphanol is a morphinan-type synthetic opioid analgesic developed by Bristol-Myers. Brand name Stadol was recently discontinued by the manufacturer. It is now only available in its generic formulations, manufactured by Novex, Mylan, Apotex and Ben Venue Laboratories. Butorphanol is most...
are also common in veterinary settings and tramadol
Tramadol
Tramadol hydrochloride is a centrally acting synthetic opioid analgesic used in treating moderate pain. The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia...
is now often used as an analgesic for cats, dogs, ferrets, rats and other small animals.
Oxymorphone is mentioned, along with buprenorphine, oxycodone, dihydrocodeine, morphine and other opioids as a possible means of mitigating refractory depression. Opioids were commonly used for this indication up until the introduction of the tricyclic antidepressants in the 1950s, even though the latter 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 darkens in color with prolonged exposure to light, though this does not affect 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 bradycardiaBradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
and hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
. In a severe case of overdose, apnea
Apnea
Apnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...
, circulatory collapse
Circulatory collapse
A circulatory collapse is defined as a general or specific failure of the circulation, either cardiac or peripheral in nature. A common cause of this could be shock or trauma from injury or surgery...
, cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
, 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 that accumulate in the system as do pethdine synthetic opioids. There is also no real evidence that oxymorphone significantly lowers the seizure threshold like tramadol and some of the other synthetics mentioned above.
Brand Names
- Numorphan (suppository and injectable solution)
- Opana ER (extended-release tablet)
- Opana IR (immediate-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.
Illicit Use
Like other effective centrally-acting analgesics, some of the additional effects of oxymorphone can include euphoria, anxiolysis, promotion of sociability, and other similar effects that can cause psychological addiction to the drug. Also, like all other opiates, oxymorphone is physically addictive and can cause opiate withdrawal symptoms.Opana does have euphoric effects, and they are short-lived. This is one of the crucial elements of a drug that can generate a serious narcotic habit rather quickly in those who take it for recreation and require more doses to maintain a stable level of euphoria. These effects however, barring enhancement with alcohol or other substances or means of administration other than oral, are less pronounced than that of morphine, fentanyl or dilaudid however, as mentioned previously, when taken intranasally the euphoric effects are far more pronounced.
The significant antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
and empathogenic properties of oxymorphone and other dihydromorphinone class semi-synthetic opioids is currently of interest to both the underground and the medical establishment, the latter of whom are "re-discovering" the anti-depressant effect and its relatively low ratio of toxic effects and lack of association with patient suicide attempts (see the oxycodone discussion
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
for further information and footnotes) and Opana ER has been proposed as an alternative to methadone and other extended-release and/or long lasting drugs like Morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, extended-release dihydrocodeine, buprenorphine, and 24-hour hydromorphone tablets for opioid detoxification and maintenance.
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 IV
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
drug using community. Because of its low bioavailability, 10% when taken orally, a 10 mg tablet represents 10 times the average IV dose in a single tablet. Known popularly as "blues" or "Nu- 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
Drugstore Cowboy
Drugstore Cowboy is a 1989 crime drama directed by Gus Van Sant and written by Van Sant and Daniel Yost, based on a novel by James Fogle. Matt Dillon stars in the title role, and Kelly Lynch, Heather Graham, and William S. Burroughs are also featured. Drugstore Cowboy was filmed mainly around...
.
Slang terms for oxymorphone include: blues, biscuits, blue heaven, new blues (although the immediate-release tablets are pink and off-white), octagons (extended release), [strength] octagons, stop signs, pink, pink heaven, biscuits (could also be Dilaudid tablets, meprobamate
Meprobamate
Meprobamate is a carbamate derivative which is used as an anxiolytic drug...
tablets, or formerly Quaaludes), pandas, pancakes, pink heaven, pink lady, Mrs O, Orgasna IR, OM, Pink O, The O Bomb (by analogy to the slang term for hydromorphone "H Bomb") and others.
Oxymorphone is not a component of "T's and blues
Pentazocine
Pentazocine is a synthetically prepared prototypical mixed agonist-antagonist narcotic drug of the benzomorphan class of opioids used to treat moderate to moderately severe pain...
", 1970s slang for a combination of pentazocine
Pentazocine
Pentazocine is a synthetically prepared prototypical mixed agonist-antagonist narcotic drug of the benzomorphan class of opioids used to treat moderate to moderately severe pain...
("T's") and pyribenzamine ("blues"). Nor are "blues" 10 mg Valium tablets, which are known as Blue Bombers and BBs.
Rare cases of users baking their own at home by extracting oxycodone from pharmaceuticals and converting it to oxymorphone have been reported in a number of countries. In some cases, codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
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
Dihydromorphine
Dihydromorphine is a semi-synthetic opioid invented in Germany in 1900. In structure, it is very similar to morphine, the only difference being the reduction of the double bond between positions 7 and 8 in morphine to a single bond...
, desomorphine
Desomorphine
Desomorphine is an opiate analogue invented in 1932 in the United States that is a derivative of morphine, where the 6-hydroxyl group has been removed and the 7,8 double bond has been saturated. It has sedative and analgesic effects, and is around 8-10 times more potent than morphine...
, 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 bioavailability boost from the latter appear to be the only means successful Opana ER misuse aside from insufflation
Insufflation (medicine)
Insufflation is the practice of inhaling a substance. Insufflation has limited medical use, but is a common route of administration with many respiratory drugs used to treat conditions in the lungs and paranasal sinus .The technique is common for many recreational drugs and is also used for some...
-- the TIMERx system appears to be making the extended release tablets useless for preparing for injection.
Chemistry
Oxymorphone is commercially produced from thebaineThebaine
Thebaine , its name coming from the Greek Θῆβαι, Thēbai, an ancient city in Upper Egypt, is an opiate alkaloid. A minor constituent of opium, thebaine is chemically similar to both morphine and codeine, but has stimulatory rather than depressant effects, causing convulsions similar to strychnine...
, which is a minor constituent of the opium poppy
Opium poppy
Opium poppy, Papaver somniferum, is the species of plant from which opium and poppy seeds are extracted. Opium is the source of many opiates, including morphine , thebaine, codeine, papaverine, and noscapine...
(Papaver somniferum) but thebaine is found in greater abundance (3%) in the roots of the oriental poppy
Oriental poppy
Papaver orientale is a perennialflowering plant native to the Caucasus, northeastern Turkey, and northern Iran, not the Orient as the name implies....
(Papaver orientale). Oxymorphone can also be synthesized from morphine or oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
, and is an active metabolite of the latter drug. The structure-activity relationship
Quantitative structure-activity relationship
Quantitative structure–activity relationship or QSPR is the process by which chemical structure is quantitatively correlated with a well defined process, such as biological activity or chemical reactivity.For example, biological activity can be expressed quantitatively as the concentration of a...
of oxymorphone and its derivatives has been well-examined. Esterification of the hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
groups yields stronger compounds. Another derivative of oxymorphone is the opioid antagonist naloxone
Naloxone
Naloxone is an opioid antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory...
(Narcan).
As reported in the July 1993 issue of Applied Environmental Bacteriology (PDF available at http://aem.asm.org/cgi/reprint/61/10/3645.pdf), the bacterium Pseudomonas putida, serotype M10 turns oxymorphone into oxymorphol
Oxymorphol
Oxymorphol is oxymorphone which has been hydroxylated at the 6-position. It is produced by the human body as an active metabolite of oxymorphone and some bacteria as an intermediate in turning morphine into hydromorphone...
by means of a one-step conversion involving morphine dehydrogenase and a naturally occurring NADH-dependent morphinone reductase that can work on unsaturated 7,8 bonds.
German patents from the middle 1930s indicate that oxymorphone as well as hydromorphone
Hydromorphone
Hydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
, hydrocodone
Hydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
, oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
, and acetylmorphone
Acetylmorphone
Acetylmorphone is an opiate analogue that is an acetylated derivative of hydromorphone which was developed in the early 1900s as a potential cough suppressant and analgesic. It is prepared by the acetylation of hydromorphone using either acetyl chloride or acetic anhydride...
can be prepared—without the need for hydrogen gas—from solutions of codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, and dionine by refluxing an acidic aqueous solution, or the precursor drug dissolved in ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
, in the presence of Column 7 metals, namely palladium
Palladium
Palladium is a chemical element with the chemical symbol Pd and an atomic number of 46. It is a rare and lustrous silvery-white metal discovered in 1803 by William Hyde Wollaston. He named it after the asteroid Pallas, which was itself named after the epithet of the Greek goddess Athena, acquired...
and platinum
Platinum
Platinum is a chemical element with the chemical symbol Pt and an atomic number of 78. Its name is derived from the Spanish term platina del Pinto, which is literally translated into "little silver of the Pinto River." It is a dense, malleable, ductile, precious, gray-white transition metal...
in fine powder or colloidal form or platina black. It is unclear from information available if aluminium
Aluminium
Aluminium or aluminum is a silvery white member of the boron group of chemical elements. It has the symbol Al, and its atomic number is 13. It is not soluble in water under normal circumstances....
or nickel
Nickel
Nickel is a chemical element with the chemical symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel belongs to the transition metals and is hard and ductile...
can be used as a catalyst in these reactions as well.
However, the aforementioned patents deal specifically with hydrogenation reactions producing dihydrocodeinone (hydrocodone), dihydromorphinone (hydromorphone), and ethyldihydromorphinone as final products. Hence it is unclear at best and rather unlikely that these particular procedures can be applied for the synthesis of oxycodone or oxymorphone, as they are not typically synthesized in this manner.
The rare practise of making homebake oxymorphone generally uses oxycodone and pyridine
Pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
amongst others, and the production of homebake hydromorphone (Dilaudid) from hydrocodone does also exist but is extremely rare. This is similar to a method especially common in New Zealand to make morphine out of codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
. The resultant morphine base is used as is, made into a salt (usually citrate, although ascorbate, acetate, hydrochloride, nitrate, phosphate, and sulphate are also possible) by dissolving the base in a solution containing the relevant acid, or treated with acetic anhydride
Acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
or rarely other chemicals capable of acetylating compounds to produce what is usually a mixture of heroin, morphine, 3-monoacetylmorphine and 6-monoacetylmorphine. Depending on the method, this can also contain acetylcodeine and leftover codeine.
See also
- Opioids
- Oxymorphone hydrazoneOxymorphazoneOxymorphazone is an opioid analgesic drug related to oxymorphone. Oxymorphazone is a potent and long acting μ-opioid agonist which binds irreversibly to the receptor, forming a covalent bond which prevents it from detaching once bound...
- OxymorpholOxymorpholOxymorphol is oxymorphone which has been hydroxylated at the 6-position. It is produced by the human body as an active metabolite of oxymorphone and some bacteria as an intermediate in turning morphine into hydromorphone...
- a metabolite of oxymorphone and an intermediate in the creation of hydromorphone - HydromorphoneHydromorphoneHydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
- OxycodoneOxycodoneOxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
- Drug addiction