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Hydromorphone, a more common synonym for dihydromorphinone and dimorphone, commonly a hydrochloride (trade names Palladone, Palladone SR, Dilaudid and numerous others) is a 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. It is, in medical terms, an opioid analgesic and, in legal terms, a narcotic. It should not be confused with hydromorphinol, also known as 14-hydroxydihydromorphine and RAM-320, or dihydromorphine (Paramorfan). While all of these are strong opioids, they are indeed different drugs. Additional confusion arises from the fact that, in a handful of countries, hydromorphinol is distributed under the trade name Numorphan, which is the trade name for oxymorphone in the rest of the world, according to the current version of The A-Z Encyclopaedia of Alcohol & Drug Abuse and other references.

Hydromorphone is known in various countries around the world by the trade names Hydal, Sophidone, Hydrostat Hydromorfan, Hydromorphan, Laudicon, Hymorphan, Opidol, Palladone and others (warning: the brand names are inconsistent from country to country). An extended-release version of hydromorphone called Palladone was available for a short time in the United States before being voluntarily withdrawn from the market after a July 2005 FDA advisory warned of a high overdose potential when taken with alcohol. As of March 2010, it is still available in the United Kingdom under the brand name Palladone SR, and in most other European countries. Another extended-release version called Hydromorph Contin, manufactured as controlled-release capsules, continues to be produced and distributed in Canada by Purdue Pharma Inc. of Pickering, Ontario. The newest extended-release preparation (and the first to last 24 hours - see below) is Jurnista, made by Janssen-Cilag. In addition to Purdue-Frederick and Janssen-Cilag, manufacturers of hydromorphone products include Knoll, Abbott, Endo, Mallinckrodt, Merck, Mundipharma, and Lannacher, among others.

Hydromorphone is used in medicine as an alternative to morphine and heroin for analgesia, and as a second- or third-line narcotic antitussive (cough suppressant) for cases of dry, painful, paroxysmal coughing resulting from continuing bronchial irritation after influenza and other ailments, inhalation of fungus, and other causes. In general, it is considered the strongest of the antitussive drugs, and was developed shortly after diacetylmorphine was removed from clinical use for this purpose in most of the world and banned outright in many countries. The effectiveness of hydrocodone as an antitussive may be partly due its being partially converted to hydromorphone in the liver.

History

Hydromorphone was first synthesized and researched in Germany in 1924 and introduced to the mass market by Knoll in 1926 under the brand name Dilaudid indicating its derivation and degree of similarity to morphine (by way of laudanum)—Cf. Dicodid (hydrocodone), Dihydrin (dihydrocodeine) and Dinarkon (oxycodone). Some authorities and publications use the name dilaudid as a synecdoche for hydromorphone. Hydromorphone may also be known by the brand name Morphodid.

Indications

Hydromorphone is used to relieve moderate to severe pain and severe, painful dry coughing. Hydromorphone is becoming more popular in the treatment of chronic pain in many countries. Hydromorphone displays superior solubility and speed of onset, a less troublesome side effect profile, and lower dependence liability as compared to morphine and diamorphine (heroin). It is thought to be 8-10 times stronger than morphine, but with a lower risk of dependency. Hydromorphone is, therefore, preferred over morphine in many areas ranging from the emergency department to the operating suite to ongoing treatment of chronic pain syndromes. Hydromorphone lacks the toxic metabolites (e.g., norpethidine) of many opioids related to pethidine and some of the methadone and tends to cause less nausea than morphine. It is a common alternative for those tending to have hallucinations from fentanyl administered through dermal patches and other dosage forms.

In addition to the above, hydromorphone usually proves to be the first alternative of choice to morphine and fentanyl in severe chronic pain.

Side effects

Adverse effects of hydromorphone are similar to those of other opioid analgesics, such as morphine. The major hazards of hydromorphone include dose-related respiratory depression and sometimes circulatory depression.^[3] More common side effects include light-headedness, dizziness, sedation, constipation, nausea, vomiting, and sweating.^[3] Massive overdoses are rarely observed in opioid-tolerant individuals, but, when they occur, they may lead to circulatory system collapse. A particular problem that may occur with hydromorphone is accidental administration in place of morphine due to a mix-up between the similar names, either at the time the prescription is written or when the drug is dispensed. This has led to several deaths and calls for hydromorphone to be distributed in distinctly different packaging from morphine to avoid confusion.^[4][5] The effects of overdose can be exaggerated by dose dumping if the medication is taken with alcohol or benzodiazepines.^[6]

A possible and likely side effect associated with hydromorphone is euphoria, achieved dually through a perceived transition from a state of pain to a state of pain-relief, or through direct stimulation of the μ opioid receptor (μ₁ and μ₂) [of which hydromorphone, related to the morphine molecule, is a primary μ agonist]. Although this can lead to addiction and reward-seeking behavior, it has been demonstrated that, when opioids are taken for pain relief, patients are very unlikely to misuse the drug (see Opioids). Nevertheless, there is a certain risk of abuse and dependence among patients prescribed any opioid, including hydromorphone.^[7]

Withdrawal

The short length of action of hydromorphone and other metabolic factors mean that the abstinence syndrome (withdrawal) is brief but intense; a heavy and/or long-term user of hydromorphone opting or otherwise forced to quit "cold turkey" can expect a withdrawal syndrome as intense as that of morphine but much more severe in that it is compressed into a spike, which will peak in 14 to 21 hours and resolve in 36 to 72 hours, provided the user was not taking other longer-acting opioids, or have abnormalities in drug metabolism and/or liver or kidney function. All of the effects of hydromorphone and its attendant withdrawal syndrome can be significantly lengthened by such factors. Possible but less common is the opposite: Some patients require oral doses of hydromorphone as frequently as every 90 minutes, and the withdrawal syndrome would compress into an even more violent spike, which can peak in as little as 9 hours.

Formulations

In the United States and some other countries, hydromorphone has long been available only as instant-release oral formulations (viz. Hydal, Sophidone, Dilaudid and numerous generic hydromorphone formulations) for breakthrough pain or taken continuously by the clock every 1½ to 4 hours during the day; this is unlike morphine, oxycodone, and oxymorphone, which have both extended and immediate release oral versions. But since the release of Palladone SR, Hydal Retard, Morphodid, HydromorphContin, and the like, hydromorphone can also be used more effectively for chronic pain. HydromorphContin is the Canadian version, whilst Palladone SR is available in other countries and Hydal Retard is the continental European version and the oldest of the three.

Jurnista, the first 24-hour extended-release preparation of hydromorphone, uses the OROS Push-Pull system to deliver a consistent level of the opioid over a 24-hour period. Developed by ALZA Corporation, Jurnista is used in Europe and elsewhere, including Australia where it has been available since May 2009 (and manufactured by Janssen-Cilag) to treat moderate-to-severe chronic pain and sometimes as a substitute for methadone in opioid substitution maintenance treatment programs when a person suffers serious side effects from the substitute opioid he/she is receiving, or when treatment with methadone or other opioids has failed. There is increasingly widespread usage of hydromorphone as a substitute for illegal opioids in maintenance treatment programs around the world, mostly because it offers a better quality of life to addicts, and lacks some of methadone's more troublesome side effects. At present, Jurnista (known as Exalgo in the US) is not approved in the USA. However, Exalgo is expected to receive approval by March 1, 2010. On May 22, 2009, Neuromed submitted a response to an Approvable Letter to the U.S. Food and Drug Administration seeking approval for Exalgo for the management of moderate to severe pain in opioid-tolerant patients requiring continuous, around-the-clock opioid analgesia for an extended period of time. On June 12, 2009, the FDA informed Neuromed that the Exalgo submission would be classified as a Complete, Class 2 Response with a corresponding PDUFA date of November 22, 2009. The FDA initiated a three-month wait to allow them to review the application again brought on by changes to the prescribing information that changed the expected approval date of November 22, 2009 to February 22, 2010. Because of federal government closings during snow conditions, the FDA briefly extended the approval date to March 1, 2010.

The U.S. commercial rights to Exalgo were acquired in June 2009 by Mallinckrodt, Inc., a subsidiary of Covidien, plc. Under the agreement, Covidien’s subsidiary Mallinckrodt Inc., which does business in both generic and brand-name medications, will be responsible for all commercialization activities for Exalgo in the United States, including marketing and sales. Neuromed will work to complete the clinical development and the regulatory approval process. Covidien’s subsidiary Mallinckrodt Inc. will be responsible for all regulatory filings post-FDA approval.

Another recent development, a hydromorphone polymer implant, which is designed to be implanted subcutaneously, could offer an alternative to methadone maintenance treatment, as well as pain management for both cancer patients and chronic pain sufferers. The device, after being implanted in a patient, releases a near-constant dosage of hydromorphone for an extended period of time — at least one month. For those involved in methadone maintenance treatment, the hydromorphone polymer implant could offer several advantages to both patients and program managers: 1) daily clinic visits are unnecessary; 2) both treatment costs and time are reduced; 3) risk of the illegal diversion of a controlled substance is greatly reduced, if not eliminated; 4) convenience could increase patient compliance; and 5) the cost, time, and convenience advantages could lead to increased treatment capacity and success. One further advantage, for anyone with a hydromorphone polymer implant, would be greater freedom to travel, especially internationally, without the need to consider local laws and restrictions on hydromorphone and other opioids.

United States manufacturers are currently producing more hydromorphone than in the recent past, and many now make 8-mg tablets, as the drug has become more popular for chronic pain, reducing or eliminating the inventory problems that would have plagued pharmacies in the past, such as those involving a long-term chronic-pain patient on Dilaudid as the sole or central agent. This scenario, uncommon but indeed observed in the past, could require monthly prescription fill quantities in the low quadruple figures over a prolonged period. Over this period, the dose is likely to escalate or at least remain constant, depleting supplies at the regional warehouse or distributor level after a few months after the beginning of the year because of the Schedule II annual production quotas and restrictions on movement of inventory imposed by the state and federal governments.

Since, as noted above, there is not currently a hydromorphone analogue of MS-Contin or OxyContin on the market in the United States, the similarity in effects of hydromorphone and oxymorphone (which does come in an extended-release form, Opana) is particularly important to note at this time, since high-dose maintenance regimens of hydromorphone for chronic pain can present the aforementioned logistical problems for pharmacists and patients. Clinical experience with oxymorphone for chronic pain, in general, shows it to be very similar to hydromorphone in its effects for most patients, with nausea and itching being even less common than with hydromorphone by a small percentage, as shown in the clinical trials for the Opana series.

Dosage forms

Hydromorphone hydrochloride (anhydrous) is the salt used in virtually all hydromorphone products and in prescription compounding at this time. The freebase conversion ratio of this salt is 0.887. Other salts that are used rarely are the sulfate (conversion factor 0.853) and the terephtalate (conversion factor 0.638), with the bitartrate, tartrate, and hydroiodide having been in some use prior to 1955.

Combination products are uncommon but do exist, such as Dilaudid-Atropin, which contains atropine and, in the past, a hydromorphone combination for the induction of Twilight Sleep was available, i.e., hydromorphone and scopolamine. The reasons for adding atropine to hydromorphone tablets or other formulations are twofold: Anticholinergics help opioids combat neuropathic pain and to discourage deliberate overdose. For the latter reason, atropine is added to diphenoxylate for anti-diarrhoeal products like Lomotil and tablets of morphine, tilidine, and methadone for pain.

Hydromorphone's oral to intravenous effectiveness ratio is 5:1 and equinalgesia conversion ratio (hydromorphone HCl to anhydrous morphine SO₄ (sulfate), IV, SC, or IM) is 8:1. The oral equianalgesic conversion rate (hydromorphone HCl to morphine SO₄) can vary between 5:1 to 8:1. Therefore, 30 mg of immediate-release morphine by mouth is similar in analgesic effect to c.4-6 mg of hydromorphone by mouth (requiring extra care during conversion & titration), 10 mg of morphine by injection, and 1.5 mg of hydromorphone by injection. These doses also correspond to about 30 mg of hydrocodone, 24 mg of oxycodone, 200 mg of codeine, 135 mg of dihydrocodeine, 20 mg of dihydromorphine, 15 mg of nicomorphine, 12 mg of heroin, 34 mg of piritramide, circa or about 18 mg of ketobemidone, and 8 mg of dextromoramide by the default routes of administration and 60 mg of extended-release morphine via the oral route. These figures can vary from person to person, especially with oral administration, on account of such things as relative and absolute levels of some liver enzymes, system pH, and others. This is especially the case with methadone, levomethadone, and phenadoxone, which require extra steps in the conversion and titration process.

At this point in time, the tablets and capsules with the highest immediate-release dose of hydromorphone are 8-mg tablets; however, 16-mg (quarter-grain), 32-mg (half-grain) and 64-mg (one grain) tablets were available at least through the late 1950s in some countries, and 24-, 36-, and 48-mg tablets less commonly. As was the case with many other medications, including most of the centrally-acting analgesics, hypodermic tablets for preparing injections were made in the past, as well, and the tablets for oral administration were in fact low- or zero-residue multi-purpose tablets, which could replace the "Solvets", as the hypodermic tablets were called, in times of emergency. In western countries, inexpensive ampoules of sterile solution for injection have largely replaced the hypodermic tablets that were so common in past decades.

True to its indication of complete interchangeability with morphine, hydromorphone is often used with other drugs such as scopolamine and other anticholinergics for neuropathic pain, with the admixed, simultaneous, or near-simultaneous administration of hydromorphone, orphenadrine and an NSAID being a common protocol for severe musculo-skeletal conditions.

The 64-mg extended-release Jurnista XR tablet, 500-mg (10 mg/ml * 50 ml) vial of Dilaudid HP injection, and 5-mg suppositories are the units with the largest doses in their respective categories at this time. The hydromorphone analogue of Roxanol (liquid for oral, sublingual, or buccal administration via a calibrated dropper—not to be confused with Dilaudid Cough Syrup, which is more dilute and contains a number of other ingredients including peach flavouring) of 1 mg per ml is available in 480 ml (17 imp fl oz; 16 US fl oz) bottles, and the 250-mg phial of lipophilised powder for preparing injections with 1000-mg and 1/8-oz. phials available in the past.

Oral formulations of hydromorphone can also be administered under the tongue and between the lower jaw and cheek; these routes increase the effectiveness of the tablets by putting hydromorphone into the bloodstream prior to passing through the liver. A liquid formulation is commonly available and recommended specifically for these routes, and uncoated low-residue oral formulations are available in some countries to take advantage of this fact. However, all tablets potentially can be used in this fashion, although they dissolve more slowly than purpose-made sublingual, buccal, and orally disintegrating tablets of other drugs like nitroglycerine, morphine, fentanyl, ondansetron, and others.

As with many other drugs, oral and soluble forms of hydromorphone, such as the oral liquid, cough syrup, soluble tablets, etc., can be mixed with water or fruit juice if so desired; carbonated beverages and effervescent medications like Alka-Seltzer have the added advantage of driving the medication through the stomach wall more rapidly. Hydromorphone has a characteristic taste that is somewhat bitter but with a slight sweet component characteristic of ketones in general; it is not as bitter as morphine.

Hydromorphone is generally believed to be the second-most-common agent (most common one being morphine) used in patient-controlled analgesia (PCA) units worldwide. The injectable forms of hydromorphone are suitable for outpatient use in a fashion similar to that of insulin once the patient and/or caretakers have been instructed on injection technique. Such related matters as aspirating before IM or SC injection to make certain that the dose is not going to be accidentally injected directly into a vein or artery should also be discussed. Dilution of the injection fluid with saline or distilled water is common is such cases and especially when the drug is administered intravenously. Pre-loaded syringes are available in some countries or can of course be prepared by a doctor, nurse, or compounding pharmacy.

Because of its potency in very small quantities, the significance of the advantage of avoiding or reducing first-pass hepatic metabolism, rapid action and short metabolic and elimination half-life and other chemical characteristics including high lipid solubility and relatively moderate to low molecular weight (identical to morphine) - hydromorphone, along with its even stronger relative oxymorphone, is among drugs mentioned as the possible analgesic agents in new formulations and methods of delivery. Some of the products said to be in development or under discussion in the pharmaceutical industries of Europe, the United States, Canada, China and/or various Pacific Rim countries as of February 2008 are:

1. Nasal sprays and drops (the former is the most commonly-used version of butorphanol in many places in the world. A related method, that of nebulizing the drug for inhalation, is often used for morphine to get near-instantaneous pain relief in some pain disorders and painful lung problems (phials and cartridges for respective nebulizers are currently available, with the rule of thumb being that 2 mg of nebulized morphine is equal to 10 mg injected by the subcutaneous, intramuscular, and intravenous route and 1 mg via the various intraspinal routes). And, since hydromorphone has an identical molecular weight, higher milligram potency, and superior lipid solubility, this method works well and is possible to implement with equipment and drug formulations currently on the market.
2. An injectable formulation that contains the drug in liposomes in an appropriate vehicle that can continue to release the active agent in sufficient quantities to maintain therapeutic concentrations in the system for up to a week following a deep intramuscular depot injection (recently introduced for morphine; has been in use for a while with other drugs for unrelated conditions, e.g., Depo-Provera)
3. New variations on the oral, sublingual, buccal and/or rectal routes of administration.
4. A transdermal/transcutaneous delivery system somewhat similar to extant transdermal drug delivery systems for fentanyl, sufentanil, lidocaine, clonidine, scopolamine, nicotine
5. An electrophoretic transdermal delivery system — a variant of the fentanyl patch, which contains electrical components to aid delivery of the drug. There is some question as to whether electrophoresis is a sine qua non for a transdermal system based on opioids outside the fentanyl family. Hydromorphone and chemically-related drugs with similar molecular weight and lipid solubility can, in theory, be delivered transdermally to an extent that is superior to the effect of morphine but most likely less than that of most of the fentanyls. Other possible candidates for this route of delivery would seem to include oxymorphone, dihydroetorphine, metopon, desomorphine, acetylmorphone, diamorphine, diacetyldihydromorphine, dihydromorphine, and some other semi-synthetics.
6. A conventional dermal patch (using ingredients in the carrier liquid/gel to change local skin characteristics to improve absorption) that delivers both a narcotic analgesic and local anaesthetic such as lidocaine, mepivacaine, bupivicaine, ropivacaine etc. (most likely from a separate reservoir and skin-contact areas within the patch rather than mixing the local anaesthetic with the narcotic) for use against low-back pain from sciatica, shingles, radiculopathy, other primary neuropathic pain conditions and chronic severe pain secondary to lumbago and other degenerative connective-tissue diseases of the spinal column. Many transdermal drug delivery systems use ethanol as the main solvent, since it also promotes skin permeability for drug transfer with minimal skin irritation.
7. An implantable osmotic pump similar to that being developed by a consortium including Durect, ALZA, and others — a pump based on a piston powered by osmotic pressure that pumps drug/s into the body over an extended period. The unit is implanted under the skin and has no external or protruding parts. This pump was specifically developed as a hydromorphone delivery system, and it is unclear whether is would be suitable or superior for drugs that are effective in much smaller quantities such as the fentanyls or Bentley Compounds like dihydroetorphine.

Available forms

• Tablets - 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 8 mg
• Capsules (Palladone) - 1.3 mg, 2.6 mg
• Modified-Release capsules (Palladone SR) - 2 mg, 4 mg, 8 mg, 16 mg, 24 mg, 30 mg, 32 mg, 52 mg
• Extended-Release (24hr) tablets (Jurnista) - 4 mg, 8 mg, 16 mg, 32 mg, 64 mg
• Controlled-Release capsules (Hydromorph Contin) - 3 mg, 6 mg, 12 mg, 18 mg, 24 mg, 30 mg
• Suppository - 3 mg, 5 mg
• Powder for injection - 250 mg (hydromorphone HCl)
• Oral liquid (HCl) - 1 mg/mL (480 mL)
• Cough Syrup - 1 mg/5 ml
• Injection (HCl) - 1 mg/mL (1 mL), 2 mg/mL (1 mL, 20 mL), 4 mg/mL (1 mL),
• Dilaudid-HP - 10 mg/ml (1 mL, 5mL, 50mL)

Pharmacology

Hydromorphone, a semi-synthetic μ-opioid agonist, is a hydrogenated ketone of morphine and shares the pharmacologic properties typical of opioid analgesics. Hydromorphone and related opioids produce their major effects on the central nervous system and gastrointestinal tract. These include analgesia, drowsiness, mental clouding, changes in mood, euphoria or dysphoria, respiratory depression, cough suppression, decreased gastrointestinal motility, nausea, vomiting, increased cerebrospinal fluid pressure, increased biliary pressure, pinpoint constriction of the pupils, increased parasympathetic activity and transient hyperglycemia.

Several different parameters explored in detail below can impact hydromorphone's Absorption, Distribution, Metabolism & Elimination profile, with the result that the normal range of the morphine:hydromorphone potency ratio can be from half to double that published via the oral route and a bit less parenterally.

CNS depressants, such as other opioids, anesthetics, sedatives, hypnotics, barbiturates, phenothiazines, chloral hydrate, and glutethimide may enhance the depressant effects of hydromorphone. MAO inhibitors (including procarbazine), first-generation antihistamines (brompheniramine, promethazine, diphenhydramine, chlorpheniramine), beta-blockers, and alcohol may also enhance the depressant effect of hydromorphone. When combined therapy is contemplated, the dose of one or both agents should be reduced.

Pharmacokinetics

The chemical modification of the morphine molecule to produce hydromorphone results in a drug with higher lipid solubility and ability to cross the blood-brain barrier and, therefore, more rapid and complete central nervous system penetration. The results shows hydromorphone to be somewhat faster-acting and about eight to ten times stronger than morphine and about three to five times stronger than heroin on a milligram basis. The effective morphine to hydromorphone conversion ratio can vary from patient to patient by a significant amount with relative levels of some liver enzymes being the main cause; the normal human range appears to be from 8:1 to a little under 4:1. It is not uncommon, for example, for the 8-mg tablet to have an effect similar to that of 30 mg of morphine sulfate or a similar morphine preparation.

Patients with kidney problems must exercise caution when dosing hydromorphone. In those with renal impairment, the half-life of hydromorphone can increase to as much as 40 hours. This could cause an excess buildup of the drug in the body, and result in fatality. The typical half-life of intravenous hydromorphone is 2.3 hours.^[8] Peak plasma levels usually occur between 30 and 60 minutes after oral dosing.^[9]

Legal status

In the United States, the main drug control agency, the Drug Enforcement Administration, reports an increase in annual aggregate production quotas of hydromorphone from 766 kilograms in 1998 to 3,300 kilograms in 2006, and an increase in prescriptions in this time of 289%, from about 470,000 to 1,830,000^{[citation needed]}.

Like all opioids used for analgesia, hydromorphone is potentially habit-forming and is listed in Schedule II of the United States' Controlled Substances Act of 1970 as well as in similar levels under the drugs laws of practically all other countries and is listed in the Single Convention On Narcotic Drugs.

In the United States, the State of Ohio has approved the use of a single intramuscular injection of Dilaudid as an alternative form of legal execution in instances where the executioners are unable to find a suitable vein for the administration of other lethal drugs.^[10]

Chemistry

Hydromorphone is made from morphine via catalytic hydrogenation and is also produced in trace amounts by human and other mammalian metabolism of morphine and occasionally appears in assays of opium latex in very small quantities, apparently forming in the plant in an unknown percentage of cases under poorly-understood conditions.

Hydromorphone is made from morphine either by direct re-arrangement (made by reflux heating of alcoholic or acidic aqueous solution of morphine in the presence of platinum or palladium catalyst) or reduction to dihydromorphine (usually via catalytic hydrogenation), followed by oxidation with benzophenone in presence of potassium tert butoxide or aluminium tert butoxide (Oppenauer oxidation). The 6 ketone group can be replaced with a methylene group via the Wittig reaction to produce 6-Methylenedihydrodesoxymorphine, which is 80x stronger than morphine.^[11]

Changing morphine into hydromorphone increases its activity and, therefore, makes hydromorphone about eight times stronger than morphine on a weight basis, all other things being equal^{[citation needed]}. Changed also is lipid solubility, contributing to hydromorphone's having a more rapid onset of action and alterations to the overall absorption, distribution, metabolism ,and elimination profile as well as the side effect profile (in general, less nausea and itching) versus that of morphine. The semi-synthetic opiates, of which hydromorphone and its codeine analogue hydrocodone are among the best-known and oldest, include a huge number of drugs of varying strengths and with differences among themselves both subtle and stark, allowing for many different options for treatment.

In most people, the liver produces hydromorphone when processing hydrocodone using the cytochrome p450 II-D-6 enzyme pathway (CYP2D6). This is the same route that is used to convert many different opiate prodrugs into the active form. The proportion of drug that is converted into the stronger form is around 10% on average although this varies markedly between individuals with some being unable to produce hydromorphone. Drugs that are bioactivated in this way include codeine into morphine, oxycodone to oxymorphone, and dihydrocodeine to dihydromorphine.

Some bacteria have been shown to be able to turn morphine into closely related drugs including hydromorphone and dihydromorphine among others. The bacterium Pseudomonas putida serotype M10 produces a naturally occurring NADH-dependent morphinone reductase that can work on unsaturated 7,8 bonds, with result that, when these bacteria are living in an aqueous solution containing morphine, significant amounts of hydromophone form, as it is an intermediary metabolite in this process; the same goes for codeine being turned into hydrocodone. ^[12]

The process gave rise to various concentrations of hydromorphone, dihydromorphine, 14β-hydroxymorphine, and 14β-hydroxymorphone during the experiments. Three paths were found: from morphine to hydromorphine with dihydromorphine as the penultimate step, from morphine to hydromorphine with morphinone as the penultimate step, and from morphine to 14β-hydroxymorphine to hydromorphone.

The same method subtituting oxycodone as the starting drug yields oxymorphone.

At this time no information has been published indicating whether or not this process can change dihydromorphine into metopon or acetylated morphine derivatives into the respective ketones of the acetylmorphone series.

Exposure to light will cause solutions of hydromorphone to darken to an amber colour, which, it has been reported, does not affect the potency of the drug. Of course, any ampoules or phials containing sediment or cloudiness should be discarded.

See also

• Opioids
• Oxymorphone
• Hydrocodone - a hepatic prodrug of hydromorphone
• Dihydromorphine
• Hydromorphinol
• Oxymorphol - a metabolite of oxymorphone and an intermediate in the creation of hydromorphone
• Morphine
• Chronic pain
• Patient-controlled analgesia
• Recreational drug use

References

Further reading

• Hydromorphone Consumer Drug Information Drugs.com.
• Exalgo: full prescribing information
• Article Discussing Withdrawal of Extended-Release Hyrdromorphone from the U.S. Market
• painCare.ca and Patient Information about Opioid Analgesics
• Dihydromorphinones From Morphine & Analogues
• United States DEA's perspective, including statistics on manufacture and prescription levels from 1998 to 2006
• "When Is a Pain Doctor a Drug Pusher?' New York Times 6-17-2007

es:Hidromorfona fr:Hydromorphone it:Idromorfone hu:Hidromorfon pl:Hydromorfon ro:Hidromorfonă ru:Гидроморфон sv:Hydromorfon

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3. ↑ ^{3.0 3.1} http://www.rxlist.com/cgi/generic/hydromorphone_ad.htm Hydromorphone Monograph (Side Effects & Drug Interactions)
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6. ↑ Palladone Pain Drug Pulled Off the Market.
7. ↑ http://www.rxlist.com/cgi/generic/hydromorphone_ids.htm Hydromorphone Monograph (Drug Abuse and Dependence)
8. ↑ That's Poppycock - Hydromorphone
9. ↑ Dilaudid Clinical Pharmacology
10. ↑ Ohio Prisons Director Announces Changes to Ohio’s Execution Process
11. ↑ PHA 4220 - Neurology Pharmacotherapeutics
12. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.