Hydromorphone
317921
225352921
2008-07-13T06:36:42Z
Mr0t1633
6585941
stopusing whilst people, we dont say thou either\
{{drugbox
| IUPAC_name = 4,5-α-epoxy-3-hydroxy-17-methyl morphinan-6-one
| image = hydromorphone.svg
| width = 180
| CAS_number = 466-99-9
| ATC_prefix = N02
| ATC_suffix = AA03
| ATC_supplemental =
| PubChem = 5284570
| DrugBank = APRD01021
| C=17 | H=19 | N=1 | O=3
| molecular_weight = 285.338 g/mol
| bioavailability = Oral: 30–35%, Intranasal: 52–58%<ref>Coda BA, Rudy AC, Archer SM, Wermeling DP. "Pharmacokinetics and Bioavailability of Single-Dose Intranasal Hydromorphone Hydrochloride in Healthy Volunteers." ''Anesthesia Analgesia''. 2003 Jul;97(1):117-23. PMID 12818953 [http://www.anesthesia-analgesia.org/cgi/content/full/97/1/117 Fulltext]</ref>
| protein_bound = 20%
| metabolism = Hepatic
| elimination_half-life = 2–3 hours<ref>Vallner JJ, Stewart JT, Kotzan JA, Kirsten EB, Honigberg IL. "Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects." ''Journal of Clinical Pharmacology''. 1981 Apr;21(4):152-6. PMID 6165742 [http://jcp.sagepub.com/cgi/reprint/21/4/152 Fulltext]</ref>
| pregnancy_category = C
| legal_status = [[Misuse of Drugs Act 1971|Class A]] (UK), <br>DEA [[Schedule II]] (USA)
| routes_of_administration = oral, intramuscular, intravenous, subcutaneous, intranasal, rectal, sublingual, transmucosal, buccal, transcutaneous (experimental)
| dependency_liability = High
| excretion = Renal
}}
'''Hydromorphone''', a more common synonym for '''dihydromorphinone hydrochloride''' (trade names '''Palladone IR''', '''Palladone SR''', '''Dilaudid''' and numerous others) is a potent centrally-acting [[analgesic]] [[medication|drug]] of the [[opioid]] class; it is a derivative of [[morphine]], specifically a [[hydrogenated]] [[ketone]] thereof -- therefore a semi-synthetic drug and both an [[opiate]] and a true [[narcotic]]. It should not be confused with [[hydromorphinol]], also known as [[14-hydroxydihydromorphine]] and RAM-320 nor [[dihydromorphine]] (Paramorfan). While all of these are strong opioids, they are indeed different drugs. Additional confusion here comes from the fact that in a handful of countries hydromorphinol is distrbuted 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 used in medicine as an alternative to [[morphine]] and [[diacetylmorphine]] 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, and is generally regarded to be the strongest of the latter class of drugs, and was developed shortly after another powerful antitussive, [[heroin]], was removed from clinical use for this purpose in most of the world and in many countries banned outright. Part of the effectiveness of [[hydrocodone]] for this purpose may be due to part of the dose being converted to hydromorphone in the liver.
This modification of the morphine molecule 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, with the result that hydromorphone is somewhat faster-acting and about eight times stronger than morphine and about three times stronger than [[heroin]] on a milligramme 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 30 mg of Roxanol or a similar morphine preparation.
In many countries of the world, hydromorphone has become more commonly used, particularly since the well-documented gradual change in attitudes in some places about proper protocols for dealing with chronic pain of non-malignant aetiologies. In the United States, the main drugs-control agency, the Drug Enforcement Administration, reports an increase in annual aggregate production quotas of hydromorphone from 766 kilogrammes in 1998 to 3,300 kilogrammes in 2006, and an increase in prescriptions in this time of 228 per cent, from about 470,000 to 1,830,000.
Hydromorphone was first synthesized and researched in Germany, in [[1924]], and introduced to the mass market by Knoll under the brand name ''Dilaudid'' in [[1926]]. Some authorities and publications use this name as a genericised brand name (e.g. like Kleenex, Xerox &c.) for hydromorphone and the name indicates its derivation and degree of similarity to [[morphine]] (by way of [[laudanum]]) -- Cf. Dicodid ([[hydrocodone]]), Dihydrin ([[dihydrocodeine]]) and Dinarkon ([[oxycodone]]). Hydromorphone may also be known by the brand name ''Morphodid''.
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.
==Uses==
Hydromorphone is used to relieve moderate to severe [[pain]] and severe, painful dry [[cough]]ing. As explored in detail below, hydromorphone is becoming more popular in the treatment of chronic pain in many countries, and it is used as a substitute for [[heroin]] and [[morphine]] where one or both of these drugs are not marketed. Hydromorphone is preferred even over morphine in many cases ranging from the emergency department to the operating suite to ongoing treatment of chronic pain syndromes on account of hydromorphone's superior solubility and speed of onset and less troublesome side effect profile and lower dependence liability as compared to morphine and heroin. Hydromorphone is also a good alternative to morphine when patients refuse morphine due to the [[stigma]] associated with it.
Hydromorphone's side effect profile is closer to that of [[dihydromorphine]] than that of morphine and importantly produces less nausea and vomiting and fewer histamine-related side effects (itching, redness of skin, &c.) than morphine as a result. In cases where significant doses are anticipated, hydromorphone may be easier to titrate to the needed dose for this and other related reasons. Like all other opioid analgesics, [[tolerance]] develops with repeated administration and there is no true maximum dose, although requirements for pain relief can often remain more or less constant for extended periods after initial titration and tolerance does indeed commonly follow a course of plateaus of this type interspersed with comparatively infrequent escalations of varying intensity and in some cases the opportunity to titrate downwards as well.
The above-mentioned properties account for hydromorphone being a useful agent for chronic pain. Many chronic pain patients find that hydromorphone has a spectrum of actions which suit them just as well as morphine, and better than synthetics like [[methadone]], [[piritramide]], [[fentanyl]], or [[levorphanol]] in alleviating ''suffering'', as contrasted with simple pain of equal objective intensity. Hydromorphone is a common alternative for those who tend to have hallucinations from fentanyl in the form of skin plasters and other dosage forms. Hydromorphone also lacks the toxic metabolites of many opioids related to [[pethidine]] and some of the [[methadone]] class. Hydromorphone also tends to cause less nausea than morphine.
In the United States and some other countries, hydromorphone has long been only available as instant release oral formulations (viz. Hydal, Sophidone, Palladone IR, 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 is a new extended-release version of hydromorphone used in parts of Eastern Europe and elsewehere for chronic pain and in Serbia is being used as an alternative to [[methadone]] for maintenance treatment of opioid dependence.
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 a long-term chronic pain patient on Dilaudid as the sole or central agent. This scenario, uncommon but indeed observed in the past, could happen where such patients could require monthly prescription fill quantites in the low quadruple figures over a prolonged period during which 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 generally 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.
Furthermore, many authorities believe that the cross-tolerance between morphine and hydromorphone is incomplete, making alternating morphine and hydromorphone or adding the two drugs to a rotation of three or more agents a strategy worthy of consideration in a case of chronic pain or other afflictions requiring use of centrally-acting analgesics for an extended period. In addition, hydromorphone is similar to other opioids and semi-synthetics in particular as having its effectiveness possibly impacted by levels of liver enzymes, kidney issues, and other drugs being taken. This is especially the case when the drug is being given by mouth and careful titration which has control of pain as its objective is particularly important and it is quite possible that the amount of hydromorphone taken per 24 hours and single-dose quantities could vary significantly -- in either direction -- from the averages predicted by equianalgesic dose tables from one patient to the next.
Hydromorphone is also an important agent for use against moderate chronic pain, sub-chronic pain from severe injury, and acute pain requiring rapidly-escalatimg doses of narcotic anaglesics in countries where the majority or all of mid-level narcotic analgesics are mixed with paracetamol, aspirin, ibuprofen, naproxen, diclofenac and the like. The effects on the liver of paracetamol are particularly dangerous in such situations, and since hydrocodone and dihydrocodeine are not available for compunding prescriptions in the United States, for example, the choices left for these cases are oxycodone in pure form, morphine, levorphanol, possibly methadone, and hydromorphone. Of the above, the agents which cause intolerable side effects in the lowest percentage of users are levorphanol and hydromorphone. In such near borderline cases, the difficulty and/or time frame of titrating the available forms of fentanyl and mitigating side effects may make that agent a less than perfect choice as well.
In addition to the above, hydromorphone usually proves to be the first alternative of choice to morphine and fentanyl in severe chronic pain situations because the other commonly available agent in the United States, Canada, and various other countries is [[oxycodone]], which a large percentage of chronic pain specialists do not rank high on the list of analgesics for maintenance treatment of most chronic pain syndromes (although a subgroup of patients do in fact respond particularly well to it, making its continued availability for this purpose very important nonetheless) for reasons ranging from stigma to regulatory and legal barriers limiting availability and/or willingness of physicians and pharmacists to deal with it, to the fact that many patients do have a very different reaction to oxycodone including a higher dependence and abuse liability than hydromorphone or most other opioids, a liability that some experts rate as uniquely combining the codeine, morphine, and cocaine types.
==Brand names and dosage forms==
Hydromorphone is known in various countries around the world by the trade names '''Hydal''', '''Sophidone''', '''Hydrostat''', '''Hydromorfan''', '''Hydromorphan''', '''Laudicon''', '''Hymorphan''', '''Opidol''', '''Palladone''' and others. An extended-release version of Palladone called '''Palladone SR''' was available for a short time in the United States before being voluntarily withdrawn from the market after an FDA advisory released in July 2005 warned of a high overdose potential when taken with alcohol; it is still available in the United Kingdom as of March 2007, 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. in Pickering, Ontario. In addition to Purdue-Frederick, other manufacturers of hydromorphone products include Ethex, Knoll, Abbott, Endo, Mallinkrodt, Merck, Mundipharma, and Lannacher amongst others.
Hydromorphone hydrochloride (anhydrous) is the salt used in virtually all hydromorphone products and in prescription compounding at this time. The free base conversion ratio of this salt is 0.887. Other salts which are used rarely are the sulphate (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 analogue of [[Twilight Sleep]] was available, i.e. hydromorphone and [[scopolamine]]. The reasons for adding atropine to hydromorphone tablets or other formulations are twofold: one, the fact that anticholinergics help opioids combat neuropathic pain, and two, 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. A technique for reducing the atropine content of readily-soluble tablets in the field is to place the tablets on a piece of blotter paper, cover each with a drop of distilled water and wait 60 to 90 seconds before removing the remaining portion from the tablet for use.
Some brands of hydromorphone tablets contain small amounts of sulphites. Hydromorphone's oral to intravenous effectiveness ratio is 5:1 and equinalgesia conversion ratio (hydromorphone HCl to anhydrous morphine sulfate, IV, SC, or IM) is 8:1 and is about 4:1 orally. This means that 30 mg of immediate-release morphine by mouth is similar in analgesic effect to 7.5 mg of hydromorphone by mouth, 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 which 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 in the past 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 32 mg extended-release Palladone SR capsule, 500 mg (10 mg/ml * 50 ml) vial of Dilaudid HP injection, and 5mg 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 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. Some tablets work better in this fashion if the coating on the tablet is first removed by sucking on it for a short time.
As with many other drugs, oral and soluble forms of hydromorphone such as the oral liquid, cough syrup, soluble tablets, &c., 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 which 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, after morphine, used in Patient-Controlled Analgesia (PCA) units worldwide. The injectable forms of hydromorphone are suitable for outpatient use in a fashion similar to insulin once the patient and/or caretakers have been instructed on injection technique and 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. 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 amongst 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 contries as of February 2008 are:
#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 nebulising 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 nebulisers are currently available, with the rule of thumb being that 2 mg of nebulised 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 milligramme potency, and superior lipid solubility, this method works well and is possible to implement with equipment and drug formulations currently on the market.
#An injectable formulation which contains the drug in [[liposomes]] in an appropriate vehicle which 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]])
#New variations on the oral, sublingual, buccal and/or rectal routes of administration.
#A transdermal/transcutaneous delivery system somewhat similar to extant transdermal drug delivery systems for [[fentanyl]], [[sufentanil]], [[lidocaine]], [[clonidine]], [[scopolamine]], [[nicotine]]
#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 solubiilty can theoretically be delivered transdermally to an extent which is superior to 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.
#A conventional skin plaster (using ingredients in the carrier liquid/gel to change local skin characteristics to improve absorption) which delivers both a narcotic analgesic and [[local anaesthetic]] such as [[lidocaine]], [[mepivacaine]], [[bupivicaine]], [[ropivacaine]] &c. (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.
#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 which 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 which are effective in much smaller quantities such as the fentanyls or [[Bentley Compounds]] like [[dihydroetorphine]].
==Available forms==
* Tablets - 0.5mg, 1mg, 2mg, 3mg, 4mg, 8mg
* Capsules (Palladone) - 1.3mg, 2.6mg
* Modified Release capsules (Palladone SR) - 2mg, 4mg, 8mg, 16mg, 24mg, 30mg, 32mg, 152 mg
* Controlled Release capsules (Hydromorph Contin) - 3mg, 6mg, 12mg, 18mg, 24mg, 30mg
* Suppository - 3mg, 5mg
* 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)
[[Image:Hydromorphone.JPG|thumb|right]]
[[Image:hydromorphone dilaudid.jpg|thumb|right]]
[[Image:hydromorphone generic.jpg|thumb|right]]
== Details ==
Hydromorphone, a semi-synthetic [[Opioid receptor#The μ-opioid receptor|μ-opioid]] [[agonist]], is a [[hydrogenation|hydrogenated]] [[ketone]] of [[morphine]] and shares the pharmacologic properties typical of [[opioid analgesic]]s. Hydromorphone and related [[opioid]]s produce their major effects on the [[central nervous system]] and [[gastrointestinal tract]]. These include [[analgesia]], drowsiness, mental clouding, changes in mood, [[Euphoria (emotion)|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, [[anesthetic]]s, [[sedative]]s, [[hypnotic]]s, [[barbiturate]]s, [[phenothiazine]]s, [[chloral hydrate]] and [[glutethimide]] may enhance the depressant effects of hydromorphone. [[MAO inhibitor]]s (including [[procarbazine]]), first-generation [[antihistamine]]s ([[brompheniramine]], [[promethazine]], [[diphenhydramine]], [[chlorpheniramine]]), [[beta-blocker]]s 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==
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.<ref>[http://www.thatspoppycock.com/opiates/hydromorphone.htm That's Poppycock - Hydromorphone]</ref> Peak plasma levels usually occur between 30 and 60 minutes after oral dosing.<ref>[http://www.rxlist.com/cgi/generic/hydromorphone_cp.htm Dilaudid Clinical Pharmacology]</ref>
==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.<ref>http://www.rxlist.com/cgi/generic/hydromorphone_ad.htm Hydromorphone Monograph (Side Effects & Drug Interactions)</ref> More common [[side effect]]s include [[light-headedness]], [[dizziness]], [[sedation]], [[constipation]], [[nausea]], [[vomiting]], and [[sweating]].<ref>http://www.rxlist.com/cgi/generic/hydromorphone_ad.htm Hydromorphone Monograph (Side Effects & Drug Interactions)</ref> 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 instead 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 to morphine to avoid confusion.<ref>Cohen MR. Doctor was thinking of the wrong drug. ''Nursing''. 1992 Jun;22(6):25. PMID 1377371</ref><ref>Tuohy N, Paparella S. Look-alike and sound-alike drugs: errors just waiting to happen. ''Journal of Emergency Nursing''. 2005 Dec;31(6):569-71. PMID 16308048</ref> The effects of overdose can be exaggerated by [[dose dumping]] if the medication is taken with [[alcohol]] or [[benzodiazepines]].<ref>[http://www.webmd.com/pain-management/news/20050714/palladone-pain-drug-pulled-off-market Palladone Pain Drug Pulled Off the Market].</ref>
A possible side effect associated with hydromorphone is euphoria, achieved dually through a perceived effect from the transition of a state of pain to a state of pain-relief induced through opioids, or through direct stimulation of the [[mu opioid receptor|μ opioid receptor]] (μ<sub>1</sub> and μ<sub>2</sub>) [of which hydromorphone, related to the morphine molecule, is a primary [[mu opioid receptor|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 [[drug abuse|abuse]] and [[Addiction|dependence]] among patients prescribed any opioid, including hydromorphone.<ref>http://www.rxlist.com/cgi/generic/hydromorphone_ids.htm Hydromorphone Monograph (Drug Abuse and Dependence)</ref> A question long debated in medicine has been whether or not addiction potential and analgesia are seperable; the existence of drugs such as [[cyclazocine]] and other benzomorphans may point to the con side of the debate yet it is easy to understand why a drug which acts against all components of pain in the way that opioids would generate a seek orientation, morbid or not, in any organism under consideration, from fish to frogs to rats to monkeys to people.
Hydromorphone appears on the street to an extent, sourced from patients selling prescriptions, armed robbery, and burglary of pharmacies. On the street, it is usually rather expensive, upwards of $50 USD for a 2 mg tablet, slang terms for it include D, dilly, dillies, dill, k4, k1, k2, k3, k8, M8, Big D, Super 8, Hydro, M-80s, white triangle, moose, hospital heroin, drugstore heroin, shake & bake, peaches, and others. The equipotency of price to dosage ranks hydromorphone among the highest priced of all opioids for sale on the street. Both licit and illicit users as well as older pharmacists and doctors refer to hydromorphone tablets by their hydromorphone content in fractions of a [[grain]] (e.g. a "sixteenth" is a 4 mg tablet, an "eighth" is 8 mg, a "thirty-second" is 2 mg, 1 mg tablets are "sixty-fourths", the 3 mg tablet is a "three sixty-fourth" and long term Dilaudid users both licit and illicit as well as pharmacists may remember quarter-grain (16 mg) tablets back in the day.
The aforementioned increase in licit use has, with time, led to downward price pressure both from changes in the simple supply and demand equation that governs all commerce and the fact that the low bioavailability of hydromorphone as compared to oxycodone means that a given reseller's clientele will usually have a large contingent of non-needle-using customers who may have tried hydromorphone by mouth and been disappointed and who who want [[oxycodone]], [[hydrocodone]], and to a lesser extent [[codeine]] and [[dihydrocodeine]], therefore affecting the demand side of the equation as well.
==Chemistry==
Commercially, 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 [[Redox|reduction]] to [[dihydromorphine]] (usually via catalytic [[hydrogenation]]), followed by [[oxidation]] with [[benzophenone]] in presence of [[t-butanol#Chemistry|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.<ref>[http://www.acsmedchem.org/module/opioid.html PHA 4220 - Neurology Pharmacotherapeutics<!-- Bot generated title -->]</ref>
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. Changed also is lipid solubility, contributing to hydromorphine having a more rapid onset of action and alterations to the overall Absorption, Distribution, Metabolism & Elimination profile as well as the side effect profile (generally less nausea and itching) versus that of morphine. The semi-synthetic opiates, of which hydromorphone and its [[codeine]] analogue [[hydrocodone]] are amongst the best-known and oldest, include a huge number of drugs of varying strengths and with differences amongst themselves both subtle and stark, allowing for many different options for treatment.
The human 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 [[prodrug]]s 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. 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 hydromorphone. As reported in the July 1993 issue of ''Applied Environmental Bacteriology'', the bacterium ''Pseudomonas putida'', serotype M10 produces a naturally occurring NADH-dependent morphinone reductase which can work on unsaturated 7,8 bonds -- with result that when these bacteria are living in an aqueous solution containing morphine, sigificant amounts of hydromophone form as it is an intermediary metabolite in this process; the same goes for [[codeine]] being turned into [[hydrocodone]]. 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 -- reportedly this does not effect the potency of the drug. Of course, any ampoules or phials containing sediment or cloudiness should be discarded.
==See also==
* [[Opioids]]
* [[Oxymorphone]]
* [[Hydrocodone]]
* [[Dihydromorphine]]
* [[Hydromorphinol]]
* [[Morphine]]
* [[Chronic pain]]
* [[Patient-controlled analgesia]]
* [[Recreational drug use]]
==References==
* [http://www.drugs.com/MTM/hydromorphone.html Hydromorphone Consumer Drug Information] ''Drugs.com.''
* [http://www.webmd.com/content/article/108/109026 Article Discussing Withdrawal of Extended-Release Hyrdromorphone from the U.S. Market]
* [http://www.paincare.ca/Patient/Default.aspx Pain Care and Patient Information about Opioid Analgesics]
* [http://www.erowid.org/archive/rhodium/chemistry/dihydromorphinones.html Dihydromorphinones From Morphine & Analogues]
* [http://www.deadiversion.usdoj.gov/drugs_concern/hydromorphone.htm United States DEA's perspective, including statistics on manufacture and prescription levels from 1998 to 2006]
==Notes==
<references />
==External links==
* [http://www.nytimes.com/2007/06/17/magazine/17pain-t.html?pagewanted=1 "When Is a Pain Doctor a Drug Pusher?' New York Times 6-17-2007]
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{{Drugs used in addictive disorders}}
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