hydromorphone hydromorphone hydromorphone, also known as dihydromorphinone, and sold under the brand name dilaudid among others, is a morphinan opioid used to treat moderate to severe pain. typically, long-term use is only recommended for pain due to cancer. it may be used by mouth or by injection into a vein, muscle, or under the skin. effects generally begin within half an hour and last for up to five hours. "dihydromorphinone" redirects here. not to be confused with dihydromorphine (paramorfan, etc.), a different opioid.. hydromorphoneclinical datatrade namesdilaudid, hydromorph contin, palladone, othersother namesdihydromorphinoneahfs/drugs.commonographmedlineplusa682013license data us dailymed: hydromorphone pregnancycategory au: c dependenceliabilityhighroutes ofadministrationby mouth, intramuscular, intravenous, subcutaneousatc coden02aa03 (who) legal statuslegal status au: s8 (controlled drug) ca: schedule i de: anlage iii (special prescription form required) nz: class b uk: class a controlled drug: schedule ii us: schedule ii un: narcotic schedule i pharmacokinetic databioavailabilityby mouth: 30–35%, intranasal: 52–58%, iv/im: 100%protein binding20%metabolismliveronset of action15 to 30 minelimination half-life2–3 hoursduration of action4 to 5 hrsexcretionkidneyidentifiers iupac name 4,5-α-epoxy-3-hydroxy-17-methyl morphinan-6-one cas number466-99-9 ypubchem cid5284570iuphar/bps7082drugbankdb00327 ychemspider4447624 yuniiq812464r06keggd08047 ychebichebi:5790 ychemblchembl398707 ycomptox dashboard (epa)dtxsid8023133 echa infocard100.006.713 chemical and physical dataformulac17h19no3molar mass285.343 g·mol−13d model (jsmol)interactive imagesolubility in waterhcl salt: 333 mg/ml (20 °c) smiles o=c45oc1c2c(ccc1o)c3n(cc253cc4)c inchi inchi=1s/c17h19no3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2,4,10-11,16,19h,3,5-8h2,1h3/t10-,11+,16-,17-/m0/s1 ykey:wvloadhcbxtijk-ynhqpcigsa-n y (verify) common side effects include dizziness, sleepiness, nausea, itchiness, and constipation. serious side effects may include abuse, low blood pressure, seizures, respiratory depression, and serotonin syndrome. rapidly decreasing the dose may result in opioid withdrawal. generally, use during pregnancy or breastfeeding is not recommended. hydromorphone is believed to work by activating opioid receptors, mainly in the brain and spinal cord. hydromorphone 2 mg iv is equivalent to approximately 10 mg morphine iv. hydromorphone was patented in 1923. it is on the world health organization's list of essential medicines. it is available as a generic medication. in 2020, it was the 250th most commonly prescribed medication in the united states, with more than 1 million prescriptions. hydromorphone is made from morphine. medical use hydromorphone is used to treat moderate to severe pain. it may be used by mouth or by injection into a vein, muscle, or under the skin. effects generally begin within half an hour and last for up to five hours. typically, long-term use is only recommended for pain due to cancer. a 2016 cochrane review (updated in 2021) found little difference in benefit between hydromorphone and other opioids for cancer pain. side effects adverse effects of hydromorphone are similar to those of other potent opioid analgesics, such as morphine and heroin. the major hazards of hydromorphone include dose-related respiratory depression, urinary retention, bronchospasm, and sometimes, circulatory depression. more common side effects include lightheadedness, dizziness, sedation, itching, constipation, nausea, vomiting, headache, perspiration, and hallucinations. these symptoms are common in ambulatory patients and in those not experiencing severe pain. simultaneous use of hydromorphone with other opioids, muscle relaxants, tranquilizers, sedatives, and general anesthetics may cause a significant increase in respiratory depression, progressing to coma or death. taking benzodiazepines (such as diazepam) in conjunction with hydromorphone may increase side effects such as dizziness and difficulty concentrating. if simultaneous use of these drugs is required, dose adjustment may be made. 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. massive overdoses are rarely observed in opioid-tolerant individuals, but when they occur, they may lead to circulatory system collapse. symptoms of overdose include respiratory depression, drowsiness leading to coma and sometimes to death, drooping of skeletal muscles, low heart rate, and decreasing blood pressure. at the hospital, individuals with hydromorphone overdose are provided supportive care, such as assisted ventilation to provide oxygen and gut decontamination using activated charcoal through a nasogastric tube. opioid antagonists, such as naloxone, also may be administered concurrently with oxygen supplementation. naloxone works by reversing the effects of hydromorphone, and only is administered in the presence of significant respiratory depression and circulatory depression. sugar cravings associated with hydromorphone use are the result of a glucose crash after transient hyperglycemia following injection, or a less profound lowering of blood sugar over a period of hours, in common with morphine, heroin, codeine, and other opiates. hormone imbalance main article: opioid § hormone imbalance as with other opioids, hydromorphone (particularly during heavy chronic use) often causes temporary hypogonadism or hormone imbalance. neurotoxicity in the setting of prolonged use, high dosage, and/or kidney dysfunction, hydromorphone has been associated with neuroexcitatory symptoms such as tremor, myoclonus, agitation, and cognitive dysfunction. this toxicity is less than that associated with other classes of opioids such as the pethidine class of synthetics in particular. withdrawal users of hydromorphone may experience painful symptoms if the drug is suspended. some people cannot tolerate the symptoms, which results in continuous drug use. symptoms of opioid withdrawal are not easy to decipher, as there are differences between drug-seeking behaviors and true withdrawal effects. symptoms associated with hydromorphone withdrawal include: abdominal pain anxiety or panic attacks depression goose bump skin inability to enjoy daily activities muscle and joint pain nausea runny nose and excessive secretion of tears sweating vomiting in the clinical setting, excessive secretion of tears, yawning, and dilation of pupils are helpful presentations in diagnosing opioid withdrawal. hydromorphone is a rapid acting pain killer; however, some formulations may last up to several hours. patients who stop taking this drug abruptly may experience withdrawal symptoms, which may start within hours of taking the last dose of hydromorphone, and last up to several weeks. withdrawal symptoms in people who stopped taking the opioid may be managed by using opioids or non-opioid adjuncts. methadone is an opioid commonly used for this kind of therapy. however, the selection of therapy should be tailored to each specific person. methadone also is used for detoxification in people who have opiate addiction, such as heroin or drugs similar to morphine. it may be given orally or intramuscularly. there is controversy regarding whether any opioid (such as methadone) should be included in the treatment of opioid withdrawal symptoms, since these agents also may cause relapse when therapy is suspended. clonidine is a non-opioid adjunct which may be used in situations where opioid use is not desired, such as in patients with high blood pressure. interactions cns depressants may enhance the depressant effects of hydromorphone, such as other opioids, anesthetics, sedatives, hypnotics, barbiturates, benzodiazepines, phenothiazines, chloral hydrate, dimenhydrinate, and glutethimide. the depressant effect of hydromorphone also may be enhanced by monoamine oxidase inhibitors (mao inhibitors), first-generation antihistamines (brompheniramine, promethazine, diphenhydramine, chlorphenamine), beta blockers, and alcohol. when combined therapy is contemplated, the dose of one or both agents should be reduced. pharmacology hydromorphone at opioid receptors affinities (ki)ratio mordorkormor:dor:kor 0.47 nm18.5 nm24.9 nm1:39:53 equianalgesic doses compoundroutedose codeinepo200 mg hydrocodonepo20–30 mg hydromorphonepo7.5 mg hydromorphoneiv1.5 mg morphinepo30 mg morphineiv10 mg oxycodonepo20 mg oxycodoneiv10 mg oxymorphonepo10 mg oxymorphoneiv1 mg hydromorphone is a semi-synthetic μ-opioid agonist. as a hydrogenated ketone of morphine, it 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, and increased pinpoint constriction of the pupils. formulations hydromorphone is available in parenteral, rectal, subcutaneous, and oral formulations, and also can be administered via epidural or intrathecal injection. hydromorphone also has been administered via nebulization to treat shortness of breath, but it is not used as a route for pain control due to low bioavailability. transdermal delivery systems are also under consideration to induce local skin analgesia. concentrated aqueous solutions of hydromorphone hydrochloride have a visibly different refractive index from pure water, isotonic 9‰ (0·9 per cent) saline and the like, especially when stored in clear ampoules and phials may acquire a slight clear amber discolouration upon exposure to light; this reportedly has no effect on the potency of the solution, but 14-dihydromorphinones such as hydromorphone, oxymorphone, and relatives come with instructions to protect from light. ampoules of solution which have developed a precipitate should be discarded. battery-powered intrathecal drug delivery systems are implanted for chronic pain when other options are ruled out, such as surgery and traditional pharmacotherapy, provided that the patient is considered a suitable fit in terms of any contraindications, both physiological and psychological. an extended-release (once-daily) version of hydromorphone is available in the united states. previously, an extended-release version of hydromorphone, palladone, was available 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, nepal under the brand name opidol, and in most other european countries. pharmacokinetics the chemical modification of the morphine molecule to hydromorphone results in higher lipid solubility and greater ability to cross the blood–brain barrier to produce more rapid and complete central nervous system penetration. on a per milligram basis, hydromorphone is considered to be five times as potent as morphine; although the conversion ratio may vary from 4–8 times, five times is in typical clinical usage. the development of tolerance also may vary among individuals. patients with renal abnormalities must exercise caution when dosing hydromorphone. in those with renal impairment, the half-life of hydromorphone may increase to as much as 40 hours. the typical half-life of intravenous hydromorphone is 2.3 hours. peak plasma levels usually occur between 30 and 60 minutes after oral dosing. the onset of action for hydromorphone administered intravenously is less than 5 minutes and within 30 minutes of oral administration (immediate release). metabolism while other opioids in its class, such as codeine or oxycodone, are metabolized via cyp450 enzymes, hydromorphone is not. hydromorphone is extensively metabolized in the liver to hydromorphone-3-glucuronide, which has no analgesic effects. as similarly seen with the morphine metabolite, morphine-3-glucuronide, a build-up in levels of hydromorphone-3-glucuronide may produce excitatory neurotoxic effects such as restlessness, myoclonus and hyperalgesia. patients with compromised kidney function and older patients are at higher risk for metabolite accumulation. chemistry with a formula of c17h19no3 and a molecular weight of 285.343, both identical to morphine, hydromorphone can be considered a structural isomer of morphine and is a hydrogenated ketone thereof. 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 may be replaced with a methylene group via the wittig reaction to produce 6-methylenedihydrodesoxymorphine, which is 80× stronger than morphine. changing morphine into hydromorphone increases its activity and, therefore, makes hydromorphone approximately eight times stronger than morphine on a weight basis, all other things being equal. 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. hydromorphone is more soluble in water than morphine; therefore, hydromorphone solutions may be produced to deliver the drug in a smaller volume of water. the hydrochloride salt is soluble in three parts of water, whereas a gram of morphine hydrochloride dissolves in 16 ml of water; for all common purposes, the pure powder for hospital use can be used to produce solutions of virtually arbitrary concentration. when the powder appeared on the street, this very small volume of powder needed for a dose means that overdoses are likely for those who mistake it for heroin or other powdered narcotics, especially those that have been diluted prior to consumption. endogenous production hydromorphone is made from morphine via catalytic