View source for Hydromorphone

{{Short description|Opioid medication used for pain relief}}
{{Redirect-distinguish-text|Dihydromorphinone|[[dihydromorphine]] (Paramorfan, etc.), a different opioid}}
{{Use dmy dates|date=November 2024}}
{{Use American English|date=September 2017}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 464191262
| image = Hydromorphone skeletal.svg
| image_class = skin-invert-image
| alt = Structural formula of hydromorphone
| width = 180
| image2 = Hydromorphone molecule spacefill.png
| image_class2 = bg-transparent
| alt2 = Space-filling model of hydromorphone
| width2 = 
| caption = 

<!-- Clinical data -->
| pronounce = 
| tradename = Dilaudid, others
| Drugs.com = {{drugs.com|monograph|hydromorphone-hydrochloride}}
| MedlinePlus = a682013
| DailyMedID = Hydromorphone
| pregnancy_AU = C
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Hydromorphone Use During Pregnancy | website=Drugs.com | date=19 November 2019 | url=https://www.drugs.com/pregnancy/hydromorphone.html | access-date=16 May 2020}}</ref>
| pregnancy_category = 
| dependency_liability = High<ref>{{cite book | vauthors = Bonewit-West K, Hunt SA, Applegate E |title=Today's Medical Assistant: Clinical and Administrative Procedures |date=2012|page=571 |publisher=Elsevier Health Sciences |isbn=978-1-4557-0150-6 |url=https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 }}</ref>
| addiction_liability = High<ref>{{cite book |vauthors=Bonewit-West K, Hunt SA, Applegate E |title=Today's Medical Assistant: Clinical and Administrative Procedures |date=2012 |page=571 |publisher=Elsevier Health Sciences |isbn=978-1-4557-0150-6 |url=https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 |access-date=20 August 2019 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110030031/https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 |url-status=live }}</ref>
| routes_of_administration = [[By mouth]], [[intramuscular]], [[intravenous]], [[Subcutaneous administration|subcutaneous]]
| class = [[Opioid]]
| ATC_prefix = N02
| ATC_suffix = AA03
| ATC_supplemental = 

<!-- Legal status -->
| legal_AU = S8
| legal_AU_comment = 
| legal_BR = A1
| legal_BR_comment = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 – Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = Schedule I
| legal_CA_comment = 
| legal_DE = Anlage III
| legal_DE_comment = 
| legal_NZ = Class B
| legal_NZ_comment = 
| legal_UK = Class A
| legal_UK_comment = Controlled Drug: Schedule II
| legal_US = Schedule II
| legal_US_comment = 
| legal_EU = 
| legal_EU_comment = 
| legal_UN = N I
| legal_UN_comment = 
| legal_status = SE: Förteckning II

<!-- Pharmacokinetic data -->
| bioavailability = By mouth: 25–50%,<ref name="FiresteinBudd2016">{{cite book| vauthors= Polsten GR, Wallace MS | chapter = Analgesic Agents in Rheumatic Disease | veditors = Firestein GS, Budd R, Gabriel SE, McInnes IB, O'Dell JR |title=Kelley and Firestein's Textbook of Rheumatology | chapter-url = https://books.google.com/books?id=kBZ6DAAAQBAJ&pg=PA1081 |date=21 June 2016|publisher=Elsevier Health Sciences|isbn=978-0-323-41494-4|pages=1081–}}</ref> Intranasal: 52–58%,<ref name="pmid12818953">{{cite journal | vauthors = Coda BA, Rudy AC, Archer SM, Wermeling DP | title = Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers | journal = Anesthesia and Analgesia | volume = 97 | issue = 1 | pages = 117–23, table of contents | date = July 2003 | pmid = 12818953 | doi = 10.1213/01.ANE.0000066311.40978.4F | s2cid = 22694749 | citeseerx = 10.1.1.551.6509 }}</ref> IV/IM: 100%
| protein_bound = 20%
| metabolism = [[Liver]]
| metabolites = 
| onset = 15–30 min<ref name=AHFS2019/>
| elimination_half-life = 2–3 hours<ref name="pmid6165742">{{cite journal | vauthors = Vallner JJ, Stewart JT, Kotzan JA, Kirsten EB, Honigberg IL | title = Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects | journal = Journal of Clinical Pharmacology | volume = 21 | issue = 4 | pages = 152–156 | date = April 1981 | pmid = 6165742 | doi = 10.1002/j.1552-4604.1981.tb05693.x | s2cid = 29864565 }}</ref>
| duration_of_action = 4–5 hours<ref name=AHFS2019/>
| excretion = [[Kidney]]

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 466-99-9
| CAS_supplemental = 
| PubChem = 5284570
| IUPHAR_ligand = 7082
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00327
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4447624
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Q812464R06
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08047
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 5790
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 398707
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = Dihydromorphinone

<!-- Chemical and physical data -->
| IUPAC_name = 4,5-α-Epoxy-3-hydroxy-17-methyl morphinan-6-one
| C = 17
| H = 19
| N = 1
| O = 3
| SMILES = O=C4[C@@H]5Oc1c2c(ccc1O)C[C@H]3N(CC[C@]25[C@H]3CC4)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = WVLOADHCBXTIJK-YNHQPCIGSA-N
| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = [[hydrochloride|HCl salt]]: 333
| sol_units = 
| specific_rotation = 
}}
<!-- Definition and medical uses -->

'''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]].<ref name=AHFS2019>{{cite web |title=Hydromorphone Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/hydromorphone-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=15 April 2019 }}</ref> Typically, long-term use is only recommended for pain due to [[cancer]].<ref name=BNF76>{{cite book|title=British national formulary: BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=978-0-85711-338-2|pages=24, 456|edition=76}}</ref> It may be used by mouth or by [[Intravenous therapy|injection into a vein]], [[intramuscular|muscle]], or [[Subcutaneous injection|under the skin]].<ref name=AHFS2019/> Effects generally begin within half an hour and last for up to five hours.<ref name=AHFS2019/> A 2016 [[Cochrane (organisation)|Cochrane]] review (updated in 2021) found little difference in benefit between hydromorphone and other opioids for cancer pain.<ref>{{cite journal |vauthors=Li Y, Ma J, Lu G, Dou Z, Knaggs R, Xia J, Zhao S, Dong S, Yang L |date=August 2021 |title=Hydromorphone for cancer pain |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue=8 |article-number=CD011108 |doi=10.1002/14651858.CD011108.pub3 |pmc=8406835 |pmid=34350974}}</ref>

<!-- Side effects and mechanisms -->
Common side effects include [[dizziness]], [[euphoria]], [[Somnolence|sleepiness]], [[nausea]],  [[itchiness]], and [[constipation]].<ref name=AHFS2019/> Serious side effects may include [[Substance abuse|abuse]], [[low blood pressure]], [[seizure]]s, [[respiratory depression]], and [[serotonin syndrome]].<ref name=AHFS2019/> Rapidly decreasing the dose may result in [[opioid withdrawal]].<ref name=AHFS2019/> Generally, use during [[pregnancy]] or [[breastfeeding]] is not recommended.<ref name=Preg2019>{{cite web |title=Hydromorphone Use During Pregnancy |url=https://www.drugs.com/pregnancy/hydromorphone.html |website=Drugs.com |access-date=15 April 2019 }}</ref> Hydromorphone is believed to work by activating [[opioid receptor]]s, mainly in the brain and spinal cord.<ref name=AHFS2019/> Hydromorphone 2&nbsp;mg [[Intravenous therapy|IV]] is [[Equianalgesic|equivalent]] to approximately 10&nbsp;mg [[morphine]] IV.<ref name=BNF76/>

<!-- History and culture -->
Hydromorphone was patented in 1923.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=526 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA526 }}</ref> Hydromorphone is made from [[morphine]].<ref>{{cite book | vauthors = Vardanyan R, Hruby V |title=Synthesis of Essential Drugs |date=2006 |publisher=Elsevier |isbn=978-0-08-046212-7 |page=25 |url=https://books.google.com/books?id=Jjc7KYWZdOYC&pg=PA25 }}</ref> Hydromorphone is a therapeutic alternative on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO24th">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list | year = 2025 | hdl = 10665/382243 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=AHFS2019/> In 2022, it was the 233rd most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Hydromorphone Drug Usage Statistics, United States, 2013 – 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Hydromorphone | access-date = 30 August 2024 }}</ref>
{{TOC limit}}

== Side effects ==

Adverse effects of hydromorphone are similar to those of other potent opioid [[analgesic]]s such as [[morphine]] and [[heroin]]. The major hazards of hydromorphone include dose-related [[respiratory depression]], urinary retention, bronchospasm, and sometimes, circulatory depression.<ref name="rxlist.com">{{cite web | url = http://www.rxlist.com/cgi/generic/hydromorphone_ad.htm | title = Hydromorphone Monograph (Side Effects & Drug Interactions) | publisher = RxList Inc. | archive-url = https://web.archive.org/web/20080213054025/http://www.rxlist.com/cgi/generic/hydromorphone_ad.htm | archive-date = 13 February 2008 | date = 2008 }}</ref> More common [[adverse effect|side effects]] include [[lightheadedness]], [[dizziness]], [[nystagmus]], [[sedation]], [[itch]]ing, [[constipation]], [[nausea]], [[vomiting]], [[headache]], [[perspiration]], and [[hallucination]]s.<ref name="rxlist.com" /> These symptoms are common in ambulatory patients and in those not experiencing severe pain.

Simultaneous use of hydromorphone with other opioids, [[muscle relaxant]]s, tranquilizers, [[sedative]]s, and [[general anesthetic]]s may significantly depress respiration, progressing to [[coma]] or death. Taking [[benzodiazepine]]s (e.g., [[diazepam]]) in conjunction with hydromorphone may increase side effects such as dizziness and difficulty concentrating.<ref>{{cite web |url = https://www.drugs.com/drug-interactions/dilaudid-with-valium-1294-768-862-441.html |title = Drug interactions between Dilaudid and Valium |access-date = 19 November 2014 }}</ref> If simultaneous use of these drugs is required, dose adjustment may be made.<ref name="app.purduepharma.com">{{cite web |title = Dilaudid (hydromorphone hydrochloride) Oral LiquidDilaudid (hydromorphone hydrochloride) Tablets |url = http://app.purduepharma.com/xmlpublishing/pi.aspx?id=dt |website = app.purduepharma.com |access-date = 5 November 2015 |archive-date = 4 March 2016 |archive-url = https://web.archive.org/web/20160304071103/http://app.purduepharma.com/xmlpublishing/pi.aspx?id=dt }}</ref>

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.<ref name="pmid1377371">{{cite journal | vauthors = Cohen MR | title = Doctor was thinking of the wrong drug | journal = Nursing | volume = 22 | issue = 6 | page = 25 | date = June 1992 | pmid = 1377371 | doi = 10.1097/00152193-199206000-00009 }}</ref><ref name="pmid16308048">{{cite journal | vauthors = Tuohy N, Paparella S | title = Look-alike and sound-alike drugs: errors just waiting to happen | journal = Journal of Emergency Nursing | volume = 31 | issue = 6 | pages = 569–571 | date = December 2005 | pmid = 16308048 | doi = 10.1016/j.jen.2005.07.012 }}</ref>

Massive [[overdose]]s 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 carbon|activated charcoal]] through a nasogastric tube. [[Opioid antagonist]]s, such as [[naloxone]], also may be administered concurrently with oxygen supplementation. Naloxone works by reversing the effects of hydromorphone, and is administered only in the presence of significant respiratory depression and circulatory depression.<ref name="app.purduepharma.com" />

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 opioids.

=== Hormone imbalance ===
{{Main|Opioid#Hormone imbalance}}

As with other opioids, hydromorphone (particularly during heavy chronic use) often causes temporary [[hypogonadism]] or [[hormone imbalance]].<ref name="pmid23414717">{{cite journal | vauthors = Brennan MJ | title = The effect of opioid therapy on endocrine function | journal = The American Journal of Medicine | volume = 126 | issue = 3 Suppl 1 | pages = S12–S18 | date = March 2013 | pmid = 23414717 | doi = 10.1016/j.amjmed.2012.12.001 }}</ref>

=== Neurotoxicity ===

In the setting of prolonged use, high dosage, and/or kidney dysfunction, hydromorphone has been associated with neuroexcitatory symptoms such as [[tremor]], [[myoclonus]], [[Psychomotor agitation|agitation]], and [[cognitive dysfunction]].<ref name="Thwaites 545–50" /><ref name="pmid23715067">{{cite journal | vauthors = Gagnon DJ, Jwo K | title = Tremors and agitation following low-dose intravenous hydromorphone administration in a patient with kidney dysfunction | journal = The Annals of Pharmacotherapy | volume = 47 | issue = 7–8 | pages = e34 | year = 2013 | pmid = 23715067 | doi = 10.1345/aph.1R784 | s2cid = 21782204 }}</ref><ref>{{cite journal | vauthors = Rapp SE, Egan KJ, Ross BK, Wild LM, Terman GW, Ching JM | title = A multidimensional comparison of morphine and hydromorphone patient-controlled analgesia | journal = Anesthesia and Analgesia | volume = 82 | issue = 5 | pages = 1043–1048 | date = May 1996 | pmid = 8610865 | doi = 10.1213/00000539-199605000-00029 | doi-access = free }}</ref> 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.<ref name=":6" /> Some people cannot tolerate the symptoms, which results in continuous drug use.<ref name=":6">{{cite web |title = Hydromorphone / Dilaudid Detox |url = http://www.rapiddrugdetox.com/detox-facts-drugs/dilaudid-detox/ |website = Rapid Drug Detox |access-date = 5 November 2015 }}</ref> Symptoms of [[opioid withdrawal]] are not easy to decipher, as there are differences between drug-seeking behaviors and true withdrawal effects.<ref name=":5">{{cite web |title = Dilaudid Abuse & Addiction Withdrawals, Signs, Symptoms & Effects – Acadiana Addiction Center |url = http://www.acadianaaddiction.com/prescription-drugs/dilaudid/symptoms-signs-effects |website = www.acadianaaddiction.com |access-date = 5 November 2015 }}</ref> Symptoms associated with hydromorphone withdrawal include:<ref name=":6" /><ref name=":5" /><ref name=":4" />
* [[Abdominal pain]]
* [[Anxiety]]
* [[Panic attack]]s
* [[Depression (mood)|Depression]]
* [[Piloerection]] (goose bumps)
* [[Anhedonia|Inability to enjoy daily activities]]
* [[Muscle pain|Muscle]] and [[joint pain]]
* [[Nausea]]
* [[Vomiting]]
* [[Rhinorrhea|Runny nose]] and excessive secretion of tears
* [[Hyperhidrosis|Sweating]]

In the clinical setting, excessive secretion of tears, [[yawning]], and [[Mydriasis|dilation of pupils]] are helpful presentations in diagnosing opioid withdrawal.<ref>{{cite journal | vauthors = McKeown NJ, West PL | date = 13 July 2022 | veditors = VanDeVoort JT, Burns MJ, Gaeta TJ | journal = Medscape |title = Withdrawal Syndromes: Practice Essentials, Background, Pathophysiology |url = http://emedicine.medscape.com/article/819502-overview }}</ref> Hydromorphone is a rapid-acting painkiller; however, some formulations may last up to several hours. Patients who stop taking this drug abruptly may experience withdrawal symptoms,<ref name=":4">{{cite web |title = Hydromorphone Drug Information |url = http://www.narconon.org/drug-information/hydromorphone.html |website = Narconon International |access-date = 5 November 2015 }}</ref><ref name=":3">{{cite web |url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019892s015lbl.pdf |title = DILAUDID® ORAL LIQUID and DILAUDID® TABLETS Package Insert |date = 2007 |access-date = 5 November 2015 |website = FDA }}</ref> which may start within hours of taking the last dose of hydromorphone, and last up to several weeks.<ref name=":6" /> Withdrawal symptoms in people who stopped taking the opioid may be managed by using opioids or non-opioid adjuncts.<ref>{{cite web |title = Opioid withdrawal protocol |url = https://www.saskatoonhealthregion.ca/locations_services/Services/mhas/Documents/Resources%2520for%2520Professionals/Opioidwithdrawalprotocol-finaldraftJan14-2010_000.pdf |website = www.saskatoonhealthregion.ca |access-date = 5 November 2015 |archive-url = https://web.archive.org/web/20151125074147/https://www.saskatoonhealthregion.ca/locations_services/Services/mhas/Documents/Resources%2520for%2520Professionals/Opioidwithdrawalprotocol-finaldraftJan14-2010_000.pdf |archive-date = 25 November 2015 }}</ref> [[Methadone]] is an opioid commonly used for this kind of therapy. However, the selection of therapy should be tailored to each specific person.<ref name=":1">{{cite book | chapter = 4 Treatment Protocols | title = Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. | series = Treatment Improvement Protocol (TIP) Series | volume = 40 |url = https://www.ncbi.nlm.nih.gov/books/NBK64246/ |date = 1 January 2004 |publisher = Substance Abuse and Mental Health Services Administration (US) | location = Rockville (MD) }}</ref> Methadone also is used for detoxification in people who have opiate addiction, such as heroin or drugs similar to morphine.<ref name=":1" /> 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.<ref name=":6" /> [[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]].<ref>{{cite journal | vauthors = Bell CC | title = Simultaneous treatment of hypertension and opiate withdrawal using an alpha 2-adrenergic agonist | journal = Journal of the National Medical Association | volume = 75 | issue = 1 | pages = 89–93 | date = January 1983 | pmid = 6131140 | pmc = 2561435 }}</ref>

== Interactions ==
CNS depressants may enhance the depressant effects of hydromorphone, such as other [[opioid]]s, [[anesthetic]]s, [[sedative]]s, [[hypnotic]]s, [[barbiturate]]s, [[benzodiazepine]]s, [[phenothiazine]]s, [[chloral hydrate]], [[dimenhydrinate]], and [[glutethimide]]. The [[depressant]] effect of hydromorphone also may be enhanced by [[monoamine oxidase inhibitor]]s (MAO inhibitors), first-generation [[antihistamine]]s (e.g., [[brompheniramine]], [[promethazine]], [[diphenhydramine]], [[chlorphenamine]]), [[beta blocker]]s, and [[alcohol (drug)|alcohol]]. When combined therapy is contemplated, the dose of one or both agents should be reduced.<ref name="Thwaites 545–50">{{cite journal | vauthors = Thwaites D, McCann S, Broderick P | title = Hydromorphone neuroexcitation | journal = Journal of Palliative Medicine | volume = 7 | issue = 4 | pages = 545–550 | date = August 2004 | pmid = 15353098 | doi = 10.1089/1096621041838362 }}</ref>

== Pharmacology ==
{| class="wikitable floatright" style="text-align: center;"
|+ Hydromorphone at opioid receptors<ref name="pmid11197347">{{cite journal | vauthors = Filizola M, Villar HO, Loew GH | title = Molecular determinants of non-specific recognition of delta, mu, and kappa opioid receptors | journal = Bioorganic & Medicinal Chemistry | volume = 9 | issue = 1 | pages = 69–76 | date = January 2001 | pmid = 11197347 | doi = 10.1016/S0968-0896(00)00223-6 }}</ref>
|-
! colspan="3" | [[Binding affinity|Affinities]] ({{abbrlink|K<sub>i</sub>|Inhibitor constant}}) || Ratio
|-
! {{abbrlink|MOR|μ-Opioid receptor}} !! {{abbrlink|DOR|δ-Opioid receptor}} !! {{abbrlink|KOR|κ-Opioid receptor}} !! MOR:DOR:KOR
|-
| 0.47 nM || 18.5 nM || 24.9 nM || 1:39:53
|}

{| class="wikitable floatright"
|+ <br />Equianalgesic doses<ref name="King2010">{{cite book| vauthors = King TL, Brucker MC |title= Pharmacology for Women's Health|url=https://books.google.com/books?id=o_rHHCsIpckC&pg=PA332|date=25 October 2010|publisher=Jones & Bartlett Publishers|isbn=978-1-4496-1073-9|pages=332–}}</ref><ref name="ChestnutWong2014">{{cite book| vauthors = Chestnut DH, Wong CA, Tsen LC, Kee WD, Beilin Y, Mhyre J |title=Chestnut's Obstetric Anesthesia: Principles and Practice E-Book|url=https://books.google.com/books?id=FMU0AwAAQBAJ&pg=PA611|date=28 February 2014|publisher=Elsevier Health Sciences|isbn=978-0-323-11374-8|pages=611–}}</ref><ref name="Tiziani2013">{{cite book| vauthors = Tiziani AP |title=Havard's Nursing Guide to Drugs|url=https://books.google.com/books?id=XpzQAgAAQBAJ&pg=PA933|date=1 June 2013|publisher=Elsevier Health Sciences|isbn=978-0-7295-8162-2|pages=933–}}</ref>
|-
! Compound !! [[Route of administration|Route]] !! [[Dose (biochemistry)|Dose]]
|-
| [[Codeine]] || {{abbr|PO|Oral administration}} || 200&nbsp;mg
|-
| [[Hydrocodone]] || {{abbr|PO|Oral administration}} || 20–30&nbsp;mg
|-
| Hydromorphone || {{abbr|PO|Oral administration}} || 7.5&nbsp;mg
|-
| Hydromorphone || {{abbr|IV|Intravenous administration}} || 1.5&nbsp;mg
|-
| [[Morphine]] || {{abbr|PO|Oral administration}} || 30&nbsp;mg
|-
| [[Morphine]] || {{abbr|IV|Intravenous administration}} || 10&nbsp;mg
|-
| [[Oxycodone]] || {{abbr|PO|Oral administration}} || 20&nbsp;mg
|-
| [[Oxycodone]] || {{abbr|IV|Intravenous administration}} || 10&nbsp;mg
|-
| [[Oxymorphone]] || {{abbr|PO|Oral administration}} || 10&nbsp;mg
|-
| [[Oxymorphone]] || {{abbr|IV|Intravenous administration}} || 1&nbsp;mg
|}

Hydromorphone is a semi-synthetic [[Opioid receptor#The μ-opioid receptor|μ-opioid]] [[agonist]]. As a hydrogenated ketone of morphine, it shares the pharmacologic properties typical of [[opioid analgesic]]s. 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 (emotion)|euphoria]] or [[dysphoria]], respiratory depression, cough suppression, decreased gastrointestinal motility, nausea, vomiting, increased cerebrospinal fluid pressure, increased [[biliary tract|biliary pressure]], and increased pinpoint constriction of the pupils.<ref name=":3" />

=== Formulations ===

[[File:Hydromorphone.JPG|thumb|]]

Hydromorphone is available in parenteral, rectal, subcutaneous, and oral formulations, and also can be administered via [[Epidural administration|epidural]] or [[Intrathecal administration|intrathecal]] injection.<ref>{{cite journal | vauthors = Nersesyan H, Slavin KV | title = Current approach to cancer pain management: Availability and implications of different treatment options | journal = Therapeutics and Clinical Risk Management | volume = 3 | issue = 3 | pages = 381–400 | date = June 2007 | pmid = 18488078 | pmc = 2386360 }}</ref> Hydromorphone also has been administered via [[Nebulizer|nebulization]] to treat [[shortness of breath]], but it is not used as a route for pain control due to low [[bioavailability]].<ref name=":0">{{cite journal | vauthors = Sarhill N, Walsh D, Nelson KA | title = Hydromorphone: pharmacology and clinical applications in cancer patients | journal = Supportive Care in Cancer | volume = 9 | issue = 2 | pages = 84–96 | date = March 2001 | pmid = 11305075 | doi = 10.1007/s005200000183 | s2cid = 22849970 }}</ref> Transdermal delivery systems are also under consideration to induce local skin analgesia.<ref name="SmithGomez-Panzani2006">{{cite journal| vauthors = Smith A, Gomez-Panzani E, Mills S, Rainey G, Tolia G, Tagliaferri F, Spratlin V |title=(807) 24-hour transdermal delivery of hydromorphone hydrochloride|journal=The Journal of Pain|volume=7|issue=4|year=2006|pages=S52|issn=1526-5900|doi=10.1016/j.jpain.2006.01.209 |type=Clinical trial abstract|doi-access=free}}</ref>

Concentrated [[aqueous solution]]s 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.<ref name=PkgInsert2004>Dilaudid HP package insert Nov 2004</ref> Ampoules of solution which have developed a precipitate should be discarded.<ref name=PkgInsert2004/>

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.<ref>{{cite journal | vauthors = Knight KH, Brand FM, Mchaourab AS, Veneziano G | title = Implantable intrathecal pumps for chronic pain: highlights and updates | journal = Croatian Medical Journal | volume = 48 | issue = 1 | pages = 22–34 | date = February 2007 | pmid = 17309136 | pmc = 2080496 }}</ref>

An extended-release (once-daily) version of hydromorphone is available in the United States.<ref name=":2">{{cite web |url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021217lbl.pdf |archive-url = https://web.archive.org/web/20110917052631/http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021217lbl.pdf |archive-date = 17 September 2011 |title = EXALGO (hydromorphone hydrochloride) extended release tablets Package Insert |date = 2010 |access-date = 5 November 2015 |website = FDA }}</ref> 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,<ref name="zalicus.com">{{cite web |url = http://www.zalicus.com/product-pipeline/exalgo.asp |title = zalicus.com |website = www.zalicus.com |access-date = 2 September 2017 }}</ref> In Canada, pre{{shy}}scrip{{shy}}tion continuous release hydro{{shy}}morphone is available as both brand name (Hydro{{shy}}morph Contin) and generic formu{{shy}}lations (Apo-Hydro{{shy}}morphone CR).<ref>{{cite web |title=Summary Safety Review – HYDROmorph Contin and generic hydromorphone controlled release capsules. – Health Canada |url=https://hpr-rps.hres.ca/reg-content/summary-safety-review-detail.php?linkID=SSR00244 |access-date=22 September 2024 |website=Government of Canada: Drugs, health & consumer products |date=10 September 2020 }}</ref>

=== 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.<ref>{{cite web |url = http://www.alfredhealth.org.au/Assets/Files/OpioidConversionChart2007.pdf |title = Opioid Conversion Guidelines |website = alfredhealth.org.au |access-date = 2 September 2017 |archive-url = https://web.archive.org/web/20160304121532/http://www.alfredhealth.org.au/Assets/Files/OpioidConversionChart2007.pdf |archive-date = 4 March 2016 }}</ref><ref>{{cite web |url = http://nationalpaincentre.mcmaster.ca/documents/opioid_manager_switching_opioids.pdf |title = Switching Opioids |website = mcmaster.ca |access-date = 2 September 2017 }}</ref>

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.<ref>{{cite web |title = Hydromorphone |work = That's Poppycock! |date = 19 February 2009 |url = http://www.thatspoppycock.com/opiates/hydromorphone/ |access-date = 5 November 2012 |archive-date = 14 October 2012 |archive-url = https://web.archive.org/web/20121014122621/http://www.thatspoppycock.com/opiates/hydromorphone/ }}</ref> Peak plasma levels usually occur between 30 and 60 minutes after oral dosing.<ref>{{cite web |url = http://www.rxlist.com/cgi/generic/hydromorphone_cp.htm |title = Dilaudid Clinical Pharmacology |website = rxlist.com |access-date = 2 September 2017 |archive-url = https://web.archive.org/web/20080612192040/http://www.rxlist.com/cgi/generic/hydromorphone_cp.htm |archive-date = 12 June 2008 }}</ref>

The onset of action for hydromorphone administered intravenously is less than 5 minutes and within 30 minutes of oral administration (immediate release).<ref name=":0" />

=== Metabolism ===

While other opioids in its class, such as [[codeine]] or oxycodone, are metabolized via CYP450 enzymes, hydromorphone is not.<ref>{{cite journal | vauthors = Gregory TB | title = Hydromorphone: evolving to meet the challenges of today's health care environment | journal = Clinical Therapeutics | volume = 35 | issue = 12 | pages = 2007–2027 | date = December 2013 | pmid = 24290733 | doi = 10.1016/j.clinthera.2013.09.027 }}</ref> 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.<ref>{{cite web |url = http://www.medicine.virginia.edu/clinical/departments/pediatrics/education/pharm-news/2006-2010/200807.pdf |title = Use of Hydromorphone in Children and Adolescents |date = July 2008 |access-date = 5 November 2015 |publisher = University of Virginia Children's Hospital | vauthors = Buck M |archive-date = 17 February 2014 |archive-url = https://web.archive.org/web/20140217121125/http://www.medicine.virginia.edu/clinical/departments/pediatrics/education/pharm-news/2006-2010/200807.pdf }}</ref>

== Chemistry ==
With a formula of C<sub>17</sub>H<sub>19</sub>NO<sub>3</sub> 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.<ref>Merck Index 2003, "Morphine" and "Hydromorphone"</ref>

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 may be replaced with a [[methylene group]] via the [[Wittig reaction]] to produce [[6-Methylenedihydrodesoxymorphine|6-methylenedihydrodesoxymorphine]], which is 80× stronger than morphine.<ref>[http://www.acsmedchem.org/module/opioid.html PHA 4220 – Neurology Pharmacotherapeutics<!-- Bot generated title -->] {{webarchive |url=https://web.archive.org/web/20070716115228/http://www.acsmedchem.org/module/opioid.html |date=16 July 2007 }}</ref>

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&nbsp;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.<ref>{{cite web | title = Hydromorphone Hydrochloride | id = MSDS No. 71681 | publisher = Purdue Pharma L.P.| location = Stamford, CT | date = 13 October 2009 | url = http://www.purduepharma.com/msdss/Dilaudid_2_4_8mgTablets_OralLiquid_MSDS.pdf | access-date = 5 November 2015 | archive-url = https://web.archive.org/web/20150117082035/http://www.purduepharma.com/msdss/Dilaudid_2_4_8mgTablets_OralLiquid_MSDS.pdf | archive-date = 17 January 2015 }}</ref>

=== Bacteria ===

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 hydromorphone form, as it is an intermediary metabolite in this process; the same goes for codeine being turned into hydrocodone.<ref name="pmid7487001">{{cite journal | vauthors = Long MT, Hailes AM, Kirby GW, Bruce NC | title = Transformations of morphine alkaloids by Pseudomonas putida M10 | journal = Applied and Environmental Microbiology | volume = 61 | issue = 10 | pages = 3645–3649 | date = October 1995 | pmid = 7487001 | pmc = 167664 | doi = 10.1128/AEM.61.10.3645-3649.1995 | bibcode = 1995ApEnM..61.3645L }}</ref>

== History ==

Hydromorphone was patented in 1923.<ref name=Fis2006/> It was introduced to the mass market in 1926 under the brand name ''Dilaudid'',<ref name="bja">{{cite journal | vauthors = Felden L, Walter C, Harder S, Treede RD, Kayser H, Drover D, Geisslinger G, Lötsch J | title = Comparative clinical effects of hydromorphone and morphine: a meta-analysis | journal = British Journal of Anaesthesia | volume = 107 | issue = 3 | pages = 319–328 | date = September 2011 | pmid = 21841049 | doi = 10.1093/bja/aer232 | doi-access = free }}</ref> indicating its derivation and degree of similarity to morphine (by way of [[laudanum]]).

== Society and culture ==

=== Names ===

Hydromorphone is known in various countries around the world by the brand names Hydal, Dimorphone, Exalgo, Sophidone LP, Dilaudid, Hydrostat, Hydromorfan, Hydromorphan, Hymorphan, Laudicon, Opidol, Palladone, Hydromorph Contin, and others. 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.<ref>{{cite web |url = https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm129288.htm |archive-url = https://web.archive.org/web/20090609220642/http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm129288.htm |archive-date = 9 June 2009 |title = Information for Healthcare Professionals: Hydromorphone Hydrochloride Extended-Release Capsules (marketed as Palladone) |date = 15 July 2005 |publisher = Center for Drug Evaluation and Research |access-date = 16 August 2016 }}</ref> As of March 2010, it is still available in Nepal under the brand name Opidol, in the United Kingdom under the brand name Palladone SR, and in most other European countries.

There has also been a once-daily prolonged release version of hydromorphone available in Australia under the brand name Jurnista as of May 2009.<ref name="nps.org.au">{{cite news |url = https://www.nps.org.au/radar/articles/hydromorphone-prolonged-release-tablets-jurnista-for-chronic-severe-disabling-pain |title = Hydromorphone prolonged-release tablets (Jurnista) for chronic severe disabling pain |newspaper = NPS Medicinewise |date = May 2009 |access-date = 7 December 2020 }}</ref>

=== 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 {{convert|766|kg|abbr=off}} in 1998 to {{convert|3300|kg}} in 2006, and an increase in prescriptions in this time of 289%, from about 470,000 to 1,830,000. The 2013 production quota was {{convert|5968|kg}}.<ref>{{cite web |url = http://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0620.htm |title = Proposed Adjustments to the Aggregate Production Quotas for Schedule I and II Controlled Substances and Assessment of Annual Needs for the List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2013 |publisher = Drug Enforcement Administration (DEA), Department of Justice |date = 20 June 2014 |access-date = 26 July 2014 |archive-date = 14 May 2017 |archive-url = https://web.archive.org/web/20170514115234/https://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0620.htm }}</ref>

Like all opioids used for analgesia, hydromorphone is potentially habit-forming and is listed in [[Schedule II controlled substance|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 it is listed in the Single Convention On Narcotic Drugs. The DEA [[ACSCN]] for hydromorphone is 9150.

Hydromorphone is listed under the German [[Betäubungsmittelgesetz]] as a Betäubungsmittel in the most restricted schedule for medicinal drugs; it is controlled similarly in Austria (Suchtgift) under the SMG and the Swiss BetmG. The Misuse of Drugs Act 1971 (United Kingdom) and comparable French, Canadian, Australian, Italian, Czech, Croatian, Slovenian, Swedish, Polish, Spanish, Greek, Russian, and other laws similarly control it, as do regulations in virtually all other countries.

=== Use in executions ===

In 2009, [[Capital punishment in Ohio|Ohio approved the use]] of an intramuscular injection of 500&nbsp;mg of hydromorphone and a [[:wikt:supratherapeutic|supratherapeutic]] dose of [[midazolam]] as a backup means of carrying out executions by [[lethal injection]] when a suitable vein cannot be found for intravenous injection.<ref>{{cite web |url = http://www.drc.ohio.gov/public/press/press342.htm |title = Ohio Prisons Director Announces Changes to Ohio's Execution Process |date = 13 November 2009 |publisher = [[Ohio Department of Rehabilitation and Correction]] |access-date = 17 January 2014 |archive-url = https://web.archive.org/web/20130115131421/http://www.drc.ohio.gov/Public/press/press342.htm |archive-date = 15 January 2013 }}</ref>

==Veterinary use==
Hydromorphone is used as an intravenous analgesic in cats and dogs. Hydromorphone's potency is 5–10 times greater than morphine when given intravenously and the length of effect is dose dependent with times ranging 1–8 hours. Anaesthetic recovery can be prolonged from long use of hydromorphone. Hydromorphone is not useful compared to morphine when given subcutaenously in cats or epidurally in cats and dogs. Hydromorphone can provide analgesia up to 12 hours when given intravenously in horses and is also effective when given intramuscular. Hydromorphone has minimal adverse effects in horses when compared to other opioids such as morphine.<ref>{{cite book | vauthors = Simon BT, Lizarraga I |chapter=Opioids | veditors = Lamont L, Grimm K, Robertson S, Love L, Schroeder C |title=Veterinary Anesthesia and Analgesia |date=11 September 2024 | edition = 6th Edition of Lumb and Jones|pages=376–378|publisher=Wiley Blackwell |isbn=978-1-119-83027-6}}</ref>

== References ==
{{Reflist}}

== External links ==
* [https://www.nytimes.com/2007/06/17/magazine/17pain-t.html When is a pain doctor a drug pusher?], ''[[The New York Times]]'', June 2007

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