Hydromorphone

"Dihydromorphinone" redirects here. Not to be confused with dihydromorphine (Paramorfan, etc.), a different opioid.

Hydromorphone
Structural formula of hydromorphone
Space-filling model of hydromorphone
Clinical data
Trade namesDilaudid, others
Other namesDihydromorphinone
AHFS/Drugs.comMonograph
MedlinePlusa682013
License data
Pregnancy
category
Dependence
liability		High[2]
Addiction
liability		High[3]
Routes of
administration		By mouth, intramuscular, intravenous, subcutaneous
Drug classOpioid
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityBy mouth: 25–50%,[5] Intranasal: 52–58%,[6] IV/IM: 100%
Protein binding20%
MetabolismLiver
Onset of action15–30 min[7]
Elimination half-life2–3 hours[8]
Duration of action4–5 hours[7]
ExcretionKidney
Identifiers
  • 4,5-α-Epoxy-3-hydroxy-17-methyl morphinan-6-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.006.713 Edit this at Wikidata
Chemical and physical data
FormulaC17H19NO3
Molar mass285.343 g·mol−1
3D model (JSmol)
Solubility in waterHCl salt: 333
  • O=C4[C@@H]5Oc1c2c(ccc1O)C[C@H]3N(CC[C@]25[C@H]3CC4)C
  • 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 checkY
  • Key:WVLOADHCBXTIJK-YNHQPCIGSA-N checkY
  (verify)

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.[7] Typically, long-term use is only recommended for pain due to cancer.[9] It may be used by mouth or by injection into a vein, muscle, or under the skin.[7] Effects generally begin within half an hour and last for up to five hours.[7] A 2016 Cochrane review (updated in 2021) found little difference in benefit between hydromorphone and other opioids for cancer pain.[10]

Common side effects include dizziness, sleepiness, nausea, itchiness, and constipation.[7] Serious side effects may include abuse, low blood pressure, seizures, respiratory depression, and serotonin syndrome.[7] Rapidly decreasing the dose may result in opioid withdrawal.[7] Generally, use during pregnancy or breastfeeding is not recommended.[11] Hydromorphone is believed to work by activating opioid receptors, mainly in the brain and spinal cord.[7] Hydromorphone 2 mg IV is equivalent to approximately 10 mg morphine IV.[9]

Hydromorphone was patented in 1923.[12] Hydromorphone is made from morphine.[13] It is on the World Health Organization's List of Essential Medicines.[14] It is available as a generic medication.[7] In 2022, it was the 233rd most commonly prescribed medication in the United States, with more than 1 million prescriptions.[15][16]

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.[17] More common side effects include lightheadedness, dizziness, sedation, itching, constipation, nausea, vomiting, headache, perspiration, and hallucinations.[17] 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 (e.g., diazepam) in conjunction with hydromorphone may increase side effects such as dizziness and difficulty concentrating.[18] If simultaneous use of these drugs is required, dose adjustment may be made.[19]

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.[20][21]

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.[19]

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 article: Opioid § Hormone imbalance

As with other opioids, hydromorphone (particularly during heavy chronic use) often causes temporary hypogonadism or hormone imbalance.[22]

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.[23][24][25] 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.[26] Some people cannot tolerate the symptoms, which results in continuous drug use.[26] Symptoms of opioid withdrawal are not easy to decipher, as there are differences between drug-seeking behaviors and true withdrawal effects.[27] Symptoms associated with hydromorphone withdrawal include:[26][27][28]

In the clinical setting, excessive secretion of tears, yawning, and dilation of pupils are helpful presentations in diagnosing opioid withdrawal.[29] 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,[28][30] which may start within hours of taking the last dose of hydromorphone, and last up to several weeks.[26] Withdrawal symptoms in people who stopped taking the opioid may be managed by using opioids or non-opioid adjuncts.[31] Methadone is an opioid commonly used for this kind of therapy. However, the selection of therapy should be tailored to each specific person.[32] Methadone also is used for detoxification in people who have opiate addiction, such as heroin or drugs similar to morphine.[32] 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.[26] 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.[33]

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 (e.g., brompheniramine, promethazine, diphenhydramine, chlorphenamine), beta blockers, and alcohol. When combined therapy is contemplated, the dose of one or both agents should be reduced.[23]

Pharmacology

Hydromorphone at opioid receptors[34]
Affinities (KiTooltip Inhibitor constant) Ratio
MORTooltip μ-Opioid receptor DORTooltip δ-Opioid receptor KORTooltip κ-Opioid receptor MOR:DOR:KOR
0.47 nM 18.5 nM 24.9 nM 1:39:53

Equianalgesic doses[35][36][37]
Compound Route Dose
Codeine PO 200 mg
Hydrocodone PO 20–30 mg
Hydromorphone PO 7.5 mg
Hydromorphone IV 1.5 mg
Morphine PO 30 mg
Morphine IV 10 mg
Oxycodone PO 20 mg
Oxycodone IV 10 mg
Oxymorphone PO 10 mg
Oxymorphone IV 1 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.[30]

Formulations

Hydromorphone is available in parenteral, rectal, subcutaneous, and oral formulations, and also can be administered via epidural or intrathecal injection.[38] 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.[39] Transdermal delivery systems are also under consideration to induce local skin analgesia.[40]

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.[41] Ampoules of solution which have developed a precipitate should be discarded.[41]

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.[42]

An extended-release (once-daily) version of hydromorphone is available in the United States.[43] 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,[44] In Canada, pre­scrip­tion continuous release hydro­morphone is available as both brand name (Hydro­morph Contin) and generic formu­lations (Apo-Hydro­morphone CR).[45]

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.[46][47]

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.[48] Peak plasma levels usually occur between 30 and 60 minutes after oral dosing.[49]

The onset of action for hydromorphone administered intravenously is less than 5 minutes and within 30 minutes of oral administration (immediate release).[39]

Metabolism

While other opioids in its class, such as codeine or oxycodone, are metabolized via CYP450 enzymes, hydromorphone is not.[50] 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.[51]

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.[52]

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.[53]

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.[54]

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.[55]

History

Hydromorphone was patented in 1923.[12] It was introduced to the mass market in 1926 under the brand name Dilaudid,[56] 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.[57] 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.[58]

In the United States, the main drug control agency, the Drug Enforcement Administration, reports an increase in annual aggregate production quotas of hydromorphone from 766 kilograms (1,689 pounds) in 1998 to 3,300 kilograms (7,300 lb) 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 5,968 kilograms (13,157 lb).[59]

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 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, Ohio approved the use of an intramuscular injection of 500 mg of hydromorphone and a 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.[60]

Hydromorphone and midazolam was injected intravenously to execute double-murderer Joseph Wood in Arizona on 24 July 2014. Wood was heavily sedated (surgical anesthesia) within four minutes from start, but took almost two hours to transition to stage 4 (cessation of respiration) and death.[61]

References

  1. ^ "Hydromorphone Use During Pregnancy". Drugs.com. 19 November 2019. Retrieved 16 May 2020.
  2. ^ Bonewit-West K, Hunt SA, Applegate E (2012). Today's Medical Assistant: Clinical and Administrative Procedures. Elsevier Health Sciences. p. 571. ISBN 9781455701506.
  3. ^ Bonewit-West K, Hunt SA, Applegate E (2012). Today's Medical Assistant: Clinical and Administrative Procedures. Elsevier Health Sciences. p. 571. ISBN 9781455701506. Archived from the original on 10 January 2023. Retrieved 20 August 2019.
  4. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  5. ^ Polsten GR, Wallace MS (21 June 2016). "Analgesic Agents in Rheumatic Disease". In Firestein GS, Budd R, Gabriel SE, McInnes IB, O'Dell JR (eds.). Kelley and Firestein's Textbook of Rheumatology. Elsevier Health Sciences. pp. 1081–. ISBN 978-0-323-41494-4.
  6. ^ Coda BA, Rudy AC, Archer SM, Wermeling DP (July 2003). "Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers". Anesthesia and Analgesia. 97 (1): 117–23, table of contents. CiteSeerX 10.1.1.551.6509. doi:10.1213/01.ANE.0000066311.40978.4F. PMID 12818953. S2CID 22694749.
  7. ^ a b c d e f g h i j "Hydromorphone Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 15 April 2019.
  8. ^ Vallner JJ, Stewart JT, Kotzan JA, Kirsten EB, Honigberg IL (April 1981). "Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects". Journal of Clinical Pharmacology. 21 (4): 152–156. doi:10.1002/j.1552-4604.1981.tb05693.x. PMID 6165742. S2CID 29864565.
  9. ^ a b British national formulary: BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 24, 456. ISBN 9780857113382.
  10. ^ Li Y, Ma J, Lu G, Dou Z, Knaggs R, Xia J, et al. (August 2021). "Hydromorphone for cancer pain". The Cochrane Database of Systematic Reviews. 2021 (8): CD011108. doi:10.1002/14651858.CD011108.pub3. PMC 8406835. PMID 34350974.
  11. ^ "Hydromorphone Use During Pregnancy". Drugs.com. Retrieved 15 April 2019.
  12. ^ a b Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 526. ISBN 9783527607495.
  13. ^ Vardanyan R, Hruby V (2006). Synthesis of Essential Drugs. Elsevier. p. 25. ISBN 9780080462127.
  14. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  15. ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  16. ^ "Hydromorphone Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  17. ^ a b "Hydromorphone Monograph (Side Effects & Drug Interactions)". RxList Inc. 2008. Archived from the original on 13 February 2008.
  18. ^ "Drug interactions between Dilaudid and Valium". Retrieved 19 November 2014.
  19. ^ a b "Dilaudid (hydromorphone hydrochloride) Oral LiquidDilaudid (hydromorphone hydrochloride) Tablets". app.purduepharma.com. Archived from the original on 4 March 2016. Retrieved 5 November 2015.
  20. ^ Cohen MR (June 1992). "Doctor was thinking of the wrong drug". Nursing. 22 (6): 25. doi:10.1097/00152193-199206000-00009. PMID 1377371.
  21. ^ Tuohy N, Paparella S (December 2005). "Look-alike and sound-alike drugs: errors just waiting to happen". Journal of Emergency Nursing. 31 (6): 569–571. doi:10.1016/j.jen.2005.07.012. PMID 16308048.
  22. ^ Brennan MJ (March 2013). "The effect of opioid therapy on endocrine function". The American Journal of Medicine. 126 (3 Suppl 1): S12–S18. doi:10.1016/j.amjmed.2012.12.001. PMID 23414717.
  23. ^ a b Thwaites D, McCann S, Broderick P (August 2004). "Hydromorphone neuroexcitation". Journal of Palliative Medicine. 7 (4): 545–550. doi:10.1089/1096621041838362. PMID 15353098.
  24. ^ Gagnon DJ, Jwo K (2013). "Tremors and agitation following low-dose intravenous hydromorphone administration in a patient with kidney dysfunction". The Annals of Pharmacotherapy. 47 (7–8): e34. doi:10.1345/aph.1R784. PMID 23715067. S2CID 21782204.
  25. ^ Rapp SE, Egan KJ, Ross BK, Wild LM, Terman GW, Ching JM (May 1996). "A multidimensional comparison of morphine and hydromorphone patient-controlled analgesia". Anesthesia and Analgesia. 82 (5): 1043–1048. doi:10.1213/00000539-199605000-00029. PMID 8610865.
  26. ^ a b c d e "Hydromorphone / Dilaudid Detox". Rapid Drug Detox. Retrieved 5 November 2015.
  27. ^ a b "Dilaudid Abuse & Addiction Withdrawals, Signs, Symptoms & Effects – Acadiana Addiction Center". www.acadianaaddiction.com. Retrieved 5 November 2015.
  28. ^ a b "Hydromorphone Drug Information". Narconon International. Retrieved 5 November 2015.
  29. ^ McKeown NJ, West PL (13 July 2022). VanDeVoort JT, Burns MJ, Gaeta TJ (eds.). "Withdrawal Syndromes: Practice Essentials, Background, Pathophysiology". Medscape.
  30. ^ a b "DILAUDID® ORAL LIQUID and DILAUDID® TABLETS Package Insert" (PDF). FDA. 2007. Retrieved 5 November 2015.
  31. ^ "Opioid withdrawal protocol" (PDF). www.saskatoonhealthregion.ca. Archived from the original (PDF) on 25 November 2015. Retrieved 5 November 2015.
  32. ^ a b "4 Treatment Protocols". Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series. Vol. 40. Rockville (MD): Substance Abuse and Mental Health Services Administration (US). 1 January 2004.
  33. ^ Bell CC (January 1983). "Simultaneous treatment of hypertension and opiate withdrawal using an alpha 2-adrenergic agonist". Journal of the National Medical Association. 75 (1): 89–93. PMC 2561435. PMID 6131140.
  34. ^ Filizola M, Villar HO, Loew GH (January 2001). "Molecular determinants of non-specific recognition of delta, mu, and kappa opioid receptors". Bioorganic & Medicinal Chemistry. 9 (1): 69–76. doi:10.1016/S0968-0896(00)00223-6. PMID 11197347.
  35. ^ King TL, Brucker MC (25 October 2010). Pharmacology for Women's Health. Jones & Bartlett Publishers. pp. 332–. ISBN 978-1-4496-1073-9.
  36. ^ Chestnut DH, Wong CA, Tsen LC, Kee WD, Beilin Y, Mhyre J (28 February 2014). Chestnut's Obstetric Anesthesia: Principles and Practice E-Book. Elsevier Health Sciences. pp. 611–. ISBN 978-0-323-11374-8.
  37. ^ Tiziani AP (1 June 2013). Havard's Nursing Guide to Drugs. Elsevier Health Sciences. pp. 933–. ISBN 978-0-7295-8162-2.
  38. ^ Nersesyan H, Slavin KV (June 2007). "Current approach to cancer pain management: Availability and implications of different treatment options". Therapeutics and Clinical Risk Management. 3 (3): 381–400. PMC 2386360. PMID 18488078.
  39. ^ a b Sarhill N, Walsh D, Nelson KA (March 2001). "Hydromorphone: pharmacology and clinical applications in cancer patients". Supportive Care in Cancer. 9 (2): 84–96. doi:10.1007/s005200000183. PMID 11305075. S2CID 22849970.
  40. ^ Smith A, Gomez-Panzani E, Mills S, Rainey G, Tolia G, Tagliaferri F, et al. (2006). "(807) 24-hour transdermal delivery of hydromorphone hydrochloride". The Journal of Pain (Clinical trial abstract). 7 (4): S52. doi:10.1016/j.jpain.2006.01.209. ISSN 1526-5900.
  41. ^ a b Dilaudid HP package insert Nov 2004
  42. ^ Knight KH, Brand FM, Mchaourab AS, Veneziano G (February 2007). "Implantable intrathecal pumps for chronic pain: highlights and updates". Croatian Medical Journal. 48 (1): 22–34. PMC 2080496. PMID 17309136.
  43. ^ "EXALGO (hydromorphone hydrochloride) extended release tablets Package Insert" (PDF). FDA. 2010. Retrieved 5 November 2015.
  44. ^ "zalicus.com". www.zalicus.com. Retrieved 2 September 2017.
  45. ^ "Summary Safety Review - HYDROmorph Contin and generic hydromorphone controlled release capsules. - Health Canada". Government of Canada: Drugs, health & consumer products. 10 September 2020. Retrieved 22 September 2024.
  46. ^ "Opioid Conversion Guidelines" (PDF). alfredhealth.org.au. Archived from the original (PDF) on 4 March 2016. Retrieved 2 September 2017.
  47. ^ "Switching Opioids" (PDF). mcmaster.ca. Retrieved 2 September 2017.
  48. ^ "Hydromorphone". That's Poppycock!. 19 February 2009. Archived from the original on 14 October 2012. Retrieved 5 November 2012.
  49. ^ "Dilaudid Clinical Pharmacology". rxlist.com. Archived from the original on 12 June 2008. Retrieved 2 September 2017.
  50. ^ Gregory TB (December 2013). "Hydromorphone: evolving to meet the challenges of today's health care environment". Clinical Therapeutics. 35 (12): 2007–2027. doi:10.1016/j.clinthera.2013.09.027. PMID 24290733.
  51. ^ Buck M (July 2008). "Use of Hydromorphone in Children and Adolescents" (PDF). University of Virginia Children's Hospital. Archived from the original (PDF) on 17 February 2014. Retrieved 5 November 2015.
  52. ^ Merck Index 2003, "Morphine" and "Hydromorphone"
  53. ^ PHA 4220 – Neurology Pharmacotherapeutics Archived 16 July 2007 at the Wayback Machine
  54. ^ "Hydromorphone Hydrochloride" (PDF). Stamford, CT: Purdue Pharma L.P. 13 October 2009. MSDS No. 71681. Archived from the original (PDF) on 17 January 2015. Retrieved 5 November 2015.
  55. ^ Long MT, Hailes AM, Kirby GW, Bruce NC (October 1995). "Transformations of morphine alkaloids by Pseudomonas putida M10". Applied and Environmental Microbiology. 61 (10): 3645–3649. Bibcode:1995ApEnM..61.3645L. doi:10.1128/AEM.61.10.3645-3649.1995. PMC 167664. PMID 7487001.
  56. ^ Felden L, Walter C, Harder S, Treede RD, Kayser H, Drover D, et al. (September 2011). "Comparative clinical effects of hydromorphone and morphine: a meta-analysis". British Journal of Anaesthesia. 107 (3): 319–328. doi:10.1093/bja/aer232. PMID 21841049.
  57. ^ "Information for Healthcare Professionals: Hydromorphone Hydrochloride Extended-Release Capsules (marketed as Palladone)". Center for Drug Evaluation and Research. 15 July 2005. Retrieved 16 August 2016.
  58. ^ "Hydromorphone prolonged-release tablets (Jurnista) for chronic severe disabling pain". NPS Medicinewise. May 2009. Retrieved 7 December 2020.
  59. ^ "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". Drug Enforcement Administration (DEA), Department of Justice. 20 June 2014. Archived from the original on 14 May 2017. Retrieved 26 July 2014.
  60. ^ "Ohio Prisons Director Announces Changes to Ohio's Execution Process". Ohio Department of Rehabilitation and Correction. 13 November 2009. Archived from the original on 15 January 2013. Retrieved 17 January 2014.
  61. ^ "Arizona execution takes two hours". BBC News. 24 July 2014. Retrieved 24 July 2014.