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Identification
Name Hydromorphone
Accession Number DB00327 (APRD01021)
Type small molecule
Groups illicit, approved
Description

An opioid analgesic derived from morphine and used mainly as an analgesic. It has a shorter duration of action and is more potent than morphine. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Dihydromorfinon [Czech]
Dihydromorphinone
Hidromorfona [INN-Spanish]
Hydromorfona [Spanish]
Hydromorphon
Hydromorphone HCL
Hydromorphonum [INN-Latin]
Salts Not Available
Brand names
Name Company
Dilaudid
Dilaudid Oros
Dilaudid-hp
DiMo
Dimorphone
Hymorphan
Idromorfone
Laudacon
Laudicon
Novolaudon
Palladone
Paramorphan
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Brand mixtures Not Available
Categories
  • Narcotics
  • Analgesics, Opioid
CAS number 466-99-9
Weight Average: 285.3377
Monoisotopic: 285.136493479
Chemical Formula C17H19NO3
InChI Key InChIKey=WVLOADHCBXTIJK-YNHQPCIGSA-N
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
Plain Text
IUPAC Name
(1S,5R,13R,17R)-10-hydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10-trien-14-one
SMILES
[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])CCC2=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Morphinans
  • Benzylisoquinolines
Substructures
  • Morphinans
  • Benzofurans
  • Hydroxy Compounds
  • Naphthalenes
  • Phenols and Derivatives
  • Benzylisoquinolines
  • Ethers
  • Benzene and Derivatives
  • Phenylpiperidines
  • Methoxyphenols
  • Aliphatic and Aryl Amines
  • Phenanthrenes
  • Catechols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Phenylpropylamines
  • (Iso)quinolines and Derivatives
  • Cyclohexenes and Derivatives
  • Phenyl Esters
  • Amphetamines
  • Catecholamines and Derivatives
  • Piperidines
  • Ketones
Pharmacology
Indication For the relief of moderate to severe pain such as that due to surgery, cancer, trauma/injury, or burns.
Pharmacodynamics Hydromorphone is a hydrogenated ketone derivative of morphine that acts as a narcotic analgesic. It has a shorter duration of action than morphine. Hydromorphone is approximately 8 times more potent on a milligram basis than morphine. In addition, hydromorphone is better absorbed orally than is morphine. In clinical settings, Hydromorphone exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Its primary actions of therapeutic value are analgesia and sedation. Hydromorphone appears to increase the patient's tolerance for pain and to decrease discomfort, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Opioids also produce respiratory depression by direct action on brain stem respiratory centers.
Mechanism of action Hydromorphone is a narcotic analgesic; its principal therapeutic effect is relief of pain. Hydromorphone interacts predominantly with the opioid mu-receptors. These mu-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve. In clinical settings, Hydromorphone exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Hydromorphone also binds with kappa-receptors which are thought to mediate spinal analgesia, miosis and sedation.
Absorption Better absorbed orally than morphine
Volume of distribution Not Available
Protein binding 20%
Metabolism Primarily hepatic. After absorption hydromorphone is metabolized by the liver to the glucuronide conjugate which is then excreted in the urine. Hydromorphone is metabolized to the major metabolites hydromorphone-3-glucuronide, hydromorphone-3-glucoside and dihydroisomorphine-6-glucuronide.
Route of elimination Only a small amount of the hydromorphone dose is excreted unchanged in the urine. Most of the dose is excreted as hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites.
Half life 2.6 hours (oral); 18.6 hours for sustained release Palladone
Clearance
  • 1.96 L/min
Toxicity Hydromorphone is a schedule II narcotic which can lead to physical dependence or addiction. High doses lead to respiratory depression, nausea, and vomiting. Overdoses lead to extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00410 Hydromorphone Pathway SMP00410
Pharmacoeconomics
Manufacturers
  • Purdue pharma lp
  • Purdue pharmaceutical products lp
  • Akorn inc
  • Barr laboratories inc
  • Hospira inc
  • Watson laboratories inc
  • Roxane laboratories inc
  • Mallinckrodt inc
  • Actavis totowa llc
  • Kv pharmaceutical co
  • Lannett holdings inc
  • Tyco healthcare mallinckrodt
Packagers
Dosage forms
Form Route Strength
Capsule, extended release Oral
Liquid Intramuscular
Liquid Intravenous
Liquid Oral
Powder, for solution Intravenous
Solution Intravenous
Suppository Rectal
Syrup Oral
Tablet Oral
Prices
Unit description Cost Unit
Hydromorphone hcl powder 166.25 USD g
Dilaudid-hp 250 mg vial 114.8 USD vial
Dilaudid Sterile Powder 250 mg/vial 78.99 USD vial
HYDROmorphone HCl 6 3 mg Suppository Box 54.92 USD box
Hydromorphone Hp 50 50 mg/ml 13.78 USD ml
Dilaudid-Xp 50 mg/ml 11.82 USD ml
Hydromorphone 3 mg suppository 11.11 USD suppository
Dilaudid-Hp-Plus 20 mg/ml 5.08 USD ml
Hydromorphone Hp 20 20 mg/ml 4.72 USD ml
Hydromorph Contin 30 mg Controlled-Release Capsule 4.21 USD capsule
Hydromorph Contin 24 mg Controlled-Release Capsule 3.52 USD capsule
Dilaudid-Hp 10 mg/ml 3.14 USD ml
Hydromorphone Hp 10 mg/ml 2.92 USD ml
Hydromorph Contin 18 mg Controlled-Release Capsule 2.75 USD capsule
Hydromorphone 10 mg/ml ampul 2.58 USD ml
Pms-Hydromorphone 3 mg Suppository 2.42 USD suppository
Dilaudid 4 mg/ml ampul 2.2 USD ml
Dilaudid 8 mg tablet 2.19 USD tablet
HYDROmorphone HCl 4 mg/ml Solution 1ml Cartridge 2.07 USD cartridge
Hydromorph Contin 12 mg Controlled-Release Capsule 1.91 USD capsule
Dilaudid 2 mg/ml ampul 1.81 USD ml
Dilaudid 1 mg/ml ampul 1.64 USD ml
Hydromorphone hcl 8 mg tablet 1.4 USD tablet
Dilaudid 4 mg tablet 1.36 USD tablet
Hydromorphone 8 mg tablet 1.32 USD tablet
Dilaudid 2 mg/ml 1.28 USD ml
Hydromorphone 2 mg/ml 1.19 USD ml
Hydromorph Contin 6 mg Controlled-Release Capsule 1.1 USD capsule
Hydromorphone-ns 0.4 mg/ml 1.08 USD ml
Hydromorphone-ns 0.3 mg/ ml 1.05 USD ml
Hydromorphone 2 mg/ml vial 1.02 USD ml
Hydromorphone-ns 25 mg/25 ml 1.01 USD ml
Dilaudid 2 mg tablet 1.0 USD tablet
Hydromorphone-ns 2.5 mg/25 ml 0.96 USD ml
HYDROmorphone HCl 4 mg tablet 0.8 USD tablet
HYDROmorphone HCl 2 mg tablet 0.77 USD tablet
Hydromorph Contin 3 mg Controlled-Release Capsule 0.73 USD capsule
Hydromorphone 4 mg tablet 0.72 USD tablet
Dilaudid 8 mg Tablet 0.55 USD tablet
Hydromorphone-ns 0.2 mg/ml 0.49 USD ml
Hydromorphone 2 mg tablet 0.37 USD tablet
Pms-Hydromorphone 8 mg Tablet 0.37 USD tablet
Dilaudid 4 mg Tablet 0.35 USD tablet
Dilaudid-5 1 mg/ml liquid 0.33 USD ml
Hydromorphone-ns 5.5 mg/55 ml 0.33 USD ml
Dilaudid 2 mg Tablet 0.23 USD tablet
Pms-Hydromorphone 4 mg Tablet 0.23 USD tablet
Dilaudid 1 mg Tablet 0.16 USD tablet
Pms-Hydromorphone 2 mg Tablet 0.15 USD tablet
Pms-Hydromorphone 1 mg Tablet 0.1 USD tablet
Dilaudid 1 mg/ml Liquid 0.09 USD ml
Pms-Hydromorphone 1 mg/ml Liquid 0.07 USD ml
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6589960 2000-11-09 2020-11-09
United States 5968551 1994-12-24 2011-12-24
Properties
State solid
Experimental Properties
Property Value Source
melting point 266.5 °C PhysProp
logP 0.9 Not Available
Predicted Properties
Property Value Source
water solubility 4.39e+00 g/l ALOGPS
logP 1.69 ALOGPS
logP 1.62 ChemAxon
logS -1.8 ALOGPS
pKa (strongest acidic) 10.11 ChemAxon
pKa (strongest basic) 8.59 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 49.77 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 78.26 ChemAxon
polarizability 30.02 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Coda BA, Rudy AC, Archer SM, Wermeling DP: Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers. Anesth Analg. 2003 Jul;97(1):117-23, table of contents. Pubmed
  2. Vallner JJ, Stewart JT, Kotzan JA, Kirsten EB, Honigberg IL: Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects. J Clin Pharmacol. 1981 Apr;21(4):152-6. Pubmed
External Links
Resource Link
KEGG Compound C07042 Link_out
PubChem Compound 5284570 Link_out
PubChem Substance 46508700 Link_out
ChemSpider 4447624 Link_out
ChEBI 5790 Link_out
ChEMBL 5790 Link_out
Therapeutic Targets Database DAP000472 Link_out
PharmGKB PA449918 Link_out
Drug Product Database 2249936 Link_out
RxList http://www.rxlist.com/cgi/generic/hydromorphone.htm Link_out
Drugs.com http://www.drugs.com/cdi/hydromorphone.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dil1137.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Hydromorphone Link_out
ATC Codes
  • N02AA03
AHFS Codes
  • 28:08.08
PDB Entries Not Available
FDA label show (78.9 KB)
MSDS show (48.3 KB)
Interactions
Drug Interactions
Drug Interaction
Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Eltrombopag Increases levels of Hydromorphone via metabolism decrease. UDP-glucuronosyltransferase inhibition with unclear significance.
Triprolidine The CNS depressants, Triprolidine and Hydromorphone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food Interactions
  • Take without regard to meals. Avoid alcohol.
Targets

1. Mu-type opioid receptor

Pharmacological action: yes
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin

Organism class: human
UniProt ID: P35372 Link_out
Gene: OPRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Quigley C: Hydromorphone for acute and chronic pain. Cochrane Database Syst Rev. 2002;(1):CD003447. Pubmed
  2. Inturrisi CE: Clinical pharmacology of opioids for pain. Clin J Pain. 2002 Jul-Aug;18(4 Suppl):S3-13. Pubmed
  3. Sarhill N, Walsh D, Nelson KA: Hydromorphone: pharmacology and clinical applications in cancer patients. Support Care Cancer. 2001 Mar;9(2):84-96. Pubmed
  4. Kumar P, Sunkaraneni S, Sirohi S, Dighe SV, Walker EA, Yoburn BC: Hydromorphone efficacy and treatment protocol impact on tolerance and mu-opioid receptor regulation. Eur J Pharmacol. 2008 Nov 12;597(1-3):39-45. Epub 2008 Aug 30. Pubmed

2. Delta-type opioid receptor

Pharmacological action: yes
Actions: partial agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins

Organism class: human
UniProt ID: P41143 Link_out
Gene: OPRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Fang X, Larson DL, Portoghese PS: 7-spirobenzocyclohexyl derivatives of naltrexone, oxymorphone, and hydromorphone as selective opioid receptor ligands. J Med Chem. 1997 Sep 12;40(19):3064-70. Pubmed
  2. Hennies HH, Friderichs E, Schneider J: Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. Arzneimittelforschung. 1988 Jul;38(7):877-80. Pubmed
  3. Jiang Q, Sebastian A, Archer S, Bidlack JM: 5 beta-Methyl-14 beta-(p-nitrocinnamoylamino)-7,8-dihydromorphinone and its corresponding N-cyclopropylmethyl analog, N-cyclopropylmethylnor-5 beta-methyl-14 beta-(p-nitrocinnamoylamino)- 7,8-dihydromorphinone: mu-selective irreversible opioid antagonists. J Pharmacol Exp Ther. 1994 Mar;268(3):1107-13. Pubmed
  4. Guay DR: Use of oral oxymorphone in the elderly. Consult Pharm. 2007 May;22(5):417-30. Pubmed
  5. Hartvig P, Neil A, Terenius L, Antoni G, Rimland A, Ulin J, Langstrom B: Brain and plasma kinetics of the opioid 11C-hydromorphone in two macaque species. Pharmacol Toxicol. 1989 Sep;65(3):214-6. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Kappa-type opioid receptor

Pharmacological action: yes
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions

Organism class: human
UniProt ID: P41145 Link_out
Gene: OPRK1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Gharagozlou P, Hashemi E, DeLorey TM, Clark JD, Lameh J: Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2D6

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Prostaglandin G/H synthase 1

Actions: substrate

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

5. UDP-glucuronosyltransferase 1-9

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols

UniProt ID: O60656 Link_out
Gene: UGT1A9 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19