General
Preferred name
HYDROMORPHONE
Synonyms
HYDROMORPHONE HYDROCHLORIDE ()
HYDROMORPHONE SULFATE ()
N02AA03 ()
NSC-19046 ()
Dilaudid-Hp ()
Dimorphone ()
Jurnista ()
IDS-NH-004 ()
Hydromorphon ()
Novolaudon ()
Dilaudid ()
Palladone ()
Palladone-SR ()
Exalgo ()
Hydromorphone hydrochloride cii ()
Hydromorphone HCl ()
Dihydromorphinone hydrochloride ()
NSC-117862 ()
Hydromorphone (hydrochloride) ()
P&D ID
PD010097
CAS
18145-12-5
466-99-9
71-68-1
Tags
drug candidate
natural product
drug
available
Approved by
FDA
First approval
1984
Drug Status
illicit
approved
withdrawn
Drug indication
Analgesic (narcotic)
Chronic pain
Pain
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
In clinical trials, hydromorphone has been shown to be suitable for pain relief in patients that do not tolerate the side effects of [morphine] or that suffer from renal failure or asthma. It has been shown to be 5-7 times more potent than morphine with a shorter duration of analgesia.[A176471] Some of the observed effects of the consumption of hydromorphone for acute pain are complete and longlasting pain relief when compared to other pain relief agents such as [meperidine], [morphine], [diamorphine], [bupivacaine], [indomethacin], and [fentanyl]. On the same trials, hydromorphone was shown to produce respiratory depression, lower cognitive function, miosis, mydriasis, constipation, hypotension, and vertigo but to present a reduced incidence of pruritus (which indicates a lower release of histamine) and nausea.[A176507] The respiratory depression is known to be caused by the effect on the brain stem respiratory centers as well as to a reduction in the responsiveness of this brain stems to increase carbon dioxide tension.[L5798]
HALF-LIFE
The half-life of hydromorphone immediate-release is of 2-3 hour while the extended release can range from 8-15 hours.[A176468]
MOA
Hydromorphone is an opioid agonist that can bind to different types of opioid receptors. Its analgesic effect is suggested to be related to the effect on the mu-opioid receptors. It has been reported to also have a minor affinity for the delta and kappa receptor.[A176495, A176504] On the other hand, it is known to act at the level of the medulla which allows it to depress the respiratory drive and suppress cough.[A176468] The onset of action of the immediate release form of hydromorphone is achieved in 15-20 minutes and having a lasting effect for 3-4 hours while the extended-release form onset of action is of 6 hours lasting for about 13 hours.[A176468]
INDICATION
Hydromorphone is indicated for the management of moderate to severe acute pain and severe chronic pain. Due to its addictive potential and overdose risk, hydromorphone is only prescribed when other first-line treatments have failed.[A176468] The WHO has proposed a three-step ladder for the management of pain in which it is suggested to start with a non-opioid medication followed by addition of weak opioids to the non-opioid treatment for moderate pain and finishing in the use of strong opioids such as hydromorphone along with the existing regimen for cases of severe pain.[A176471] Off-label, hydromorphone can be administered for the suppression of refractory cough.[A176468]
ROE
The main elimination route of hydromorphone is through the urine in the form of the main metabolite hydromorphone-3-glucuronide. The elimination of the parent compound represents 7% of the urine elimination and 1% of the fecal elimination.[A176468]
TOXICITY
The reported LD50 of hydromorphone in the mouse was of 104 mg/kg when given intravenously and 84 mg/kg when given orally.[F4181] The reports of overdose with hydromorphone are characterized by respiratory depression, somnolence, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, myosis, mydriasis, bradycardia, hypotension, apnea, circulatory collapse, cardiac arrest, and even death.[FDA label] The management of an overdose might require assisted ventilation, supportive measures, as well as cardiac massage and defibrillation. It can be recommended the use of [naloxone] solely in the cases of respiratory depression. The use of opioid antagonist should be restricted to patients that present respiratory depression as they can produce acute abstinence symptoms.[FDA label] Hydromorphone was not shown to be mutagenic nor clastogenic and long-term studies of carcinogenicity studies have not been performed. On the other hand, reduced implantation sites and viable fetuses were noted at a 2X normal concentration.[FDA label]
ABSORPTION
The immediate release version of hydromorphone reaches its peak concentration after 30-60 minutes while the extended-release version reaches the peak concentration after 9 hours.[A176468] When administered orally, hydromorphone is absorbed mainly in the upper small intestine with a bioavailability of 60% due to intensive first-pass metabolism. In the controlled-release version of hydromorphone, the absorption follows a biphasic pharmacokinetic profile. However, even though there are clear distinctions in the absorption pathway of hydromorphone, the AUC of both versions is reported to be of 34 ng.h/ml which indicates an equivalence.[A176471] The parenteral administration of hydromorphone, which is the most common pathway, presents an almost immediate absorption as observed by the presence of peak plasma concentration almost immediately. This peak plasma concentration declines rapidly due to fast redistribution into liver, spleen, kidney and skeletal muscle. In the parenteral route, the pharmacokinetic profile is log-linear and dose-dependent and to present a higher bioavailability of 78%.[A176471] Other administration routes such as rectal, nasal, intraspinal and transdermal present lower bioavailability and changes in their pharmacokinetic profile.[A176471]
PHARMACODYNAMICS
In clinical trials, hydromorphone has been shown to be suitable for pain relief in patients that do not tolerate the side effects of [morphine] or that suffer from renal failure or asthma. It has been shown to be 5-7 times more potent than morphine with a shorter duration of analgesia.[A176471]; ; Some of the observed effects of the consumption of hydromorphone for acute pain are complete and longlasting pain relief when compared to other pain relief agents such as [meperidine], [morphine], [diamorphine], [bupivacaine], [indomethacin], and [fentanyl]. On the same trials, hydromorphone was shown to produce respiratory depression, lower cognitive function, miosis, mydriasis, constipation, hypotension, and vertigo but to present a reduced incidence of pruritus (which indicates a lower release of histamine) and nausea.[A176507]; ; The respiratory depression is known to be caused by the effect on the brain stem respiratory centers as well as to a reduction in the responsiveness of this brain stems to increase carbon dioxide tension.[L5798]
MOA
Hydromorphone is an opioid agonist that can bind to different types of opioid receptors. Its analgesic effect is suggested to be related to the effect on the mu-opioid receptors. It has been reported to also have a minor affinity for the delta and kappa receptor.[A176495, A176504] On the other hand, it is known to act at the level of the medulla which allows it to depress the respiratory drive and suppress cough.[A176468]; ; The onset of action of the immediate release form of hydromorphone is achieved in 15-20 minutes and having a lasting effect for 3-4 hours while the extended-release form onset of action is of 6 hours lasting for about 13 hours.[A176468]
INDICATION
Hydromorphone is indicated for the management of moderate to severe acute pain and severe chronic pain. Due to its addictive potential and overdose risk, hydromorphone is only prescribed when other first-line treatments have failed.[A176468]; ; The WHO has proposed a three-step ladder for the management of pain in which it is suggested to start with a non-opioid medication followed by addition of weak opioids to the non-opioid treatment for moderate pain and finishing in the use of strong opioids such as hydromorphone along with the existing regimen for cases of severe pain.[A176471]; ; Off-label, hydromorphone can be administered for the suppression of refractory cough.[A176468]
TOXICITY
The reported LD50 of hydromorphone in the mouse was of 104 mg/kg when given intravenously and 84 mg/kg when given orally.[F4181] The reports of overdose with hydromorphone are characterized by respiratory depression, somnolence, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, myosis, mydriasis, bradycardia, hypotension, apnea, circulatory collapse, cardiac arrest, and even death.[FDA label]; ; The management of an overdose might require assisted ventilation, supportive measures, as well as cardiac massage and defibrillation. It can be recommended the use of [naloxone] solely in the cases of respiratory depression. The use of opioid antagonist should be restricted to patients that present respiratory depression as they can produce acute abstinence symptoms.[FDA label]; ; Hydromorphone was not shown to be mutagenic nor clastogenic and long-term studies of carcinogenicity studies have not been performed. On the other hand, reduced implantation sites and viable fetuses were noted at a 2X normal concentration.[FDA label]
METABOLISM
The metabolism of hydromorphone is mainly hepatic and it is represented by the generation of hydromorphone-3-glucuronide through glucuronidation reactions.[A176468] This primary metabolic pathway is done by the activity of the UDP-glucuronosyltransferase-2B7.[A176501] The first-pass hepatic metabolism is so large that it represents 62% of the initial administered dose.[A176495]; ; On the other hand, hydromorphone is also characterized by the presence of minor metabolic pathways such as the CYP3A4- and CYP2C9-driven generation of norhydromorphone.[A39478]
ABSORPTION
The immediate release version of hydromorphone reaches its peak concentration after 30-60 minutes while the extended-release version reaches the peak concentration after 9 hours.[A176468] When administered orally, hydromorphone is absorbed mainly in the upper small intestine with a bioavailability of 60% due to intensive first-pass metabolism. In the controlled-release version of hydromorphone, the absorption follows a biphasic pharmacokinetic profile. However, even though there are clear distinctions in the absorption pathway of hydromorphone, the AUC of both versions is reported to be of 34 ng.h/ml which indicates an equivalence.[A176471]; ; The parenteral administration of hydromorphone, which is the most common pathway, presents an almost immediate absorption as observed by the presence of peak plasma concentration almost immediately. This peak plasma concentration declines rapidly due to fast redistribution into liver, spleen, kidney and skeletal muscle. In the parenteral route, the pharmacokinetic profile is log-linear and dose-dependent and to present a higher bioavailability of 78%.[A176471]; ; Other administration routes such as rectal, nasal, intraspinal and transdermal present lower bioavailability and changes in their pharmacokinetic profile.[A176471]
DESCRIPTION
Hydromorphone is a semi-synthetic opioid receptor agonist.
(GtoPdb)
METABOLISM
The metabolism of hydromorphone is mainly hepatic and it is represented by the generation of hydromorphone-3-glucuronide through glucuronidation reactions.[A176468] This primary metabolic pathway is done by the activity of the UDP-glucuronosyltransferase-2B7.[A176501] The first-pass hepatic metabolism is so large that it represents 62% of the initial administered dose.[A176495] On the other hand, hydromorphone is also characterized by the presence of minor metabolic pathways such as the CYP3A4- and CYP2C9-driven generation of norhydromorphone.[A39478]
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
18
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
ReFrame library
Withdrawn 2.0
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
55
Molecular Weight
285.14
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
1
Rotatable Bonds
0
Ring Count
5
Aromatic Ring Count
1
cLogP
1.63
TPSA
49.77
Fraction CSP3
0.59
Chiral centers
4.0
Largest ring
6.0
QED
0.79
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
ATC
N02AA03
Toxicity type
multiple
Therapeutic Class
Analgesics
Source data
