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.[ Effects generally begin within half an hour and last for up to five hours.][ A 2016 Cochrane review (updated in 2021) found little difference in benefit between hydromorphone and other opioids for cancer pain.]
Common side effects include dizziness, Somnolence, nausea, itchiness, and constipation.[ Serious side effects may include Substance abuse, low blood pressure, , respiratory depression, and serotonin syndrome.][ Rapidly decreasing the dose may result in opioid withdrawal.][ Generally, use during pregnancy or breastfeeding is not recommended.][ Hydromorphone 2 mg IV is Equianalgesic to approximately 10 mg morphine IV.][
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Hydromorphone was patented in 1923.[ In 2022, it was the 233rd most commonly prescribed medication in the United States, with more than 1million prescriptions.]
Side effects
Adverse effects of hydromorphone are similar to those of other potent opioid such as morphine and heroin. The major hazards of hydromorphone include dose-related respiratory depression, urinary retention, bronchospasm, and sometimes, circulatory depression.
Simultaneous use of hydromorphone with other opioids, , tranquilizers, , and general anesthetics may significantly depress respiration, progressing to coma or death. Taking (e.g., diazepam) in conjunction with hydromorphone may increase side effects such as dizziness and difficulty concentrating.
A particular problem that may occur with hydromorphone is accidental administration in place of morphine due to a mix-up between the similar names, either at the time the prescription is written or when the drug is dispensed. This has led to several deaths and calls for hydromorphone to be distributed in distinctly different packaging from morphine to avoid confusion.
Massive 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 through a nasogastric tube. Opioid antagonists, such as naloxone, also may be administered concurrently with oxygen supplementation. Naloxone works by reversing the effects of hydromorphone, and only is administered in the presence of significant respiratory depression and circulatory depression.
Sugar cravings associated with hydromorphone use are the result of a glucose crash after transient hyperglycemia following injection, or a less profound lowering of blood sugar over a period of hours, in common with morphine, heroin, codeine, and other opioids.
Hormone imbalance
As with other opioids, hydromorphone (particularly during heavy chronic use) often causes temporary hypogonadism or hormone imbalance.
Neurotoxicity
In the setting of prolonged use, high dosage, and/or kidney dysfunction, hydromorphone has been associated with neuroexcitatory symptoms such as tremor, myoclonus, agitation, and cognitive dysfunction.
Withdrawal
Users of hydromorphone may experience painful symptoms if the drug is suspended.
In the clinical setting, excessive secretion of tears, yawning, and Mydriasis are helpful presentations in diagnosing opioid withdrawal.
Interactions
CNS depressants may enhance the depressant effects of hydromorphone, such as other , , , , , , , chloral hydrate, dimenhydrinate, and glutethimide. The depressant effect of hydromorphone also may be enhanced by monoamine oxidase inhibitors (MAO inhibitors), first-generation (e.g., brompheniramine, promethazine, diphenhydramine, chlorphenamine), , and alcohol. When combined therapy is contemplated, the dose of one or both agents should be reduced.
Pharmacology
+ Hydromorphone at opioid receptors |
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| 1:39:53 |
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Equianalgesic doses |
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| 200 mg |
| 20–30 mg |
| 7.5 mg |
| 1.5 mg |
| 30 mg |
| 10 mg |
| 20 mg |
| 10 mg |
| 10 mg |
| 1 mg |
Hydromorphone is a semi-synthetic μ-opioid agonist. As a hydrogenated ketone of morphine, it shares the pharmacologic properties typical of . 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 tract, and increased pinpoint constriction of the pupils.
Formulations
Hydromorphone is available in parenteral, rectal, subcutaneous, and oral formulations, and also can be administered via epidural or intrathecal injection.
Concentrated 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.[Dilaudid HP package insert Nov 2004] Ampoules of solution which have developed a precipitate should be discarded.[
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Battery-powered intrathecal drug delivery systems are implanted for chronic pain when other options are ruled out, such as surgery and traditional pharmacotherapy, provided that the patient is considered a suitable fit in terms of any contraindications, both physiological and psychological.
An extended-release (once-daily) version of hydromorphone is available in the United States.
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.
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.
The onset of action for hydromorphone administered intravenously is less than 5 minutes and within 30 minutes of oral administration (immediate release).
Metabolism
While other opioids in its class, such as codeine or oxycodone, are metabolized via CYP450 enzymes, hydromorphone is not.
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.[Merck Index 2003, "Morphine" and "Hydromorphone"]
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 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.[ PHA 4220 – Neurology Pharmacotherapeutics ]
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.
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.
History
Hydromorphone was patented in 1923.[ It was introduced to the mass market in 1926 under the brand name Dilaudid,]
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.
There has also been a once-daily prolonged release version of hydromorphone available in Australia under the brand name Jurnista as of May 2009.
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 in 1998 to 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 .
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.
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.
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