Dimorphone
Dimorphone Uses, Dosage, Side Effects, Food Interaction and all others data.
Dimorphone is a pure opioid, a semi-synthetic hydrogenated ketone derivative of morphine that has been available clinically since 1920. Structurally, hydromorphone derived from morphine in the modification of the hydroxyl group in the carbon 6 to a carbonyl and the absence of a double bond between the carbon 7 and 8. Due to these modifications, it presents a very high potency and comparable side effect profile to the parent compound. Even though hydromorphone does not present a 6-hydroxyl group, it is categorized under the family of phenanthrenes and it is considered a chemical under the schedule II (medical purposes with high addiction potential).
The first reported approved product containing hydromorphone in the form of hydromorphone hydrochloride was developed by Fresenius Kabi USA and FDA approved in 1984.
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.
| Trade Name | Dimorphone |
| Availability | Prescription only |
| Generic | Hydromorphone |
| Hydromorphone Other Names | 7,8-Dihydromorphinone, Dihydromorfinon, Dihydromorphinone, Dimorphone, Hidromorfona, Hydromorfona, Hydromorphone, Hydromorphonum, Idromorfone |
| Related Drugs | Buprenex, Subutex, aspirin, acetaminophen, tramadol, duloxetine, naproxen, Tylenol, oxycodone, Cymbalta |
| Type | |
| Formula | C17H19NO3 |
| Weight | Average: 285.3377 Monoisotopic: 285.136493479 |
| Protein binding | The protein-bound form of hydromorphone corresponds to about 8-19% of the administered dose. |
| Groups | Approved, Illicit |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Dimorphone is an opioid analgesic used to treat moderate to severe pain when the use of an opioid is indicated.
Dimorphone 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.
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.
Off-label, hydromorphone can be administered for the suppression of refractory cough.
Dimorphone is also used to associated treatment for these conditions: Neuropathic Pain, Pain, Refractory Chronic Cough
How Dimorphone works
Dimorphone 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. 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.
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.
Toxicity
The reported LD50 of hydromorphone in the mouse was of 104 mg/kg when given intravenously and 84 mg/kg when given orally. 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.
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.
Dimorphone 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.
Food Interaction
- Avoid alcohol.
- Take with or without food. Food does not significantly affect absorption.
[Major] GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydromorphone.
Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills.
In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.
GENERALLY AVOID: Consumption of alcohol while taking sustained-release formulations of hydromorphone may cause rapid release of the drug, resulting in high systemic levels of hydromorphone that may be potentially lethal even in opioid-tolerant patients.
Alcohol appears to disrupt the extended release mechanism, causing 'dose-dumping' into the bloodstream.
In 48 healthy volunteers, coadministration of a 12 mg dose of sustained-release hydromorphone with 240 mL of 40% (80 proof) alcohol resulted in a mean peak hydromorphone concentration (Cmax) approximately six times greater than when taken with water.
One subject had a 16-fold increase in hydromorphone Cmax with 40% alcohol compared to water.
In some subjects, coadministration with 8 ounces of 4% alcohol (equivalent to 2<3 of a typical serving of beer) resulted in almost twice the hydromorphone Cmax than when coadministered with water.
The effect of alcohol was more pronounced in a fasted state.
MANAGEMENT: Patients taking sustained-release formulations of hydromorphone should not consume alcohol or use medications that contain alcohol on days of hydromorphone dosing.
In general, potent narcotics such as hydromorphone should not be combined with alcohol.
Dimorphone Drug Interaction
Major: fentanyl, fentanyl, pregabalin, pregabalin, morphine, morphine, alprazolam, alprazolamModerate: duloxetine, duloxetine, ondansetron, ondansetronUnknown: acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Dimorphone Disease Interaction
Major: impaired GI motility, infectious diarrhea, liver disease, prematurity, acute alcohol intoxication, drug dependence, gastrointestinal obstruction, hypotension, intracranial pressure, respiratory depressionModerate: adrenal insufficiency, biliary spasm, hypothyroidism, renal dysfunction, seizure disorders, urinary retention, arrhythmias
Volume of Distribution
The volume of distribution of hydromorphone is reported to be of 4 L/kg.
Elimination Route
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. 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.
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%.
Other administration routes such as rectal, nasal, intraspinal and transdermal present lower bioavailability and changes in their pharmacokinetic profile.
Half Life
The half-life of hydromorphone immediate-release is of 2-3 hour while the extended release can range from 8-15 hours.
Clearance
The mean plasma clearance of hydromorphone is reported to be of 105.7 ml/min. The systemic clearance is reported to be of 1.96 L/min.
Elimination Route
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.
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