Hydromorphone Alcohol

Depending on the country where the drug is manufactured, a number of different time-release preparations are available. Palladone , a controlled-release preparation consisting of hydromorphone HC1 pellets, was withdrawn from the U.S. market in 2005. When taken with alcohol the pellets rapidly released their contents leading to dangerously elevated peak plasma concentrations.60 Interaction with ethanol and dose dumping is not the only concern. Any CNS depressant may enhance the depressant effects of hydromorphone. 

Hydromorphone is available through injections, tablets, oral solution, and suppositories. The usual route of administration is by way of swallowing tablets. For patients who have difficulty swallowing tablets, a flavored oral solution is available. This liquid form of the drug can be poured into a medicine dropper for measurement by the patient or a nurse. The liquid can also be added to soft foods to make it easier for the patient to ingest. Some of these liquid formulations may contain alcohol. 

Hydromorphone should never be combined with other drugs that depress the central nervous system. Such drugs include sedatives, tranquilizers, alcohol, and anesthetics. In addition, other types of drugs, such as antidepressants, antihistamines, anticonvulsants, and... 

Hydromorphone Hydrochloride, U5P. Hydromor-phone hydrochloride, dibydromurphinonc hydrochloride (Dilaudid). (K-curs as a light-sensitive, while cry.sialline powder that is freely soluble in water (l .1).. sparingly soluble in alcohol, and practically insoluble in ether. It is used in about one-fifth die dose of morphine for any of the indications of morphine. It is available in tablet, liquid, parenteral, and suppository dosage forms. The dose is I to 8 mg. 

C-3 phenolic hydroxyl C-6 allylic alcohol and C = C between C-7 and C-8 as depicted in the following stmcture(s). It is, however, pertinent to mention here that several synthesized structural analogues even before 1930 are still constituted as vital and potential drugs in the therapeutic armamentarium, for instance codeine ethyl morphine (Dionin ) diacetyl morphine (heroin) hydromorphone... 

Various studies regarding the biotransformation of xenobiotic ketones have established that ketone reduction is an important metabolic pathway in mammalian tissue. Because carbonyl compounds are lipophilic and may be retained in tissues, their reduction to the hydrophilic alcohols and subsequent conjugation are critical to their elimination. Although ketone reductases may be closely related to the alcohol dehydrogenases, they have distinctly different properties and use NADPH as the cofactor. The metabolism of xenobiotic ketones to free alcohols or conjugated alcohols has been demonstrated for aromatic, aliphatic, alicyclic, and unsaturated ketones (e.g., naltrexone, naloxone, hydromorphone, and daunorubicin). The carbonyl reductases are distinguished by the stereospecificity of their alcohol metabolites. 

In general the opioid analgesics can enhance the CNS depressant effects of alcohol, which has been fatal in some cases this appears to be a particular problem with dextropropoxyphene. Alcohol has been associated with rapid release of hydromorphone and morphine from extended-release preparations, which could result in potentially fatal doses. Acute administration of alcohol and methadone appears to increase the blood levels of methadone. The bioavailability of dextropropoxyphene is increased by alcohol... 

A young man died from the combined cardiovascular and respiratory depressant effects of hydromorphone and alcohol. He fell asleep, the serious nature of which was not recognised by those around him. Post-mortem analysis revealed alcohol and hydromorphone concentrations of 90 mg% and 100 nanograms/mL, respectively, neither of which is particularly excessive. A study in 9 healthy subjects found that pre-treatment with hydromorphone 1 or 2 mg did not significantly affect the subject-rated effects of alcohol 0.5 or 1 g/kg. However, hydromorphone enWiced the sedative scores of alcohol on the adjective rating scale." See also, controlled-release opioids, below. 

Pharmacokinetic data in healthy subjects has shown that consuming alcohol with a particular 24-hour extended-release formulation of hydromorphone (Palladone XL Capsules Purdue Pharma, USA) could lead to rapid release (dose dumping) and absorption of a potentially fatal dose of hydromorphone. Although no reports of serious problems had been re-... 

Rush CR. Pretreatment witii hydromorphone, a ja-opioid agonist, does not alter the acute behavioral and physiological effects of ethanol in humans. Alcohol Clin Exp Res (2001) 25, 9-17. 

Hydromorphone (launched by Knoll in 1926 under the brand name Dilaudid with intended connotation to laudanum ) is more active than morphine, and is indicated for medium to severe pain. Hydromorphone can cause severe dependence. The starting material for its synthesis is morphine, which is first hydrogenated, and its alcohol ftmction is then submitted to an Oppenauer oxidation with cyclohexanone. 

Hydromorphone is a potent semi-synthetic phenan-threne-derived centrally acting opiate agonist. Hydromorphone is very lipid-soluble, which allows for rapid central nervous system penetration. Hydromorphone is second only to morphine in its use as an analgesic in the acute post-operative setting. It was first researched and synthesized in 1924 in Germany, and marketed by Knoll Pharmaceuticals in 1926 under the brand name Dilaudid . Hydromorphone hydrochloride is a fine, white or essentially white, crystalline powder and is freely soluble in water and sparingly soluble in alcohol. 

Sathyan G, Sivakumar Thipphawong ]. Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence of alcohol. CurrMed Res Opin 2008 24(l) 297-305. 

Walsh SL, Nuzzo PA, Lofwall MR, Holtman Jr. JR. The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription opioid abusers. Drug Alcohol Depend 2008 98(3) 191-202. 

Next, exposure of 255 to trifluoroacetic acid resulted in rearomatization of the A ring of morphine and cleavage of the carbamate (256), which prepared the substrate for the intended hydroamination and elaboration of the D ring of the title compound. All attempts failed to achieve ring closure from 255, either via aminomercuration or addition of lithium amide, and the material was converted to the corresponding tosyl amide before the ethylamino bridge was established. The cyclization was accomplished by addition of lithium to 257 and delivered the desired product in excellent yield. Oxidation of the secondary alcohol with benzophenone and t-BuOK allowed the isolation of e t-hydromorphone (258) in 12 steps from p-bromoethylbenzene. 

---