Hydromorphone

Sold as Dilaudid in the U.S., hydromorphone is a semisynthetic, differing from morphine only by presence of a 6-keto group, and the hydrogenation of the double bond at the 7-8 position of the molecule.57 Like morphine, it acts primarily at the mu opioid receptors, and to a lesser degree at delta receptors. 

As a hydrogenated ketone of morphine, it shares common pharmacologic properties with other opioid analgesics.25 These include the expected changes in the CNS, including increased cerebrospinal fluid pressure, increased biliary pressure, and increased parasympathetic activity. It can also 

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 Palladone , a controlled-release preparation consisting of hydromorphone HC1 pellets, was withdrawn from the U.S. market in 2005.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. 

Association of intravenous morphine use and outcomes in acute coronary syndromes results from the CRUSADE Quality Improvement Initiative, 

Hoskin, P.J. and G.W. Hanks, Morphine pharmacokinetics and clinical practice, Br. J. Cancer 62(5), 

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ANALGESICS,ANTIPYRETICS,AND ANTIINFLAA 4ATORYAGENTS] (Vol2) Hydromorphone [466-99-9]... 

Hydromorphone [466-99-9] (31) and hydrocodone [125-29-1] (32) are isomers of morphine and codeine, respectively. Hydromorphone can be prepared by catalytic rearrangement of morphine (49) or by oxidation of the aliphatic hydroxyl group of dihydromorphine (50). Hydrocodone can be similarly prepared. As an antitussive, hydromorphone is several times more active than morphine and hydrocodone is slightly more active than codeine. Hydromorphone has a much higher addiction potential than hydrocodone. 

When morphine is subjected to a similar reduction-oxidation sequence (1- 10), there is obtained hydromorphone (10). ... 

Alfentanil, codein, dihydromorphine, etor-phine, fentanyl, heroin, hydromorphone, levo-methadone, morphine, oxycodone, pethidine, piritramide, remifentanil, sufentanil, tilidine, tramadol Buprenorphine, pentazocine Naloxone, naltrexone... 

Morphine, when extracted from raw opium and treated chemically, yields the semisynthetic narcotics hydromorphone, oxymorphone, oxycodone, and heroin. Heroin is an illegal narcotic in the United States and is not used in medicine. Synthetic narcotics are those man-made analgesics with properties and actions similar to the natural opioids. Examples of synthetic narcotic analgesics are methadone, levorphanol, remifen-tanil, and meperidine Additional narcotics are listed in the Summary Drug Table Narcotic Analgesics. 

C 7H,7N03 57-27-2) see Apomorphine Codeine Ethylmorphine Hydromorphone Nalorphine Pholcodine... 

Morphinone can be reduced by Pseudomonas putida MIO to hydromorphone using an enzyme of which one of the subunits contains FMN (French and Bruce 1994). 

The oxidation of morphine by Pseudomonas putida MIO gave rise to a large number of transformation products including hydromorphone (dihy-dromorphinone), 14/3-hydroxymorphine, 14 6-hydroxymorphinone, and dihydromorphine. Similarly, in incubations with oxymorphone (14/3-hydroxy-... 

The inifial sfeps in fhe mefabolism of morphine and codeine by Pseudomonas putida MIO involve oxidafion of fhe C-6 hydroxy group and subsequenf reducfion of fhe 7,8-olefinic bond, forming hydromorphone (dihydromorphinone) and hydrocodone (dihydrocodeinone), respectively (Scheme 4) [52], These products have important industrial appUcations hydromorphone is an analgesic some seven times more potent than morphine [53],... 

Schemes Transformation steps involved in the oxidation of morphine by incubation with Pseudomonas putida MIO, which gave hydromorphone (dihydromorphinone), 14 d-hydroxymorphine, 14 8-hydroxymorphinone, and dihydromorphine [52]...

Severe 7-1 0/1 0 Switch to a high-potency opioid regular scheduled dosing Morphine 10 mg every 4 hours Hydromorphone 4 mg every 4 hours ... 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

Epidural analgesia is frequently used for lower extremity procedures and pain (e.g., knee surgery, labor pain, and some abdominal procedures). Intermittent bolus or continuous infusion of preservative-free opioids (morphine, hydromorphone, or fentanyl) and local anesthetics (bupivacaine) may be used for epidural analgesia. Opiates given by this route may cause pruritus that is relieved by naloxone. Adverse effects including respiratory depression, hypotension, and urinary retention may occur. When epidural routes are used in narcotic-dependent patients, systemic analgesics must also be used to prevent withdrawal since the opioid is not absorbed and remains in the epidural space. Doses of opioids used in epidural analgesia are 10 times less than intravenous doses, and intrathecal doses are 10 times less than epidural doses (i.e., 10 mg of IV morphine is equivalent to 1 mg epidural morphine and 0.1 mg of intrathecally administered morphine).45... 

Codeine, hydrocodone, morphine, methadone, and oxycodone are substrates of the cytochrome P-450 isoenzyme CYP2D6.47 Inhibition of CYP2D6 results in decreased analgesia of codeine and hydrocodone due to decreased conversion to the active metabolites (e.g., morphine and hydromorphone, respectively) and increased effects of morphine, methadone, and oxycodone. Methadone is also a substrate of CYP3A4, and its metabolism is increased by phenytoin and decreased by cimetidine. CNS depressants may potentiate the sedative effects of opiates. 

Few studies have explored the efficacy of opioids specifically for OA. The APS recommends against the use of codeine and propoxyphene for OA because of the high incidence of adverse effects and limited analgesic effectiveness. Oxycodone is the most extensively studied of the agents recommended for OA. However, other narcotic analgesics such as morphine, hydromorphone, methadone, and transdermal fentanyl are also effective. 

Severe pain should be treated with an opioid such as morphine, hydromorphone, methadone, or fentanyl. Moderate pain can be treated effectively in most cases with a weak opioid such as codeine or hydrocodone, usually in combination with acetaminophen. Meperidine should be avoided owing to its relatively short analgesic effect and its toxic metabolite, normeperidine. Normeperidine may accumulate with repeated dosing and can lead to central nervous system side effects including seizures. 

Morphine 0.1 -0.1 5 mg/kg per dose every 3-4 hours for children 5-10 mg/dose for adults Continuous infusion 0.04-0.05 mg/kg per hour titrate to effect Hydromorphone 0.015 mg/kg per dose every 3 1 hours for children 1.5-2 mg/dose for adults Continuous infusion 0.004 mg/kg per hour titrate to effect Intravenous anti-inflammatory agents ... 

Analgesics are given to reduce abdominal pain. In the past, parenteral meperidine (50 to 100 mg) every 3 to 4 hours was usually used because it causes less spasm of the sphincter of Oddi than other opioids. Meperidine is used less frequently today because it is not as effective as other opioids and is contraindicated in renal failure. Parenteral morphine is sometimes used, but it is thought to cause spasm of the sphincter of Oddi, increases in serum amylase and, rarely, pancreatitis. Hydromorphone may also be... 

Severe pain should be treated aggressively with an opioid, such as morphine, hydromorphone, fentanyl, and methadone. Moderate pain should... 

Opioids and derivatives (e.g., meperidine, butorphanol, oxycodone, hydromorphone) provide effective relief of intractable migraine but should be reserved for patients with moderate to severe infrequent headaches in whom conventional therapies are contraindicated or as rescue medication after failure to respond to conventional therapies. Opioid therapy should be closely supervised. 

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