Oxycodone compounds

Oxycodone compounds that are combined with aspirin, acetaminophen, or ibuprofen are limited in dose by the amount of the non-opioid component. These combination products provide enhanced analgesic effect with fewer opioid side effects, and possibly better compliance because the patient does not need two separate medications. Use of oxycodone alone may be advantageous in those patients who are at risk for toxicity from NSAIDs or acetaminophen. The maximum daily dose of acetaminophen is 4000 mg in a person with no liver impairment. 

Oxycodone compounds containing acetaminophen can be overprescribed and overused, increasing the risk of hepatotoxicity. The FDA has recommended removal of acetaminophen or a marked reduction in compounded dose. 

Oxycodone compounds containing aspirin increase risks of gastric irritation and bleeding. 

There are two types of pharmaceutically important derivatives (a) Compounds with a hydroxyl substituent at position 14, such as in oxycodone and the antagonists naloxone and naltrexone, and (b) Diels-Alder adducts such as etorphine and buprenorphine, where the latter compounds are all derived from another opium alkaloid, (—)-thebaine (12) (Scheme 5.10). Because thebaine is a rather scarce alkaloid, several syntheses have been investigated. Quite recently, Australian scientists have been able to modify P. somniferum in such a way that thebaine is now a main alkaloid, so that it is becoming better available [28],... 

Agonists include natural alkaloids of opium (morphine, codeine, and a large blend of natural alkaloids, pantopon, and omnopon), their analogs (hydrocodon and hydromor-phone, oxycodone, and oxymorphone), derivatives of morphinane (levorphanol), and a number of synthetic compounds derivatives of phenylpiperidine (meperidine, promedol), 4-anilidopiperidines (fentanyl, sufentanyl, alfentanil), and derivatives of diphenylheptane (methadone, propoxyphene). 

The most widely used agonists in medical practice are the opium alkaloids morphine and codeine. However, semisynthetic derivatives (hydromorphone, oxymorphone, hydrycodon, oxycodone), whose use is even preferred in certain cases, and strong, purely synthetic compounds (methadone, meperidin, fentanyl, sufentanyl, and others) have found wide use. 

The double bond is then hydrogenated, transforming the compound into oxycodone... 

The most known narcotics are the opium alkaloids such as morphine, codeine, thebaine, papaverine, noscapine and their derivatives and modified compounds such as nalmorphine, apomorphine, apomopholcodine, dihydrocodeine, hydro-morphone and heroine, also known as diamorphine. Synthetic narcotics share the structural skeleton of morphine and include dextromethorphan, pentazocine, phenazocine meperidine (pethidine), phentanyl, anfentaitil, remifentalin, methadone, dextropropoxyphene, levoproxyphene, dipipanone, dextromoramide, meptazinol and tramadol. Thebaine derivatives are also modified narcotics and include oxycodone, oxymorphone, etorphine, buprenorphine, nalbuphine, naloxone or naltrexone. Narcotics can be semi-synthesized or totally synthesized from the morphine and thebaine model. The compounds serve various purposes in clinical practise. 

Among the compounds that fall within this class are hydrocodone (e.g., Vicodin), oxycodone (e.g., OxyContin—an oral, controlled-release form of the drug), morphine, fentanyl, codeine, and related medications. Morphine and fentanyl are often used to alleviate severe pain, while codeine is used for milder pain. Other examples of opioids prescribed to relieve pain include propoxyphene (Darvon) hydromorphone (Dilaudid) and meperidine (Demerol), which is used less often because of its side effects. In addition to their effective pain-relieving properties, some of these medications can be used to relieve severe diarrhea (for example, Lomotil, also known as diphenoxylate) or severe coughs (codeine). 

After 10 years of intensive research, no significant dissociation of potent analgesia and dependence liability was accomplished. As an indirect result of the systematic program the identification of the 17-hydroxy-7,8-dihydro compounds oxycodone (patented in 1925 by E. Merck AG, Germany) and oxymorphone, derived from thebaine, are of particular note. 

Opioid receptor binding Oxycodone (Chen et al., 1991) is a p-selective opioid with a 10-fold higher receptor affinity than codeine. Both the parent compound and the high affinity metabolite oxymorphone mediate the opioid effects of the compound (Cleary et al., 1994). 

Side-effects Oxycodone has a morphine-like side-effect profile. Respiratory depression has been found in children. The compound has a relevant abuse and dependence potential and illicit use of the retarded preparations has been reported. 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

Codeine (Figure 31-1), oxycodone, dihydrocodeine, and hydrocodone are all somewhat less efficacious than morphine (they are partial agonists) or have adverse effects that limit the maximum tolerated dose when one attempts to achieve analgesia comparable to that of morphine. These compounds are rarely used alone but are combined in formulations containing aspirin or acetaminophen and other drugs. 

The prototypical opioid is morphine (A.137) (Figure A.39). Isolated in a crude form, called opium, morphine has been recognized as a potent pain killer for thousands of years. Although effective, morphine has a low oral availability (F = 25%). Two common derivatives of morphine include hydrocodone (Vicodin, A.138) and oxycodone (A.139), both of which have oral availabilities of greater than 75%. Oxycodone is often sold in an oral continuous-release form under the trade name of OxyContin. Not all opioids are semisynthetic derivatives of morphine. Dextropropoxyphene (Darvon, A.140) and tramadol (Tramal, A.141) are fully synthetic opioids. Both compounds preserve the pharmacophore of morphine as described in the morphine rule (see Chapter 11). Dextropropoxyphene and tramadol are depicted in Figure A.39 to highlight possible pharmacologically active conformations that resemble morphine. 

The gold standard of opiate pain relievers is morphine. It was one of the first compounds extracted, isolated, and purified from the opium poppy, and it continues to be one of the most widely used pain relievers today. Morphine and other opiate drugs such as heroin, codeine, oxycodone, and hydrocodone have very similar chemical structures (Figure 3.2). However, other opiates such as fentanyl and meperidine (Demerol) have a slightly different structure (Figure 3.3). 

Thalidomide and metabolites Methylamphetamine and impurities Related opiate compounds (morphine, hydromorphone, nalorphine, codeine, oxycodone, diacetylmorphine) Theophylline, caffeine, sulfanilamide... 

Narcotic Analgesics Anilendine, codeine, dextromoramide, diamorphine, dihydrocodeme, dipipanone, ethylmorphme, hydrocodone, hydromorphone, levorphanol, methadone, morphine, oxycodone, oxymorphone, pentazocine, pethidme, phenazocme, pimmodme, thebacon, tnmeperidine, and related compounds... 

Morphine, heroin, and oxycodone are three addicting analgesic narcotics. How could IR spectroscopy be used to distinguish these three compounds from each other ... 

Among opioids, morphinans (Fig. 1) play an important role as therapeutically valuable drugs. Representative examples of the morphinan class of compounds (Fig. 2) are p-opioid analgesic agents for the treatment of moderate-to-severe pain such as naturally occurring alkaloids (e.g. morphine, codeine), semisynthetic derivatives (e.g. oxycodone, oxymorphone, buprenorphine), and synthetic analogs (e.g. levorphanol, butorphanol) [19-21], Codeine is also an effective antitussive drug. The oxymorphone derivatives naloxone [22] and naltrexone [23] represent... 

Canada has the dubious distinction of having the world s largest per capita consumption of precursor opiate-containing compounds (e g., codeine, oxycodone, and hydrocodone) (Korcok 1979). A drug utilization review of opiate use in Canada from 1978 to 1989 shows continued increase in the use of prescribed codeine combination products. The defined daily dose (DDD)/1000 inhabitants/day for prescribed codeine-acetaminophen products has increased from 3.3 DDD/1000 inhabitants/day in 1982 to 8.1 DDD/1000 inhabitants/day in 1989. Oxycodone-acetaminophen containing products have also been increasing from 0.04 DDD/1000 inhabitants/day in 1978 to 0.21... 

Many semisynthetic derivatives are made by relatively simple modifications of morphine or thebaine. Codeine is methyhnorphine, the methyl substitution being on the phenolic hydroxyl group. Thebaine differs from morphine only in that both hydroxyl groups are methylated and that the ring has two double bonds (A , A ). Thebaine has little analgesic action but is a precursor of several important 14-OH compounds, such as oxycodone and naloxone. Certain derivatives of thebaine are more than 1000 times as potent as morphine (e.g., etorphine). Diacetylmorphine, or heroin, is made from morphine by acetylation at the 3 and 6 positions. Apomorphine, which also can be prepared from morphine, is a potent emetic and dopaminergic agonist. 

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