Hydrocodone compounds

Other examples of analgesics or their metabolites that have been found in the environment include 4-aminoantiyrine, aminophenazone, codeine, fenoprofen, hydrocodone, indometacine, ketoprofen, mefenamic acid, naproxen, propyphenazone diclofenac, ibuprofen, phenazone, gentisic acid and N-methylphenacetin. Many studies have identified these compounds in various locations around the world and in different water resources (e.g., Heberer et al. 1997, 2001a, 2001b Ternes 2001 Stumpf et al. 1999 Ahrer et al. 2001 Sedlak and Pinkston 2001 Holm et al. 1995 Ahel and Jelicic 2001 Sacher et al. 2001). 

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). 

Hydrocodone Hydrocodone, 4,5-epoxy-3-methoxy-Af-methyl-6-oxomorphinane (3.1.27), is a compound that is chemically related to morphine and codeine. Hydrocodone is synthesized by the isomerization of codeine (3.1.20) using a palladium or platinum catalyst [18]. This drug has also been suggested to be synthesized by the hydration of codeinone [19] and by oxidation of dihydrocodeine [20]. 

One of the more benign ancillary activities of morphine lies in its activity in suppressing the cough reflex. Catalytic reduction of codeine (1-2) leads to the dihydro derivative (4-1). Oppenauer oxidation of the hydroxyl group leads to hydrocodone (4-2) [3], a compound used extensively in cough remedies it is of note, however, that this drug retains considerable opioid activity. 

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). 

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). 

Nitromorphine is given by direct nitric acid nitration of morphine(163) however, with nitric oxide, 2-nitromorphine results. These compounds may be elaborated further to amino derivatives and by diazomethane treatment to the corresponding codeines. Codeine with concentrated H2S04 at ambient temperature afforded the zwitterion 68, which in nitric acid gave 1 -nitrocodeine. A similar conversion was achieved with ethylcodeine and hydrocodone.<164)... 

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... 

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... 

The opium alkaloid thebaine, although therapeutically useless (causes seizures and has little analgetic action), is important as the chemical starting point for the commercial synthesis of methyldihydromorphinone (Metopon), hydrocodone and hydromorphone, oxy-morphone, and the very interesting oripavine compounds (see later). Since these drugs are modifications of a natural alkaloid, they may be referred to as semisynthetic opiates. 

Morphine and related drugs possessing potent narcotic analgesic properties, are used in clinical practice. A few examples belonging to this class of compounds are morphine sulphate diamorphine hydrochloride codeine dihydrocodeine phosphate hydromorphone hydrochloride hydrocodone tartrate oxymorphone hydrochloride. 

Abstract. Using the PCILO method and the supermolecule approach, the hydration of the acid and base forms of the closely related pairs of compounds, oxymorphone and hydromorphone, and oxycodone and hydrocodone, have been studied. The presence of the axial Ci4—OH group in the oxy compounds causes a substantial increase in total hydration energy and an increase in proton affinity. These two effects should combine to cause a lowering of both apparent and intrinsic partition coefficients as well as provide an explanation of the observed increase in pKa of the oxy compounds. 

Hydrocodone bitartrate is absolutely contraindicated in patients with known hypersensitivity reactions to hydrocodone. Commercial preparations may also contain sulfite compounds that can produce allergic reactions, including bronchospasm and anaphylaxis, in certain susceptible individuals, particularly asthmatic patients. In addition, the dye tartrazine is present in one preparation of hydrocodone bitartrate, combined with chlorpheniramine maleate and phenylephrine hydrochloride, that is used as an antitussive and expectorant agent (Vanex). Also known as FD C yellow No. 5, tartrazine can cause asthmatic and other allergic reactions in some susceptible patients, especially those with aspirin sensitivities. 

The class of narcotic drugs encompasses the opium-derived drugs of morphine, heroin, and codeine (Figure 16.1) as well as other narcotics, such as meperidine, hydromorphone, hydrocodone, and the fentanyl compounds. Because these are highly polar compounds and often require high temperatures for elution, GC is difficult and often demands derivatization. Morphine, for example, because of its amphoteric nature, is not only difficult to extract but must be derivatized to obtain good quantitative data. 

Opioids can be classified according to stractural similarity with morphine in semisynthetic and synthetic derivatives. Structurally similar, semisynthetic morphinelike derivatives as well as stracturally distinct opioids have been synthesized to search for compounds able to improve analgesic effects that minimize side effects. Semisynthetic derivatives include morphine-related agonists (hydromorphone, hydrocodone, oxycodone, oxymorphone, and codeine), and moiphine-related partial agonist and antagonists (buprenorphine, naloxone, and naltrexone). Synthetic derivatives include phenylpiperidines (meperidine and loperamide), diphenylpropylamines (methadone and propoxyphene), and piperidines (fentaityl, alfentanyl, sufentanil, and remifen-tanil) (Dumas and Pollack, 2008). 

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