Codeine preparation

Roslyn Monroe is taking Tylenol 3, which contains codeine, since 7/7/ 95. Probably the codeine preparation is being abused, and Dr. Rogers should be informed. 

Schedule V Substances with limited potential for abuse for example, some codeine preparations for cough, and Lomotil (which contains the opioid diphenoxylate) for diarrhea. 

Schedule V Codeine preparations—200 mg/ml or 100 g (Cosanyl, Robitussin A-C , Cheracol , Cerose , Pedciacof )... 

Pulmo-protective medication - calcium preparations and vitamin C ampoule combined applied venally, codein preparations combined with analgin and expectorating syrups perorally, inhalation of solution containing sodium bicarbonate, cortison preparations, Novphyllin etc. - upon indication. 

Schedule 111 drugs have an accepted medical use, but a lower potential for abuse than do Schedules I or II, and have a potential for low or moderate physical dependency or high psychological dependency. Examples are all barbiturate preparations (except phenobarbital) not covered under Schedule II, some codeine preparations, and steroid preparations, such as testosterone and its esters. 

Codeine, like morphine, is isolated from the opium poppy. However, the low yield of 0.7—2.5% does not provide sufficient material to meet commercial demands. The majority of marketed codeine is prepared by methylating the phenolic hydroxyl group of morphine. Morphine yields from opium poppy are 4—21%. When prescribed for cough, the usual oral dose is 10—20 mg, three to four times daily. At these doses, adverse side effects are very few. Although the abuse potential for codeine is relatively low, the compound can substitute for morphine in addicts (47). 

Molecular modifications of the morphine skeleton have produced numerous derivatives with antitussive properties, some of which have become commercially significant. Ethyknorphine [76-58-4] (29), a simple homologue of codeine, is prepared by ethylating morphine. It is pharmacologically similar to codeine but is seldom used clinically. Pholcodine [509-67-1] (30), the morpholinoethyl derivative of morphine, is used as an antitussive in a number of European countries. It is about one and a half times as potent as codeine, has Htde or no analgesic activity, and produces minimal physical dependence. The compound is prepared by the amino alkylation of morphine (48). 

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. 

Levopropoxyphene [2338-37-6] (42), the optical antipode of the dextrorotatory analgetic propoxyphene, is an antitussive without analgetic activity. The 2-naphthalenesulfonate salt has a less unpleasant taste than the hydrochloride salt, and is widely used. Clinical effectiveness has been demonstrated against pathological and artificially induced cough, but the potency is somewhat less than codeine. The compound is reported not to cause addiction. Levopropoxyphene can be prepared (62) by first resolving [ -dimethylamino-CX-methylpropiophenone with dibenzoyl-(+)-tartaric acid. The resolved... 

Diphenhydramine [58-73-1] (55) was originally developed as an antihistamine and was first used clinically for this purpose in 1946 (see HiSTAMlNE AND HISTAMINE antagonists). In addition to this primary effect, however, central antitussive activity has also been demonstrated in animals (75,76) and in humans (77). Its antitussive activity is about half that of codeine. Drowsiness is the most frequent side effect. Diphenhydramine can be prepared as follows (78) ... 

The processes used in the manufacture of morphine are believed to be still based on that described by the Scottish chemist Gregory,in 1833, with improvements devised by Anderson. A description has been published by Schwyzer, who also deals with the manufactme of codeine, narcotine, cotarnine, and the commercially important morphine derivatives, diamorphine (diacetylmorphine), and ethylmorphine (morphine ethyl ether). More recently Barbier has given an account of processes, based on long experience in the preparation of alkaloids from opium. Kanewskaja has described a process for morphine, narcotine, codeine, thebaine and papaverine, and the same bases are dealt with by Chemnitius, with the addition of narceine, by Busse and Busse, and by Dott. It is of interest to note that a number of processes for the extraction and separation of opium alkaloids have been protected by patent in Soviet Russia. ... 

Codeine, C18H21O3N. This alkaloid was isolated from opium by Robiquet in 1833. It occurs in opium to the extent of 0-1 to 3 per cent., and is isolated therefrom as the hydrochloride along with morphine hydrochloride in the first stage of Gregory s process. It is a methyl ether of morphine and is usually made from the latter by methylation, for which there are numerous patents. An extensive series of ethers of morphine and its isomerides, including ethers of the alcoholic hydroxyl group (Aeterocodeines) has been prepared by Faris and SmaU. ... 

A number of homologues of codeine have been prepared by the alkylation of morphine for example, ethylmorphine, which is used in medicine... 

Codeinone, CjaHijOgN. This ketone (XLVII) corresponds to the secondary alcohol codeine and its stereoisomeride wocodeine. It may be prepared by oxidising codeine with potassium permanganate in acetone or with potassium dichromate in dilute sulphuric acid and in various other ways. Codeinone can be reduced to codeine electrolytically or by chemical methods. It crystallises from alcohol in prisms, m.p. 185-6, [a]J, ° — 205° (EtOH). The hydrochloride, B. HCl. HjO, has m.p. 179-80°, picrate, m.p. 205°, methiodide, B. CHjI. 2H2O, m.p. 180°. 

Considerable progress has also been made with the alternative line of work, the search for a synthetic analgesic as effective as morphine and without its disadvantages. The work of the American Committee has shown that it is possible to produce analgesics with a dibenzofuran or carbazole nucleus in place of the phenanthrene or phcnanthrylene oxide nucleus of morphine and it is stated that synthetic products with analgesic potency equal to that of codeine have been prepared. In the 1938 report moderate analgesic potency was recorded for preparation No. 421, 9-methyl-2-(l-hydroxy-3-diethylamino)-propylcarbazole at 10 mgm. by injection. 

Solutions. Prepare the following series of standard solutions of codeine and morphine, each of which should cover the range 5-20 mg L-1 ... 

Prepare solutions of the accurately weighed sample (codeine-morphine mixture) in H2S04 (0.05M) and in NaOH (0.1 M). 

Typical examples that fall in this group would be the determination of the active ingredients in analgesic tablets for pharmaceutical use, such as aspirin or codeine or the analysis of a food product such as margarine. Examples of both these analyses will be described to illustrate the sample preparation procedure. 

Morphine and related opiates are known to suppress the cough reflex these compounds have thus been used extensively in antitussive preparations. Since this activity is not directly related to the analgesic potency, the ideal agent is one that has much reduced analgesic activity and thus, presumably, lower addiction potential. The weak analgesic codeine (4) is... 

Pharmacological clinical activity bias. An AE that is already present due to the disease may be increased if it is also an ADR of the drug or vice versa. For example, the diarrhea of gastroenteritis may be alleviated by codein-containing preparations given to relieve pain while the inertia of a severely depressed patient may be sufficiently resolved by an antidepressant to enable the patient to commit suicide. 

A pharmacist had 10 g of codeine sulfate. If he used it in preparing 5 capsules each containing 0.025 g, 10 capsules each containing 0.010 g, and 12 capsules each containing 0.015 g, how many g of codeine sulfate were left after he prepared all the capsules ... 

A formula for a cough syrup contains 1/8 gr of codeine phosphate per teaspoonful. How many grams of codeine phosphate should be used in preparing two pints of the cough syrup ... 

It was postulated [152, 153] that the aryl amine is oxidized by direct oxygen transfer from Compound I to the substrate. In contrast, for the oxidation of alkaloids, e.g. morphine, codeine and thebaine (Eq. 12), to the corresponding N-oxi-des by hydrogen peroxide in the presence of HRP or crude enzyme preparation from poppy seedlings, a radical mechanism was proposed [154]. 

Co-codamol is a combination of paracetamol (nonnapioid analgesic) and codeine (opioid analgesic). One of the side-effects of opioids is constipation. Naprosyn is a proprietary (trade name) preparation of the non-steroidal antiinflammatory drug naproxen Adalat is a proprietary preparation of the calcium-channel blocker nifedipine Amoxil is a proprietary preparation of the beta-lactam amoxicillin and Dulco-lax is the brand name of the stimulant laxative bisacodyl. 

Nabitan (39) is a cannabis-inspired analgesic whose nitrogen atom was introduced in order to improve water solubility and perhaps to affect the pharmacological profile as well. The phenolic hydroxyl of benzopyran synthon is esterified with 4-(l-piperidino)butyric acid under the influence of dicyclohexyl carbodi mi de. In addition to being hypotensive and sedative-hypnotic, nabitran (39) is a more potent analgesic than codeine. The preparation of synthon begins with aceto-... 

Catalytic reduction of codeine gives dihydrocodeine and Oppenauer oxidation (a ketone such as acetone and an aluminum alkoxide, the ketone being reduced to an alcohol) gives hydrocodone. Hydrocodone can also be prepared directly from codeine with a metal catalyst, which isomerizes the allylic alcohol to a ketone. Codeine is prepared by methylation of morphine, which is isolated from the opium poppy. Hydrocodone is more potent than codeine. Acetaminophen is a mild analgesic and is discussed in Section 8. 

Codeine occurs naturally in opium but the amount is too small to be useful. It is prepared from morphine by methylating the phenolic hydroxyl group with diazomethane, dimethyl sulfate, or methyl iodide. Codeine does not possess the same degree of analgesic potency as morphine but is used as an antitussive, a cough suppressant. Hydrocodone was discussed in Section 3.4. It is made from codeine. 

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