Codeine absorption

In situ quantitation The absorption photometric evaluation in reflectance was carried out at the wavelength k = 540 nm (Fig. 3). The detection limits in substance per chromatogram zone were 20 ng for thebaine and papaverine, 200 ng for codeine, 300 ng for morphine and 500 ng for narceine. 

Codeine phosphate was duly extracted into CS2 and quantitatively determined by measuring its absorption at 942 cm1. 

Opioids such as diamorphine, pethidine, and pentazocine strongly inhibit gastric emptying and greatly reduce the absorption rate of paracetamol. Codeine, however, has no significant effect on paracetamol absorption. Morphine and diamorphine have been shown to reduce the absorption of antiarrhyth-mics such as mexiletine in patients with myocardial infarction. 

Oxycodone is nearly 10 times as strong as codeine, with absorption equal to that of orally administered morphine. Neither hydromorphone nor oxycodone is approved for use in children, and hydromorphone is contraindicated in obstetrical analgesia and in asthmatics. 

The antidiarrheal activity of codeine results from two actions. First, there is a decrease in the propulsive contractile activity of the small and large intestines, which delays the forward movement of the contents of the intestines. Second, codeine causes an increase in the absorption of water from the intestinal contents. These gastrointestinal effects are mediated by specific opioid receptors in the gut (as we will see in... 

Together, the chemistry of codeine and the drug s absorption into the bloodstream, distribution to various compartments and tissues in the body, metabolism (breakdown of the parent compound into smaller molecules, or metabolites), and excretion are intimately related to how codeine exerts its medicinal or therapeutic effects. Codeine s chemical properties and pharmacologic characteristics explain how, figuratively speaking, a spoonful of codeine can relieve pain, suppress cough, or act as an antidiarrheal. 

The absorption spectrum of morphine has been determined by Hartley [594], Mayer (in sulphuric-nitric acid) [595], and Kitasato [596], and the ultra-violet absorption spectrum (shown in comparison with that of codeine in Chap. IV) by other workers [597-602],... 

Thermochemical studies have been made by Leroy [394-5], The absorption spectrum of codeine in the visible [396-7] and in the ultraviolet [398-9] has been determined. The ultra-violet absorption curve, compared with those of morphine and thebaine is given in Mg. 1. That of ethylmorphine is closely similar [400]. 

N ic opine was first isolated by Dobbie and Lauder from the last mother liquors from the processing of the opium alkaloids after all other bases had been eliminated [1], This remains the only source of the base. The method of isolation has since been improved and the alkaloid can ho separated from codeine through the sulphates [2], The base was first allotted the formula C18H2404N and the name hydroxycodeine it was shown to contain one —OMe, one —NMe, and to be a tertiary base. Its colour reactions and ultra-violet absorption spectrum are practically idontical with those of codeine [1]. 

Thebainone-B [xm] is best prepared as its hydrobromide by the hydrolysis of dihydrothebaine- [iv] with alcoholic hydrobromic acid [13], but it is also formed by the hydrolysis of the same base with mineral acid in aqueous solution [13], a reaction first reported to give an ill-defined substance, isocodeine [18], and later said to give a coloured, varnish-like substance [3]. Thebainone-B appears to be stable only as its salts in the dry state, the damp salts and free base readily degenerating to brown tars [13]. The ultra-violet spectra of thebainone-A, /3-thebainone-A, and thebainone-B closely resemble those of dihydrothebaine- and codeine, whilst that of thebainone-C is widely different (Fig. 8) and the frequencies of the carbonyl-absorption in the infra-red indicate that whereas thebainone-A and /3-thebainone-A are a /3-unsaturated ketones, the unsaturation is /3 y- in thebainone-B and thebainone-C [13]. On this evidence thebainone-B is allotted the structure [xm]. It can be catalytically reduced to dihydrothebainone [ix], in which the configuration at C-14 is the same as in codeine [13] (cf. the production of dihydrocodeine on reduction of neopine [xiv] [19]). 

Codeine dihydromethine [xn] has now been prepared by the sodium-ammonia reduction of codeine methiodide, together with dihydrodesoxy-codeine-C dihydromethine [xiii]. Both [xii] and [xni] result from the sodium and liquid ammonia reduction of a-codeimethine [xiv] [2] (cf. p. 106). The sodium and liquid ammonia reduction of dihydrocodeine methiodide affords a-tetrahydrocodeimethine, and the reduction of /3-codeimethine [xv] yields neopine dihydromethine [xvi]. When the methiodide of the latter is heated with sodium cyciohexyloxide in cyciohexanol a mixture of methyl-morphenol [xvn] and (-f-)-6-hydroxy-3-methoxy-5 6 7 8 9 10-hexahydro-phenanthrylene-4 5-oxide [xviii] is obtained. The latter structure is assigned to the product on account of the close resemblance of its ultra-violet absorption spectrum to that of a-codeimethine. This represents a new type of degradation with hydrolytic scission of the side-chain [2]. Metathebainone methine has also been degraded in this way [2]. 

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