Codeine

CODEINE (Codeinum, ФУП), methylmorphine, one of the alkaloids of opium, contained in different varieties of it in amounts of 0.25-0.75%; it is the monomethyl ether of morphine C₁₇H₁₇NO(OH)(OCH₃)H₂O. Synthetically, C. is obtained by the action of methyl iodide or methyl sulfuric acid potassium on morphine. Codeine is a colorless crystalline powder, levorotatory; it dissolves in 120 parts of cold water (5 times more soluble compared to morphine), in 17 parts of hot water, easily dissolves in alcohol and chloroform, less easily in ethyl ether (1:10) and almost does not dissolve in petroleum ether. Dried at 100° and having lost its crystallization water, C. melts at 153-155°. A solution of 1 g of C. in 10 cm³ of concentrated sulfuric acid, to which a solution of ferric chloride (1 drop per 100.0 of sulfuric acid) was added, takes on a blue-violet color upon heating. C. easily forms salts, of which the official phosphate is (Ph. VII). Aqueous solutions of C. have an alkaline reaction and a bitter taste. The absorbability of C. by mucous membranes does not differ from that of morphine; however, C. is excreted, unlike morphine, mainly with urine and only partially with feces. Like morphine, it is also excreted by the mammary glands (which may be important when C. is given to nursing mothers). Unlike morphine, it is not destroyed or transformed in the body, which is associated with the methylation of the hydroxyl group, making the C. molecule more stable. C. has almost no local action, except for the slightly depressing effect on sensitive nerve endings, which to a certain degree is characteristic of many alkaloids. The resorptive action of C. manifests itself mainly on the central nervous system and, being close to the action of morphine, can best be characterized by comparison with the latter. The narcotic, resp. depressing action of C. is expressed significantly weaker than that of morphine. The respiratory center is depressed much less, and respiratory arrest occurs only from doses five times exceeding morphine doses. Along with this relatively weak effect on the respiratory center, C. still sufficiently lowers the excitability of the 'cough center', which makes it possible to widely use it for suppressing the cough reflex without risk of causing depression of respiratory activity. In addition, in the action of C., a certain depressing effect on the vomiting center is observed, which manifests itself in the fact that C. prevents the onset of vomiting when apomorphine is administered. The depression of pain centers is expressed in C. much weaker than in morphine and can be established in humans only upon administration of 20 mg (i.e., approximately 4 times a larger dose than with morphine). Like morphine, C. causes depression of the temperature-regulating centers, lowering the temperature caused by a heat injection. Finally, unlike morphine, C. does not cause the characteristic euphoria of the latter. With the less expressed depressing narcotic action compared to morphine, C. has a stronger exciting effect, which in sufficient doses manifests itself in the appearance of convulsions. The latter can be obtained both in experiments on cold-blooded and on warm-blooded animals. In smaller doses, this exciting effect manifests itself in increased reflex excitability, which some researchers (Kraevsky) have established even in relation to the respiratory center. The action of C. on the functions of the digestive tract, so intensely expressed in morphine, is so weak that in therapeutic doses, even repeated ones, it does not play a special role. However, a weak constipating effect is still noted here, and in experiments on the isolated intestine, C., like morphine, shows an exciting effect. A significant difference from morphine is also the fact that C. much less frequently causes addiction and in the latter case does not cause such severe withdrawal phenomena upon cessation of its administration to the body. The rarity of addiction to C. may be partly associated with the absence of C.'s ability to cause euphoria. In therapy, C. is used mainly for the purpose of calming the cough reflex as a substance that has a more selective action in this regard compared to morphine and does not cause side effects in the form of depression of the respiratory center, constipation, etc., and also does not cause the dangerous addiction of morphine. Sometimes its narcotic action is also used, which is unreliable and more pronounced in children. In combination with other medicinal substances, such as analgetics from the group of antipyretics (aspirin, etc.), hypnotics used in fractional doses (veronal, luminal and others), bromides, etc., C. proves to be more capable of providing a general sedative effect. Here we are dealing with a phenomenon of synergism widely used in modern therapy. Like morphine, C. can cause phenomena of the so-called idiosyncrasy, in which the exciting effect of C. predominates: hallucinations, motor excitement, tremor, muscle twitching, diarrhea (due to increased peristalsis). Toxic doses of C. begin from 0.2, but even a dose of 1.0, causing severe phenomena, is not necessarily fatal. The toxic phenomena are expressed in nausea, pains in the intestines, colic, slowing of respiration and drowsiness. Symptoms of circulatory disturbance are not expressed. C. causes, like morphine, narrowing of the pupils, however, in the stage of convulsions or somewhat earlier, their dilation occurs.-Therapeutic measures in poisoning should be directed mainly to maintaining the activity of the respiratory center (stimulants-caffeine, lobelia, etc., inhalation of oxygen, etc.) and to removing the not yet absorbed poison by means of washing the stomach. Preparations. Codeinum purum; 0.05(!) per dose, 0.2(!) per day. Codeinum phosphoricum-colorless needle-shaped crystals, soluble in 3.2 parts of water; 0.1(!) per dose, 0.3(!) per day. Therapeutic doses. for adults begin from 10-15 mg; for children 10 years old, up to 10 mg is prescribed; for children 3 years old-4-8 mg; for infants-1.5-3 mg. It is often prescribed in 1-2% solutions for administration in drops and is added to various mixtures prescribed for diseases of the respiratory tract accompanied by severe coughing.-Kodeonal, Codeonal, a mixture of Codeini diaethylbarbiturici (20 mg) and medinal (150 mg), a white crystalline powder of bitter taste, soluble in 30 parts of hot water; prescribed in tablets as a sedative (1 tablet = 0.17 g) and for insomnia associated with cough (2 tablets = 0.34 g).-Eucodal, s hydrochloric dihydroxycodeinon-chloride C₁₈H₂₁O₄NHC1 + 3H₂O, a white crystalline powder, easily soluble in water, pharmacologically closer to morphine than to C., has significant narcotic, analgesic and hypnotic action, leads to addiction (severe eucodalism). Used as a substitute for morphine in 5-10 mg per dose, subcutaneously or per os 0.03(!) per dose, 0.1(!) per day.-Eucodin, Codeinum methylbromatum-C₁₈H₂₁O₃N(CH₃)Br, the bromide of codeine methylated at nitrogen; a crystalline substance, easily soluble in water. Prescribed in the same cases as codeine, in doses of 0.05 in tablets, powders, mixtures. Apocodeine - see Apocodeine HYDROCHLORIDE.

V. Karasiy. Discovery of C. in judicial cases. When examining internal organs, vomit, medicines, etc., C. passes into chloroform from an alkaline solution (see Poisons, isolation). Unlike morphine, C. passes into chloroform from a solution rendered alkaline with caustic soda. The residue after evaporation of the chloroform extract is tested with the general reactions for alkaloids (see), then the following reactions are performed: 1) a solution of formaldehyde in concentrated sulfuric acid gives a yellowish coloring (see Morphine), 2) a solution of molybdate salt in concentrated sulfuric acid gives a yellow-green coloring (difference from morphine), 3) C. does not give a reaction with ferric chloride (difference from morphine).