CHAPTER XIV.COCAINE AND ITS SALTS.
COCAINA, Cocaine.
Dose.—¹⁄₂₀ to 1 grain, in a pill or tablet.
This now important alkaloid, obtained from Coca, was first isolated by Niemann in 1860. From analysis he gave it the formula of C₃₂H₂₀NO₈ (old notation), but Lossen in 1862 assigned it the now accepted formula of C₁₇H₂₁NO₄₁ (new notation). It crystallizes in shining monoclinic prisms, and requires 700 or more parts of water to dissolve it; according to Dr. Paul, it takes upwards of 1,300 parts; it dissolves more readily in hot water, but rapidly undergoes decomposition, forming an acid solution which contains benzoyl-ecgonine, ecgonine, and benzoate of cocaine, which do not separate upon cooling. It is also soluble in alcohol (about 1 in 20), freely so in chloroform, ether(about 1 in 3), oil of cloves, and many other volatile oils, and 1 in 10 respectively of melted vaseline, castor oil, and other fixed oils. The latter solutions have proved serviceable in eye cases. The following are also ready solvents, each taking up about 1 of it in 3 parts: benzol, toluol, and amylic alcohol; of petroleum spirit about 25 parts are required, much less if hot; from this solution, also from hot alcohol, wood spirit, acetone and chloroform it readily crystallizes on cooling. It is almost tasteless, but produces a tingling numbness on the tongue, and local anæsthetic action on all mucous membrane. Good Coca leaves yield 0.5 per cent. or more of Cocaine, but the average is less—if fermented, oftennil. Cocaine seems to be very sensitive to chemical and physical action, and readily yields derivatives. In working the dried leaves the following compounds are also met with, Hygrine (a volatile alkaloid), Benzoyl-Ecgonine and Ecgonine, Cocamine and Cocaidine, accompanied by Coca-tannin and Coca-wax. All the Coca alkaloids, according to Hesse,[30]are derived from ecgonine methyl ester, and the ecgonine itself from pyridine. Cocaine is the most important, whilst the others, so far as is known, do not appear to be distinctly noxious, but at the same time they are inferior to Cocaine in anæsthetic properties. Ecgonine (together with benzoic acid and methyl alcohol) may also be obtained as a derivative from Cocaine when the latter is heated with hydrochloric acid, thus:—
Dr. W. Merck, by operation with hydrochloric acid on benzoyl-ecgonine, a by-product obtained in the manufacture of, and probably a derivative from Cocaine, converted this into benzoic acid and ecgonine, thus:—
With this substance also, he, as well as Skraup, has made Cocaine synthetically by heating in a tube to100° C., a mixture of benzoyl-ecgonine, iodide of methyl, and methyl alcohol; the excess of the two latter is driven off by heat and the Cocaine extracted as a syrupy hydriodate; from the salt is produced pure Cocaine, melting at 98° C. and answering all other tests. (Ber. D. Chem. Ges. 1885, 2264.) Dr. Merck has also made the synthesis from anhydrous ecgonine by combining it with benzoic acid and iodide of methyl.—Ib.2952.
As atropine can be saponified by the action of alkalies into tropic acid and tropine, and as Cocaine and atropine act on the eye as mydriatics, Dr. Einhorn has demonstrated their chemical relationship by converting anhydrous ecgonine into tropidine (the anhydride of tropine), from which it only differs in containing the carboxyl group in place of an atom of hydrogen.
On combining Cocaine with benzoic acid, benzoyl-ecgonine appears to be formed—the aqueous solution of these is not precipitated by ammonia.
Cocaine is prepared by treating powdered coca leaves with a solution of carbonate of sodium, drying the mixture and exhausting it with petroleum spirit. The latter, which dissolves the cocaine with very little colouring matter, is agitated with very dilute hydrochloric acid, the petroleum is decanted and the cocaine precipitated from the aqueous solution by adding carbonate of sodium again. The precipitate is separated by shaking with ether, which on evaporation yields crystals of almost pure Cocaine. Most of the Cocaine now used is manufactured in a crude form in Lima, and imported from Callao. It yields about 85 per cent. of pure alkaloid, and is recrystallized or converted into the hydrochlorate after its arrival in Europe.
No coloration is produced by dissolving pure Cocaine or its hydrochlorate in cold concentrated sulphuric acid; with the salt, effervescence occurs, owing to hydrochloric acid gas being set free. Some samples give a faint evanescent yellow coloration, and others give a magenta tinge which gradually passes to a brownish yellow, and eventually the solution becomes almost colourless.
If Cocaine or a salt be moistened with nitric acid, evaporated to dryness, and a drop of alcoholic caustic potashadded, a characteristic peppermint odour is developed.—P.J. 1890, 162.
Report on action of ecgonine, benzoyl-ecgonine, and cocamine.—Th. Gaz. Oct. 1889, 698.
As pure Cocaine (the alkaloid) is soluble in fats and oils, and its salts are not, it should always be used when it has to be combined with fatty or oily substances, for use externally,e.g.:—
Bougies of Cocaine.½ grain each or more, with cacao-butter.Are useful in painful affections of the urethra.Ceratum Cocainæ.1 in 30 of petroleum cerate.Is useful in burns, scalds, urticaria, pruritus, &c.Collodium Cocainæ.2 per cent. in flexible collodion.Allays the itching, and is a cure for inflamed chilblains.Emplastrum Cocainæ.1 dissolved in 50 of lead plaster heated in a water bath.
Bougies of Cocaine.½ grain each or more, with cacao-butter.
Are useful in painful affections of the urethra.
Ceratum Cocainæ.1 in 30 of petroleum cerate.
Is useful in burns, scalds, urticaria, pruritus, &c.
Collodium Cocainæ.2 per cent. in flexible collodion.
Allays the itching, and is a cure for inflamed chilblains.
Emplastrum Cocainæ.1 dissolved in 50 of lead plaster heated in a water bath.
Useful for intercostal neuralgia, sciatica, tender corns, bruises, &c.
Oleatum Cocainæ.
A saturated solution of the alkaloid in oleic acid; heated, one part will dissolve in two parts of oleic acid; it may be further diluted with oleic acid or oil. Has not proved so satisfactory a preparation as
Oleum cum Cocaina.
A 2 per cent. solution, more or less, if ordered, in almond oil, is mostly used. This is useful for earache. For the eye a 2 per cent. solution in castor oil is used; for catheters, a solution in equal parts castor and almond oils does well, it is viscid, and does not congeal in winter.
SuppositoriesandPessaries of Cocainehave ½ grain (or more, if ordered) in each with cacao-butter.
Tabellæ Cocainæ, Cocaine Tablets. ¹⁄₂₀ grain in each, with chocolate (or more, if ordered).
Dose.—1 every quarter, half-hour, or hour, quickly eaten and swallowed. Useful for sea-sickness, chloroform or alcohol sickness, sickness of pregnancy, &c.
Unguentum Cocainæ.1 in 30 of lard or lanoline (more or less, if ordered). Cocaine is soluble 1 in 2 of anhydrous lanoline if gently warmed.
Useful where absorption is required, as in facial neuralgia, shingles, eczema, erysipelas, urticaria, and pruritus.
Vaselinum Cocainæ.4 per cent. (more or less, if ordered).
Suitable for the eye; is very bland; also for smearing catheters, burns, scalds, &c.
Cocainæ Citras, Citrate of Cocaine.
Dose.—¹⁄₂₀ to 1 grain or more.
Is in deliquescent small white crystals; used by dentists.
Cocainæ Hydrobromas, Hydrobromate of Cocaine.
Dose.—¹⁄₂₀ to 1 grain, in a pill or solution. Is a stable salt, in odourless, small, white, hard, acicular crystals.
Cocainæ Hydrochloras, Hydrochlorate of Cocaine (Off.).
Off. Dose.—⅕ to 1 grain, but less and more may be given, in aqueous solution, pill, or pastil.
This salt has been most used: if pure it is in hard, colourless, short, acicular, granular-looking crystals, or, now more frequently met with, in light, shining, lamellar crystals, free from odour and almost tasteless; being soluble in half its weight of water, the tingling numbness and local anæsthesia which it produces on the tongue are more intense than that produced by pure cocaine.
Freely soluble in spirit and in glycerine, insoluble in ether, fats, and oils, and therefore it is not so compatible with them. This salt will crystallize with two molecules (9·5 per cent.) of water, but the anhydrous salt alone is official. It dissolves with effervescence but without colour in cold sulphuric acid (seeCocaine, p. 56), but chars if heated. Ignited in the air, it burns without residue. Its aqueous solution gives a white precipitate with carbonate of ammonium, soluble in excess. If one drop of solution of permanganate of potassium, B.P., be added to a solution of 1 grain of it in a drachm ofdistilled water, acidulated with three drops of diluted sulphuric acid, the bright deep colour of the solution, if kept covered, should not change during half an hour, indicating absence of other alkaloids of Coca, or any other organic matter. The salt should not only be in good crystals, but should yield a distinctly crystalline precipitate of pure cocaine within three minutes, when 1 grain of it is dissolved in 2 ounces of distilled water, and six to eight drops of solution of ammonia, B.P., are added and well stirred. The precipitate redissolves after twenty-four hours or more, the cocaine being converted into methyl alcohol and benzoyl-ecgonine.—P.J. 1888, 783. If a trace be mixed with a minute quantity of calomel and breathed upon, the mixture assumes a black colour. This will only answer with the salts of cocaine, not with the alkaloid itself.
As with an aqueous solution of sulphate of atropine, so with an aqueous solution of hydrochlorate of cocaine, some samples seem prone to grow fungi, while others will not. Evil results having followed the application of Cocaine as a local anæsthetic in several dental and eye operations, the bad effects have been attributed to these fungoid growths. Whether due to these, to impurity of the salt, or to the condition or idiosyncrasy of the patient, is not clear. Three London surgeons who have used it very largely inform me they have never seen any untoward results from its use in simple aqueous solution. Various modes of keeping the solution free from fungi have been suggested; carbolic, boric, and benzoic acids, perchloride of mercury, thymol, camphor, and chloroform have been added to check their growth; a half to one per cent. of boric acid has been particularly recommended, but it is of little use, as an aqueous solution of boric acid itself sometimes grows a fungus; chloroform is probably unobjectionable except for eye drops. Perchloride of mercury is useless, as it forms a double salt with the Cocaine. But salicylic acid has been found to be the most effective, and its addition is now ordered in the official solution. (See p. 60.)
The brush applying it should not be dipped in the stock solution.
Buginaria Cocainæ Hydrochloratis,Nasal Bougies of Hydrochlorate of Cocaine.
One-sixth of a grain in each with gelato-glycerine basis. Useful in hay fever, sometimes combined with ¹⁄₁₂₀ grain of Sulphate of Atropine in each.
Injectio Cocainæ Hydrochloratis Hypodermica.1 in 20.
Dose.—2 to 10 minims. For sciatica and many local affections acts better than morphine.
Hypodermic Lamelsare prepared containing ¼ grain in each.
Lamellæ Cocainæ, Discs of Cocaine(Off.).
Discs of gelatine, each containing ¹⁄₂₀₀ grain of hydrochlorate of Cocaine. These should be prepared in an atmosphere carefully freed from dust and germs of fungi and disease. Also prepared containing ¹⁄₅₀ grain in each, and in combination with Atropine, Homatropine, and Physostigmine.
Liquor Cocainæ Hydrochloratis(Off.) 10 per cent.Solution of Hydrochlorate of Cocaine.[31]
Dose.—2 to 10 minims. Hydrochlorate of Cocaine 100, Salicylic Acid 1½, Boiling Distilled Water to produce 1,000 fluid parts when cold.
Pastillus Cocainæ Hydrochloratis.¹⁄₂₀ grain in each (to ⅒ or ⅕ grain, or more if ordered).
Useful in allaying irritation of the throat and hoarseness. They invigorate the vocal organs of singers and public speakers.
Pastillus Cocainæ et Morphinæcontains ¹⁄₃₀ grain Cocaine and ¹⁄₆₀ grain morphine. Useful for coughs.
Pilula Cocainæ Hydrochloratis.⅕ grain in each (or more, if ordered), with sugar of milk and syrupq.s.to make a grain pill.
Tabloids of Hydrochlorate of Cocaine.⅒ and ⅙ grain each.
Are prepared for hypodermic injection.
Trochisci Cocainæ Hydrochloratis.¹⁄₁₂ grain in each. Used for similar purposes to the pastils.
Cocainæ Salicylas.
Dose.—⅕ to 1 grain or more.
Is in minute snow-white crystals, slightly deliquescent, and is recommended for the use of oculists, as it forms a solution which keeps well.
In spasmodic asthma the hypodermic injection of a good dose (6 grains) at the beginning, relieves the attack.—B.M.J. ii./86,117.
Dentifricium Cocainæ.
Mix, and add in solution:—
Triturate well together and add ammoniacal solution of carmine, 15 minims. Mix well and sift.
Said to be useful for toothache and spongy gums.
Cocaine and its salts, although selling at one time as high as 3s. 6d. per grain, are now reduced to a very moderate price.