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, often _nil_. 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:—
C₁₇H₂₁NO₄ + 2H₂O = C₉H₁₅NO₃ + C₇H₆O₂ + CH₄O
Cocaine. Water. Ecgonine. Benzoic Methyl
Acid. Alcohol.
[Footnote 30: A Study of Coca Leaves and their Alkaloids:—P.J. 1891,
1109, 1129, 101.]
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:—
C₁₆H₂₁NO₄ = C₉H₁₅NO₃ + C₇H₆O₂
Benzoyl- Ecgonine. Benzoic Acid.
Ecgonine.
With this substance also, he, as well as Skraup, has made Cocaine
synthetically by heating in a tube to 100° 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 potash added, 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.
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.
=Suppositories= and =Pessaries of Cocaine= have 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 (_see_ Cocaine, 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 of distilled
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 Lamels= are 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.
[Footnote 31: This forms a stable 10 per cent. solution, which
for the use of oculists may be diluted to a 2 per cent. solution,
and still remain free from tendency to develop fungoid growths.
The salicylic acid remains as free acid in the mixture, as with
perchloride of iron it gives a more permanent violet coloration than
the so-called salicylate of cocaine. The official solution may be used
as an application for producing local anæsthesia or for hypodermic
injection, for which purpose it is found to be unirritating. A
solution up to the strength of 50 per cent. may be prepared in
salicylic acid solution of the above strength, which is nearly
saturated.]
=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 Morphinæ= contains 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 syrup _q.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.=
Phosphate of Calcium (dry), 2 ounces.
Orris, in powder, 1 ounce.
Myrrh, in powder, 30 grains.
Mix, and add in solution:—
Cocaine, 1½ ”
Oil of Eucalyptus, 12 minims.
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.